\..S!; 


BRAIN  MECHANISMS  AND  LEARNING 


BRAIN  MECHANISMS 

AND 

LEARNING 


A  SYMPOSIUM 

organized  by 

THE  COUNCIL  FOR  INTERNATIONAL 

ORGANIZATIONS  OF  MEDICAL  SCIENCES 

Established  under  the  joint  auspices  of 
UNESCO  and  WHO 


Coiisiihiug  Editors 
A.  Fessard         R.  W.  Gerard        J.  Konorski 

Editor  for  tlic  Council 
J.  F.  Delafresnaye 

C.LO.M.S. 

Paris,  France 


BLACKWELL 

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OXFORD 


(jC)  Blackwell  Scientific  Publications  Ltd.,  ig6i 

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CONTENTS 

Page 

List  of  those  participating  in  the  symposium  vii 

Foreword  by  J.  F.  Dclafresnayc,  Executive  Secretary,  CIOMS  ix 

Prefacio  by  A.  Establicr,  Director,  LASCO  xi 

Introduction  by  A.  Fcssard,  ori^mnzer  of  the  symposium  xiii 

Darwin  and  concepts  of  brain  function,  by  H.  W.  Magoun  i 

The  fixation  of  experience,  by  R.  W.  Gerard  21 
Distinctive  features  of  learning  in  the  higher  animal,  by  D.  O. 

Hcbb  37 
The    interactions    of    unlearned    behaviour    patterns    and 

learning  in  mammals,  by  I.  Eibl-Eibcstcldt  S3 
Some  characteristics  of  the  early  learning  period  in  birds,  /))' 

W.  H.  Thorpe  75 
Some  aspects  of  the  elaboration  of  conditioned  connections 

AND  FORMATION  OF  THEIR  PROPERTIES,  by  E.  A.  Asratyaii  95 

The  PHYSIOLOGICAL  APPROACH  TO  THE  PROBLEM  OF  RECENT  MEMORY, 

by  ].  Konorski  1 15 

Conditioned    reflexes    established    by    coupling    electrical 

EXCITATIONS  OF  TWO  CORTICAL  AREAS,  by  R.  W.  Doty  and  C. 

Giurgca  133 

Interference    and    learning    in    palaeocortical    systems,    by 

J.  Olds  and  M.  E.  Olds  153 

A  NEW  CONCEPTION  OF  THE  PHYSIOLOGICAL  ARCHITECTURE  OF  CONDI- 
TIONED REFLEX,  by  P.  K.  Anokhin  i8y 

Changing  concepts  of  the  learning  mechanism,  /))'  R.  Galanibos     331 

The  significance  of  the  earliest  manifestations  of  conditioning 

in  the  mechanism  of  learning,  by  E.  Grastyan  243 

Behavioural  and  EEG  effects  of  tones  'reinforced'  by  cessation 
OF  PAINFUL  stimuli,  /)/  J.  P.  Segundo,  C.  Galcano,  J.  A. 
Sommer-Smith  and  J.  A.  Roig  265 

Neurohumoral  factors  in  the  control  of  animal  behaviour, 

by  K.  Lissak  and  E.  Endroczi  293 

Considerations  on  the  histological  bases  of  neurophysiology, 

by  C.  Establc  309 

The  effects  of  use  and  disuse  on  synaptic  function,  by].  C.  Ecclcs     335 

La  facilitation  de  post-activation  comme  facteur  de  plasticite 
dans  l'etablissement  des  liaisons  temporaires,  par  A. 
Fessard  et  Th.  Szabo   y^JolCik  4  r^  i   9  353 


^ 


U8RA«Y  ,^ 


vi  contents 

Lasting  changes  in  synaptic  organization  produced  by  con- 
tinuous NEURONAL  BOMBARDMENT,  by  F.  Morrcll  375 

Functional  role  of  subcortical  structures  in  habituation 
AND  CONDITIONING,  by  R.  Hernandcz-Peoii  and  H.  Brust- 
Carmona  393 

Functions  of  bulbo-pontine  reticular  formation  and  plastic 

PHENOMENA  IN  THE  CENTRAL  NERVOUS  SYSTEM,   by  M.   PalcStilli 

and  W.  Lifschitz  413 

Changes  in  cortical  evoked  potentials  by  previous  reticular 

STIMULATION,   /)/  M.   R.   Covian,   C.   Timo-Iaria  and  R.   F. 

Marscillan  43:5 

Recherches  sur  les  mecanismes  neurophysiologiques  du  som- 

MEiL  ET  DE  l'apprentissage  negatif,  par  M.  Jouvct  445 

Corpus  callosum  and  visual  gnosis,  by  R.  E.  Myers  481 

Anatomical    and    electrographical    analysis    of    temporal 

neocortex  in  relation  to  visual  discrimination  learning 

IN  monkeys,  by  K.  L.  Chow  507 

Observations  sur  le  conditionnement  instrumental  alimen- 

taire  CHEZ  LE  CHAT,  par  P.  Busci"  et  A.  Rougcnl  527 

Non-sensory  effects   of    frontal    lesions   on    discrimination 

learning  and  performance,  /)}'  rt.  E.  Rosvold  and  M.  Mishkin  555 
Studies  of  hippocampal  electrical  activity  during  approach 

LEARNING,  by  W.  R.  Adcy  577 

Role  of  the  cerebral  cortex  in  the  learning  of  an  instru- 
mental conditional  response,  by  T.  Pinto  Hamuy  589 
Significance  of  the  photic  stimulus  on  the  evoked  responses 

in  man,  by  E.  Garcia-Austt,  J.  Bogacz  and  A.  Vanzulli  603 

Conditionnement  de  decharges  hypersynchrones  epileptiques 

CHEZ  l'homme  et  l'animal,  par  R.  Naquct  625 

General  discussion  641 

Bibliography  665 

Index  •  699 


LIST  OF  PARTICIPANTS 
W.  Ross  Adey 

University  of  California,  Los  Angeles  (U.S.A.) 

P.  K.  Anokhin 

Academy  of  Medical  Sciences,  Moscow  (U.S.S.R.) 

E.    ASRATYAN 

Academy  of  Sciences,  Moscow  (U.S.S.R.) 

P.    BUSER 

Universite  de  Paris  (France) 

K.  L.  Chow 

University  of  Chicago  (U.S.A.) 

M.    COVIAN 

Faculdadc  de  Medicina,  Sao  Paulo  (Brazil) 

R.  W.  Doty 

University  of  Michigan,  Ann  Arbor  (U.S.A.) 

J.    C.    ECCLES 
The  Australian  National  University,  Canberra  (Australia) 

I.    ElBL-ElBESFELDT 
Max-Planck-Institut  tucr  Verhaltensphysiologie,  Seewiesen  (Germany) 

C.    ESTABLE 
Instituto  de  Investigacion  de  Ciencias  Biologicas,  Montevideo  (Uruguay) 

A.  Fessard 

College  de  France,  Paris  (France) 

R.  Galambos 

Walter  Reed  Army  Medical  Center,  Washmgton  (U.S.A.) 

E.  Garci'a-Austt 

Instkuto  de  Neurologia,  Montevideo  (Uruguay) 

R.  W.  Gerard 

University  of  Michigan,  Ann  Arbor  (U.S.A.) 

E.  Grastyan 

University  of  Pecs  (Hungary) 

D.  O.  Hebb 

McGill  University,  Montreal  (Canada) 

R.  Hernandez-Peon 

Centro  Medico  del  Distrito  Federal,  Mexico 

M.  JOUVET 

Faculte  de  Medecine  de  Lyon  (France) 


VIU  LIST  OF  PARTICIPANTS 

J.    KONORSKI 

Institute  of  Experimental  Biology,  Warsaw  (Poland) 

K.    LiSSAK 
University  of  Pecs  (Hungary) 

J.  Luco 

Universidad  Catolica,  Santiago  (Chile) 

H.  W.  Magoun 

University  of  California,  Los  Angeles  (U.S.A.) 

F.    MORRELL 

University  of  Minnesota,  Minneapolis  (U.S.A.) 

R.  E.  Myers 

Walter  Reed  Army  Institute  of  Research,  Washmgton  (U.S.A.) 

R.  Naquet 

Facultc  de  Mcdccine  de  Marseille  (France) 

J.  Olds 

The  University  of  Michigan,  Ann  Arbor  (U.S.A.) 

M.  Palestini 

Facultad  de  Mcdicina,  Santigo  (Chile) 

T.  Pinto  Hamuy 

Universidad  de  Chile,  Santiago  (Chile) 

H.  E.  RosvoLD 

National  Institute  of  Mental  Health,  Bethesda  (U.S.A.) 

J.  P.  Segundo 

Instituto  dc  Investigacion  de  Cicncias  Biologicas,  Montevideo  (Uruguay) 

W.  H.  Thorpe 

University  of  Cambridge  (U.K.) 


FOREWORD 

Six  years  after  the  Laurentian  symposium  on  'Brain  Mechanisms  and 
Consciousness',  the  Council  for  International  Organizations  of  Medical 
Sciences  (C.I.O.M.S.)  convened  a  meeting  to  explore  the  neurophysio- 
logical  basis  of  learning.  The  meeting  was  held  in  Montevideo,  from 
August  2nd  to  8th,  1959,  and  was  jointly  sponsored  by  and  organized  with 
the  Science  Co-operation  Office  of  Unesco  for  Latin  America. 

Dr  A.  Fessard  was  responsible  for  the  scientific  planning  of  the  meeting 
and  shared  with  Dr  Ralph  Gerard  the  responsibility  of  presiding  over  it. 
May  they  both  find  here  an  expression  of  the  Council's  gratitude  for  the 
magnificent  way  in  which  they  discharged  their  duties. 

Looking  back  over  the  years,  it  is  impossible  not  to  draw  a  parallel 
between  the  meeting  held  in  Canada  and  the  one  held  in  Uruguay. 

In  each  case,  the  meeting  was  co-ordinated  with  the  International 
Physiological  Congress.  Both  were  'firsts':  the  first  CIOMS  symposium 
in  North  America  and  the  tirst  in  Latin  America.  And  then,  of  course,  a 
number  of  scientists  took  part  in  both  meetings.  But  here  the  parallel 
must  end. 

In  Montevideo,  we  were  able  to  cast  our  net  wider  and  we  were  pleased 
to  welcome  a  number  of  distinguished  investigators  from  Australia, 
Brazil,  Chile,  Hungary,  Mexico,  Poland,  Uruguay,  and  the  U.S.S.R., 
who  had  not  attended  the  meeting  in  Canada.  An  organizing  committee 
composed  of  Drs  R.  Arana,  D.  Bennati,  C.  Estable,  and  of  Drs  E.  Garcia- 
Austt  and  J.  P.  Segundo,  who  acted  as  joint  secretaries,  took  charge  ot  all 
technical  arrangements  and  provided  much  appreciated  entertainment  for 
all  who  took  part  in  the  meeting.  Credit  must  go  to  this  committee  for 
having  created  the  right  conditions  for  the  development  of  an  atmosphere 
of  understanding  and  friendliness.  May  this  committee  find  here  an 
expression  of  the  Council's  gratitude. 

It  is  also  a  pleasant  task  to  put  on  record  the  Council's  indebtedness  to 
the  various  agencies  which  supported  directly  or  indirectly  the  meeting, 
and  in  particular  to  the  European  Office,  A.R.D.C.-^  whose  grant  was 
used  to  cover  the  travelling  expenses  of  a  number  of  participants. 

I  am  also  pleased  to  thank  Miss  Henderson  and  Dr  Christie,  who 
transcribed  the  discussion,  and  the  secretarial  staff,  who  worked  very  hard 
to  get  everything  ready  in  time. 

^  Contract  No.  AF61  (052)-207. 

ix 


X  FOREWORD 

This  monograph  is  the  record  of  what  happened  in  Montevideo  and 
has  been  put  together  with  the  help  of  the  consuking  editors.  May  I  thank 
all  three  but  especially  Dr  Fessard  who,  being  on  the  spot,  has  advised  me 
on  many  points. 

It  is  the  hope  of  all  who  contributed  to  this  book  that  it  will  be  of  value 
to  all  those  who  study  the  fundamental  processes  of  learning,  wherever 
they  may  be. 

J.  F.  Delafresnaye 


PREFACIO 

El  Centro  de  Cooperacion  Cicntifica  de  la  UNESCO  para  America 
Latina  ha  contribuido  a  organizar  la  reunion  que  sobre  'Brain  Mecha- 
nisms and  Learning'  decidio  celebrar  en  Montevideo  el  Consejo  Intcr- 
nacional  de  Organizaciones  dc  Cicncias  Medicas  (C.I.O.M.S.). 

Es  ya  de  tradicion  la  organizacion  de  Symposia  por  los  Centros  de 
Cooperacion  Cientifica  de  la  UNESCO  y  comienza  a  ser  habitual  el 
que  algunos  de  ellos  se  monten  con  la  colaboracion  de  la  C.I.O.M.S., 
organizacion  que  tan  activamente  se  ocupa  de  los  problemas  basicos  de  la 
Medicina. 

La  iniciativa  de  esta  reunion  vino  dc  un  latinoamericano,  el  Dr.  Raul 
Hcrnandcz-Peon,  y  era  logico  pensar  que  el  Centro  de  Montevideo 
aportase  su  plena  colaboracion  a  esta  manifestacion. 

Hace  varios  anos,  igualmente  en  Montevideo,  organize  el  Centro  de 
Cooperacion  Cientifica  un  Symposium  scerca  dc  otro  tenia  de  fisiologia, 
nos  referimos  al  titulado  Symposium  sobre  'Problemas  fundamentales  de 
cstructura  y  fisiologia  celular'  que  reunio  a  invcstigadorcs  latino- 
amcricanos,  norteamcricanos  y  europcos. 

Esta  insistencia  en  organizar  este  tipo  dc  reuniones  sobre  tcmas  de 
Biologia  en  Montevideo  se  justifica  por  la  prescncia  en  el  Uruguay  del 
Institute  de  hivestigaciones  de  Ciencias  Biologicas  dirigidopor  elconocido 
Profesor  Clcmente  Establc. 

El  Symposium  sobre  'Brain  Mechanisms  and  Learning'  es  un  ejemplo  de 
la  cooperacion  entre  organismos  internacionales  y  comites  nacionales.  La 
C.LO.M.S.  orientada  cientificamente  en  esta  reunion  por  el  Dr.  A. 
Fessard,  con  la  incansable  tenacidad  de  su  Secretario,  el  Dr.  J.  F.  Dela- 
fresnaye,  encontro  el  apoyo  de  un  Comite  local  uruguayo  que  le  brindo  su 
plena  colaboracion.  El  Centro  de  Cooperacion  Cientifica  de  la  UNESCO 
para  America  Latina  aporto  toda  la  ayuda  que  podia  prestar.  Ha  sido  una 
reunion  de  un  alto  nivel  cientifico  y  que  ha  demostrado  plenamente  hasta 
que  punto  puede  llegarse  en  la  colaboracion  cientifica  cuando  se  consigue 
una  pcrfecta  coordinacion  de  esfuerzos. 

A.  Establier 
Director  del  Centro  de  Cooperacion 

Cientifica  para  America  Latina  de  la 

UNESCO 
xi 


'lu'  LIBRARY    ,3= 
INTROD  UCTION  \  J'f--.  ^/ass-^^  \ 

Lcs  mccanismes  du  ccrvcau  oftrcnt  uiic  niaticrc  incpuisablc  pour  des 
themes  de  symposiums.  Apres  le  Brain  Mccluviisiiis  and  Coiiscioiisiiess  de 
Ste  Marguerite  (Canada),  en  aoiit  1953,  bien  d'autres  reunions  scienti- 
hqucs  de  meme  espece  eurent  lieu,  ou  I'interet  se  porta  tantot  sur  lcs 
proprietcs  de  la  formation  rcticulee,  tantot  sur  lcs  rapports  des  reflexes 
conditionncs  avcc  relectroenccphalogramme,  ou  encore  sur  les  bases 
nervcuses  du  comportement,  pour  ne  citer  que  trois  exemples.  Le  sym- 
posium dont  il  s'agit  ici  iut  consacre  aux  problcmes  de  I'Apprentissage, 
ou  Learning,  I'accent  etant  mis  sur  lcs  mccanismes  ncurophysiologiques 
dont  CCS  phenomenes  dependent. 

L'initiativc  du  choix  de  cc  sujet,  ainsi  que  la  conception  generale  du 
symposium,  reviennent  au  Dr  Raul  Hernandez-Peon  dont  on  connait  les 
importantcs  contributions  cxperimcntales  dans  cc  domaine.  Son  projet 
re^ut  un  excellent  accucil.  Il  cut  aussi  la  bonne  fortune  de  pouvoir  etre 
parrainc  par  le  CIOMS,  cc  qui  signifiait  que  son  execution  scrait  remise 
aux  mains  du  Dr  Dclafrcsnayc,  dont  lcs  qualites  d'organisateur  eurent 
ainsi  I'occasion  de  se  manitester  une  fois  de  plus.  Il  vicnt  dc  nous  rappelcr 
tout  cc  que  cette  reunion  a  du  a  rextreme  obligeancc  et  a  I'activitc  dili- 
gcnte  de  nos  botes  uruguayiens  et  aux  institutions  qui  aidcrent  matcricllc- 
ment  le  projet  a  se  realiscr.  Il  n'appartient  pas  aux  organisateurs  de  porter 
un  jugement  sur  la  valcur  du  resultat:  comme  il  est  de  regie,  Icurs  buts  nc 
turent  que  partiellemcnt  attcints  et  ils  ne  sc  croient  pas  a  I'abri  de  toutc 
critique. 

Tout  d'abord,  un  theme  connnc  cclui-ci  pourrait  ctre  traite  de  points  dc 
vue  bien  diflerents.  On  nous  reprochcra  probablement  ccrtaines  lacuncs, 
(HI  d'avc^ir  donne  trop  peu  dc  place  a  certains  aspects.  Il  etait  impossible  en 
iait  dc  couvrir  entierement  un  champ  aussi  vaste  que  cclui  qui  nous  etait 
impose.  On  notera  cependant  que  nous  nous  sommes  efforccs  de  fairc 
appcl  a  des  disciplines  differcntcs.  Si  lcs  neurophysiologistes  formcrent, 
comme  il  se  devait,  notrc  majorite,  les  points  dc  vue  du  psychologuc  et 
de  I'ethologiste  purent  s'exprimcr,  ct  du  cote  des  donnecs  de  base,  une 
place  fut  rcservee  a  I'anatomie  et  aux  aspects  physicochimiqucs.  Les 
neurophysiologistes  eux-mcmcs  representaient  des  tendances  diverses, 
depuis  les  electrophysiologistcs  du  cerveau  jusqu'aux  specialistes  du 
rcflexc  conditionne  classique. 

Le  choix  des  participants  a  etc  —  est-il  besoin  de  le  dire  ?  —  le  probleme 

xiii 


XIV  INTRODUCTION 

le  plus  cmbarrassant  pour  les  organisateurs.  Il  y  a  partout  dans  Ic  mondc 
d'excellents  representants  de  ce  genre  de  recherches  ct  bcaucoup  d'entre 
eux  nous  ont  manque.  Quelques-uns,  dont  le  noni  s'iniposait,  prcssentis, 
declinerent  I'invitation.  Lorsqu'il  y  eut  necessite  de  choix,  ce  furent 
generalement  des  raisons  contingcntes  qui  dccidcrent.  L'idce  a  prevalu 
qu'il  etait  souhaitable  de  niettre  en  presence  sur  ce  theme  de  I'Apprentis- 
sage,  des  representants  de  pays  que  les  circonstances  avaient  longtemps 
empeches  de  confronter  leurs  theses.  Que  ccux  qui  sont  venus  de  I'Europe 
de  I'Est  aient  eu  ainsi  la  possibilite  de  discutcr,  sur  un  sol  sud-americain 
avec  les  representants  de  ce  qu'on  appelle  I'Occident,  voila  un  signe 
encourageant  pour  I'avenir  des  relations  scientifiqucs  internationales. 

Le  Symposium  de  Montevideo  n'a  ete  comme  tout  autre-,  qu'un  echan- 
tillonnage,  dans  I'ordre  des  personnes,  comme  dans  celui  des  questions 
traitees,  et  une  grande  part  de  hasard  a  preside  a  cet  echantillonnage.  Nous 
espcrons  cependant  que  le  livre  qui  en  est  le  reflet  apportera  a  peu  prcs  ce 
qu'ils  cherchent  a  ceux  qui  desirent  prendre  une  vue  d'ensemble  sur  une 
question  qui  represente  un  aspect  majeur  de  la  connaissance  de  THomme 
et  des  lois  de  la  nature. 

A.  Fessard 


DARWIN  AND  CONCEPTS  OF  BRAIN  FUNCTION 
H.  W.  Magoun 

It  is  appropriate  in  the  Darwin  Centennial  Year  (1959)  to  recall  the 
impressions  made  by  a  visit  to  South  America  upon  a  young  graduate  of 
Cambridge  whose  studies,  begun  in  theology,  had  turned  instead  to  the 
sciences.  Darwin  arrived  in  South  America  as  a  naturalist  on  the  voyage  of 
H.M.S.  Beagle,  circumnavigating  the  globe.  Reaching  Buenos  Aires,  in 
October  of  1832,  he  found  a  violent  revolution  had  broken  out  and 
wrote,  'I  was  glad  to  escape  on  board  a  packet  bound  tor  Monte  Video, 
the  second  town  of  importance  on  the  banks  of  the  Plata'  (Darwin,  1S39). 

His  young  man's  eye  was  critical,  and  his  opinions  mixed:  'The  Plata', 
he  wrote,  'looks  hke  a  noble  estuary  on  the  map;  but  it  is  in  truth  a  poor 
affair.  A  wide  expanse  of  muddy  water,  it  has  neither  grandeur  nor 
beauty.  At  one  time  of  the  day  the  two  shores,  both  of  which  are  extremely 
low,  could  just  be  distinguished  from  the  deck.  The  land,  with  the  one 
exception  of  the  Green  Mount,  450  feet  higli,  from  which  it  takes  its  name, 
is  level.  Very  little  of  the  undulating  grassy  plain  is  enclosed,  but  near  the 
town,  there  are  a  few  hedgebanks.  There  is  something  very  delightful  in 
the  free  expanse,  where  nothing  guides  or  bounds  your  walk,  yet  I  am 
disappointed  as  regards  scenery.' 

The  short  surveying  trips  of  the  Beagle  up  anci  down  the  coast  left 
Darwin  with  time  ashore.  'In  the  sporting  line,  I  never  enjoyed  anything 
so  much  as  ostrich  hunting  with  the  wild  soldiers.  They  catch  the  birds  in 
a  fine,  animated  chase  by  throwing  two  balls  which  are  attached  to  the 
ends  of  a  thong  so  as  to  entangle  their  legs.'  (One  was  a  new  species,  later 
named  Rhea  Darwinii.)  The  young  man  took  an  interest  in  gaining  dex- 
terity with  the  bolas:  'One  day  as  I  was  amusing  myself  by  galloping  and 
whirling  the  balls  around  my  head,  by  accident  the  free  one  struck  a 
bush  and,  like  magic,  caught  one  hind  leg  of  my  horse;  the  other  ball  was 
then  jerked  out  of  my  hand,  and  the  horse  was  fairly  secured.  The  gauchos 
roared  with  laughter ;  they  cried  out  that  they  had  seen  every  sort  of  an 
animal  caught,  but  had  never  before  seen  a  man  caught  by  himself 

On  a  trip  into  the  interior,  Darwin's  party  stayed  at  an  estancia  belong- 
ing to  one  of  the  greatest  land  owners  of  the  country,  with  whom  was  a 
captain  in  the  Army.  'Considering  their  station,  their  conversation  was 

I 


BRAIN    MECHANISMS    AND    LEARNING 


rather  amusing.  Upon  fniding  out  wc  did  not  catch  our  horses  and  cattle 
in  England  with  the  lazo,  they  cried  out,  'Ah,  then,  you  use  nothing  but 
the  bolas.'  The  idea  of  an  enclosed  country  was  quite  new  to  them.  The 
Captain  at  last  said  he  had  one  question  to  ask  me.  I  trembled  to  think  how 
deeply  scientific  it  might  be.  It  was  'whether  the  ladies  of  Buenos  Ayres 
were  not  the  handsomest  in  the  world'.  I  replied  like  a  renegade,  'Charm- 
ingly so.'  He  added,  'Do  ladies  in  the  other  part  of  the  world  wear  such 
large  combs?'  I  solemnly  assured  him  that  they  did  not. 

'They  were  absolutely  delighted.  The  Captain  exclaimed,  'Look  there! 
A  man  who  has  seen  half  the  world  says  it  is  the  case;  we  always  thought  so 
but  now  we  know  it.'  My  excellent  judgment  in  combs  and  beauty 
procured  me  a  most  hospitable  reception.'  Darwin's  remarks  may  have 
expressed  more  than  disinterested  diplomacy,  however,  for  at  this  time  a 
letter  to  his  sister  read:  'On  shore,  our  chief  amusement  was  riding  about 
and  admiring  the  Spanish  ladies.  After  watching  one  of  these  angels 
gliding  down  the  street,  involimtarily  we  groaned,  "How  foolish  English 
women  are.  They  can  neither  walk  nor  dress."  And  then,  how  ugly  Miss 
sounds  after  Signorita.' 

Leaving  now  the  attractive  ladies  of  Buenos  Aires,  the  experiences  of 
Darwin's  South  American  visit  led  gradually  to  his  formulation  of  the 
theory  of  evolution  by  natural  selection,  certainly  one  of  the  most  out- 
standing contributions  to  biology  and  one  with  many  broad  implications. 
The  ScaJa  naturae,  in  which  living  beings  were  arranged  in  a  spectrum  of 
increasing  complexity,  was  familiar  to  earlier  naturalists  and  to  the  bio- 
logists of  the  eighteenth  century,  by  whom  its  order  was  generally  con- 
ceived as  the  immutable  product  of  divine  creation.  Darwin's  revolu- 
tionary conception,  published  a  century  ago,  as  the  Origin  of  Species 
(1859),  proposed  instead  that  natural  selection,  working  on  the  range  of 
normal  variations,  led  to  survival  of  the  fittest  and  so  accounted,  in  a 
materiahstic  way,  both  for  evolution  and  for  the  adaptation  of  existing 
forms  to  their  environments. 

Darwin's  later  writings,  on  the  Descent  of  Man  (1871)  and  the  Expression 
of  Emotion  in  Man  and  A)iinials  (1872),  called  more  particular  attention  to 
the  phylogenetic  development  of  the  brain.  In  keeping  with  his  contribu- 
tions, and  related  to  the  interest  in  evolution  created  by  them,  views  were 
subsequently  developed  by  Hughlings  Jackson  in  neurology,  by  Pavlov  in 
physiology  and  by  Freud  in  psychiatry,  each  of  whom  accounted  for  the 
phylogenetic  elaboration  of  the  central  nervous  system  in  terms  of  a  series 
of  superimposed  levels,  added  successively  as  the  evolutionary  scale  was 
ascended. 


H.    W.    MAGOUN  3 

In  each  of  these  conceptual  systems  (Fig.  i),  the  management  of  pnmi- 
tive,  innate,  stereotyped  behaviour,  having  to  do  with  the  preservation  of 
the  individual  and  the  race,  was  attributed  to  older,  subcortical,  neuraxial 
portions  of  the  central  nervous  system,  which  formed  Jackson's  lowest 
level  and  subserved  the  Pavlovian  unconditioned  reflex  and  the 
Freudian  id. 


ENGLISH 

RUSSIAN 

COMPARATIVE 

PSYCHOANALYTIC 

NEUROLOGY 

NEUROPHYSIOLOGY 

NEUROANATOMY 

PSYCHIATRY 

SYNTHESIS 

Hughlings  Jockson 

Ivan  P  Pavlov 

Edinger,  Koppers,  Herrick 

Sigmund   Freud 

HIGHEST 
LEVEL 

SECOND 
SIGNAL 
SYSTEM 

^ 

SUPER 
EGO 

ABSTRACTION 
DISCRIMINATION 
SYMBOLIZATION 
COMMUNICATION 

MIDDLE 

CONDITIONED 

r/^ 

ACQUIRED 

LEVEL 

REFLEX 

-^ 

EGO 

ADAPTIVE 
BEHAVIOR 

LOWEST 

UNCONDITIONED 

'Ti 

INNATE 

LEVEL 

REFLEXES 

^ 

10 

STEREOTYPED 
PERFORMANCE 

Fig.  I 
Chart  coinpanng  the  evolutionary  concepts  of  the  organization  and  function  ot  the  brain 
whiclr  developed  after  Darwin  and  Spencer. 

Modified  from  a  chart  by  Stanley  Cobb,  Human  nature  and  the  understandintj;  of  disease, 
in:  Faxon,  N.W.  The  Hospilnl  in  Coiiiciiipordry  Lift'.  Harvard  Univ.  Press,  Cambridge,  Mass., 
1949- 


Next,  the  more  mutable,  adaptive,  learned  behaviour  of  Pavlov's 
conditioned  reflex,  together  with  the  capacity  of  the  Freudian  ego  for 
perception  and  the  initiation  of  movement  were  ascribed  to  higher  neural 
structures,  including  the  sensori-motor  cortex  of  Jackson's  middle  level, 
which  developed  above  or  upon  the  older  subjacent  parts. 

Finally,  in  the  brain  of  man,  hypertrophy  of  the  associational  cortices  of 
the  frontal  and  parieto-occipito-temporal  lobes,  forming  Jackson's  highest 
level,  was  correlated  with  the  capacities  of  Freud's  superego  and,  in  the 


4  BRAIN    MECHANISMS    AND    LEARNING 

dominant  hemisphere,  with  the  capabihties  of  Pavlov's  second  signal 
system  for  symbolization  and  communication  by  means  of  spoken  and 
written  language. 

Further  testimony  for  the  evolution  of  neurological  function  in  these 
terms  was  provided  by  Jackson's  view  of  dissolution,  or  reversal  of  the 
phylogenetic  process  when  clinical  impairment  proceeded  from  highest 
through  middle  to  lowest  levels  during  neurological  disease  in  man 
(Jackson,  1958).  Jackson  specified  that  the  resulting  deficit  was  usually 
accompanied  by  some  release  of  lower  activity,  normally  subjugated  to 
higher  control.  This  latter  feature  was  elaborated  also  in  the  Freudian 
system,  in  which  conflicting  interests  of  the  different  levels  were  emphasized 
as  a  source  of  psychic  disturbance. 

In  much  the  same  way  that  increased  complexity  and  specialization 
appeared  as  the  ladder  of  nature  was  ascended  by  the  earlier  classification- 
ists,  more  and  more  elaborate  functions  came  to  view  as  one  climbed 
cephalically  up  the  successive  levels  of  the  central  nervous  system.  In  its 
progressive  enccphalization,  the  brain  came  to  resemble  the  earth  itself,  not 
simply  in  its  globular  form  but  in  consisting  as  well  of  a  series  of  strata  laid 
down  like  those  of  geology,  one  upon  the  other,  in  evolutionary  time. 
Each  neural  accretion  was  associated  with  a  characteristic  increment  of 
function  and,  following  Jackson,  a  dis-solutionary  school  of  neurophysio- 
logy developed,  in  which  enccphalization  was  reversed  by  operative 
transection  and  evolution  traced  backward  by  observing  residual  capaci- 
ties diminish  in  the  increasingly  truncated,  decorticate,  decerebrate  and 
spinal  preparations. 

Probably  because  such  views  arc  still  so  contemporary,  little  attention 
has  been  given  to  exploring  the  role  of  Darwin,  and  the  interest  in  evolu- 
tion excited  by  his  work,  in  establishing  these  concepts  of  neural  organiza- 
tion and  function.  The  views  of  Hughlings Jackson  (1958),  which  might  be 
presumed  to  be  the  most  directly  Darwinian,  were,  on  the  contrary, 
derived  chiefly  from  Thomas  Laycock,  with  wht~)m  Jackson  began  his 
career  in  York,  and  from  Herbert  Spencer,  whom  he  admired  greatly. 
Both  Laycock  and  Spencer  had  applied  evolutionary  principles  to  con- 
cepts of  the  organization  and  function  of  the  brain  independently  of  and 
preceding  Darwin.  In  his  Mind  and  Brain,  first  published  in  1859,  Laycock 
wrote:  'As  wc  ascend  the  scale,  the  difterentiation  of  tissue  takes  place  and 
instincts  of  plants  or  animals  appear.  As  we  ascend  still  higher  in  animal 
life,  the  instincts  gradually  lose  their  unknowing  character  and  the  mental 
facidties  emerge  with  their  appropriate  organic  basis  in  the  encephalon. 
Finally,  with  the  highest  evolution,  we  find  man  evincing  in  art  and 


H.    W.    MAGOUN  5 

science  the  results  of  the  operation  of  mental  powers  which  in  the  lower 
animals  are  purely  nistinctive  and  in  the  lowest  organisms  simply  vital 
processes.' 

There  can  also  be  found  in  Laycock  an  expression  of  the  conflicting 
interests  of  the  different  levels  with  the  higher  holding  the  lower  in  check, 
to  be  elaborated  later  by  Jackson  and  by  Freud:  'This  entire  group  of 
corporeal  appetites  and  animal  instincts  is  characterized  by  the  quality  of 
necessity.  They  are  imperative  on  the  individual;  in  lower  organisms  they 
are  performed  blindly.  In  man  and  higher  vertebrates,  in  whom  there  is  a 
development  of  cognitive  faculties,  they  may  be  made  to  act  as  a  check 
upon  each  other  and  thus  states  of  consciousness,  termed  motives,  will 
coincide  with  a  knowing  restraint  exercised  over  them.  But  even  with  the 
highest  and  strongest  of  human  motives,  it  is  often  found  difficult  to  curb 
them  effectually.  The  entire  group  constitutes  "the  Flesh"  of  St  Paul. 
Those  classed  under  the  head  of  primordial  instincts  or  corporeal  appetites, 
most  necessary  to  the  well  being  and  maintenance  of  the  organism  anci  the 
species,  are  the  farthest  removed  from  the  will  and  consciousness.' 

His  clinical  observations  in  neurology  led  Laycock  to  consider  disease 
as  'retrocession',  in  which  changes  taking  place  were  the  inverse  of  evolu- 
tionary. He  proposed  a  law  of  'disvolution  in  certain  kinds  of  brain 
disease,  when  there  was  a  decay  of  the  mental  powers  and  return  to  an 
earlier,  infantile  status.  Concepts  of  evolutionary  levels  of  function,  con- 
flicting in  their  interests  and  exhibiting  dissolution  in  neurological  disease, 
can  thus  be  detected  in  a  germinal  stage  in  Laycock's  views. 

Jaekson's  psychological  concepts  were  strongly  influenced  by  Herbert 
Spencer,  from  whom  Darwin  borrowed  the  term  'survival  of  the  fittest'. 
After  having  been  an  evolutionist  for  some  time,  in  1851  Spencer  formu- 
lated the  basic  principles  that  were  to  be  elaborated  in  most  of  his  later 
work.  He  had  been  asked  to  write  a  notice  of  a  new  edition  of  Carpenter's 
Principles  oj  Physiology  and  'in  the  course',  he  noted  (1904),  'of  such  perusal 
as  was  needed  to  give  an  account  of  its  contents',  came  across  the  theory  of 
von  Baer  —  that  the  development  of  all  plants  and  animals  was  from  homo- 
geneity to  heterogeneity.  This  concept  of  progressive  differentiation, 
added  to  that  of  Lamarckian  adaptation,  became  his  distinctive  evolu- 
tionary principle. 

Having  just  turned  forty,  Spencer  determined  to  devote  the  remainder 
of  his  life  to  the  systematic  apphcation  of  this  concept  to  the  whole  field 
of  knowledge.  Flagging  a  dilatatory  cerebral  circulation,  with  which  he 
was  hypochondriacally  preoccupied,  with  bouts  of  exercise  preceding 
dictation  to  an  amanuensis,  Spencer  embarked  on  the  exposition  of  a 


6  BRAIN    MECHANISMS    AND    LEARNING 

System  of  Syiitlictic  Philosophy,  the  successive  parts  of  which  appeared  at 
intervals  through  the  balance  of  the  nineteenth  century. 

In  the  first  edition  of  his  Priiicipk'S  of  Psychohii^y,  published  in  1855,  and 
thus  four  years  before  the  Orij^iii  of  Species,  Spencer  (1899)  pointed  out 
that  his  arguments  'imply  a  tacit  adhesion  to  the  development  hypothesis, 
that  Life  in  its  multitudinous  and  infinitely  varied  embodiments  has  risen 
out  of  the  lowest  and  simplest  beginnings,  by  steps  as  gradual  as  those 
which  evolve  a  homogenous,  microscopic  germ  into  a  complex  organism, 
by  progressive  unbroken  evolution,  and  through  the  instrumentality  of 
what  we  call  natural  causes.  Save  for  those  who  still  adhere  to  the  Hebrew 
myth  or  to  the  doctrine  of  special  creation  derived  from  it,  there  is  no 
alternative  but  this  hypothesis  or  no  hypothesis'. 

Applying  his  'development  hypothesis'  to  psychology,  Spencer 
reasoned:  'If  the  doctrine  of  Evolution  is  true,  the  inevitable  implication 
is  that  Mind  can  be  understood  only  by  observing  how  Mind  is  evolved. 
If  creatures  of  the  most  elevated  kinds  have  reached  those  highly  inte- 
grated, very  definite  and  extremely  heterogeneous  organizations  they 
possess,  through  modification  upon  modification  accumulated  during  an 
immeasurable  past,  if  the  developed  nervous  systems  of  such  creatures 
have  gained  their  complex  structure  and  functions  little  by  little;  then, 
necessarily,  the  involved  forms  of  consciousness,  which  are  the  correlates 
of  these  complex  structures  and  functions,  must  also  have  arisen  by 
degrees.' 

In  the  study  of  Mind,  'in  its  ascending  gradations  through  the  varic^us 
types  of  sentient  beings',  Spencer  conceived  of 'a  nascent  Mind,  possessed 
by  low  types  in  which  nerve  centres  are  not  yet  clearly  differentiated  from 
one  another',  and  consisting  of 'a  confused  sentiency  formed  of  recurrent 
pulses  of  feeling  having  but  little  variety  or  combination.  At  a  stage  above 
this,  while  yet  the  organs  of  the  higher  senses  are  rudimentary.  Mind  is 
present  probably  under  the  form  of  a  few  sensations  which,  like  those 
yielded  by  our  own  viscera,  are  simple,  vague  and  incoherent.  From  this 
upwards,  mental  evolution  exhibits  a  difterentiation  of  these  simple 
feelings  into  the  more  numerous  kinds  which  the  special  senses  yield;  an 
ever  increasing  integration  of  such  more  varied  feelings,  an  ever  increasing 
multiformity  in  the  aggregates  of  feelings  produced,  and  an  ever  increas- 
ing distinctness  of  structure  in  such  aggregates;  that  is  to  say,  there  goes  on 
subjectively  a  change  from  an  indefinite,  incoherent  homogeneity  to  a 
definite,  coherent  heterogeneity. 

Support  for  his  views  was  marshalled  also  from  pharmacological 
observations,   when  Spencer  presented,  in  remarkably  vivid  detail,  the 


H.    W.    MAGOUN  7 

subjective  impressions  during  induction  of  chloroform  anaesthesia  for 
dental  extraction,  and  concluded :  'This  degradation  of  consciousness  by 
chloroform,  abolishing  fnst  the  higher  faculties  and  descending  gradually 
to  the  lowest,  may  be  considered  as  rcversnig  that  ascending  genesis  of 
consciousness  which  has  taken  place  in  the  course  of  evolution;  and  the 
stages  of  descent  may  be  taken  as  showing  in  opposite  order  the  stages  of 
ascent.' 

"What  is  the  implication  oi  this  law  as  applying  to  different  grades  of 
men?'  Spencer  asked.  And  answered,  'It  is  that  those  having  well  developed 
nervous  systems  will  display  a  relatively  marked  premeditation,  a  greater 
tendency  to  suspense  of  judgment  and  an  earlier  modification  of  judg- 
ments that  have  been  formed.  Those  having  nervous  systems  less  developed 
will  be  prone  to  premature  conclusions  that  arc  difficult  to  change. 
Unlikeness  of  this  kind  appears  when  we  contrast  the  larger  with  the 
smaller  brained  races,  when,  from  the  comparatively  judicial  intellect  of 
the  civilized  man,  we  pass  to  that  of  the  uncivilized  man,  sudden  in  its 
inferences,  incapable  of  balancing  evidence  and  adhering  obstinately  to 
first  impressions.'  Tliough  Spencer's  association  with  the  female  sex  was 
limited,  he  nevertheless  felt  qualified  'to  observe  a  difference  similar  in 
kind  but  smaller  in  degree  between  the  modes  of  thought  of  men  and 
women;  for  women  are  more  quick  to  draw  conclusions  and  retain  more 
pertinaciously  beliefs  once  formed'. 

Returning  to  the  problem  'of  how  such  higher  co-ordinations  are 
evolved  out  of  lower  ones  and  how  the  structure  of  the  nervous  system 
becomes  progressively  complicated',  Spencer  proposed  the  interpolation 
of  new  plexuses  of  fibres  and  cells  between  those  originally  existing.  In 
diagrammatic  sketches,  apparently  of  an  invertebrate  ganglion,  Spencer 
distinguished  (Fig.  2,)  'a  nervous  centre  to  which  afferent  fibres  bring 
all  order  of  peripheral  feelings,  and  from  which  efferent  fibres  carry 
to  muscle  the  stimuli  producing  their  appropriately  combined  contrac- 
tions'. If  a  part  of  the  co-ordinating  plexus  (A)  'takes  on  a  relatively  greater 
development  in  answer  to  new  adjustments  which  environing  conditions 
furnish,  we  may  expect  one  part  of  this  region  (a)  to  become  protruberant, 
as  at  A".  Because  space  within  the  plexus  was  already  pre-empted,  'the 
interpolated  plexus,  which  effects  indirect  co-ordination,  must  be  super- 
imposed [Fig.  2,  A'  above;  d,  below],  and  the  co-ordinating  discharges 
must  take  roundabout  courses  as  shown  by  the  arrow.  Little  by  little,  there 
is  an  enlargement  of  the  superior  co-ordinating  centre  by  the  interpolation 
of  new  co-ordinating  plexuses  at  its  periphery'  (Fig.  2,  e,  f,  g,  below). 

With  the  publication  of  Darwin's  Origin  of  Species,  Spencer  gave  some 


BRAIN    MECHANISMS    AND    LEARNING 


consideration  to  the  concept  of  natural  selection,  but  continued  to  account 
for  the  more  complex  portions  of  neural  evolution  primarily  in  Lamarc- 
kian  terms:  'Regarding  as  superimposed,  each  on  the  preceding,  the 
structural  effects  produced  generation  after  generation  and  species  after 
species,  we  have  formed  a  general  conception  of  the  manner  in  which  the 
most  complex  nervous  systems  have  arisen  out  of  the  simplest.   This 


A'.... 


Fig.  2 
Diagrams  of  a  ganglion  prepared  by  Spencer  (17),  sliowing  the 
development   of  superimposed   levels  of  neural  co-ordination^ 


general  principle  can  be  alleged  only  on  the  assumption  that  changes 
wrought  in  nervous  structures  by  nervous  functions  are  inheritable. 
Throughout  the  earlier  stages  of  nervous  evolution,  a  leading  and  perhaps 
most  active  cause  has  been  the  survival  of  individuals  in  which  indirect 
influences  have  produced  favourable  variations  of  nervous  structure  but, 
throughout  its  later  stages,  the  most  active  cause  has  been  the  direct 


H.    W.    MAGOUN 


production  by  functional  changes  of  corresponding  changes  in  nervous 
structure,  and  the  transmission  of  these  to  posterity.  Considering  how 
involved  are  the  nervous  systems  of  superior  creatures,  there  apply  here 
with  special  force  reasons  for  concluding  that  natural  selection  is  an 
inadequate  cause  of  evolution  where  many  co-operative  parts  have  to  be 
simultaneously  modified;  and  that  in  such  cases,  inheritance  of  functionally 
produced  modifications  becomes  the  leading  agency  —  survival  of  the 
fittest  serving  as  an  aid.' 

Ii'ivi  P.  Parlor.  Though  Pavlov's  work  in  the  physiology  of  the  central 
nervous  system  did  not  commence  until  his  fifties,  its  conceptualization 
was  influenced  strongly  by  the  ideas  of  Darwin  and  of  Spencer,  encoun- 
tered in  liis  youth  through  the  writings  of  Pisarev  and  Sechenov.  In  his 
Aiirohio^irapliY  (1955),  Pavlov  wrote:  T  was  born  in  the  town  of  Ryazan 
in  1849  and  received  my  secondary  education  at  the  local  theological 
seminary,  hifluenced  by  tlie  literature  of  the  'sixties,  and  particularly  by 
Pisarev,  our  intellectual  interests  turned  to  natural  science  and  many, 
myself  included,  decided  to  take  the  subject  at  the  university.' 

Pisarev  was  a  writer  and  critic  whose  articles  in  the  Riisskoyc  Sloro 
promoted  revolutionary-democratic  anti  materialistic  ideas  among  the 
intelligentsia  of  the  'sixties.  There  seems  little  doubt  that  Pavlov  first 
became  captivated  by  Darwin  and  the  theory  of  evolution  from  reading 
Pisarev's  lengthy,  systematic,  popular  exposition  of  the  Ori'^iii  of  Species 
entitled,  Proi^ress  in  the  Aiii)iuil  (vui  Ve^ietable  li'orlds  (1858).  The  ecstatic 
attitude  towards  Darwin,  which  Pavlov  preserved  to  the  end  of  his  days, 
can  easily  be  identified  with  Pisarev's  lofty  expression: 

'This  brilliant  thinker,  whose  knowledge  is  enormous,'  Pisarev  wrote  of 
Darwin,  'took  in  all  the  life  of  nature  with  such  a  broad  view  and  pene- 
trated so  deeply  into  all  its  scattered  phenomena  that  he  discovered,  not  an 
isolated  fact,  but  a  whole  series  of  laws  according  to  which  all  organic  life 
on  our  planet  is  governed  and  varies;  and  he  told  of  them  so  simply, 
proves  them  so  irrefutably  and  bases  his  arguments  on  such  obvious  facts, 
that  you,  a  common  human,  uninitiated  in  natural  science,  are  in  a  state  of 
continual  astonishment  at  not  having  thought  out  such  conclusions  your- 
self long  ago. 

'For  us  ordinary  and  unenlightened  people,  Darwin's  discoveries  are 
precious  and  important  just  because  they  are  so  fascinating  in  their 
simplicity,  so  easy  to  understand;  they  not  only  enrich  us  with  new 
knowledge,  they  give  fresh  life  to  all  the  system  of  our  ideas  and  widen 
our  mental  horizon  in  all  dimensions.  In  nearly  all  branches  of  natural 
science,    Darwin's    ideas    bring    about    a    complete    revolution.    Even 


TO  BRAIN    MECHANISMS    AND    LEARNING 

experimental  psychology  tmds  in  his  discoveries  the  guiding  principle 
that  will  link  up  the  numerous  observations  already  niade  and  put  investi- 
gators on  the  way  to  new  fruitful  discoveries. 

'Every  educated  man',  Pisarev  continued,  'must  make  himself  familiar 
with  the  ideas  of  this  thinker  and,  therefore,  I  think  it  fitting  and  useful  to 
give  our  readers  a  clear  and  fairly  detailed  exposition  of  the  new  theory. 
In  it,  readers  will  find  the  rigorous  precision  of  an  exact  science,  the 
boundless  breadth  of  philosophical  generalization  and,  finally,  the 
superior  and  irreplaceable  beauty  which  is  the  mark  of  vigorous  and 
healthy  human  thought.  Darwin,  Lyell  and  thinkers  like  them  are  the 
philosophers,  the  poets,  the  aestheticians  of  our  time.  When  human  reason, 
in  the  person  of  its  most  brilliant  representatives,  has  succeeded  in  rising 
to  a  height  from  which  it  can  survey  the  basic  laws  of  universal  life,  we 
ordinary  people,  unable  to  be  creative  in  the  realm  of  thought,  owe  it  to 
our  own  human  dignity  to  raise  ourselves  at  least  enough  to  be  able  to 
understand  the  leading  brilliant  minds,  to  appreciate  their  great  achieve- 
ments, to  love  them  as  the  ornament  and  pride  of  our  race;  to  live  in 
thought  in  the  bright  and  boundless  realm  that  they  open  for  every 
thinking  being.  We  are  wealthy  and  powerful  through  the  works  of  these 
great  men.' 

A  second  early  influence  upon  Pavldv  was  provided  by  the  writings  of 
Sechenov  (1935).  Later  in  his  career,  Pavlov  referred  (1928)  to  the  begin- 
ning study  of  higher  nervous  activity  with  the  objective  techniques  of 
conditional  reflex  physiology:  'The  most  important  motive  for  my 
decision,  even  though  an  unconscious  one,  arose  out  of  the  impression 
made  upon  me  during  my  youth  by  the  monograph  of  I.  M.  Sechenov, 
the  Father  of  Russian  physiology,  entitled  Cerebral  Reflexes  and  published 
in  1863.  The  influence  of  thoughts  which  are  strong  by  virtue  of  their 
novelty  and  truth,  especially  when  they  act  during  youth,  remains  deep 
and  permanent,  even  though  concealed.  In  this  book,  a  brilliant  attempt 
was  made,  altogether  extraordinary  for  that  time,  to  represent  our 
subjective  world  from  the  standpoint  of  neurophysiology.' 

In  a  report  on  objective  study  of  higher  nervous  activity  in  191 3, 
Pavlov  (1928)  began:  'With  full  justice,  Charles  Darwin  must  be  counted 
as  the  founder  and  instigator  of  the  contemporary  comparative  study  of 
the  higher  vital  phenomena  of  animals;  for,  as  is  known  to  every  educated 
person,  through  his  highly  original  support  of  the  idea  of  evolution,  he 
fertilized  the  whole  mentahty  of  mankind,  especially  in  the  field  of 
biology.  The  hypothesis  of  the  origin  of  man  from  animals  gave  a  great 
impetus  to  the  study  of  the  higher  phenomena  of  animal  life.  The  answer 


H.    W.    MAGOUN 


II 


to  the  question  as  to  how  this  study  should  be  carried  out  and  the  study 
itself  have  become  the  task  of  the  period  following  Darwin.' 

Pavlov  concluded:  'I  have  hnished  my  communication,  but  I  should 
like  to  add  what  seems  to  me  to  be  of  great  importance.  Exactly  half  a 
century  ago,  ni  1863,  was  published  in  Russian  the  article  Reflexes  of  the 
Brain,  which  presented  in  clear,  precise  and  charming  form  the  funda- 
mental idea  which  we  have  worked  out  at  the  present  time  [see  Fig.  3]. 
What  power  of  creative  thought  was  necessary  under  the  then  existing 


Fig.  3 
Diagram  of  the  central  nervous  system  of  the  frog  (left),  from  Sechenov  (16).  Stimulatiiin  of 
the  sites  marked  by  crosses  inhibited  spinal  reflexes,  illustrating  the  hierarchy  of  neural  levels 
and  the  domination  of  higher  over  louder. 

At  the  right  is  a  diagram  of  the  mechanism  of  the  Pavlovian  conditioned  reflex  (13).  The 
animal  makes  adaptive  adjustments  to  its  environment  by  means  of  new  links  between  the 
cortical  analvsers  and  connections  from  them  to  subcortical,  unconditioned  reflex  arcs. 


physiological  knowledge  of  nervous  activity  to  give  rise  to  this  idea! 
After  the  birth  of  this  idea,  it  grew  and  ripened  until,  in  our  time,  it  has 
become  an  immense  force  for  directing  the  contemporary  investigation 
of  the  brain.  Allow  me  at  this  fiftieth  anniversary  of  the  Reflexes  of  the 
Brain  to  invite  your  attention  to  the  author,  Ivan  M.  Sechenov,  the  pride 
of  Russian  thought  and  the  Father  of  Russian  physiology!' 

It  is  interesting  to  note  that  Sechenov,  like  Jackson  a  contemporary  ot 
both  Darwin  and  Spencer,  was  more  directly  influenced  by  Spencer's 


12  BRAIN    MECHANISMS    AND    LEARNING 


writing  than  by  that  of  Darwin.  Though  not  in  time  to  influence  prepara- 
tion of  the  Reflexes  of  the  Brain  (1863),  both  Darwin's  and  Spencer's  works 
were  early  translated  into  Russian:  the  Orii^iii  of  Species  in  1864,  by  Pro- 
fessor S.  A.  Rashinsky  of  Moscow  University,  of  whose  efforts  Pisarev 
was  highly  critical;  and  a  year  later  in  shorter  exposition,  by  K.  A. 
Tiniiryazev,  the  leading  Russian  Darwinist  (Platonov,  1955).  Spencer 
(1904)  learned  of  a  Russian  translation  of  his  First  Principles  in  1866  and,  a 
decade  later,  heard  with  surprise,  from  Professor  Sontchitzici,  of  the 
University  of  Kiev,  that  all  of  his  works  had  then  been  translated  into 
Russian,  excepting  the  Sociology,  which  was  soon  to  be  added  to  the  list. 

In  his  Elements  of  Thought,  published  in  1883,  Sechenov  (1935)  wrote: 
'Darwin's  great  theory  of  the  evolution  of  species  has  placed  the  idea  of 
evolution  on  such  a  firm  basis  that  it  is  at  present  accepted  by  the  vast 
majority  of  naturalists.  This  logically  necessitates  the  recognition  of  the 
principle  of  evolution  of  psychical  activities.  Spencer's  hypothesis  may 
actually  be  called  the  application  of  Darwinism  to  the  sphere  of  psychical 
phenomena.' 

And  later:  'Another  and  no  less  important  success  in  the  study  of  the 
mental  development  of  man  in  general  we  owe  to  the  famous  English 
scientist,  Herbert  Spencer.  It  is  only  on  the  ground  of  Spencer's  hypothesis, 
concerning  the  sequence  of  stages  of 'neuropsychical  development  from 
age  to  age  that  we  can  solve  the  ancient  philosophical  problem  of  the 
development  of  mature  thought  from  initial  infantile  forms.  To  Spencer 
we  owe  the  establishment,  on  the  basis  of  very  wide  analogies,  of  the 
general  type  of  mental  development  in  man,  as  well  as  the  proofs  of  the 
fact  that  the  type  of  evolution  of  mental  processes  remains  unchanged 
through  all  stages  of  the  development  of  thought.  The  present  essay  is 
based  on  the  theories  of  Spencer;  therefore,  our  first  task  will  be  to 
expound  the  main  principles  of  his  theory.  It  even  appeared  at  the  same 
time  as  Darwin's  theory  and  is  practically  a  part  of  the  general  theory  of 
organic  evolution.' 

Signiund  Freiid.  Passing  now  to  Freud,  his  autobiography  refers  to  the 
influences  leading  him  to  medicine  as  a  career:  'At  the  time  the  theories 
of  Darwin,  which  were  then  of  topical  interest,  strongly  attracted  me,  for 
they  held  out  hopes  of  an  extraordinary  advance  in  our  understanding  of 
the  world;  and  it  was  hearing  Goethe's  beautiful  essay  on  Nature  read 
aloud  at  a  popular  lecture,  just  before  I  left  school,  that  decided  me  to 
become  a  medical  student.' 

There  are  singularly  few  other  allusions  to  Darwin  in  Freud's  writings, 
and  the  factors  responsible  for  his  visualization  of  the  psychic  apparatus 


H.    W.    MAGOUN  13 

as  spatially  stratified  were,  doubtless,  unconscious  ones.  It  seems  an 
exaggeration  to  propose  that  a  continuum  can  be  detected,  in  any  literal 
sense,  in  Freud's  anatomical,  neurological  and  psychoanalytical  works. 
Instances  of  a  recurring  effort  to  interpret  neural  organization  and  function 
in  evolutionary  terms  can,  however,  be  noted.  In  his  monograph  on 
Aphasia,  published  in  1891,  Freud  wrote  (1953):  'In  assessing  the  functions 
of  the  speech  apparatus  under  pathological  conditions,  we  are  adopting  as 
a  guiding  principle  Hughhngs  Jackson's  doctrine  that  all  these  modes  of 
reaction  represent  instances  of  functional  retrogression  (disin volution)  of  a 
highly  organized  apparatus,  and  therefore  correspond  to  earlier  stages  of 
its  functional  development.  This  means  that  under  all  circumstances  an 
arrangement  of  associations  which,  having  been  acquired  later,  belongs  to 
a  higher  level  of  functioning,  will  be  lost,  while  an  earlier  and  simpler  one 
will  be  preserved.  From  this  point  of  view,  a  great  number  of  aphasic 
phenomena  can  be  explained.' 


Pcpt-C5 


Fig.  4 
Two  diagrams  by  Freud  (8,  8b),  presenting  the  mental  apparatus  as 
though  spatially  stratified. 


In  a  letter  to  Fleiss  in  1896,  Freud  (1954)  discussed  a  revision  of  his 
Project  for  a  Scientific  Psychology  and  referred  to  his  'latest  bit  of  specula- 
tion, the  assumption  that  our  psychical  mechanism  has  come  about  by  a 
process  of  stratification'.  A  quarter  of  a  century  later,  Freud  made  two 
attempts  to  diagram  these  ideas,  with  interesting  differences  in  the  form  of 
the  figures.  The  first  (Fig.  4,  left),  prepared  in  1923,  resembled  an  inverted 
brain,  although  reference  was  made  to  it  as  an  ovum.  The  second  (Fig.  4, 
right),  prepared  a  decade  later,  was  on  the  other  hand  really  egg-shaped. 
In  his  lecture  on  'The  Anatomy  of  the  Mental  Personality',  Freud  (1933) 
elaborated  upon  the  contents  of  these  figures:  'Superego,  ego  and  id  are 


14  BRAIN    MECHANISMS    AND    LEARNINC; 

the  throe  reahns,  regions  or  provinces  into  which  we  divide  the  mental 
apparatus  of  the  individual,  and  it  is  their  mutual  relations  with  which  we 
shall  be  concerned. 

'The  id  is  the  obscure,  inaccessible  part  of  our  personality  and  can  only 
be  described  as  being  all  that  the  ego  is  not.  We  can  come  nearer  to  the  id 
with  images,  and  call  it  a  chaos,  a  cauldron  of  seething  excitement.  We 
suppose  that  it  is  somewhere  in  direct  contact  with  somatic  processes  and 
takes  over  from  them  instinctual  needs.  These  instincts  till  it  with  energy, 
but  it  has  no  organization  and  no  unified  will,  only  an  impulsion  to  obtain 
satisfaction  for  the  instinctual  needs  in  accordance  with  the  pleasure 
principle.  Contradictory  impulses  exist  side  by  side  in  it,  without  neutral- 
izing each  other  or  drawing  apart;  at  most  they  combine  in  comprtMnise 
formations  under  the  overpowering  pressure  towards  discharging  their 
energy.  In  the  id,  there  is  nothing  corresponding  to  the  idea  of  time. 
Conative  impulses  which  have  never  got  beyond  the  id,  and  even  impres- 
sions which  have  been  pushed  down  into  it  by  repression,  are  virtually 
immortal  and  are  preserved  for  whole  decades,  as  though  they  had  only 
recently  occurred.  They  can  only  be  recognized  as  belonging  to  the  past, 
deprived  of  their  significance,  and  robbed  of  their  charge  of  energy,  after 
they  have  been  made  conscious  by  the  work  of  analysis,  and  no  small  part 
of  the  therapeutic  effect  of  analytic  treatment  rests  upon  this  fact.  Natur- 
ally the  id  knows  no  values,  no  good  and  evil,  no  morality.  There  is 
nothing  in  the  id  which  can  be  compared  to  negation.  Instinctual  cathexes 
seeking  discharge  —  that,  in  our  view,  is  all  that  the  id  contains. 

'The  (\'o  is  directed  onto  the  external  world;  it  mediates  perceptions  of 
it  and  in  it  are  generated,  while  it  is  functioning,  the  phenomena  of 
consciousness.  The  ego  has  taken  over  the  task  of  representing  the  external 
world  for  the  id.  In  the  fulfilment  of  this  function,  it  has  to  observe  the 
external  world  and  preserve  a  true  picture  of  it  in  the  memory  traces  left 
by  its  perception.  The  ego  also  controls  the  path  cif  access  to  motility,  but 
it  interpolates  between  desire  and  action  the  procrastinating  factor  of 
thought,  during  which  it  makes  use  of  the  residues  of  experience  stored  up 
in  memory.  In  this  way,  it  dethrones  the  pleasure  principle,  which  exerts 
undisputed  sway  over  the  processes  in  the  id,  and  substitutes  for  it  the 
reality  principle,  which  promises  greater  security  and  success.  The 
relation  to  time,  too,  is  contributed  to  the  ego  by  the  perceptual  systems; 
indeed,  it  can  hardly  be  doubted  that  the  mode  in  which  this  system  works 
is  the  source  of  the  idea  of  time.  What,  however,  especially  marks  the  ego 
out  in  contradistinction  to  the  id  is  a  tendency  to  synthesize  its  contents,  to 
bring  together  and  unify  its  mental  pr(^cesses,  which  is  entirely  absent  from 


H.    W.    MAGOUN  15 

the  id.  In  popular  language,  we  may  say  that  the  ego  stands  for  reason  and 
circumspection,  while  the  id  stands  for  the  untamed  passions.  One  might 
compare  the  relation  of  the  ego  to  the  id  with  that  between  a  rider  and  his 
horse:  the  horse  provides  the  locomotive  energy,  and  the  rider  has  the 
prerogative  of  determining  the  goal  and  of  guiding  the  movements  of  his 
powerful  mount. 

'The  role  which  the  supcrc<^o  undertakes  later  in  life  is  at  hrst  played  by 
an  external  power,  by  parental  authority.  It  can  be  traced  back  to  the 
influence  of  parents,  teachers  and  so  on,  and  is  based  upon  an  over- 
whelmingly important  biological  fact,  namely,  the  lengthy  dependence 
of  the  human  child  on  his  parents.  We  have  allocated  to  the  superego  the 
activities  of  self-observation,  conscience  and  the  holding  up  of  ideals.  It 
is  the  representative  of  all  moral  restrictions,  the  advocate  of  the  impulse 
towards  perfection.  In  short,  it  is  as  much  as  we  have  been  able  to  appre- 
hend psychologically  of  what  people  call  the  "higher  things  in  human 
life".  It  becomes  the  vehicle  of  tradition  and  of  all  the  age-long  values 
which  have  been  handed  down  from  generation  to  generation.  The 
ideologies  of  the  superego  perpetuate  the  past,  the  traditions  of  the  race 
and  the  people,  which  yield  but  slowly  to  the  influence  of  the  present  and 
to  new  developments.' 

In  discussing  the  interrelations  ot  these  parts,  Freud,  like  Spencer, 
appeared  to  invoke  Lamarckian  views :  'The  ego  has  the  task  of  bringing 
the  influence  of  the  external  world  to  bear  upon  the  id.  In  the  ego,  percep- 
tion plays  the  part  which,  in  the  id,  develops  upon  instinct.  The  experiences 
undergone  by  the  ego  seem  at  tnst  to  be  lost  to  posterity ;  but,  when  they 
have  been  repeated  often  enough  and  with  sufficient  intensity  in  the 
successive  individuals  of  many  generations,  they  transform  tlicmselves  so 
to  say  into  experiences  of  the  id,  the  impress  of  which  is  preserved  by 
inheritance.  Thus  in  the  id,  which  is  capable  of  being  inherited,  are  stored 
up  vestiges  of  the  existences  led  by  countless  former  egos;  and,  when  the 
ego  forms  its  superego  out  of  the  id,  it  may  perhaps  only  be  reviving 
images  of  egos  that  have  passed  away  and  be  securing  them  a  resurrection. 

'The  poor  ego  has,  then,  to  serve  three  harsh  masters  and  to  do  its  best 
to  reconcile  their  claims  and  demands.  These  demands  are  always  diver- 
gent and  often  seem  quite  incompatible;  no  wonder  the  ego  so  frequently 
gives  way  under  its  task.  The  three  tyrants  arc  the  external  world,  the 
superego  and  the  id.  It  feels  itself  hemmed  in  on  three  sides  and  threatened 
by  three  kinds  of  danger,  towards  which  it  reacts  by  developing  anxiety 
when  too  hard  pressed. 

'Having  originated  in  the  experiences  of  the  perceptual  system,  it  is 


l6  BRAIN    MECHANISMS    AND    LEARNING 

designed  to  represent  the  demands  of  the  external  world,  but  it  also  wishes 
to  be  a  loyal  servant  to  the  id,  and  to  draw  the  id's  hbido  onto  itself.  In  its 
attempt  to  mediate  between  the  id  and  reality,  it  is  often  forced  to  clothe 
the  unconscious  commands  of  the  id  with  its  own  preconscious  rationaliza- 
tions, to  gloss  over  the  conflicts  between  the  id  and  reality. 

'On  the  other  hand,  its  every  movement  is  watched  by  the  severe 
superego,  which  holds  up  certain  norms  of  behaviour  without  regard  to 
any  difficulties  coming  from  the  id  and  the  external  world;  and  if  these 
norms  are  not  acted  up  to,  it  punishes  the  ego  with  feelings  of  tension 
which  manifest  themselves  as  a  sense  of  inferiority  or  guilt.  In  this  way, 
goaded  on  by  the  id,  hemmed  in  by  the  superego,  and  rebuffed  by 
reality,  the  ego  struggles  to  cope  with  its  task  of  reducing  the  forces  and 
influences  which  work  in  it  and  upon  it  to  some  kind  of  harmony.  When 
the  ego  is  forced  to  acknowledge  its  weakness,  it  breaks  out  into  anxiety; 
reality  anxiety  in  the  face  of  the  external  world,  normal  anxiety  in  the 
face  of  the  superego,  and  neurotic  anxiety  in  the  face  of  the  strength  of 
the  passions  of  the  id. 

'It  can  easily  be  imagined  that  certain  practices  of  mystics  may  succeed 
in  upsetting  the  normal  relations  between  the  different  regions  of  the  mind 
so  that,  for  example,  the  perceptual  system  becomes  able  to  grasp  relations 
in  the  deeper  layers  of  the  ego  and  in  the  id  which  would  otherwise  be 
inaccessible  to  it.  Whether  such  a  procedure  can  put  one  in  possession  of 
ultimate  truths,  from  which  all  good  will  flow,  may  be  safely  doubted. 
All  the  same,  we  must  admit  that  the  therapeutic  efforts  of  psychoanalysis 
have  chosen  much  the  same  method  of  approach;  for  their  object  is  to 
strengthen  the  ego,  to  make  it  more  independent  of  the  superego,  to 
widen  its  field  of  vision,  and  so  to  extend  its  organization  that  it  can  take 
over  new  portions  of  the  id.  Where  id  was,  there  shall  ego  be.  It  is  re- 
clamation work,  like  the  draining  of  the  Zuyder  Zee.' 

Spciiar  and  Darwin.  From  what  has  been  presented  it  seems  clear  that,  to 
their  contemporaries,  Spencer's  ideas  of  the  evolution  of  the  brain  and 
its  functions  were  fully  as  influential  as  Darwin's,  if  not  more  so.  This  may 
be  attributable  in  part  to  the  fact  that  Spencer  applied  evolutionary  prin- 
ciples to  an  understanding  of  the  brain  earlier  than  Darwin  and,  indeed, 
before  the  lattcr's  ideas  were  published  at  all.  Additionally,  appeal  doubt- 
less attached  to  the  broad  sweep  of  Spencer's  interests  and  to  his  efforts  to 
account  for  the  whole  range  of  neural  function,  from  instincts  to  the  most 
complex  features  of  the  mind,  in  keeping  with  his  propensity  for  global 
syntheses. 

Darwin,    by   contrast,    stuck   closer   to   the   observational    data   then 


H.    W.    MAGOUN  17 

available  with  emphasis  mainly  upon  instinctive  behaviour,  supporting 
the  survival  of  the  individual,  in  feeding,  aggression  or  defence,  as  well  as 
survival  of  the  species,  in  behaviour  relating  to  sex.  Even  in  Darwin's 
Descent  of  Man  (1871),  for  example,  greater  emphasis  was  placed  upon  an 
exposition  of  sexual  selection  than  upon  development  of  the  associational 
and  communicative  functions  of  the  brain,  which  are  easily  the  most 
strikingly  distinctive  features  of  human  evolution. 

Darwin  and  Spencer  might  be  rated  cquivalcntly  in  the  impressions 
they  made  upon  Pisarev  and  Sechcnov  and,  through  these  latter,  upon 
Pavlov  and  Russian  neurophysiology.  There  is  no  question,  however,  of 
the  predominant  influence  of  Spencer  upon  Hughlings  Jackson  and, 
through  him  upon  the  formation  of  evolutionary  concepts  of  the  organiza- 
tion and  function  of  the  brain  in  Western  neurological  thought. 

Contrasting  features  of  their  personalities  and  outlooks  appeared  to  have 
led  Darwin  and  Spencer  to  develop  reservations  about  one  another.  An 
early  phrenological  characterization  of  Spencer  (Spencer,  1904)  con- 
cluded: 'Such  a  head  as  this  ought  to  be  in  the  Church.  The  self-esteem  is 
very  large.'  Darwin's  tendency  to  personal  deprecation  seemed,  on  the 
other  hand,  to  have  amounted  to  a  real  sense  of  inferiority  when  compar- 
ing himself  with  Spencer.  Each  seemed  also  to  have  cultivated  a  possibly 
wilful  ditiiculty  in  understanding  the  other's  views.  In  a  letter  to  Hooker 
in  1868,  Darwin  (1925)  wrote:  'I  feel  Painyeiiesis  is  stillborn.  H.  Spencer 
says  the  view  is  quite  difl:erent  from  his  (and  this  is  a  great  relief  to  me,  as  I 
feared  to  be  accused  of  plagiarism  but  utterly  failed  to  be  sure  what  he 
meant,  so  thought  it  safest  to  give  my  view  as  almost  the  same  as  his),  and 
he  says  he  is  not  sure  he  understands  it.' 

In  other  letters,  Darwin  blew  hot  and  cold.  He  characteristically 
acknowledged  Spencer's  brilliance,  but  usually  expressed  some  question 
of  the  soundness  or  reliability  of  his  views.  In  a  note  thanking  Spencer  for 
a  present  of  his  Essays  in  1858,  Darwin  wrote:  'Your  remarks  on  the 
general  argument  of  the  so-called  development  theory  seem  to  me  admira- 
ble. I  am  at  present  preparing  an  Abstract  of  a  larger  work  on  the  changes 
of  species;  but  I  treat  the  subject  simply  as  a  naturalist,  and  not  from  a 
general  point  of  view;  otherwise,  in  my  opinion,  your  argument  could 
not  have  been  improved  on,  and  might  have  been  quoted  by  me  with 
great  advantage.' 

In  a  letter  to  Hooker  in  1866,  Darwin  wrote:  'I  have  now  read  the  last 
No.  of  H.  Spencer  {Principles  of  Biology).  It  is  wonderfully  clever  and  I 
daresay  mostly  true.  I  feel  rather  mean  when  I  read  him:  I  could  bear  and 
rather  enjoy  feeling  that  he  was  twice  as  ingenious  and  clever  as  myself;  but 


l8  BRAIN    MECHANISMS    AND    LEARNING 

when  I  feel  he  is  ahnost  a  dozen  times  my  superior,  even  in  the  master  art 
of  wrigghng,  I  feel  aggrieved.  If  he  had  trained  himself  to  observe  more, 
even  at  the  expense,  by  the  law  of  balancement,  of  some  loss  of  thinking 
power,  he  would  have  been  a  wonderful  man.' 

In  a  letter  to  E.  Ray  Lankester  in  1870,  Darwni's  regard  reached  a  high 
point:  'It  has  pleased  me  to  see  how  thoroughly  you  appreciate  (and  I  do 
not  think  this  is  general  with  men  of  science)  H.  Spencer;  I  suspect  that 
hereafter  he  will  be  looked  at  as  by  far  the  greatest  living  philosopher  in 
England;  perhaps  equal  to  any  that  have  lived.'  Darwin's  regard  was  also 
expressed  in  a  note  to  Spencer  himself  at  this  time  (1872):  'Dear  Spencer 
—  I  daresay  you  will  think  me  a  foolish  fellow  but  I  cannot  resist  the  wish 
to  express  my  unbounded  admiration  for  your  article.  Everyone  with  eyes 
to  see  and  ears  to  hear  (the  number,  I  fear,  are  not  many)  ought  to  bow 
their  knee  to  you,  and  I  for  one  do.' 

In  a  letter  to  Fiske,  in  1874,  reaction  had  set  in:  'With  the  exception  of 
special  points,  I  did  not  even  understand  H.  Spencer's  general  doctrine; 
for  his  style  is  too  hard  work  for  me.  This  may  be  very  narrow  minded; 
but  the  result  is  that  such  parts  of  H.  Spencer  as  I  have  read  with  care 
impressed  my  mind  with  the  idea  of  his  inexhaustible  wealth  of  suggestion, 
but  never  convinced  me.' 

In  a  fmal  judgment,  in  his  Aiitohi(\^rapliy  (1958),  Darwin  commented: 
'Herbert  Spencer's  conversation  seemed  to  mc  very  interesting  but  I  did 
not  like  him  particularly  and  did  not  feel  that  I  could  easily  become 
intimate  with  him.  I  think  he  was  extremely  egotistical.  After  reading  any 
of  Spencer's  books,  I  generally  feel  enthusiastic  admiration  for  his  trans- 
cendent talents  and  have  often  wondered  whether  in  the  distant  future  he 
would  rank  with  such  great  men  as  Descartes,  Leibniz,  etc.,  about  whom, 
however,  I  know  very  little.  Nevertheless,  I  am  not  conscious  of  having 
profited  in  my  own  work  by  Spencer's  writings.  His  deductive  manner  of 
treating  every  subject  is  wholly  opposed  to  my  frame  of  mind.  His 
conclusions  never  convince  me:  and  over  and  over  again  I  have  said  to 
myself  after  reading  one  of  his  discussions,  "Here  would  be  a  fine  subject 
for  half  a  dozen  year's  work."  His  fundamental  generalizations  (which 
have  been  compared  in  importance  by  some  persons  with  Newton  s 
Laws !)  —  which  I  daresay  may  be  very  valuable  under  a  philosophical 
point  of  view  —  are  of  such  a  nature  that  they  do  not  seem  to  me  to  be  of 
any  strictly  scientific  use.  They  partake  more  of  the  nature  of  definitions 
than  of  laws  of  nature.  They  do  not  aid  one  in  predicting  what  will 
happen  in  any  particular  case.  Anyhow,  they  have  not  been  of  any  use  to 
me.' 


H.    W.    MAGOUN  19 

Reciprocal  comments  on  Darwin  and  his  work,  by  Spencer,  were  made 
primarily  from  the  point  of  view  of  their  relations  to  Spencer's  own  ideas 
and  niterests.  With  publication  of  the  Orioiii  of  Species,  Spencer  wrote 
(1904) :  'That  reading  it  gave  me  great  satisfaction  may  be  safely  inferred. 
Whether  there  was  any  set-oft  to  this,  I  cannot  now  say;  for  I  have  quite 
forgotten  the  ideas  and  feelings  I  had.  Up  to  that  time,  I  held  that  the  sole 
cause  of  organic  evolution  is  the  inheritance  of  functionally-produced 
moditications.  The  Ori^Ui  of  Species  made  it  clear  to  me  that  I  was  wrong; 
and  that  the  larger  part  of  the  facts  cannot  be  due  to  any  such  cause. 
Whether  proof  that  what  I  had  supposed  to  be  the  sole  cause,  could  be  at 
best  but  a  part  cause,  gave  me  any  annoyance,  I  cannot  remember;  nor 
can  I  remember  whether  I  was  vexed  by  the  thought  that,  in  1852,  I  had 
fiiled  to  carry  further  the  idea  then  expressed  that,  among  human  beings, 
the  survival  of  those  who  are  the  select  of  their  generation  is  a  cause  of 
development.  But  I  doubt  not  that  any  such  feelings,  if  they  arose,  were 
overwhelmed  in  the  gratification  I  felt  at  seeing  the  theory  of  organic 
evolution  justified. 

'To  have  the  theory  of  organic  evolution  justified  was,  of  course,  to  get 
further  support  for  that  theory  of  evolution  at  large,  with  which,  as  we 
have  seen,  all  my  conceptions  were  bound  up.  Believing  as  I  did,  too,  that 
right  guidance,  individual  and  social,  depends  upon  acceptance  of 
evolutionary  views  of  mind  and  of  society,  I  was  hopeful  that  its  effects 
wouki  presently  be  seen  on  educational  methods,  political  opinions  and 
men's  ideas  about  human  life.  Obviously,  these  hopes  that  beneficial 
results  would  presently  be  wrought,  were  too  sanguine.  My  confidence  in 
the  rationality  of  mankind  was  much  greater  then  than  it  is  now.' 

On  the  revision  of  his  Principles  of  Psycholooy,  in  1870,  Spencer  wrote,  in 
a  similar  vein:  'Several  feelings  united  in  making  me  enjoy  the  resumption 
of  this  topic,  which  I  dealt  with  in  1854-55.  At  that  date,  an  evolutionary 
view  of  Mind  was  foreign  to  the  ideas  of  the  time,  and  voted  absurd:  the 
result  of  setting  it  forth  brought  pecuniary  loss  and  a  good  cieal  of  reproba- 
tion. Naturally,  therefore,  after  the  publication  of  the  Ori(^iii  of  Species 
had  caused  the  current  oi  public  opinion  to  set  the  other  way,  a  more 
sympathetic  reception  was  to  be  counted  upon  for  the  doctrine  of  mental 
evolution  in  its  elaborated  form.' 

In  1872,  Spencer  acknowledged  a  copy  of  Darwin's  work  on  The 
Expression  of  the  Emotions  as  follows:  "Dear  Darwin:  I  have  delayed  some- 
what longer  than  I  intended  acknowledging  the  copy  of  your  new 
volume  which  you  have  been  kind  enough  to  send  me.  I  delayed  partly  in 
the  hope  of  being  able  to  read  more  of  it  before  writing  to  you;  but  my 

c 


20  BRAIN    MECHANISMS    AND    LEARNING 

reading  powers  arc  so  small,  and  they  arc  at  present  so  much  eniployed 
in  getting  up  materials  for  work  in  hand,  that  I  have  been  unable  to  get  on 
far  with  it.  I  have,  however,  read  quite  enough  to  see  what  an  immense 
mass  of  evidence  you  have  brought  to  bear  in  proof  of  your  propositions. 

'I  will  comment  only  on  one  point,  on  which  I  see  you  tiifter  from 
me  ...  ' 

Differing  interests  in  the  presentation  of  observational  data  and  in  the 
derivation  from  it  of  speculative  syntheses,  so  apparent  in  the  attitudes  of 
Darwin  and  Spencer,  will  doubtless  appear  in  the  programme  of  this 
present  conference  as  well.  To  find  a  topic  upon  which  all  may  initially 
agree,  let  us  return  to  Darwin's  South  American  visit  of  a  century  ago. 
His  narrative  (1839),  under  December  6th,  1832,  notes: 

'The  Bcai^lc  sailed  from  the  Rio  Plata  never  again  to  enter  its  muddy 
stream  . . .  When  speaking  of  these  countries,  the  manner  in  which  they 
have  been  brought  up  by  their  unnatural  parent,  Spain,  should  always  be 
borne  in  mind.  On  the  whole,  perhaps,  more  credit  is  due  for  what  has 
been  done,  than  blame  for  what  may  be  deficient.  It  is  impossible  to 
doubt  but  that  the  extreme  liberalism  of  these  countries  must  ultimately 
lead  to  good  results.  The  very  general  toleration  of  foreign  religions,  the 
regard  paid  to  the  means  of  education,  the  freedom  of  the  press,  the 
facilities  offered  to  all  foreigners,  and  especially,  as  I  am  bound  to  add,  to 
everyone  professing  the  humblest  pretensions  to  science,  should  be  re- 
collected with  gratitude  by  all  those  who  have  visited  Spanish  South 
America.' 

The  most  cordial  reception  which  has  been  providec^  the  present  visitors 
to  Montevideo,  in  1959,  will,  I  know,  make  each  of  us  wish  to  echo  and 
approve  emphatically  of  Darwin's  concluding  remarks. 


THE  FIXATION   OF  EXPERIENCE^ 
R.  W.  Gerard 

The  tixation  of  experience  is  a  wider  topic  than  is  learning,  which  is  a 
subhead  under  it.  It  inckides  changes  in  an  nidividual  system,  at  all  levels 
from  molecule  to  taxa  or  society,  that  have  become  irreversible  under 
single  or  repeated  experiences  and  so  have  left  some  material  record  of  a 
past  activity;  and  it  includes  racial  changes  that  have  cumulated  over 
generations  of  a  self-reproducing  system.  It  miderlies  one  of  the  three 
universal  attributes  of  all  systems  at  all  levels;  'becoming'.  The  architec- 
ture oi  any  system,  its  inhomogenities  at  a  given  cross  section  of  time 
which  remain  reasonably  constant  over  succeeding  cross  sections,  its 
'being',  is  the  base  of  the  behaviour  or  functioning  of  the  system  along 
time.  'Behaving'  represents  the  transient  or  functional  responses  of  the 
system  to  stimuli  or  stresses  imposed  by  the  environment  and  are  rever- 
sible, so  that  the  system  essentially  reverts  after  the  perturbations  have 
passed.  When,  however,  the  stimuli  are  sufficiently  intense  or  repetitive  or 
meaningful  to  the  system  as  to  leave  an  irreversible  change,  and  therefore 
a  material  residue,  the  system  undergoes  a  secular  change  along  the 
longitudinal  time  axis  and  has  tixed  experience.  'Becoming'  thus  encom- 
passes individual  development,  racial  evolution,  cultural  history,  and 
many  other  basic  phenomena  of  orgs  in  general  (niaterial  systems)  and  of 
animorgs  ni  particular  (living  material  systems). 

Irreversible  changes  of  individual  units  at  the  molecular  level  include 
gene  mutations  and  adaptive  enzymes  and  antibodies.  At  the  cellular  level, 
comes  the  whole  process  of  cellular  differentiation,  including  the  fornia- 
tion  or  lack  of  formation  of  particular  organelles  and  particulates.  At  the 
organ  level,  inductions  and  gradients  and  mechanical  forces  mold  the 
particular  organs  during  cievelopment,  just  as  their  use  through  life  leaves 
behind  hypertrophied  soles  or  muscles,  wrinkled  and  weathered  skin, 
bone  shapes  to  meet  functional  strains,  and  the  like.  Engrams  within  the 
nervous  system  are  entirely  comparable  residues  of  experience.  At  the 
individual  level,  come  the  collective  processes  of  ageing,  perceptual  and 
motor  habits,  conscious  memories  and  the  like.  And  at  the  group  or  social 
level,  individual  cultures  create  customs,  laws,  languages,  artifacts,  libraries 
and  many  other  concrete  entities  or  functional  roles  occupied  by  concrete 
entities. 

1  Aided  by  a  grant  from  the  National  Institute  of  Mental  Health,  U.S.P.H. 

21 


BRAIN    MECHANISMS    AND    LEARNING 


At  the  racial  dimension,  or  successive  generations  in  time,  there  are  the 
typical  character  changes  which  come  to  identify  a  taxa — morphological, 
physiological,  chemical  and,  progressively,  behavioural  attributes  that 
have  accumulatively  changed,  in  a  more  or  less  directional  manner,  over 
many  generations.  More  important,  and  less  universally  recognized,  has 
been  the  evolution,  not  of  adaptations,  but  of  adaptability.  Selection 
pressures  from  an  environment  will  prociuce  evolutionary  changes  only 
when  the  stock  is  malleable  and  can  respond  to  the  pressures.  Systems  must 
be  able  to  respond  to  experience  and  to  tix  it  in  some  way  if  they  arc  to  be 
changed  by  it;  and  since  heredity  must  supply  the  initial  plasticity  which 
enables  the  system  to  respond  adaptively  to  selection  pressures  —  and  there 
is  much  current  evidence  that  natural  selection  does  not  operate  quite  so 
blindly  as  was  at  one  time  believed  (e.g.  Waddington,  1950,  i960; 
Gerard,  1960b)  —  the  sharp  line  between  Darwin  and  Lamarck  is  begin- 
ning to  blur.  One  can  inherit  not  only  mutated  genes,  but  genes  that  are 
more  mutable,  even  genes  that  induce  mutations  in  others.  Adaptive 
enzymes  come  into  being  only  when  both  the  genetic  potentiality  and 
also  the  environmental  substate  are  present.  An  organism  not  only  can 
learn,  it  can  learn  to  learn.  Learning  set,  attention  level,  motivation 
intensity,  past  experience,  present  physiological  state,  type  of  stimulus 
presentation  and  many  other  factors  can  influence  the  speed  and  effective- 
ness of  learning.  And  the  contributions  of  heredity,  of  individual  experi- 
ence, and  of  current  situation  to  many,  if  not  all,  of  these  factors  have  not 
remotely  been  disentangled. 

It  remains  true,  none  the  less,  that  learning  to  learn,  accelerating  adapta- 
tion, speeding  auto-  and  hetero-  catalysis  is  the  great  invention  of  life 
stuff".  This  is  the  epigcnetic  mode.  It  allows  living  organisms  to  respond 
ever  more  rapidly  and  adaptively  to  the  environmental  challenge;  it 
similarly  enables  mindful  organisms  to  meet  their  environmental  problems 
with  greater  skill  and  speed;  and  it  has  brought  about  that  accelerating 
cultural  change  in  civilizations  which  seems  almost  to  have  reached  an 
explosive  point.  Epigenesis  was  enhanced  by  increased  gene  mutability,  by 
the  development  of  chromosomes  and  sex  assortment,  by  adaptive  changes 
in  individual  characteristics  (in  themselves  or  as  a  richer  array  for  the 
action  of  simple  natural  selection),  by  the  invention  of  a  nervous  system 
and  of  highly  differentiated  or  coded  responses. 

Environment  operates  upon  a  system  at  all  levels,  differentially  selecting 
for  survival  particular  genes  or  gene  arrays,  cells  and  cell  aggregates, 
organs  and  organ  systems,  and  individuals  and  groups  of  various  sizes. 
The  environment  operates  not  so  much  on  the  finished  product  as  on  the 


R.    W.    GERARD  23 

formative  process.  It  supplies  the  physico-chemical  milieu  determining 
molecular  changes,  the  electro-chcmico-mechanical  held  guiding  cellular 
changes,  the  neuro-chemico-mechanical  influences  modulating  organ 
development,  the  material  and  biotic  stimuli  that  guide  the  maturation  oi 
the  individual,  and  the  coded  and  meaning-laden  signs  and  symbols  which 
arc  added  to  these  in  the  course  ot  enculturating  an  individual  into  his 
group.  The  stresses  applied  by  the  environment  determine  the  direction  of 
development  of  the  individual  and  the  selection  of  the  individual  in  the 
group.  It  may  deternnne  the  adaptations  of  the  body,  the  behaviour  of 
the  individual,  the  nornis  of  the  culture,  and,  in  general,  the  goals  or  values 
that  guide  the  course  of  future  change  of  a  system. 

Living  thmgs  are  engaged  in  a  continuous  tracking  operation,  attempt- 
ing to  bring  their  existing  state  or  their  anticipated  state  into  congruence 
with  a  desu-ed  state.  At  any  instant  in  time,  the  system  faces  its  universe, 
from  which  it  is  separated  by  some  kind  of  boundary,  with  a  certain 
patterned  inhomogenity  which  is  by  then  its  enduring  property.  In  the 
course  of  interacting  with  its  environment,  u-reversible  changes  are 
produced  in  the  system  and  it  reaches  a  new  state,  the  new  architecture 
which  it  then  offers  for  interaction  with  further  environmental  stimuli  or 
stresses.  Any  individual  system,  and  all  its  sub-systems,  thus  brings  a  new 
self  to  succeeding  chunks  of  time.  What  the  zygote  brings  we  ordinarily 
call  heredity,  the  end-product  of  ancestral  learning  and  selection.  What 
happens  to  the  zygote  we  call  individual  experience,  often  divided  further 
into  experiences  ///  iitero,  which  we  call  congenital,  and  those  affecting  the 
separate  organism,  tirst  the  infant  and  then  the  adult. 

At  each  stage  and  at  each  level,  the  system  or  sub-system  presents  to  the 
environment  a  structure  which  has  at  least  some  aspects  of  a  template,  and 
so  can  lead  to  the  production  of  more  or  itself;  and  at  least  some  aspects  of 
a  programme  or  set  of  operation  rules,  so  that  the  kinds  of  responses  it 
will  make  to  certain  situations  are  roughly  indicated.  The  outcomes  are 
never  identical  and  never  foreseeably  deterministic,  because  the  tine 
details  of  the  particular  template  and  programme,  even  in  identical  twins, 
are  not  absolutely  identical  and,  even  more,  because  the  environmental 
conditions  to  which  these  are  exposed  are  never  even  roughly  identical. 
Despite  relative  constancy  in  'beings',  therefore,  outcomes  are  always 
more  variable,  the  exact  one  in  each  case  depending  on  the  particular,  often 
chance,  details  of  the  individual — environment  interaction.  Clearly,  the 
line  between  heredity  and  individual  experience  becomes  vague  indeed.  A 
gene  array  is  a  template  and  a  programme;  so  is  an  engram. 

It  is  a  duty  of  neurobiology  to  discover  the  action  rules.  (If  the  nervous 


24  BRAIN    MECHANISMS    AND    LEARNING 

system  knows  the  equation  for  tt,  it  can  grind  out  an  unlimited  number  of 
digits,  and  yet  carry  none  of  this  as  bits  of  information.)  It  is  its  function, 
also,  to  decipher  how  existing  engrams  form  the  scaffolding  for  new  ones. 
Here  is  the  crux  of  the  problem  of  learning.  It  depends  upon  the  evolved 
structures  —  the  improved  units,  patterns,  and  numbers  in  the  more 
advanced  nervous  systems,  but  it  depends  no  less  on  the  improved 
physiology  —  lowered  thresholds,  faster  conduction,  greater  spontaneity, 
easier  fixation,  and  a  host  of  other  attributes,  which  arc  just  coming  to  be 
recognized  as  important  characteristics  of  the  'higher'  animals  as  compared 
with  the  'lower'  ones.  But  before  coming  to  grips  with  the  problem  of 
the  neural  mechanisms  of  learning,  a  few  more  general  considerations 
involving  the  fixation  of  expierience  will  be  helpful. 

Several  questions  must  be  faced  for  all  systems  that  fix  experience.  The 
first,  of  course,  is:  How  does  a  system  at  a  given  time,  with  an  enduring 
architecture,  contributed  by  the  past  experience  of  the  race  or  itself, 
interact  with  the  environment  to  give  a  new  enduring  architecture?  As 
alreaciy  indicated,  this  applies  at  each  level  and  over  all  time  spans. 
Second,  when  does  a  reversible  change  —  a  homeostatic  response  to  stress, 
or  a  behavioural  change  in  response  to  a  stimulus  —  become  irreversible? 
What  is  the  limit  of  homeostatic  tolerance,  the  Rubicon  that  is  crossed, 
when  the  transient  response  becomes  either  an  adaptive  change  or  a  non- 
adaptive  (pathic)  breakdown?  When  does  a  dynamic  memory  become  a 
structural  one,  much  as  the  spoken  word  becomes  fixed  in  writing?  At 
what  stage  does  the  totipotent  embryonic  cell  become  irreversibly  differen- 
tiateci  and  specialized  for  a  particular  function?  When  does  the  individual 
growing  up  in  his  society  acquire  the  set  of  values,  customs,  skills  that 
characterize  it?  When  can  he  no  longer  learn  a  new  language  without  an 
accent,  or  face  a  different  culture  with  no  sense  of  xenophobia  ?Third, 
what  is  the  mechanism,  or  the  carrier,  of  the  operation?  How  is  the 
change  in  the  system  given  an  adaptive  (or  a  non-adaptive)  direction? 
Fourth,  turning  from  the  individual  to  the  race,  how  is  the  adapted 
individual  selected  or,  to  the  extent  that  individual  change  is  passed  on, 
how  is  this  achieved?  Last,  what  is  the  mechanism  of  cumulative  racial 
change? 

Such  questions  are  not  merely  disembodied  abstractions,  even  as  regards 
the  nervous  system  and  behaviour.  Learning  must  utimately  be  at  the 
molecular  level,  as  well  as  at  cellular,  organ,  and  individual  levels.  The 
material  record  of  experience  must  be  found  in  some  change  in  the 
number,  kind,  or  position  of  particles;  in  the  pattern  of  ions  or  molecules 
in  neurones  or  at  their  junctions.  As  acquired  racial  information  is  passed 


R.    W.    GERARD  2$ 

on  by  the  molecular  array  m  the  nucleus,  the  gene  number,  kind  and 
position,  so  the  acquired  individual  information  must  be  carried  somati- 
cally, perhaps  at  synapses.  But  that  experience  fixation  may  go  beyond  the 
comfortable  level  of  ordinary  neural  activity  is  nidicated  by  such  pheno- 
mena as  result  from  operative  manipulation  of  organisms.  The  classical 
experiments  of  Weiss  and  of  Sperry,  for  example,  demonstrated  that  the 
discharge  of  impulses  along  motor  nerves  depends  on  the  peripheral 
comiections ;  if  a  supernumerary  sartorius  muscle  is  implanted  in  the  back 
of  a  frog  and  neurotized  by  any  nerve  from  the  back  or  legs,  the  muscle 
w^ill  come  to  contract  simultaneously  with  the  normal  muscle  of  the  same 
name.  Some  kind  of  micro-specification  of  the  centres  connected  to  the 
new  muscle  'teaches'  them  to  respond  to  the  same  central  activity.  More 
recently,  the  work  of  Thompson  (1957,  1958)  and  McConnell  ct  al. 
(1955,  1959)  has  shown  that  learning  occurs  in  the  essentially  non-neural 
tail  of  a  planarian  at  least  as  well  as  in  the  ganglionated  head.  If  an  indivi- 
dual planarian  is  taught  a  conditioned  response,  cut  in  two,  and  the 
pieces  allowed  to  regenerate,  the  new  worm  formed  from  the  tail  end 
performs  almost  perfectly  as  soon  as  put  to  the  test. 

Turning  at  last  specifically  to  the  nervous  system,  the  same  interaction 
of  heredity  and  environment  is  seen  in  full  operation.  Heredity  gives  the 
embryonic  cells  which  will  form  neurones  under  their  normal  environ- 
ment, but  become  skin  or  lens  under  a  different  one;  which  will  continue 
to  multiply,  or  biturcate,  their  extensions  sufficiently  to  satisfy  fully  the 
physiological  field  or  need  (Weiss,  1955);  which  will  grow  fibres  in  a 
direction  guided  by  micellar  structure  and  by  chemical  concentration 
(Cohen  cr  nl.,  1954),  to  reach  an  appropriate  end  organ  (as  shown  by 
various  regeneration  experiments),  or  the  appropriate  central  neurone, 
despite  operative  mixing  (Detwiler,  1936).  But  all  these  capacities  are 
present  only  in  the  very  young  embryo;  at  each  successive  stage  of 
development  the  potency  shrinks  further.  Totipotent  cells  can  later  be- 
come only  neurones,  distorted  patterns  can  no  longer  be  corrected  and,  in 
general,  new  growth  and  chemical  metabolism  decrease  m  rate.  Rate  falls 
off' with  life  time,  a  basic  ageing  process,  roughly  as  a  decaying  exponen- 
tial curve;  growth  and  its  special  manifestation,  learning,  shrink  in  speed 
and  scope  with  advancing  years  until  plasticity  is  essentially  lost.  Then  no 
new  material  trace  is  formed  and  experience  is  no  longer  fixed  by  the 
individual. 

Specifically  for  the  nervous  system,  the  following  questions  are  impor- 
tant :  what  experience  is  retained ;  under  what  conditions ;  where  does  the 
change  occur,  is  it  local  or  diffuse;  what  is  the  nature  of  the  change, 


26  BRAIN    MECHANISMS    AND    LEARNING 

chemical,  electrical,  structural;  and  how  does  fixation  occur,  at  the 
molecular  and  at  the  cellular  levels?  Some  attention  will  be  given  to  the 
nature  and  the  locus  of  the  material  record,  but  most  attention  will  be 
given  to  the  mechanism  of  fixation. 

A  neurone,  at  least  in  tissue  culture,  is  a  restless  entity.  It  shows  the  usual 
swellings  and  churnings  of  other  cells  and  its  processes  thrust  out  and 
retract  pseudopodial  branches  and  terminations  unceasingly.  The  neurone 
has  an  unusually  high  rate  of  metabolism  and,  judging  by  the  rate  of 
regeneration  and  of  peripheral  flow  in  axons,  a  neurone  may  renew  its 
entire  mass  of  protoplasm  three  times  daily.  It  is  hard  to  see,  therefore, 
how  an  enduring  modification  can  be  left  at  the  cellular  level.  Experience 
must  presumably  alter  some  macromolecule,  DNA  or  RNA  or  protein, 
which  can  continue  to  reproduce  itself  in  the  altered  form,  much  as  a 
mutated  gene.  But  then  other  formidable  problems  arise.  How  docs 
neural  activity,  and  the  particular  pattern  of  electric  currents  and  attendant 
change  in  position  and  concentration  of  ions  and  polar  molecules  which 
activity  engenders,  lead  to  an  altered  array  of  nucleotides  or  amino-acid 
moieties  in  a  macromolecule?  How  does  such  an  altered  complement  of 
macromolecules  in  a  neurone  come,  in  turn,  to  modify  its  future  physio- 
logical activity  so  as  to  give  a  new  and  appropriate  pattern  of  discharges? 
How  is  the  specificity  of  the  molecular  change  related  to  the  specific 
functional  past  and  functional  future  in  an  adaptive  fashion?  Is  a  sort  of 
natural  selection  process  in  a  neurone  population  involved;  if  not,  we 
again  face  the  sort  of  problem  raised  by  Lamarck. 

Whatever  the  answer  at  the  molecular  level,  there  are  certainly  morpho- 
logical changes  with  neural  activity  at  the  levels  of  organelle  and  of  cell, 
and  some  of  these  endure  for  a  relatively  long  time.  The  chromatolysis  of 
fatigue,  with  diminished  Nissl  substance,  swollen  and  rounded  cytoplasm, 
and  eccentric  nucleus,  has  long  been  known.  More  recently,  a  change  in 
microsome  number  and  locus  arouiid  the  nucleus  has  been  shown  to 
accompany  changes  in  activity  of  neurones  in  tissue  culture  (Geiger,  1957). 
The  apical  dendrite  of  pyramidal  neurones  becomes  thicker  and  more 
twisted  with  continuing  activity.  Nerve  fibres  swell  when  active  (Hill, 
1950;  Tc^bias,  1952),  sprout  additional  branches,  as  seen  in  the  spinal  cord 
(McCouch  ct  (iL,  1958),  and  presumably  increase  the  size  and  number  of 
their  terminal  knobs.  New  fibre  branches  and  ccMincctions,  at  least,  might 
endure  long  enough  to  constitute  a  morphological  engram. 

It  is  highly  doubtful,  both  from  the  total  number  of  bits  remembered 
and  from  the  survival  of  memories  despite  extensive  brain  lesions,  that 
each  remembered  item  is  located  at  a  particular  neurone  or  synapse.  Some 


R.    W.    GERARD  27 

localization  is,  of  course,  present,  as  shown  by  the  aphasic  defects  with 
regional  lesions  and  by  particularized  recollections  inducec^  by  local 
temporal  stimulations.  But  even  these  are  hardly  cell  by  cell;  and  it  is  far 
more  probable  that  large  numbers  of  neurones,  in  assemblies  or  masses,  in 
different  patterns  and  other  orderings,  are  involved  in  each  memory. 
Partial  engrams  —  of  percepts,  images  and  acts  —  are  built  into  larger  ones 
—  concepts,  imaginings  and  skills  —  much  as  a  small  assortment  of  amino- 
acids  is  used  to  build  a  limitless  variety  of  proteins.  In  the  same  way,  learn- 
ing goes  from  letters  to  words  to  sentences,  with  plateaux  of  achievement 
at  each  larger  unit;  and  bits  of  information  become  aggregated  into  larger 
'chunks'  so  that  a  greater  quantity  can  be  handled  in  a  given  time  (Miller, 
1956).  Not  only  spacial  relations,  but  also  temporal  ones  must  be  proper, 
witness  the  great  disturbances  to  thought  and  speech  produced  by  delayed 
auditory  feed-back. 

Whatever  the  micro-locus  of  the  memory  trace,  most  learning  involves 
the  cortex.  Besides  the  evidence  of  cortical  localization  by  stimulation  and 
lesion,  there  is  the  further  evidence  of  a  general  parallel  between  learning 
and  memory  capacity  on  the  one  hand  and  general  cortical  size  on  the 
other,  and  also  there  are  the  recent  psycho-physiological  experiments 
initiated  by  Sperry  (1959).  With  the  optic  chiasm  cut,  so  that  incoming 
messages  from  each  eye  reach  only  the  ipsilatcral  hemisphere,  the  two 
hemispheres  remain  connected  primarily  through  the  corpus  callosum. 
If  conditioning  is  carried  on  with  cMie  eye,  a  correct  response  can  be  elicited 
through  either  eye  so  long  as  the  callosum  is  intact;  but  after  this  is  also 
cut,  only  the  eye  used  in  training  can  elicit  the  learned  response.  The 
engram,  while  available  to  both  hemispheres  when  these  remain  anatomi- 
cally connected,  is  as  clearly  localized  in  only  one.  Comparable  tmdings 
have  been  made  on  learning  set  or  learning  to  learn.  Other  evidence  for  a 
cortical  engram,  and  one  which  acts  as  a  template  for  further  engram 
development,  comes  from  the  work  of  Meyer  (1958).  Removal  of  both 
occipital  lobes,  but  with  a  two-week  interval  between  ablations,  leaves  a 
rat  with  pattern  vision  essentially  intact  if  ordinary  visual  experience  is 
possible  during  the  interval;  but  if  the  animal  experiences  no  pattern 
vision  between  the  removal  of  the  hrst  lobe  and  that  of  the  second,  a 
pernianent  loss  of  pattern  vision  results.  The  endurance  for  months  of 
figural  after-effects  in  the  Kohler's  satiation-illusion  (Wertheimer  and 
Leventhal,  1958)  further  indicates  a  cortical  locus  of  the  engram. 

Not  all  fixation,  however,  is  in  the  cortex.  Although  ordinary  condi- 
tioning of  the  spinal  animal  remains  highly  dubious,  there  is  solid  evidence 
of  card  changes  produced  in  the  intact  animal.  If  one  cerebellar  hemisphere 


28  BRAIN    MECHANISMS    AND    LEARNING 

or  peduncle  is  cut  a  few  hours  prior  to  a  high  spinal  section,  an  enduring 
postural  asymmetry  remains  in  the  hind  quarters  (de  Giorgio,  1943).  This 
is  reminiscent  of  the  continued  unidirectional  circling  by  a  decorticate 
dog,  the  direction  depending  upon  which  hemisphere  was  first  removed. 
A  comparable  postural  asymmetry  in  the  spinal  cat  is  seen  long  after  a 
severe  inflammatory  lesion  is  produced  in  one  paw;  the  previously 
damaged  leg  is  pulled  into  sharp  flexion,  with  crossed  extension  of  the 
other,  when  a  spinal  section  is  made  (Sperensky,  1944)-  Clinical  experience 
with  trigger  points,  and  the  demonstration  that  anginal  and  other  pains 
can  develop  a  permanent  referral  to  another  bociy  region  which  has  been 
irritated  at  the  time  the  pain  occurs,  points  in  the  same  direction  (see 
Gerard,  1951). 

The  growing  evidence  of  a  relation  of  deep  forebrain  structures  to 
learning  and  recall  has  not  yet  crystallized.  The  amygdala  seems  to  exert 
an  adverse  influence  on  fixation,  and  the  reticular  formation  and  hypo- 
thalamus have  also  been  found  to  be  involved.  Conversely,  recent  memory 
fails  with  damage  to  the  mammilary  body,  the  fornix,  and  the  amygdala 
(Morrell,  1956;  Bickford  ct  ah,  i9.vS;  Jasper  and  Rasmussen,  1958; 
Samuels,  1959;  Doty,  1960;  Gerard,  1960a).  Recently,  the  stimulation  of 
the  midbrain  tegmentum  has  been  reported  (Thompson,  1958;  Glickman, 
1958)  to  cause  forgetting;  while  stimulation  of  the  caudate  impairs  fixa- 
tion. The  whole  situation  is  confused  by  difliculties  in  distinguishing 
between  fixation  on  the  one  hand  and  retention  and  recall  on  the  other. 
The  use  of  hypnosis  as  a  tool  to  maximize  recall  has  long  given  unexpected 
results;  and  recent  reports  by  responsible  workers  —  such  as  the  hypnotic 
recall  of  a  conversation  which  occurred  during  surgical  anaesthesia  of  the 
individual  doing  the  recalling;  or  recall  of  experiences  during  a  given  year 
of  childhood  but  only  when  an  hypnotic  suggestion  had  brought  the 
individual  back  to  that  age  (Sheerer  and  Reift,  1959)  —  demonstrates  our 
small  understanding  of  the  complex  phenomena  of  fixation  and  recall. 

The  mechanism  of  fixation  of  experience  is  not  known,  but  two  sets  of 
data  give  strong  clues  concerning  its  nature.  First,  is  a  group  of  well- 
known  changes  that  attend  continued  activity  of  neurones:  thresholds  go 
through  increased  and  decreased  phases;  after-potentials  are  increased 
enormously  in  magnitude  and  duration;  post-tetantic  potentiation  is 
associated  with  greatly  increased  reflex  responses ;  and  the  like.  The  other 
phenomena  relate  to  the  existence  c^f  a  considerable  period,  of  minutes  to 
hours,  between  having  an  experience  and  fixing  it.  If  neural  activity  is 
interfered  with  during  this  fixation  period,  by  electroshock,  by  cold, 
by  heat-block,  and  the  like,  fixation  is  interfered  with  and  permanent 


R.    W.    GERARD  29 

memories  are  feeble  or  abolished  (Duncan,  194.S ;  Gerard,  [953  ;  Ransmeier, 
1954;  Leukcl,  1957;  Otis  and  Cerf,  1959).  Thus,  hamsters  or  rats  trained  in 
grouped  runs  on  some  learning  situation  —  a  maze  or  an  avoidance 
conditioning  or  the  like  —  show  a  normal  learning  curve  if  a  convulsive 
electroshock  is  delivered  after  each  set  of  runs  with  an  interval  of  4  hours 
or  more.  It  the  shocks  follow  the  experience  by  an  hour  there  is  some 
deterioration,  at  1 5  minutes  loss  is  very  considerable,  and  at  5  minutes  or 
less  learning  is  in  effect  prevented.  If  a  hamster  is  promptly  cooled  after 
the  learning  experience,  a  shock  given  an  hour  later  can  be  as  deleterious 
as  one  given  a  few  minutes  later  at  body  temperature;  the  Q^^  of  the 
fixation  process  has  been  thus  determined  at  nearly  three  (Ransmeier  and 
Gerard,  1954). 

Anoxia  acts  much  like  electroshock,  and  the  two  sum  their  effects 
(Ransmeier  and  Gerard,  1954;  Thompson,  1957).  A  number  of  drugs  has 
now  been  tested  for  influences  on  the  electroshock  effect.  Reserpine,  like 
anoxia,  potentiates  the  ECS  disruption  of  learning  (Weyner  and  Reimonis, 
1959);  ether  protects  against  electroshock  effects  (Seigel  ct  al,  1949; 
Potter  and  Stone,  1947);  and,  in  man,  meprobamate  decreases  the  con- 
tusion produced  following  electroshock  (Thai,  1956).  Miss  Rabc  and  I 
(1959)  have  just  completed  studies  of  the  action  of  phenobarbital  and  of 
meprobamate  on  ECS  action  in  rats  on  an  avoidance  conditioning  test.  In 
effect,  phenobarbital  slows  and  prolongs  the  fixation  time,  as  judged  by 
the  greater  disruptive  effects  of  a  convulsive  stimulus  at  i,  2,  5  and  15 
minutes  in  animals  under  the  barbiturate  as  compared  with  undrugged 
ones;  while  meprobamate,  contrary  to  expectation,  seems  to  have  the 
reverse  effect.  Interestingly  enough,  meprobamate,  but  not  phenobarbital, 
slows  the  learning  process,  aside  from  any  ECS.  Strychnine,  according  to 
an  informal  communication  from  Dr  Krech,  shortens  the  fixation  time;  a 
convulsive  shock  at  a  given  time  interval  is  less  disruptive  in  the  strychnized 
rat  than  in  one  without  the  drug. 

The  above  facts  fit  well  into  a  theory  of  continued  activity  in  the  nervous 
system,  following  the  arrival  of  sensory  impulses,  in  the  course  of  which  a 
dynamic  memory  is  fixed  as  a  structural  one  (Gerard,  1960a).  Summation, 
irradiation  and  reverberation  of  messages  would  lead  to  repeatec^  activity 
of  the  same  neurones,  with  progressively  greater  and  greater  residual 
changes  from  the  continued  activity.  At  50  reverberations  per  second, 
100,000  actions  could  easily  occur  during  the  fixation  time;  presumably 
sufficient  to  leave  an  indelible  trace. 

Any  change  that  would  enhance  the  extent  or  intensity  of  reverberation 
should  hasten  the  fixation  process;  any  agent  acting  in  the  converse 


30  BRAIN    MECHANISMS    AND    LEARNING 

direction,  should  slow  it.  A  fall  in  threshold  of  cortical  neurones,  or  an  in- 
crease in  impulse  bc:)mbardment,  should  hasten  tixation.  Since  epinephrine 
lowers  thresholds,  and  is  released  in  vivid  emotional  experiences,  such  an  in- 
tense adventure  should  be  highly  menaorablc.  Perhaps  during  imprinting 
periods,  the  relevant  neurones  arc  similarly  in  a  low  threshold  or  'soft- 
shell'  stage.  Strychnine,  by  enhancing  general  activity  level  and  lowering 
thresholds,  should  also  speed  up  the  fixation  process.  The  reticular  forma- 
tion, the  amygdala  and  other  components  of  the  limbic  system,  the  hypo- 
thalamus, etc.,  act  through  one  another  or  directly  on  cortical  neurones  to 
alter  their  dendrite  potentials,  their  thresholds,  and  their  responsiveness  to 
the  discrete  impulses  which  reach  the  cortex  by  non-diffuse  afterents  or  by 
spread  within  it.  By  raising  or  lowering  thresholds  of  cortical  neurones, 
associated  with  lov/ered  or  increased  attention  and  vigilance,  these  deep 
regions  could  easily  modify  the  ease  and  completeness  of  experience 
fixation  even  if  the  nuclei  were  not  themselves  loci  of  engrams.  Ether  and 
meprobamate,  by  raising  thresholds,  should  slow  reverberation  and 
therefore  make  electroshock  effects  more  severe;  unless  they  also 
decrease  the  effect  of  the  shock  itself  due  to  the  increased  neurone  thresholds. 
This  last  possibility  is  being  further  tested  in  the  case  of  meprobamate;  it 
does  explain  the  synergy  of  rescrpine  and  shock,  and  of  anoxia  and  shock, 
since  both  anoxia  and  rescrpine  lower  convulsive  thresholds. 

Fixation  would  also  be  modified  by  changing  impulse  bombardment; 
in  fact  it  is  the  interference  with  such  continued  bombardment,  by  shock 
or  cold  or  concussion  —  which  latter  rather  nicely  parallels  clinically  the 
amnesic  effects  of  electroshock  m  animals  or  man  —  that  interrupts  the 
fixatic^n  process.  Early  in  any  learning  experience,  as  the  organism's 
actions  fail  to  solve  the  problem  and  eliminate  the  disturbing  input,  there 
is  great  central  irradiation;  muscle  tension  is  increased,  there  is  generalized 
contraction  of  irrelevant  as  well  as  of  the  desired  muscles,  autonomic  dis- 
charges occur,  tension  and  attention  are  intense,  the  'consciousness  of 
necessity'  is  high,  and  many  neurones  m  cortex  and  deep  centres  show 
electrical  activity  on  mass  or  micro-electrode  recording.  Later,  when 
learned  responses  have  been  established,  general  radiation  disappears, 
muscles  relax,  there  is  little  tension  and  maybe  not  even  attention, 
habituation  is  evident  in  performance  and  experience,  and  electric  activity 
has  disappeared  from  all  neurones  except  those  specifically  involved  in  the 
response.  With  errors  or  other  kinds  of  emergency  situations,  the  electrical 
activity  and  other  signs  of  irradiation  promptly  return  (see  Gerard,  1960a 
for  references).  As  an  action  is  learned  and  certain  paths  through  the 
nervous  system  become  canalized,  irradiation  is  eliminated.  This  requires 


R.    W.    GERARD  3 1 

cither  feed-back  inhibitory  arcs  or  a  decrease  in  the  general  level  of 
facilitation,  as  interneurones  become  less  active.  This  latter  would  follow 
the  diminished  irradiation  consequent  to  effective  responses. 

Although  the  effect  of  continuing  or  recurring  activity  has  been 
described  in  terms  of  simple  feed-back  loops,  the  same  results  can  be 
obtained  by  improved  synchrony  of  beating  neurones  or,  especially,  by 
repeated  waves  of  activity  passing  through  a  sheet  of  neurones.  This  last 
model,  developed  by  Beurle  (1957),  depends  only  on  more  or  less  random 
connections  of  neurones  in  a  mass,  activated  only  fractionally  by  con- 
trolled waves  passing  through  them.  Such  waves  can  cross  and  at  the 
locus  o(  intersection  will  leave  a  group  ot  lowered-threshold  neurones. 
From  such  a  locus  the  original  waves  can  reinitiate  without  external 
stimulation;  such  loci  thus  of^er  engrams  for  memory,  recall,  planning  of 
action  and  for  the  combination  of  smaller  elements  of  perception  and 
action  into  larger  wholes  of  conception  and  of  planning.  The  model  and 
the  physiological  support  for  and  predictions  from  it  are  more  fully 
discussed  elsewhere  (Gerard,  1960a). 

Reverberation,  or  some  form  of  continuing  reactivation,  is  probably 
involved  in  a  number  of  other  mental  processes,  including  perception, 
attention,  repression,  anxiety,  and  the  like;  but  this  is  not  the  place  to 
develop  these  points.  Certainly  attention  is  necessary  ior  learning  and  for 
discrimination.  A  dog,  faced  with  an  impossible  oval  or  circle  choice, 
develops  a  neurosis  only  after  it  has  already  learned  to  pay  attention  to  this 
discrimination  as  a  problem.  Presumably  the  structures  feeding  diffuse 
system  impulses  to  the  cortex,  discussed  above  in  connection  with  the 
altering  of  fixation  and  recall,  are  involved  in  such  influence  of  attention 
on  the  learning  process. 

The  nature  of  the  material  change  in  the  brain,  of  its  locus,  and  of  the 
mechanism  of  fixation  that  brings  it  about  are  not  established,  but  all  these 
questions  are  clearly  on  the  way  to  satisfactory  solution.  The  really  diffi- 
cult problem  is  none  of  these,  however,  and  it  remains  as  mysterious  as 
ever.  This  has  to  do  with  spccificiry  in  the  selection  and  discrimination  of 
what  is  perceived,  in  the  degree  of  attention  given  it,  in  the  presence  and 
firmness  of  fixation  of  a  memory,  in  its  retention  and  subsequent  recall  to 
consciousness.  This  qualitative  aspect  is,  of  course,  not  limited  to  the 
receiving  and  retention  of  experience,  but  is  equally  present  on  the 
behavioural  side  and  is  attached  to  plans,  to  values  and  to  actual  per- 
formance. How  choices  are  made,  how  priorities  are  assigned,  how  shifts 
occur  from  one  set  of  active  neural  processes  to  a  different  one,  remains 
scill  a  complete  mystery. 


32  BRAIN    MECHANISMS    AND    LEARNING 

Certainly  this  is  related  to  our  subjective  experience  of  free  will  in 
choosing  what  we  do  and  what  we  attend  to.  But  before  accepting  un- 
caused causes,  let  us  recall  that  computers  can  also  learn  to  develop  a  set  of 
values  and  to  choose  between  programmed  activities,  so  that  we  need  not 
yet  despair  of  finding  the  neural  mechanisms  for  this  ultimate  core  of 
higher  behaviour.  Given  a  programme  or  plan,  a  computer  can  rapidly 
scan  the  existing  situation  and  select  that  set  of  actions  which  will  come 
closest  to  matching  an  'ideal'  that  has  been  given  it.  Behaviour  is  similarly 
tracking;  as  individual  or  as  race,  organisms  respond  to  the  challenge  of 
their  environment.  Behaviour,  as  remarked  earlier,  is  such  as  to  bring  the 
expected  future  condition  of  the  organism  into  congruence  with  the 
desired  condition.  This  can  be  done  blindly,  starting  from  the  existent 
state,  or  it  can  be  done  with  greater  or  lesser  foresight  bv  projecting  the 
existing  state  into  its  probable  future  condition. 

The  nervous  system  and  learning  endow  the  animals  possessing  them 
with  this  ability  to  extrapolate  the  curve  of  existence  and  so  to  act  with 
foresight.  The  cat  jumps  not  to  where  the  mouse  is,  but  to  where  it  may 
be  expected  to  be.  Man  not  only  can  himself  run  away  from  the  batter  in 
order  to  catch  a  flyball;  he  can  also  build  into  computing  tracking 
mechanisms,  as  anti-aircraft  guns,  the  same  ability.  Man  himself,  with  his 
ten  billion  or  more  cortical  neurones',  can  out-perform  all  other  projecient 
machines,  so  far  built  by  nature  or  by  him,  in  projecting  further  and  more 
elaborately  into  the  future.  This  is  possible  because  of  a  great  repertoire  of 
past  memories,  or  partially  organized  and  interacting  programmes,  and  of 
complex  probability  computers  that  take  account  of  past  and  present 
factors  and  assign  value  or  utile  weights  to  them.  The  basic  molecular, 
cellular  and  organismic  mechanisms  involved,  however,  are  probably  not 
much  different  from  frog  to  physiologist.  It  is  an  intriguing  question 
whether  equally  effective  ones  will  one  day  be  evolved  for  man's  machines. 

GROUP   DISCUSSION 

Hebb.  I  would  like  to  raise  two  points.  One  is  with  respect  to  the  work  or 
McConnell  on  the  flatworm  which  I  found  extremely  puzzling.  I  do  not  know 
whether  it  can  be  compared  to  learning  in  mammals.  If  this  type  of  mechanism 
applied  in  the  mammal,  presumably  Sperrv's  work  should  not  have  given  the  result 
it  did  by  just  cutting  the  corpus  callosum.  We  must  be  dealing  with  a  different 
phenomenon,  when  we  talk  of  learning  in  the  mammals,  from  the  phenomenon 
that  McConnell  studied.  Secondly,  with  respect  to  the  effects  of  anaesthetics  on  the 
consolidation  period  of  learning,  I  would  like  to  cite  some  work  by  Muriel  Stern, 
concerning  the  effect  of  barbiturates  on  learning.  The  effect  you  observed  may  be  a 
general  disturbance,  rather  than  a  specific  interference  with  the  retention  period. 
The  effect  of  barbiturates  is  that  of  depressing  learning  capacity  for  a  period  of  some 


R.    W.    GERARD  33 

weeks  111  the  laboratory  rat.  The  effect  disappears  in  5  or  6  weeks.  The  effect  is  not 
found  with  other  anaesthesia. 

Gerard.  I  am  not  prepared  to  go  along  with  the  extreme  psychiatrists  who  say 
that  learning  is  all  over  the  body  and  not  in  the  brain,  nor  with  the  slogan  that 
'we  think  with  our  blood'.  We  think  in  the  nervous  system  and  in  the  upper  part 
of  it,  but  there  is  continuity.  The  same  kind  of  mechanisms,  which  are  specialized 
in  the  nervous  system  as  a  basis  tor  recording  experience,  probably  evolved  from 
basic  cellular  processes,  which  are  seen  at  the  chemical  level,  hi  the  case  of  the 
flatworm  this  is  closer  to  the  level  ot  total  behaviour.  As  to  the  second  point,  the 
action  of  these  drugs  on  the  fixation  process  and  on  learning  processes  is  very 
complicated  and  depends  on  many  parameters.  With  increasing  doses  of  mepro- 
bamate,  one  finds  an  increasing  interference  with  the  learning  curve.  These  experi- 
ments were  on  rats  with  an  avoidance  conditioning,  given  massed  trials  and  tested 
the  next  day.  The  drug,  when  given,  was  injected  i  hour  for  meprobamatc,  or 
3  hours  for  the  barbital  (depending  on  maximum  time  of  action),  before  the  learn- 
ing experience.  Rats  were  given  electroconvulsive  shocks  at  i,  2,  5,  or  15  minutes 
after  the  mass  runs,  which  were  completed  usually  well  within  15  minutes  total 
time.  Although  meprobamate  definitely  interfered  with  learning,  it  did  not  inter- 
fere with  the  hxation;  it  even  improved  it.  hi  other  words,  an  electric  shock  at  one 
minute  did  not  interfere  so  much  with  retention  on  second  test  of  a  rat  with,  as 
for  one  without,  meprobamate.  We  are  checking  to  be  certain  that  a  raised  threshold 
is  not  a  fictor,  even  though  all  shocks  gave  typical  convulsions.  The  phenobarbital 
had  a  marked  effect  in  prolonging  fixation  time;  as  shown  by  much  deterioration 
with  electroshock,  and  the  greatest  deterioration  with  the  closest  shock.  It  did  not 
interfere  with  initial  learning.  Your  findings  seem  contrary  to  what  happened  in 
our  laboratory;  we  should  examine  differences  in  conditions. 

Chow.  May  I  just  make  a  point  about  this  ffatworm  work,  because  that  work 
seems  to  me  to  be  most  striking.  If  it  is  true  it  will  probably  inffuence  our  thinking 
about  learning  at  the  cellular  level.  There  are  two  points  I  wish  to  make  about  this 
particular  piece  of  work,  the  results  of  which  I  think  should  be  accepted  with  some 
caution.  First,  there  are  probably  nerve  cells  in  the  nerve  tract,  therefore  you  have 
a  second  or  caudal  half  which  still  remembers  the  problem,  which  may  not  be  due 
to  memory  in  the  nerve  fibre  itself.  Secondly,  a  very  important  point  is  that 
apparently  an  essential  control  was  not  made.  This  control  is :  they  should  have  a 
group  of  animals  which  are  given  a  series  of  shocks  without  learning,  and  cut  them 
into  two,  wait  until  they  regenerate  and  do  the  conditioning,  and  see  if  this  group 
without  previous  training,  also  show  a  fast  learning. 

Gerard.  These  controls  have  now  been  done.  I  talked  to  McConnell  some 
months  ago  and,  as  I  recall,  results  were  going  in  the  proper  direction.  Even  with- 
out them,  however,  it  seems  hard  to  explain  awa\'  the  fict  that,  even  if  there  are  a 
few  neurones  in  the  tail  as  compared  to  the  many  in  the  head,  the  tail  did  do  as  well 
as,  or  better  than,  the  head.  Maybe  if  one  gets  too  much  stuff"in  the  head,  ideas  get 
fixed  in  a  certain  way  and  performances  are  no  longer  malleable;  a  sort  of  ageing 
phenomenon.  The  work  will  certainly  have  to  be  examined  carefully,  because  it  is 
a  very  disturbing  finding.  However,  the  appearance  of  certain  phenomena  at  this 
primitive  level  does  not  necessarily  explain  those  at  a  more  complicated  level.  It 
may  well  be  true  that  this  is  a  perfectly  good  type  of  learning,  but  it  is  certainly  not 
the  whole  story  of  our  learning.  Let  me  give  one  example  of  this:  Many  years  ago 


34  BRAIN    MECHANISMS    AND    LEARNING 

Dr.  Libet  and  I  found  that  travelling  slow  waves  in  the  hemisphere  ot  the  frog, 
starting  at  the  olfactorv  bulb,  would  cross  a  complete  section  through  the  brain  if 
this  was  made  with  a  sliarp  razor  blade  and  if  the  two  halves  were  accurately  placed 
together.  (I  do  not  think  neurohumoural  agents  were  involved).  Several  investi- 
aators  checking  in  mammals  found  the  spread  of  epileptic  activity  was  blocked  by 
cutting.  Aside  from  the  fact  that  they  were  not  able  to  get  anything  like  an 
equivalent  opposition,  there  was  no  necessity  that  this  be  the  same  phenomenon. 

AsRATYAN.  I  would  like  to  ask  a  question  about  the  same  experiment.  For  how 
long  is  It  possible  to  evoke  these  responses  from  the  head  part  and  the  caudal  part  ? 
How  long  does  this  habit  remain?  Is  it  possible  to  elaborate  reflexes  on  the  head 
part  and  on  the  caudal  part  of  the  animal  after  cutting  the  animal  in  two  and  what 
is  the  difference  m  the  rate  of  elaboration  and  of  appearance  of  learning? 

Gerard.  I  do  not  know  the  answer  to  the  second  question.  As  to  the  first,  it 
takes  about  3  weeks  for  regeneration  and,  as  I  recall,  the  test  was  made  a  month 
after  cutting.  Uncut  planaria  also  retained  the  learning  for  such  a  period. 

BusER.  Did  the  author  exclude  the  possibility  of  peripheral  network  as  happens 
in  many  invertebrates,  as  being  hypodermic  and  distinct  from  the  C.N.S.  It  could 
be  a  diffuse  system.  1      •         j 

Gerard.  I  can  only  answer  that  work  is  now  in  progress  with  a  zoologist  and 
histological  tests  are  being  made  more  extensively.  This  is  perhaps  the  widest  loop- 
hole; whether  there  are  as  yet  unrecognized  neurones  in  the  tail  part  of  the  animal. 

RosvOLD.  I  was  interested  in  your  statement  that  there  is  no  necessary  reason  why 
what  happened  m  planaria  need  concern  us  with  respect  to  man's  brain  or  monkey's 

brain  ...  ,  i   1  •   1    ■ 

Gerard.  May  I  correct  that?  I  would  not  say  it  does  not  concern  us;  1  think  it 
concerns  us  enormously  or  I  would  not  have  mentioned  it.  But  I  do  not  think  it  is 
the  whole  story.  It  is  part  of  the  story,  the  substrate  on  which  other  mechanisms 

are  built.  , 

RosvoLD.  From  a  comparative  point  of  view,  however,  where  can  one  draw  tiie 
line?  How  close  can  one  make  the  analysis?  If  one  takes  your  statement  literally 
could  not  one  always,  so  to  speak,  wriggle  out  of  an  inconsistency?  Simply  statmg 
that  the  comparison  is  too  remote  and,  therefore,  is  hardly  appropriate. 

Gerard.  I  am  not  really  clear  as  to  the  question.  Is  this  responsive :  I  have  become 
a  behavioural  scientist  lately  and  am  m  an  Institute  which  devotes  itself  to  be- 
havioural science.  We  are  concerned  with  finding  the  constants  in  the  properties  of 
systems  at  all  levels  from  molecules  to  societies.  We  are  often  attacked  for  dealing 
with  meaningless  analogies  because  the  details  are  different  in  each.  I  suggest  that  it 
is  extremely  Important  to  be  aware  both  of  the  particularities  wliich  differentiate 
the  one  from  the  other  and  of  the  general  likeness.  When  I  say,  as  I  do,  that  an  idea 
in  society  is  in  many  ways  like  a  gene  in  biology,  and  that  this  is  the  new  disturbmg 
element  which  makes  social  evolution  possible  as  a  new  gene  makes  biological 
evolution  possible,  I  do  not  mean  that  male  and  female  ideas  mate  and  that  there 
are  mitoses  and  all  the  rest  of  it.  This  would  be  arrant  nonsense.  But  it  is  still  useful 
to  see  some  of  the  likenesses.  If  one  can  in  fact  get  something,  assummg  that  this 
holds  up,  which,  objectivelv,  we  would  have  to  call  learning,  in  non-neural  cells, 
even  though  they  have  undergone  division  to  form  a  new  nervous  system,  this  is 
something^vhich  I  should  expect  to  apply  in  any  comparable  situation  that  could 
be  found  In  man.  Indeed,  the  reason  I  brought  up  these  findings  is  the  high  prob- 


R.    W.    GERARD  35 

ability  that  the  engram  in  neurones,  which  themselves  undergo  'regeneration'  by 
changing  their  material  three  times  a  da\',  might  also  be  something  at  a  molecular 
level.  Whatever  the  mechanism,  in  either  case,  a  new  kind  ot  template  is  formed, 
new  molecules  are  reproduced  according  to  the  template,  and  this  is  the  way 
fixation  ot  experience  or  learning  is  carried  on  in  the  nervous  system. 

Thorpe.  With  regard  to  this  matter  ot  the  planaria  there  have  been  a  number  of 
examples  of  what  have  been  called  pre-imaginal  conditioning  in  insects  where  the 
larva  was  exposed  to  an  intluence  which  produced  the  corresponding  modification 
of  behaviour  in  the  adult.  This  was  first  done  with  regard  to  exposure  to  chemical 
substances,  but  there  was  also  a  series  of  experiments  reported  by  Borell  du  Vernay 
(1942)  in  which  the  larvae  of  the  beetle  Tciiehrio  iiwliter  were  trained  to  take  a 
certain  path  in  a 'T'  maze  and  the  same  effect  was  observed  significantly  in  the  adults. 

Gerard.  To  what  extent  is  the  nervous  system  discontinuous? 

Thorpe:  A  steady  change  takes  place.  Although  the  locomotory  systems  of  the 
larva  and  the  adult  are  very  different  there  would  certainly  have  been  organized 
nervous  tissue  present  throughout.  So,  though  we  are  not  here  dealing  with  a 
complete  replacement  of  nervous  tissue,  I  think  nevertheless  that  these  experiments 
are  interesting  to  recall  in  connection  with  the  subject  of  our  present  discussion. 

Might  I  ask  you  about  one  other  point?  A  very  different  one.  You  referred  to 
this  matter  of  fixation  and  recall  and  the  distinction  between  it.  I  was  very  puzzled 
some  years  ago  by  some  work  that  Dr  McCulloch  reported,  on  the  ability  of  some 
patients  to  recall,  when  under  hypnosis,  extraordinary  details  of  their  own  early 
actions  and  experiences.  One  particular  case  I  remember  concerned  a  bricklayer 
who  was  able  to  recall  minute  details  of  the  bricks  he  had  laid  at  a  certain  date  of  his 
life.  I  tried  to  get  the  exact  particulars  ot  this  trom  Dr  McCulloch  at  the  time  but 
he  was  not  able  to  give  anytliing  like  the  detail  which  I  hoped  would  be  torth- 
coming.  I  mentioned  it  in  the  hope  that  other  people  here,  such  as  Dr  Hebb, 
might  have  some  fresh  data  to  give  us  on  this  particularly  important  topic.  Only 
last  year  Wilder  Penfield  {Pwc.  Nat.  Acad.  Sci.,  44)  stated  his  belief,  based  on  25 
years  experience  ot  surgical  treatment  of  brains  of  epileptics,  that  the  temporal 
lobes  possess  a  permanent  record  of  the  stream  of  consciousness  in  amazing  detail 
—  as  if  the  brain  cells  behaved  like  a  tape  recorder  which  may  be  played  back  by  a 
suitable  electrical  stimulus. 

Gerard.  I  have  also  been  intrigued  by  that  report.  As  I  recall,  a  bricklayer  in  his 
sixties  or  seventies  was  asked  to  describe,  say,  the  fifth  brick  in  the  seventh  tier  of  a 
wall  that  he  had  laid  in  his  twenties.  The  bumps  on  the  top  and  the  bottom  of  the 
brick  he  described  under  hypnosis  could  be  checked  and  they  were  there.  It  is  a 
dramatic  statement  and  I  have  referred  to  it  in  a  paper.  I  do  hope  McCulloch  is 
correct,  for  he  is  also  my  source. 

Another  example,  given  informallv,  at  a  symposium  in  Kansas  City  along  with 
the  statement  about  recall  of  events  under  deep  surgical  hypnosis,  frightened  me 
even  more,  because  it  makes  me  think  ot  Bridie  Murphy.  An  adult  was  asked  to 
recall  some  details  of  a  classroom,  desks,  etc.,  in  which  he  sat  when  6  years  old.  He 
was  quite  unable,  even  under  hypnosis,  to  recall  any  of  these  things  until  the 
suggestion  had  been  made:  'You  are  now  6  years  old'.  Then  he  described  them. 
When  he  was  told  he  was  7  years  old,  he  couldn't  do  so.  I  can  only  say  that  a 
thoroughly  reputable  psychologist  told  us  this  with  fear  and  trembling,  but  he 
could  not  find  anything  wrong  with  his  experiments. 

D 


DISTINCTIVE  FEATURES  OF  LEARNING  IN  THE 
HIGHER  ANIMAL 

D.  O.  Hebb^ 

In  the  study  of  learning  our  problem  is  not  only  to  understand  the  way 
in  which  synaptic  function  is  modified;  it  also  fundamentally  involves 
control  of  the  concurrent  activity  of  the  rest  of  the  central  nervous  system. 
One  question  is  more  'molecular'  and  physiological,  essentially  concerned 
with  the  relations  between  two  individual  neurones ;  the  other  is  'molar' 
and  psychological,  involving  the  operations  of  the  total  system.  The 
second  part  of  my  thesis  is  that  we  must  develop  means  of  dealing  experi- 
mentally with  the  so-called  autonomous  central  processes  whose  activity 
is  at  the  heart  of  the  learning  process  in  the  higher  animal,  and  some 
research  is  reported  which  attempts  to  make  a  contribution  of  this  kind. 

THE    PROBLEM    OF   EXCESS    ACTIVITY    IN    CNS 

Learning  consists  of  a  modified  direction  of  transmission  in  the  CNS  so 
that,  in  the  clearest  example,  a  sensory  excitation  is  now  conducted  to 
effectors  to  which  it  was  not  conducted  before.  A  new  S-R  or  stimulus- 
response  connection  has  been  established  (the  clearest  example,  but  not  the 
only  form  of  learning).  The  term  learning  may  be  used  to  refer  to  other 
changes  of  behaviour  in  primitive  animals,  but  at  least  in  the  case  of  the 
mammal's  acquisition  of  prompt,  efticicnt  responses,  dependent  on  the 
all-or-none  action  of  neural  cells  conducting  over  considerable  distances, 
the  direction  of  transmission  must  be  determined  at  the  synapse  (or  close 
to  it:  Milner,  1959).  It  might  therefore  be  thought  that  the  problem  of 
learning  is  simply  to  discover  when  and  how  synaptic  function  is  modified. 

The  question  is  indeed  fundamental,  and  must  be  answered  before  the 
problem  of  learning  will  be  solved;  but  it  is  by  no  means  the  whole 
problem,  because  of  complexities  introduced  by  the  structure  of  the  CNS 
in  higher  animals,  and  particularly  in  mammals  and  in  primates.  In  the 
learning  process  we  do  not  have  a  one-to-one  relation  between  progres- 
sive changes  of  behaviour  and  changes  at  the  synapse.   The  simplest 

^  The  presentation  of  this  paper,  and  some  of  the  experimental  work  reported  herein,  was 
made  possible  by  the  National  Research  Council  of  Canada.  The  experiments  were  done  by 
Jean  Campbell,  Joseph  Deitcher  and  Eric  Renncrt. 

37 


38  BRAIN    MECHANISMS    AND    LEARNING 

mammalian  behaviour  involves  an  enormous  number  of  synapses,  the 
changes  that  occur  simultaneously  may  be  in  opposite  directions,  and 
there  may  be  little  detectable  relation  between  the  course  of  events  at  any 
one  synapse  and  changes  of  overt  behaviour  —just  as  there  may  be  little 
relation  between  the  activity  of  an  individual  neurone  and  the  gross  record 
of  the  EEC 

If  we  assume  that  many  of  the  neurones  in  the  brain  of  a  waking 
mammal  arc  tning  at  any  given  time,  and  especially  if  we  further  assume 
that  some  of  these  are  inhibitory,  there  are  certain  consequences  which 
have  sometimes  been  overlooked  in  physiological  discussions  of  learning. 
The  possession  of  a  large  brain  capable  of  learning  a  great  many  different 
things  inevitably  nieans  that  there  are  far  more  neurones  present  than  is 
necessary  for  learning  some  one  specific  task.  Any  random  activity  in 
these  excess  neurones  (the  ones  not  needed  for  the  task  being  learned)  is 
'noise',  which  must  tend  to  interfere  with  the  learning.  (If  the  activity  is 
organized  instead  of  random  it  is  not  noise,  technically  speaking,  but  the 
effect  may  still  tend  to  be  adverse.)  It  seems  obvious  that  the  number  of 
excess  neurones  must  be  very  much  greater  —  perhaps  thousands  of  times 
greater  in  the  brain  of  the  higher  animal  —  than  those  needed  for  the 
learning  going  on  at  the  moment.  It  therefore  seems  that  the  rate  of 
learning,  as  observed  in  the  behaviour  of  the  whole  animal,  may  be  not 
an  index  of  capacity  tor  adding  new  synaptic  connections  so  much  as  an 
index  of  the  noise  level,  and  that  learning  will  be  fast  or  slow  according  as 
one  is  successful  in  establishing  an  environmental  control  of  the  excess 
neural  activity,  in  order  to  prevent  or  niinimize  interference. 

Practically,  the  significance  of  this  point  of  view  is  clear  in  the  term  'lack 
of  concentration',  in  the  case  of  the  student  whose  learning  is  inefficient 
even  in  a  quiet  environment,  because  other  thoughts  obtrude  besides  the 
ones  he  should  be  concerned  with.  Experimentally,  the  point  is  made  by 
Ricci,  Doane  andjasper  (1957),  in  reporting  that  a  significant  part  of  the 
conditioning  process  —  perhaps  the  main  part  —  is  in  the  dropping  out  of 
irrelevant  connections,  rather  than  the  acquisition  of  new  ones.  It  is 
clearest  of  all  in  a  classic  experiment  of  Yerkes. 

Yerkes  (19 12)  trained  an  earthworm  to  choose  one  arm  of  a  T-maze, 
using  electric  shock  as  punishment  for  error  and  the  moist  burrow  as 
reward  for  correct  choice.  The  habit  was  acquired  in  twenty  trials,  2  days 
at  ten  trials  per  day,  about  what  might  be  necessary  for  the  laboratory  rat. 
No  errors  were  made  on  the  third  day,  though  behaviour  was  somewhat 
inconstant  in  the  following  week  as  between  good  days  and  bad  days 
(even  worms  have  them).  Yerkes  then  removed  the  brain,  or  principal 


D.    O.    HEBB  39 

ganglia,  by  cutting  oft  the  head  —  the  anterior  four  and  a  halt  segments. 
The  animal  continued  to  respond  correctly,  showing  that  there  were 
suiTicient  synaptic  modifications  in  the  remaining  ganglia  to  mediate  the 
response  —  until  the  new  head  regenerated,  at  which  time  the  habit  was 
lost.  The  noise  generated  by  the  new  ganglia,  the  irrelevant  neural  activity 
of  the  uneducated  brain,  was  sufficient  to  disrupt  learning  completely. 

In  this  case  we  are  dealing  with  the  effects  of  noise  on  an  established 
habit,  and  in  a  lower  animal.  It  seems  clear  that  the  potential  disrupting 
effects  must  be  as  great  or  greater  while  learning  is  still  going  on,  and  in 
the  large  brain  of  the  higher  animal.  If  then  the  rate  of  learning  reflects  the 
noise  level  in  the  system,  it  becomes  intelligible  that  the  higher  animal 
does  not  learn  faster  than  the  lower,  when  each  is  given  a  task  to  which  it 
is  constitutionally  adapted.  The  rate  of  learning  per  sc  is  not  an  index  of 
intelligence  or  level  in  the  phylctic  scale  (Lashley,  1929);  we  may  note, 
for  example,  the  occurrence  of  one-trial  learning,  by  inspection  only,  in 
the  solitary  wasp  (Baercnds,  and  Tinbcrgen  and  Kruyt,  cited  by  Tinber- 
gen,  195 1).  There  is  of  course  no  reason  why  modifications  of  the  individual 
synapse  should  be  made  more  quickly  in  a  system  with  many  synapses 
than  in  one  with  few.  When  receptors,  effectors  and  intervening  neural 
structures  are  adapted  to  a  small  number  of  acquired  responses,  and  there 
is  little  or  no  irrelevant  concurrent  activity,  the  necessary  synaptic 
modification  may  occur  very  rapidly.  Much  that  is  considered  to  be 
innate,  because  there  is  little  evidence  of  practice,  may  in  fact  depend  on 
immediate  learning  at  first  exposure  to  the  stimulating  conditions. 

The  problem  of  excess  activity  or  noise  in  the  larger  brain  is  character- 
istic of  those  regions  of  divergent  (rather  than  parallel)  conduction  in 
which  learning  is  supposed  to  occur.  If  the  experimental  stimulation  is  to 
result  in  a  modification  of  function  at  the  appropriate  synapses,  the 
excitation  produced  by  the  stimulus  must  be  conducted  to  those  particular 
synapses.  From  the  sensory  surface  to  the  cortical  projection  area  there  is 
no  difficulty;  here  conduction  is  in  parallel  and  the  same  population  of 
units  can  be  reliably  excited,  time  after  time,  since  the  units  which  begin 
together  (and  thus  are  simultaneously  excited)  end  together,  and  reinforce 
one  another's  action  at  the  next  synaptic  level  (Hebb,  1958).  But  this 
condition  does  not  hold  for  the  further  cortical  transmission,  especially 
where  the  mass  ratio  of  association  to  sensory  cortex  is  large  (the  A/S  ratio: 
Hebb,  1949).  A  relatively  small  sensory  projection  area  cannot  dominate  a 
large  region  of  divergent  conduction,  maintaining  on  successive  trials  the 
same  conditions  of  transmission  with  respect  to  single  units.  This  applies 
to    the    large    thalamo-cortical    sectors    which    comprise    the   so-called 


40  BRAIN    MECHANISMS    AND    LEARNING 

association  areas,  and  also  to  other  rhinencephalic  and  basal-gangliar  regions 
which  seem  to  be  involved  in  higher  mental  processes  (cf.  the  recent 
review  by  Rosvold,  1959).  Whether  a  given  synaptic  junction  will  be 
activated  in  such  regions  of  divergent  conduction  cannot  be  determined 
by  control  of  the  stimulating  environment,  the  experimental  situation  in 
which  the  learning  is  to  be  established.  It  is  fully  dependent  also  on 
whether  the  units  concerned  are  ready  to  be  fired,  and  on  the  concurrent 
activity  of  other  units,  not  controlled  by  the  present  sensory  stimulation, 
which  impinge  on  the  synapse  in  question  and  which  may  produce  either 
summation  or  inhibition.  Cumulative  learning,  in  which  the  second  trial 
adds  to  a  synaptic  modification  begun  by  the  first,  thus  depends  on  what 
activity  is  already  going  on  in  these  regions. 

Here  is  a  point  at  which  we  tmd  a  full  convergence  of  the  physiological 
with  the  psychological  evidence.  Psychologically,  the  problem  is  that  of 
'set',  'attention',  'motivation',  'attitude',  or  the  like:  all  terms  developed 
in  an  earlier  day  to  refer  to  (i)  the  puzzling  but  unmistakable  deviation  of 
behaviour  from  control  by  environmental  stimulation,  and  (2)  deviations 
of  learning  from  the  simple  S-R  and  CR  conceptions,  implying  a  direct, 
through  connection  which,  as  we  have  seen,  cannot  be  expected  to  occur 
in  regions  of  divergent  conduction,  though  it  was  taken  for  granted  by 
earlier  physiologists  as  well  as  psychologists. 

Even  today,  the  problems  involved  here  have  not  always  been  faced, 
perhaps  because  of  the  complications  which  they  entail.  The  histological 
structure  of  the  tissue  in  question  appears  to  mean  that  transmission  is  via  a 
series  of  the  closed  pathways  described  by  Lorente  dc  No  (1943),  or 
groups  of  them  functioning  as  systems  capable  of  self-maintained  activity. 
Such  systems  are  what  I  have  called  'cell-assemblies'  (Hebb,  1949),  and 
Lashley  (1958)  'trace  systems';  the  most  adequate  discussion  of  their  pos- 
sible mode  of  development  and  internal  function  is  that  of  Milner  (1957). 
Such  conceptions  certainly  introduce  complexities  into  behavioural 
theory,  but  on  the  other  hand  the  behaviour  itself  is  even  more  complex, 
and  means  of  experimental  analysis  arc  becoming  available.  Burns  (1958) 
for  example  has  provided  us  with  much  information  about  the  conditions 
in  which  self-maintained  activity  is  possible  in  a  slab  ot  isolated  cortex, 
from  a  physiological  approach ;  and  such  studies  of  perception  as  those  of 
Broadbcnt  (1956)  with  respect  to  hearing,  and  Heron  (1957),  Kimura 
(1959)  and  Bryden  (1958)  with  respect  to  vision,  have  begun  to  transform 
a  very  speculative  class  of  theory  into  something  more  solidly  grounded 
in  fact  and  susceptible  of  direct  experimental  attack.  The  following  experi- 
mental work  attempts  to  carry  this  process  further. 


D.    O.    HEBB  41 

THE    NATURE    OF   THE    TRACE    IN    SHORT-TERM    MEMORY 

In  principle,  we  may  distinguish  two  ways  in  which  a  memory  trace 
can  be  estabhshed  (cf.  e.g.  Eccles,  1953).  One  is  a  kind  of  after-discharge,  a 
reverberatory  activity  set  up  without  necessarily  depending  on  any 
change  in  the  units  involved,  other  than  the  discharge  of  impulses;  and 
one  consists  of  some  change  in  the  units  which  outlasts  their  period  of 
activity.  The  first  can  be  called  for  convenience  an  actii'iry  trace,  the  second 
a  stniaiiral  trace. 

In  discussing  this  point  earlier  (Hebb,  1949)  I  assumed  that  the  repetition 
of  digits  in  a  test  of  memory  span  provides  a  pure  example  oi  the  activity 
trace.  Here  the  experimenter  presents  verbally  a  series  of  digits,  and  the 
subject  is  asked  to  reproduce  them  in  the  same  order.  After  the  subject  has 
attempted  one  series,  the  experimenter  presents  a  second  series  and  the 
subject  seems  to  forget  the  preceding  series  completely.  He  docs  not  get 
the  two  mixed  up  just  as,  in  a  calculating  machine,  punching  a  second  set 
of  numbers  wipes  out  the  preceding  set  completely.  But  is  this  what 
happens?  Is  there  no  lasting  after-effect:  no  structural  change  produced  by 
hearing  and  repeating  the  digits? 

With  this  question  in  mind,  and  with  the  intention  of  learning  more 
about  the  nature  of  the  trace,  in  short-term  memories  for  highly  familiar 
material,  the  following  experiments  were  carried  out. 

Method:  the  subjects  were  college  students,  each  tested  individually. 
They  were  informed  that  the  purpose  of  the  experiment  was  to  see 
whether  the  memory  span  for  digits  would  improve  with  practice. 
Twenty-four  series  of  digits  were  presented.  On  each  of  these  trials,  the 
experimenter  read  aloud  a  series  of  nine  digits  at  the  rate  of  about  one  per 
second.  The  subject  was  instructed  to  listen  carefully  and  repeat  the  digits 
in  exactly  the  same  order. 

Each  series  consisted  of  the  digits  from  i  to  9,  in  varying  order,  each 
digit  occurring  once  only.  An  example  is 

591437826. 

There  was,  however,  one  special  feature  about  which  the  subject  was  not 
informed.  On  every  third  trial  (3rd,  6th,  9th  ...  24th)  the  same  series  was 
repeated,  and  the  object  of  the  experiment  was  to  discover  what  effect  this 
had.  Would  the  repetition  result  in  learning?  If  immediate  memory  for 
digits  in  these  circumstances  is  mediated  solely  by  an  activity  trace,  with 
no  structural  changes,  each  new  stimulus-event  would  be  expected  to 
wipe  the  slate  clean  and  set  up  a  new  pattern  of  activities.  No  cumulative 
learning  would  occur.  If  such  learning  occurs,  however,  we  may  conclude 


42 


BRAIN    MECHANISMS    AND    LEARNING 


that  there  is  some  structural  modification,  in  the  sense  defined  above  (in 
addition  to  ■whatever  activity  trace  there  may  be). 


25 

^^ 

ZQ 

/ 

Repeat  tcL      Series 

^ 

ys 

/ 

\ 

\^ 

"^ 

10 
5 

1 

\ 
\ 

?■ 

— 1 — , 

/ 

/  ^  ^ 
— \ — . — . — 1 — 1 — , — 1— 

•- 

/ 

' — I — . 

— . — 1 — . — 1 — 1 — I — 1 — \ — 

Fig.  I 


/5 


I? 


II 


Zf 


Number  of  subjects  (out  of  forty)  successfully  repeating  nine  digits  on  each  of  twenty-four 
trials,  when  every  third  set  of  digits  is  the  same  ('repeated  series') ;  non-correction  method. 

The  results  show  clearly  that  cumulative  learning  occurs.  Fig.  i  illustrates 
the  data  for  one  procedure.  Here  the  subject's  errors  are  not  corrected,  and 
the  record  is  made  in  terms  of  the  number  of  trials  in  wliich  the  nine  digits 


3.5 


-I — I — I — I- 


IZ 

Fig.  2 


/5 


z/ 


Z¥ 


Mean  number  of  digits  correctly  repeated  on  each  of  twenty-four  trials,  by  twenty-five  sub- 
jects, when  every  third  set  of  digits  is  the  same  ('repeated  series');  correction  method. 

are  repeated  without  error.  Fig.  2  shows  the  similar  result  that  is  obtained 
when  the  subject  is  stopped  as  soon  as  he  gives  one  digit  out  of  the  proper 


D.    O.    HEBB  43 

order  (thus  providing  'negative  reinforcement',  or  'punishment'  for 
error) ;  here  the  record  is  in  terms  of  the  number  of  digits  correctly 
repeated  on  each  trial.  In  both  cases  it  is  clear  that  learning  occurs. 

This  can  be  seen  in  another  v^ay.  The  forty  subjects  v^hose  results  are 
diagrammed  in  Fig.  i  were  each  asked,  following  the  nineteenth  trial, 
whether  they  had  'noticed  anything  unusual'  about  the  procedure. 
Twenty-two  reported  that  there  had  been  some  repetition  in  the  series 
presented  to  them,  and  three  of  these  could  give  the  crucial  series  without 
error.  If  the  subject  did  not  volunteer  anything,  he  was  asked  explicitly 
about  the  repetition;  three  more  subjects  reported  that  they  had  observed 
it,  and  one  of  them  could  repeat  the  crucial  series  correctly.  The  remaining 
fifteen  subjects  had  not  observed  the  repetition.  (The  questioning  was 
done  between  trials  19  and  20  in  order  not  to  direct  attention  to  the 
crucial  scries,  occurring  on  trials  18  and  21;  none  the  less,  the  questions 
may  have  affected  the  subsequent  performance  on  trials  21  and  24,  which 
can  be  seen  in  Fig.  i  to  show  a  further  sharp  improvement.) 

The  implications  of  this  rather  simple-minded  experiment  are  more 
extensive  than  may  be  apparent  at  first.  With  such  results,  I  can  find  no 
way  of  avoiding  the  conclusion  that  a  single  repetition  of  a  set  of  digits, 
with  or  without  the  reinforcement  of  being  told  when  an  error  has  been 
made,  produces  a  structural  trace  which  can  be  cumulative.  I  assume  that 
an  activity  trace  may  also  be  involved  in  the  actual  repetition,  but  it  is  the 
structural  change  which  is  of  interest  here. 

It  is  important  to  note  that  we  are  dealing  with  highly  practised  material. 
Associative  connections  already  exist  between  any  two  digits,  for  the 
educated  subject  especially.  In  addition  to  the  very  highly  practiced 
sequence  1-2-3-4  ...,  the  learning  of  historical  dates,  telephone  numbers, 
street  addresses,  quantitative  values  such  as  the  speed  of  light  or  the  number 
of  feet  in  a  mile,  and  the  batting  averages  of  the  Boston  Red  Sox  in  1937 
—  all  these  varied  uses  of  the  nine  digits  mean  that  the  subject  has  already 
learned  many  sequences,  in  one  or  other  of  which  any  digit  is  followed  by 
any  other  digit.  When  he  is  given  a  specific  series  to  repeat,  the  memory 
for  that  scries  must  depend  somehow  on  a  further  strengthening  of  the 
connections  already  established.  This  is  diagrammed  in  Fig.  3,  where  for 
simplicity  the  trace  systems  or  cell-assemblies  of  three  numbers  only  are 
represented.  1  has  a  strong  connection  with  2,  and  2  with  j  (because  of  the 
frequency  with  which  the  sequence  1-2-3  ■••  has  been  repeated  in  the 
past) ;  but  2  has  connections  with  /  as  well  as  with  j,  and  j  with  _'  and  i  as 
well  as  with  4  (not  shown). 

Now  let  us  suppose  that  the  subject  is  given  the  sequence  3-2-1  ...  to 


44 


BRAIN    MECHANISMS    AND    LEARNING 


repeat.  Some  change  occurs  which  means  that  when  the  experimenter 
stops  speaking,  the  corresponding  trace  systems  fire,  and  in  the  proper 
order.  Undoubtedly  there  are  complexities  which  this  does  not  take 
account  of;  there  is  certainly  not  a  mere  chaining  of  the  systems  involved, 
because  —  for  example  —  the  subject  may  be  able  to  tell  you  what  the 
first  and  last  of  a  group  of  digits  were,  though  he  has  lost  the  intervening 
ones.  Memory  for  the  individual  item  in  the  scries  is  not  entirely  depen- 
dent on  the  preceding  item.  But  the  order  of  repetition  seems  to  require  a 
changed  synaptic  relation  between  the  specific  cell-assembly  groups,  or 
trace  systems,  so  that  in  the  example  of  Fig.  3,  j  tires  2,  and  not  4  or  the 


Fig,  3 
Diagrammatic  representation  of  the  synaptic 
relations  involved  in  the  repetition  of  the 
digits  3-2-1.  The  heavier  arrows  1-2  and  2-3 
represent  more  strongly  established  connec- 
tions ;  the  encircled  .v  indicates  the  temporary 
strengthening  of  less  strongly  established 
ones. 


central  representative  of  some  other  number;  and  2  fires  1  and  not  j.  The 
synaptic  'strengthening'  implied  is  shown  by  the  encircled  .v  in  the  figure. 
What  can  this  be? 

The  difficulty  here  is  that  all  the  synapses  concerned  must  be  already 
asymptotic,  in  the  development  of  their  structural  connections.  Synapses 
connecting  system  2  with  other  systems  are  highly  developed;  if  now 
when  2  fires  it  is  to  fire  1  reliably,  and  not  4  or  6  or  some  other  system,  it 
must  be  sii^^iifiavitly  more  closely  related  to  1  for  the  moment,  and  it  seems 
most  unlikely  that  this  closer  relation  can  consist  of  a  sudden  further 
development  of  the  size  of  the  knobs  of  the  systeiii-2  —  system- 1  synapses. 
Some  other  mechanism  besides  growth  of  the  knob,  or  its  closer  juxta- 
position with  the  cell  body,  must  be  involved. 

The  mechanism  could  well  be  that  recently  proposed  by  Milner  (i959)- 
He  has  pointed  out  that  failure  of  conduction  along  some  axon  fibrils  may 


D.    O.    HEBB  45 

readily  occur  where  they  begin  to  enlarge  to  form  knobs  —  that  is,  short 
of  the  synapses  proper.  When  there  is  already  some  depolarization  of  cell 
body  or  dendrites,  the  flow  of  current,  it  is  argued,  will  make  the  bottle- 
neck traversable,  and  the  subsequent  depolarization  will  keep  it  open  for 
an  appreciable  period  of  time.  This  will  be  particularly  true  if  there  is  any 
considerable  activity  of  the  dendrites. 

Such  a  mechanism  would  clearly  help  to  account  for  the  short-term 
memories  of  the  present  experiment,  where  we  are  dealing  with  associative 
connections  which  are  already  highly  practised  (i.e.  whatever  growth 
process  there  may  be  at  the  synapse  is  near  its  maximum),  and  where  a 
momentary  experience  is  able  to  make  one  set  of  well-developed  synaptic 
connections  temporarily  dominant  over  others.  The  conditions  of  the 
experiment  demand,  of  course,  that  this  dominance  must  be  very  brief, 
lasting  only  for  the  period  in  which  one  set  of  digits  is  being  held  and 
giving  way  when  the  next  is  presented. 

The  explanation  is  of  course  speculative,  but  it  accounts  in  principle  for 
phenomena  which  cannot  be  plausibly  dealt  with  solely  in  terms  of  (i) 
a  reverberatory  trace,  and  (2)  growth  at  the  synapse.  What  I  am  saying,  in 
short,  is  that  there  may  be  three  mechanisms  of  the  memory  trace  and  not 
two,  as  suggested  earlier.  It  should  be  clear,  of  course,  that  these  are  not 
alternative  mechanisms  in  the  actual  phenomena  of  brain  function;  they 
occur  together,  and  reinforce  one  another's  actions. 


WIDER   IMPLICATIONS 

It  has  been  urged  above  that  we  have  no  hope  of  understanding  learning 
in  the  adult  mammal  until  we  know  much  more  about  the  organized 
activity  (in  cell-assembly  or  trace  system)  of  the  regions  of  divergent 
conduction  in  the  cerebrum.  Lack  of  such  knowledge  is  the  main  reason 
for  the  great  gap  between  the  theory  of  learning  and  the  practical  advice 
one  can  give  to  the  student  who  wants  to  know  how  to  study  more 
efficiently.  The  great  question  always  is  how  to  'concentrate',  and  how  to 
'motivate  oneself  —  that  is,  to  keep  on  concentrating  —  and  this,  clearly, 
is  the  theoretical  problem  of  the  control  of  the  excess  activity,  to  prevent 
its  interference  with  the  task  in  hand.  If  such  experiments  as  the  one  des- 
cribed can  help  us  codify  the  ideas  involved,  and  if  further  they  provide 
some  information  about  the  interaction  of  cell-assembly  groups  in 
learning,  we  can  also  see  them  as  a  slight  contribution  to  the  ultimate 
understanding  of  the  problem  of  serial  order  which,  as  Lashley  (195 1)  has 
shown,  is  the  crux  of  the  problem  of  behaviour  in  the  higher  animal. 


4.6  BRAIN    MECHANISMS    AND    LEARNING 

A  more  specific  implication  is  with  respect  to  delayed  response.  If 
extrinsic  reinforcement  is  not  necessary  for  the  establishment  of  a 
structural  trace  —  if  the  subject  who  only  hears  and  tries  to  repeat  a  series 
of  digits  none  the  less  has  some  memory  of  that  specific  series  which  can 
last  despite  hearing  and  repeating  other  series  afterwards  —  then  some 
revision  is  called  for  in  my  interpretation  of  the  phenomenon  of  the 
delayed  response  (Hebb,  1958).  A  monkey  sees  a  piece  of  food  being  put 
under  a  cup  at  the  left,  none  under  a  cup  at  the  right;  his  only  response  at 
the  time  is  to  look  at  the  left  cup,  since  both  are  out  of  reach.  Both  cups 
are  then  hidden  by  lowering  a  screen,  let  us  say  for  20  seconds.  When  the 
monkey  is  permitted  to  choose  he  goes  at  once  to  the  left  cup  and  gets  the 
food.  It  seemed  to  me  that  this  could  only  be  accounted  for  in  terms  of  a 
perceptual  activity  held  in  reverbcratory  circuits.  In  view  of  the  present 
results,  this  does  not  follow.  One  look  may  be  enough  to  establish  what  is, 
in  effect,  an  S-R  connection  between  the  stimulation  of  the  sight  of  the 
two  cups,  and  an  eye  movement  to  the  left.  When  the  monkey  is  again 
exposed  to  the  same  visual  stimulation,  he  looks  left,  his  hand  follows  the 
direction  of  gaze,  and  he  obtains  the  food.  It  is  still  clear  that  this  'S-R 
connection'  in  the  brain  of  the  higher  animal  can  hardly  be  the  kind  of 
direct,  one-way  route  envisaged  by  earlier  theory,  and  that  it  must  also 
involve  some  transmission  by  re-entrant  circuits,  but  it  is  still  a  relatively 
simple  mode  of  learning.  In  a  lower  animal,  presumably,  the  closed-circuit 
element  may  not  be  present,  and  we  can  understand  better  the  one-trial 
learning  in  the  wasp  already  referred  to  (Tinbergcn,  195 1). 

GROUP   DISCUSSION 

EcCLES.  I  am  very  grateful  to  Dr  Hebb  for  putting  up  some  clear  ideas  to  shoot 
at.  I  want  to  shoot  at  the  synaptic  knob  story  he  has  given  wliich  is  based  on  the 
outmoded  theory  of  electrical  synaptic  transmission.  However,  I  thought  I  might 
leave  this  synaptic  story  until  tomorrow  when  I  will  be  talking  about  the  details  of 
what  goes  on  in  the  synaptic  knob  during  repetitive  stimulation  and  afterwards. 

I  would  like  also  to  comment  on  one-trial  learning.  I  was  listening  very  carefully 
when  Dr  Hebb  spoke  his  series  of  digits.  As  soon  as  he  started  off  the  series  I  repeated 
this  mentally  and  I  went  over  the  first  3  digits  quickly  when  he  got  to  3,  and  so  on 
at  the  4  and  the  5,  so  as  to  develop  my  memory.  It  wasn't  a  single  trial  for  me. 

Hebb.  Did  you  get  it  right?  That  is  the  question. 

EccLES.  I  don't  suppose  I  did.  (Checking)  The  first  ones  were  right,  and  also  the 
last  two ;  there  was  some  muddle  in  the  middle. 

Hebb.  I  think  you  will  find  another  method  is  better.  Just  to  listen  and  then 
repeat. 

EccLES.  While  you  are  even  listening  to  one  digit  there  will  be  continued  activity 
in  the  cortex.  In  1949  both  Dr  Gerard  and  Dr  Hebb  published  the  concept  that 
reverberating  circuits  played  the  key  role  at  the  early  stages  o(  learning.  I  have 


D.    O.    HEBB  47 

always  thought  that  it  is  a  very  good  idea  that  rcvcrberatory  circuit  activity  gives 
the  basis  for  tormation  of  memory  traces. 

Hebb.  As  Dr  Eccles  has  picked  me  as  a  target,  I  would  say  that,  in  my  opinion, 
the  notion  that  transmission  is  solely  chemical  is  pure  dogma.  That  is  to  say,  I 
think  that  Dr  Eccles  has  provided  convincing  and  powerful  evidence  that  the 
primary  transmission  is  chemical.  However  I  can't  see  what  evidence  possibly 
could  rule  out  an  electrical  current  flow  as  an  ancillary  or  supporting  mechanism 
of  synaptic  transmission. 

The  second  point  is  that  I  would  agree  entirely,  and  I  take  it  that  I^r  Gerard  docs 
also,  that  one  trial  means  one  presentation  of  the  stimulus,  but  it  doesn't  mean  one 
burst  of  impulses.  Of  course  I  don't  suppose  that  'one  trial  learning'  means  that 
only  one  impulse  passes  the  synapse,  and  does  the  trick.  But  further  I  would  point 
out  that  in  this  experiment  of  course  we  are  dealing  with  cumulative  effects 
because  we  have  no  direct  evidence  of  learning  after  one  presentation  oi  the 
digits. 

Gerard.  First,  I  think  it  is  unfortunate  that  l^r  Hebb  has  jumped  three  levels: 
from  total  behaviour,  to  organ,  to  cell,  organelle  or  molecule.  This  is  just  too  far  a 
jump  at  any  one  time  to  be  profitable  theoretically.  I  think  it  unfortunate  that  he 
contaminated  some  very  precise  and  provoking  issues  by  bringing  in  the  synaptic 
endings,  which  are  irrelevant  at  this  point.  I  don't  think  the  argument  that  is 
brewing,  as  to  whether  the  synaptic  change  is  electrical  or  chemical,  or  whatever,  is 
really  relevant  to  the  particular  problem  raised.  It  is  relevant  to  all  kinds  of 
problems  but  too  diffuse  to  matter  for  this  one. 

Second,  I  raise  the  question  whether  you  really  are  dealing  in  your  experiments 
with  a  structural  memory,  in  contrast  to  a  dynamic  one.  It  seems  to  me  you  have 
something  very  similar  to  what  happens  when  I  look  up  a  telephone  number  in  the 
phone-book,  keep  it  in  my  mind  for  a  bit,  make  the  call  and  immediately  forget 
the  number  so  completely  that  if  something  goes  wrong,  and  I  must  dial  again,  I 
must  look  it  up  again.  This  is  perhaps  related  to  the  point  that  Dr  Eccles  was  making 
about  keeping  the  memory  going;  and  the  psychologists  here  are  certainly  aware 
ot  Broadbent's  work  on  the  temporary  storage  of  information  before  passing  it 
into  a  permanent  storage  as  a  lasting  memor\-,  whatever  the  neurological  mechan- 
isms there  may  be. 

Third,  I  completely  agree  with  the  point  that  Dr  Hebb  makes  about  what  we 
might  call  'imput  overload',  and  the  fact  that  the  more  elaborate  nervous  systems 
often  tangle  themselves  up  in  their  own  sophistication.  Let  me  remind  you  of  two 
experiments.  Some  of  the  original  work  of  Bavelas,  following  Kurt  Lewin, 
involved  five  people  in  a  certain  communication  network.  Each  started  with  part 
of  the  answer  to  a  problem,  such  as  what  the  colours  of  certain  marbles  are;  and  by 
communicating  in  the  intervals  each  had  to  get  the  total  information.  This  they  did 
very  easily  when  the  marbles  were  solid  colours;  but,  having  worked  with  a  pattern 
problem,  they  could  not  solve  the  solid  colour  problem  because  their  attention 
focused  on  minute  flaws  in  the  colour.  This  kind  of  knowing  too  much  was  proved 
at  another  level,  of  disease  dia2;nosis.  Skilled  clinicians  diagnosed  trom  a  history  less 
correctly  than  did  clerks  given  certain  key  items  to  look  for. 

So  I  am  not  surprised  that  monkeys  may  learn  certain  simple  problems  with 
greater  difficulty  than  rats,  and  perhaps  man  with  even  greater  difficulty  than 
monkeys.  But  it  is  going  much  too  far  from  that  to  say  that  learning  has  nothing 


48  BRAIN    MECHANISMS    AND    LEARNING 

to  do  with  the  mass  of  the  brain  or  the  number  of  neurones.  The  minute  one  goes 
from  these  simple  things  to  complex  ones,  there  arc  correlations  of  performance 
with  the  total  mass  of  the  brain.  Indeed  I  find  myself  in  most  exciting  conflict  with 
Dr  Hebb  on  the  role  of  large  numbers  ot  neurones.  I  have  used  the  term  'physio- 
logical neurone  reserve',  distinguishing  the  potentially  activable  neurones  of  the 
brain,  in  contradiction  to  the  anatomical  population.  For  various  reasons  of  in- 
creased thresholds  or  previous  activation,  many  neurones  may  not  at  a  given  time 
be  functionally  available.  The  functional  neurone  reserve  does  seem  to  parallel 
nicely  the  ability  to  'master  a  situation',  a  broader  and  more  behaviourally  interest- 
ing term  than  simple  learning,  hi  other  words,  while  one  may  not  do  better  on  a 
prescribed  simple  stimulus  response  relation,  when  it  is  necessary  to  find  the  correct 
concatenation  oi  possible  behaviours  out  of  an  almost  infinite  variety,  then  the 
larger  neurone  complement  is  certainly  an  advantage  and  allows  greater  richness. 
Such  an  endowed  brain  can  learn  things  that  the  other  cannot.  Maybe  in  this  last 
point  I  am  violating  what  you  meant  to  say,  but  that  is  the  way  it  struck  me. 

Hebb.  I  don't  believe  the  synapse  is  irrelevant  (what  has  happened  is  that  I  have 
been  restricted  to  a  15-page  document  by  Dr  Delafresnaye  and  to  a  30-minute 
presentation  by  Dr  Gerard).  Behind  this  statement  of  mine  is  an  extremely  long 
attempt  to  see  if  there  was  any  other  way  of  dealing  with  the  problem.  The  fact  of 
the  matter  is  that  the  theory  may  be  bad.  I  have  no  doubt  that  the  position  suggested 
by  Dr  Galambos,  by  Dr  Olds  and  by  others  is  logically  sound.  But  the  flict  also 
is  that  people  do  think  of  a  simple  theoretical  dichotomy  —  structural  modification 
or  a  reverberation; 

Gerard.  It  need  not  be  one  or  the  other,  but  either  or  both  —  or  neither. 

Hebb.  I  understand  that.  My  only  point  is  that  I  didn't  mean  to  suggest  that  it  is 
only  structural,  and  not  reverberatory.  I  had  thought  before,  as  you  did  with  the 
telephone  book,  that  I  could  look  up  a  telephone  number,  dial  it,  and  forget  it 
completely.  That  I  could  listen  to  a  set  of  digits,  repeat  them  and  forget  them 
completely.  I  suggest  to  you  that  your  statement  about  completely  forgetting  the 
telephone  number  is  almost  certainly  wrong,  on  the  basis  of  the  experimental 
evidence  that  I  have  reported.  I  would  have  agreed  with  you  4  years  ago.  My  idea 
now  is  that  it  is  a  little  more  complicated. 

One  last  point  on  rate  of  learning  in  different  species.  I  assumed  that  we  were 
dealing  with  simple  learning  in  all  cases.  Man  certainly  learns  some  complex  tasks 
quicker  than  a  monkey  does,  but  the  complex  task  may  be  regarded  as  the  equiva- 
lent of  a  number  of  simpler  ones.  But  there  is  a  point  that  I  think  needs  to  be  made. 
It  has  happened  that  Baerend's  and  Tinbergen's  data  have  not  been  believed  because 
the  wasp  is  too  low  in  the  scale  to  have  as  fast  learning  as  we  have.  But  I  propose 
that  learning  for  which  an  organism  is  suited  is  likely  to  be  faster,  rather  than 
slower,  at  the  lower  levels. 

KoNORSKi.  According  to  my  opinion  any  neurophysiologist  concerned  with  the 
problems  of  conditioned  reflexes  is  entitled,  and  even  obliged,  to  explain  the  facts 
he  deals  with  in  the  terms  of  synaptic  transmission.  As  a  matter  of  fact  our  first- 
hand knowledge  about  the  principles  of  this  transmission  comes  out  from  the  most 
simple  two-neurone  reflex  arcs  studied  by  the  most  refined  electrophysiological 
techniques.  We  extrapolate  these  findings  to  interpret  the  more  complicated  spinal 
reflexes,  and  we  have  also  a  right  to  utilize  them  to  understand  the  mechanisms  of 
conditioned  reflexes,  although  they  are  much  more  complicated. 


D.    O.    HEBB  49 

As  far  as  L)r  Hcbb's  experimental  data  are  concerned,  I  hnd  them  very  interesting 
and  possibly  requiring  further  elucidaton.  They  show  that  the  d}-namic  memory 
trace,  produced  by  presentation  ot  a  given  series  of  numbers,  is  not  totally  oblite- 
rated by  the  subsequent  scries.  It  would  be  interesting  to  know  what  will  be  the 
rate  of  memorizing  of  the  repeated  series  if  it  recurs  less  frequently  than  in  Dr 
Hebb's  experiments,  and  whether  it  is  possible  in  this  way  to  prevent  memorizing 
of  tliis  series  at  all. 

I  realize  the  difficulty  connected  with  the  understanding  of  transient  memory  of 
series  of  items  in  terms  of  reverberating  circuits.  May  be  that  the  place  of  a  given 
item  in  the  sequence  is  determined,  among  other  things,  by  the  strength  of  the 
retroactive  inliibition  produced  b}'  the  following  items.  I  also  agree  with  Dr  Hebb 
that  all  the  series  he  used  in  his  expermients  are  in  a  greater  or  lesser  degree  already 
included  in  our  stable  memory  repertory  and  one  has  only  to  remember  that  this 
and  not  that  sequence  was  presented  at  the  given  moment. 

Hebb.  I  should  make  clear  that  Milner  did  not  develop  liis  conception  to  account 
for  those  results.  On  the  contrary,  I  was  still  struggling  to  find  some  intelligibility 
in  the  data  when  I  saw  Milner's  paper. 

If  I  have  given  the  impression  of  thinking  that  Dr  Eccles's  position  was  pure 
dogma  I  should  like  to  get  that  corrected  right  away.  It  seems  to  me  that  it  is  dogma 
to  maintain  the  negative  proposition  that  something  like  electrical  fiicilitalion 
cannot  happen.  The  positive  side  ot  chemical  transmission  has  been  established  well 
beyond  anv  questioning  bv  me,  but  there  is  still  the  possibility  that  you  might  have 
some  ancillary  mechanism. 

I  can  find  no  way,  to  come  to  Dr  Konorski's  second  question,  of  accounting  for 
the  ordering  in  that  series.  I  remind  you  that  the  same  digits  are  used  trial  after 
trial,  and  that  the  essence  of  the  successful  response  is  in  the  proper  ordering. 
Suppose  that  each  one  of  these  systems  is  firing  and  reverberating.  What  deter- 
mines the  order  in  which  the)'  cause  the  motor  sequence?  I  would  only  say  that  as 
nearly  as  I  can  determine  there  must  be  in  addition  to  reverberation,  some  sort  of 
connection  between  the  separate  reverberation  systems,  so  that  A  fires  its  motor 
paths  and  then  causes  B  to  do  so  —  and  not  vice  versa.  There  is  some  short-term, 
essentially  structural,  modification  which  with  repetition  may  turn  into  something 
more  lasting. 

Gerard.  Dr  Konorski,  I  was  not  for  one  moment  objecting  to  going  down  to 
the  synapse;  you  will  remember  I  went  all  the  way  down  to  the  molecule  in  the 
first  paper.  I  simply  said  that  whatever  specific  mechanism  one  assumes  at  the 
synapse  is  irrelevant  to  the  problem  Dr  Hebb  is  facing.  The  problem  is  whether  or 
not  a  message  gets  to  the  synapse,  not  how  it  produces  a  change  there.  The  questions 
are  at  different  levels. 

Thorpe.  With  reference  to  the  one  trial  learning  experiments  with  the  insects 
Philaiitliiis  and  Auiuiophila  bv  Tinbergen  and  Baerends  I  would  like  to  say  first  that  I 
don't  think  there  is  the  slightest  doubt  about  the  facts.  It  is  quite  easy  to  observe  the 
orientation  flights  of  these  insects.  Secondly  I  would  like  to  point  out  that  the  task 
learned  on  these  flights  is  in  itself  a  very  complex  one.  Moreover  it  is  a  kind  of 
serial  learning  since,  because  of  its  very  nature,  the  insect's  eye  cannot  be  getting  a 
unitary  vision  of  the  whole  field;  on  the  contrary  it  is  flying  around  picking  up  the 
various  landmarks  one  after  the  other  —  and  they  may  be  numerous.  So  it  seems  to 
me  to  be  a  decidedly  complex  piece  of  learning;  not  as  complex  a  task  perhaps  as 


50  BRAIN    MECHANISMS    AND    LEARNING 

learning  these  large  numbers  that  Dr  Hcbb  was  discussing,  but  very  complex  when 
one  compares  it  with  the  kind  ot  learning  task  the  insect  normally  has  to  achieve. 
1  think  that  there  is  a  very  real  problem  here,  namely  that  of  explaining  the  very 
rapid  mastery  by  the  insect  brain  ot  a  substantial  task  in  serial  learning.  And  then  of 
course  one  must  remember  that  there  are  no  synaptic  knobs,  so  far  described,  in 
the  insect's  nervous  system  which  could  be  acting  m  the  way  that  Milncr  proposed. 

EccLES.  If  I  understood  Dr  Hebb  correctly,  he  said  he  couldn't  see  how  he  could 
explain  some  of  the  digital  learning  processes  on  the  basis  of  synaptic  trace  changes. 

Hebb.  Only  when  dealing  with  synapses  already  so  highly  developed  as  must  be 
the  case  in  repeating  a  sequence  as  much  practised  as  1-2-3.  Here  a  single  exposure, 
a  single  repetition,  could  hardly  make  a  significant  additional  change. 

EccLES.  Against  that  concept  I  would  like  to  say  that  in  the  very  simplest  cerebral 
actions  w^e  are  using  millions  of  neurones  in  the  most  complicated  imaginable 
patterns.  In,  say  the  1-2-3  sequence,  we  don't  have  a  group  of  neurones  that  are 
related  to  i,  another  group  for  2,  and  another  for  3.  I  think  that  in  each  digital 
association  the  most  complicated  neuronal  network  is  in  operation.  With  a  2-1-3 
sequence,  we  would  have  a  quite  different  asseinblage  of  neurones  in  activity.  It  is 
not  sutf  iciently  realized  what  an  immense  number  of  neurones  we  have  to  draw 
upon  for  the  simplest  memory.  Lashley  says  that  in  the  simplest  engram  there  are 
millions  of  neurones  involved.  I  would  go  much  further  than  that  myself  There  is 
evidence  from  EEG  record.  During  mental  arithmetic  there  may  be  disturbance  of 
the  EEG  over  a  wide  region  of  the  cerebral  cortex.  Thus  immense  assemblage  of 
neurones  are  used  doing  some  unusual  multiplication,  say  23  X43.  Therefore  I 
don't  subscribe  to  Dr  Gerard's  idea  that  there  is  a  functional  neurone  reserve.  I  like 
to  think  that  we  are  using  all  the  neurones  in  some  kind  of  pattern  or  other  and 
using  them  thousands  of  times  over  in  patterns,  but  that  we  can  still  use  them  many 
more  thousand  times  over.  It  is  the  pattern  that  is  important,  not  the  neurones. 

Gerard.  This  is  not  contrary  to  my  notion,  except  that  the  more  neurones  you 
have  the  more  patterns  you  can  deal  with. 

Eccles.  I  agree  entirely.  One  final  point,  and  that  is  if  there  is  electrical  interac- 
tion, and  we  have  seen  from  Dr  Estable's  work  the  complexity  of  connections, 
and  we  now  know  from  the  electronmicroscopists  that  there  is  no  free  space,  only 
200  A.  clefts,  everywhere  in  the  central  nervous  system,  then  everything  should  be 
electrically  interacted  with  everything  else.  I  think  this  is  only  electrical  background 
noise  and,  that  when  we  lift  with  specific  chemical  connections  above  that  noise  we 
get  a  significant  operational  system.  I  would  say  that  there  is  electrical  interaction 
but  it  is  just  a  noise,  a  nuisance. 

Hebb.  I  think  we  are  in  agreement,  at  least  in  part,  if  I  understood  this  last  com- 
ment. When  you  say  that  the  whole  cortex  is  thrown  into  action  when  somebody 
multiplies  23  X  43  you  are  suggesting  that  most  of  the  activity  contributes  nothing 
positive.  The  Jasper,  Ricci  and  Doane  experiments  at  least  suggest  strongly  that  the 
course  of  learning  is  throwing  out  the  neurones  that  are  irrelevant,  keeping  them 
out  of  the  way  wliile  the  others  do  the  job.  And  this  may  mean  that  the  course  of 
learning  involves  many  more  neurones  than  would  be  desirable.  It  may  be  that 
though  the  operation  is  very  complex,  it  could  be  done  better  if  there  were  no  other 
neurones  present,  for  that  operation.  But  the  great  characteristic  of  the  human 
brain  is  the  extraordinary  variety  and  complexity  of  things  it  can  deal  wih. 

Gerard.  I  might  add,  since,  the  work  of  Jasper's  group  has  been  mentioned  so 


D.    O.    HEBB  51 

many  times  in  connection  with  this,  that  extensive  studies  have  been  done  by  Beck 
along  the  same  hnes,  showing  the  dropping  out  of  neurones. 

Chow.  I  think  that  the  problem  Dr  Hebb  proposes  is  a  very  important  one. 
What  kind  of  mechanism  can  produce  such  effects  that  one  exposure  will  redirect 
nerve  impulses  in  a  certain  direction? 

I  would  like  to  point  out  Lashley's  notion  that  maybe  you  are  creating  some 
kind  of  field  effect  by  your  repeating  the  digits.  Therefore,  in  essence  you  may 
create  a  DC  potential  gradient  there,  as  if  you  had  applied  an  external  DC  current. 
This  presumably  will  modify  all  your  neuronal  excitability  and  will  make  your 
impulse  flow  easily  in  one  direction.  I  think  this  may  be  a  possible  mechanism. 

Hebb.  It  appears  to  me  that  we  are  dealing  very  often,  not  with  the  activity  of  all 
neurones  in  one  topographical  area  as  against  the  neurones  in  another  topographical 
area  but  with  selective  fictors  among  neurones  interlinked  with  one  another.  It  is 
very  diflicult  to  conceive  a  functional  value  from  a  DC  field  that  is  more  extensive 
than  a  single  neurone  or  2  or  3  neurones.  This  is  my  problem. 


THE  INTERACTIONS  OF  UNLEARNED  BEHAVIOUR 
PATTERNS  AND  LEARNING  IN  MAMMALS 

Irenaus  Eibl-Eibesfeldt 


I.    INTRODUCTION    AND    OBJECTIVES 

The  term  'innate'  as  applied  to  behaviour  patterns  has  become  con- 
troversial. Beach,  1954,  Hebb,  1953,  Lehrmann,  1953,  1956  and  Schneirla, 
1956  have  criticized  the  ethological  approach,  which  they  accuse  of 
performing  an  artificial  dichotomy  into  innate  and  acquired  patterns.  'I 
strongly  urge  that  there  are  not  two  kinds  of  factors  determining  behaviour 
and  that  the  term  "instinct"  is  completely  misleading,  as  it  implies  a 
nervous  process  or  mechanism  which  is  independent  of  environmental 
factors  and  different  from  the  processes  into  which  learning  enters  '(Hebb, 
1953).  Lehrmann  (1953)  accuses  ethologists  in  general  and  Lorenz  in 
particular  of  misrepresenting  unanalysable  part-function  in  such  a  way  as 
to  give  them  the  specious  appearance  of  natural  units,  caused  by  the  same 
physiological  mechanism. 

The  main  task  of  this  paper  is  to  show  that  the  two  oldest  and  most 
important  ethological  conceptions,  that  of  the  fixed  motor  pattern  and 
that  of  the  Innate  Releasing  Mechanism  (IRM),  correspond  to  very  real 
functional  units  and  that  they  prove  their  analytical  value  in  the  attempt 
to  analyse  the  ontogenetic  process  by  which  unlearned  and  learned 
behaviour  becomes  integrated  into  an  adaptive  functional  unit. 

2.    EXPERIMENTAL    EVIDENCE 

((?)  The  analysis  of  nest  biiildiw^  and  rctricvuK^  yotiin^  in  the  rat.  As  is  well 
known,  every  rat  raised  in  isolation  is  capable  of  building  a  nest.  A  number 
of  scientists  have,  therefore,  termed  this  behaviour  instinctive.  In  Mumi's 
(1950)  Handbook  oj  Psychological  Research  on  the  Rat,  it  is  discussed  under 
the  heading  'unlearned  behaviour',  along  with  retrieving  activity;  every 
rat  which  has  given  birth  retrieves  nestlings  which  were  put  outside  the 
nest. 

Riess  (1947)  has  investigated  the  problem  of  the  imiateness  of  this 
behaviour.  He  raised  rats  under  conditions  which  gave  them  no  oppor- 
tunity to  manipulate  solid  objects.  From  the  age  of  21  days  (some  even  as 

53 


54  BRAIN    MECHANISMS    AND    LEARNING 

young  as  14  days)  they  were  kept  isolated  in  wiremesh  cages  and  fed  only 
with  powdered  food.  After  they  had  mated  he  put  them  in  a  wooden  box 
with  strips  of  paper  hanging  from  the  walls.  Nest  building  and  retrieving 
were  looked  for  in  this  testbox,  but  the  animals  failed  to  build  nests  and  to 
retrieve  their  babies.  They  only  carried  the  young  around  and  scattered 
the  paper  strips  all  over  the  floor.  Most  of  the  nestlings  died,  as  they  were 
not  sufficiently  cared  for  by  their  mother.  From  this  failure  to  build  nests 
and  to  retrieve,  Riess  concluded  that  the  nest-building  behaviour  of  the 
rat  must  be  learned  during  ontogeny  through  handling  solid  objects.  One 
could  not  apply  the  term  instinct,  therefore,  to  this  type  of  behaviour. 
The  way  in  which  the  rat  might  learn  nest  building  was  pointed  out  by 
Lehrmami  (1954).  The  rat  might  collect  food  and  other  objects  at  its 
sleeping  place  and  thereby  observe  that  some  of  these  collected  objects 
can  be  used  to  prevent  loss  of  heat.  It  would  in  this  way  learn  to  build  a 
nest  as  soon  as  it  felt  cold.  No  attempt  was  made  to  gain  detailed  observa- 
tional information  concerning  either  recurring  motor  patterns  or  the 
stimulus  situations  indispensable  to  elicit  them. 

From  observing  a  small  number  of  different  rodents  [Miis  iiiiisaihis  L., 
Rattiis  uorve^iais  L.,  Merioiies  persiciis  Blanf.,  Meriones  shawi,  GerbiUus 
gerhilhis  L.,  Jaciihis  jaciihis  L.,  Cricctiis  cricetus  L.,  Mesocrketus  aiiratiis 
Waterhouse,  Mkrotus  arvalis  Pall.,  CitclUis  citeUiis  L.,  Glaiicoiuyys  t'ohms 
Thomas,  Sciiinis  i'iiJ(^ciris  L.,  Glis  glis  L.,  Muscardiinis  avellaiiariiis  L., 
Dasyprocta  aguti,  Oryctolagiis  ciiiiiciihis  L.)  I  was  familiar  with  a  number  of 
motor  patterns  recurring  in  most  or  all  of  them  (Eibl-Eibesfeldt,  1958). 

In  all  ground-dwelling  rodents  observed,  two  phases  of  nest  building 
can  be  distinguished:  (i)  The  digging  of  a  burrow  (2)  the  construction  of  a 
nest  for  sleeping  and  nursing. 

The  nest-building  Norway  rat  for  example  starts  digging  a  tunnel, 
20  to  30  cm.  under  the  surface,  which  ends  after  about  i  metre  in  a  small 
nesting  chamber.  Later,  additional  tunnels  are  added  (Steiniger,  1950).  The 
forelegs  scratch  the  earth  with  alternating  movements  from  the  front 
under  the  belly  [scratchiiiii).  From  there  the  accumulating  earth  is  pushed 
backwards  by  the  hindlegs  {kicking  backwards).  From  time  to  time  the 
animal  turns  around  pushing  the  earth  by  alternating  movements  of  its 
forelegs  out  of  the  tunnel  (piisliiiig).  Pushing  with  the  snout  is  also  observed. 
After  digging  the  animal  collects  nesting  material.  This  collection  activity 
consists  in  grasping  the  nesting  material  with  the  teeth,  piillitig  it  free  and 
if  necessary  biting  it  loose  from  where  it  is  attached,  then  carrying  it  to  the 
nesting  site  and  depositing  it  there. 

The  nesting  material  is  pushed  into  a  heap  by  movements  of  the  fore- 


IRENAUS   EIBL-EIBESFELDT  55 

legs,  identical  with  those  performed  when  pushing  earth  out  ot  the  tuimel 
and  by  shoving  with  the  snout.  In  the  centre  of  the  heap  the  rat  starts 
scratchiiiii,  forming  a  bowl  and,  furthermore,  turning  on  its  axis  and 
pyiishiiK^  the  nest  material  towards  the  periphery,  it  forms  a  ring-shaped 
mound  around  itself.  Intermittently  the  rat  reaches  over  the  mound, 
grasping  scattered  nesting  material  with  its  teeth,  and  deposits  it  on  the 
rim  of  the  mound  or  inside  the  nest.  It  reminds  one  of  the  way  geese 
construct  their  nests,  but  whereas  the  latter  are  able  only  to  lay  the 
material  backwards  over  their  shoulder,  the  rat  shows  more  plasticity, 
being  capable  of  depositing  nesting  material  from  different  positions  in 
relation  to  the  nest.  Coarse  nesting  material,  like  straw,  is  split  with  the 
teeth  longitudinally.  The  rat  holds  the  material  at  both  ends  m  its  paws 
and  bites  along  it  with  the  lower  incisors.  By  a  sudden  lifting  of  its  head 
it  splits  the  straw  [splittiiKT).  Straw,  and  even  solid  wood,  are  transformed 
into  soft  nesting  material.  Similar  movements  of  nest  building  are  ob- 
served in  many  other  rodents  and  the  patterns  of  splitting,  scratching,  or 
pushing,  are  common  to  all  those  species  mentioned  above.  Sometimes 
additional  movements  are  observed.  Tree  squirrels,  for  example,  have 
special  movements  for  bundling  the  nesting  material  before  transport. 

In  addition,  I  was  aware  of  certain  environmental  situations  which  were 
obviously  indispensable,  for  instance,  previously  explored  environment 
containing  known  nest  locality,  or  else  good  cover. ^  At  once  I  suspected 
that  the  failure  of  Riess's  rats  to  build  was  due  to  the  fact  that  they  did  not 
have  a  definite  nesting  place  in  the  unfamiliar  testing  situation  with  which 
they  were  confronted. 

When  I  took  ten  virgin  rats  experienced  in  nest  building,  duplicating 
Riess's  test  situation,  none  oi  them  started  building.  After  they  had  over- 
come their  shyness  they  first  started  exploring,  in  between  retreating  to 
one  corner  where  they  cleaned  themselves  and  rested.  Some  pulled  out 
paper  strips  and  scattered  them  all  over  the  Hoor,  thus  behaving  like  the 
rats  of  Riess.  But  none  built  a  nest  within  the  first  hour  and  only  three 
built  within  5  hours. 

On  the  basis  of  my  observations  on  different  species  of  rodents,  Riess's 
statement  of  the  problem,  asking  whether  'nest  building'  as  a  whole  was 
innate  or  not,  seemed  much  too  simple  and  consequently  his  conclusions 
too  strongly  generalized.  Therefore,  I  attempted  to  clarify  the  following 
special  problems,  using  experimental  procedures  as  closely  as  possible 
similar  to  those  employed  by  Riess.  The  question  was: 

1  The  rats  have  furthermore  to  be  fainihar  with  the  presence  of  an  observer,  otherwise  they 
are  irritated,  showing  curiosity  or  shyness. 


56  BRAIN    MECHANISMS    AND    LEARNING 

(i)  Do  any  motor  patterns  and  taxis  components  exist  which  are 
developed  in  the  individual  independently  of  learning  ? 

(2)  Does  the  assumption  made  by  ethologists  hold  true  that  motor 
patterns  which,  by  the  comparison  of  species  can  be  shown  to  be  phylo- 
genetically  homologous,  are  independent  of  learning  ? 

(3)  What  is  the  role  of  individual  learning,  (a)  in  changing  or  developing 
the  pattern  itself  and  {b)  in  intcgratnig  such  innate  elements,  it  any,  into  a 
functional  whole  ? 

Albhio  rats  [Ratttis  iion'c[^ictis  Erxl.)  were  isolated  from  the  age  ot  11  to 
21  days  and  raised  in  cages  with  a  grill  floor  and  given  powdered  iood. 
Since,  in  the  absence  of  nest  material,  rats  often  carry  their  own  tails, 
these  were  amputated  in  the  experimental  animals.  In  contrast  to  Riess,  I 
tested  the  rats  in  their  living  cages,  snicc  it  has  been  shown  that  in  rodents 
placed  in  a  new  room,  escape  and  exploratory  behaviour  predominate 
over  other  activities.  For  the  test,  a  rack  holdnig  30  g.  of  crepe  paper 
strips  was  fastened  on  one  wall  of  the  cage.  The  room  temperature  varied 
between  17'  and  19  C.  In  this  way,  the  ncst-building  behaviour  of  ((7) 
eighty-two  virgin  rats  (2-3  months  old),  (/))  three  pregnant  rats  and  the 
nest  building  and  retrieving  of  {c)  forty-two  females,  4  months  old, 
immediately  after  parturition,  were  tested. 

Of  group  ((?)  (subgroup  i)  thirty-seven  animals  had  nothing  else  ni  their 
cage  than  the  glass  with  powdered  food,  fastened  on  one  wall,  and  the 
phial  with  water  hanging  from  the  roof  Eight  of  these  animals  started 
nest  building  as  soon  as  the  paper  was  presented  and  four  started  within 
an  hour.  Thirteen  of  the  animals  ran  around  with  paper  strips  in  their 
mouths,  and  eventually  let  them  fall,  thus  behaving  as  Riess  described, 
and  six  gnawed  or  played  with  the  strips.  They  all  built  nests  within 
5  hours.  The  remaining  six  rats  of  group  ((7)  (subgroup  i),  however,  did 
not  build  a  nest.  Observations  in  the  previous  days  had  shown  that 
twelve  of  these  rats  had  had  definite  sleeping  places.  All  eight  animals 
that  built  immediately  belonged  to  this  group.  I,  therefore,  conjectured 
that  the  structural  poverty  of  the  experimental  cage  might  have  interfered 
with  the  establishment  of  a  definite  nesting  place.  Indeed,  this  may  have 
hindered  many  experimental  animals  and  made  building  in  some  cases 
impossible.  That  some  of  the  experimental  animals  built  in  two  places 
is  evidence  favouring  this  assumption.  To  facilitate  the  choice  of  a  place, 
I  divided  one  corner  of  the  cages  of  the  other  experimental  animals 
(subgroup  2)  with  a  small  vertical  screen.  Of  forty-five  virgin  rats  tested 
in  such  a  cage,  thirty-three  immediately  started  nest  building  behind  the 


IRENAUS    ElBL-EIBESFELDT  57 

screen.  Among  these  were  animals  who  tended  to  sleep  in  another  corner 
of  the  cage.  An  unlearned  preference  for  the  most  covered  place  prevailed 
in  these  cases  over  the  effects  of  previous  experience.  Three  of  the  experi- 
mental animals  started  behind  the  screen  within  i  hour.  Nine  decided, 
within  5  hours,  to  build  in  another  corner.  To  sum  up:  of  the  eighty-two 
virgin  females,  seventy-six  built  a  nest,  forty-four  of  these  within  the  fnst 
hour  of  the  test,  and  only  six  rats  did  not  build. 

In  all  animals  that  showed  an  interest  in  the  nesting  material,  the  above 
mentioned  movements  of  nest  building  were  observed.  Most  of  the 
animals  explored  the  rack  and  the  paper  at  their  first  encounter  by  nibbling 
and  sniffing.  Then  they  tore  one  or  a  few  strips  out  of  the  rack  and  carried 
them  without  much  hesitation  to  the  prospective  nesting  site.  There  they 
deposited  the  nesting  material,  and  often  nest-building  movements  like 
splitting,  scratching  and  pushing  appeared,  although  of  no  use  at  this 
stage.  These  movements  usually  lasted  for  only  a  few  seconds  before  they 
started  for  more  paper.  From  the  behaviour  of  the  animal  one  did  not  get 
the  impression  that  they  had  any  idea  what  the  result  of  their  behaviour 
would  be.  The  behaviour  released  by  the  nesting  material  consisted  simply 
of  certain  building  movements,  in  disorderly  sequence.  But,  in  all  cases, 
a  nest  was  the  result  of  the  rat's  activity.  In  five  cases  the  experimental 
animals  were  given  pieces  of  straw  instead  of  paper.  These,  too,  started  to 
build,  and  all  started  to  split  the  straw,  in  the  characteristic  way  previously 
described,  thus  producing  soft  nesting  material.  Here,  too,  it  was  evident 
that  the  rat  did  not  follow  a  certain  plan  by  insight.  It  did  not,  for  example, 
split  one  piece  of  straw  after  another,  but  oidy  grasped  one  piece  after 
another,  making  the  splitting  movements  and  dropping  the  straw  after- 
wards without  looking  at  the  result.  Often  the  blade  was  only  cracked,  or 
a  small  piece  ripped  off  when  it  was  dropped  in  order  to  grasp  the  next 
blade  of  straw.  There  was  only  one  tendency  evident,  namely,  to  let 
certain  movements  run  off  on  certain  material.  But  by  repetition  of  this 
behaviour,  all  the  straw  got  split  eventually.  Experienced  rats,  by  the  way, 
seem  to  follow  a  plan  or  scheme,  but  that  still  has  to  be  studied  in  detail. 

Although  I  was  interested  only  in  actual  nest  construction,  I  let  ten  of 
the  experimental  animals,  after  testing  nest  building,  dig  in  earth.  They 
did  so  with  complete  co-ordination  of  all  digging  movements. 

For  the  purpose  of  filming,  three  females  (group  (/;))  were  tested  when 
pregnant.  The  reason  was  that  we  needed  light  to  film  but  this  produced 
heat,  and  as  is  well  known  (Kinder,  1927)  virgin  females  do  not  build  a 
sleeping  nest  when  it  is  too  warm.  But  in  pregnant  females,  temperature 
does  not  influence  the  behaviour  as  much.  The  urge  to  build  a  nest  is  then 


58  BRAIN    MECHANISMS    AND    LEARNING 

very  strong.  As  Kollcr  (1955)  has  shown,  this  is  due  to  the  corpus-hiteum 
hormone,  progesterone.  All  three  females  built  immediately;  their 
behaviour  is  shown  in  the  film. 

Forty-two  inexperienced  females  (group  [c))  were  tested  for  retrieving 
and  nest  building  immediately  after  they  had  given  birth  in  the  experi- 
mental cage.  Thirty-five  of  these  females  retrieved  a  nestling  taken  from 
the  corner  where  they  were  suckling  and  deposited  in  another  corner. 
Only  seven  of  the  females  did  not  carry  back  their  babies.  In  six  of  these 
seven  cases  the  nestlings,  which  were  not  protected  by  nesting  material, 
were  so  cold,  that  they  seemed  nearly  lifeless,  and  did  not  squeak.  Squeak- 
ing is,  however,  one  of  the  sign  stimuli  for  the  females,  releasing  search 
and  retrieving  in  the  mother  (Zippelius  and  Schleidt,  1956;  Eibl-Eibesfeldt, 
1958).  Those  retrieving  behaved  like  normally  raised  mothers,  with  the 
only  difference  that  they  showed  some  hesitation  in  grasping  the  nestlings 
and  often  lost  them  during  transport  and  had  to  pick  them  up  again. 
When  the  nestling  squeaked  while  being  grasped,  the  female  changed  the 
grip,  a  behaviour  which  is  now  being  studied  in  more  detail. 

All  forty-two  females,  including  those  that  did  not  retrieve,  started 
immediately  with  the  construction  of  a  nest  when,  after  the  retrieving 
test,  nesting  material  was  offered.  Furthermore  they  showed  the  covering 
of  the  nestlings  typical  for  the  breeding  mother.  This  will  be  shown  in  the 
film. 

Our  experiments  have  shown  that  the  handling  of  solid  objects  during 
ontogeny  is  not  a  prerequisite  for  the  development  of  nest-building  and 
retrieving  behaviour.  Riess  did  not  realize  this  and  he  furthermore  over- 
looked that  nest  building  is  a  complex  behaviour,  and  therefore  did  not 
look  for  the  elements  which  compose  it. 

The  several  motor  patterns  which,  on  the  basis  of  a  comparative  study 
of  many  species  of  rodents,  had  been  assumed  to  be  unlearned  'fixed 
patterns'  appeared  completely  unchanged  in  the  rats  reared  in  the  manner 
employed  by  Riess.  One  important  difference  was,  however,  found 
between  experienced  and  inexperienced  rats.  The  sequence  in  which  the 
above-mentioned  motor  patterns  are  used  was  considerably  better  adapted 
to  the  function  in  experienced  rats,  inexperienced  rats  often  employing 
motor  patterns  which  can  develop  their  function  only  at  an  advanced 
stage  of  the  newly  built  nest,  at  a  very  early  stage  of  building  at  which  the 
patterns  in  question  did  not  yet  perform  their  function.  The  question 
whether  'nest  building'  must  be  learned  or  not  cannot  be  given  a  simple 
answer.  Certain  essential  motor  patterns  and  taxis  components  are 
completely  independent  of  learning.   The  proper  sequence  in  which 


IRENAUS    EIBL-EIBESFELDT  59 

several  patterns  are  best  employed  to  perform  an  integrated  function  is 
indubitably  learned.  But  no  ethologist  had  ever  doubted  —  as  critics  of 
ethology  often  imply  —  that  learning  processes  are  of  the  greatest  impor- 
tance in  behaviour,  Lorenz  (1937)  has  often  emphasized  that  learned  and 
innate  elements  of  behaviour  are  closely  interwoven.  His  ravens  for 
example  had  innate  nest-building  movements,  but  had  to  learn  which 
material  to  use  for  nest  building.  Eibl-Eibesfeldt  (1956b)  has  recently 
shown  that  red  squirrels  develop  individually  different  techniques  of  nut 
opening  on  the  basis  of  a  few  innate  patterns,  such  as  gnawing  and  a 
certain  splitting  movement. 

In  retrieving,  learning  plays  a  lesser  role  than  in  nest  building.  The 
inhibition  of  biting  the  nestling  seemed  even  stronger  in  inexperienced 
rats.  It  would  seem  that  the  rat  has  to  learn  that  a  baby  is  not  so  vulnerable 
after  all. 

(h)  The  killing  tecluiiqtic  of  the  pok'cat  (Putorius  putorius  L.).  The  follow- 
ing deals  with  the  technique  of  prey  killing  of  inexperienced  and  exper- 
ienced polecats.  Kuo  (1930)  has  studied  the  behaviour  of  cats  raised  under 
different  conditions  towards  albino  rats,  grey  Norway  rats  and  nnce. 
Twenty  cats  were  raised  in  isolation  from  weaning,  twenty-one  cats 
remained  with  their  mother  and  were  allowed  to  observe  how  she  killed 
prey,  and  eighteen  cats  isolated  from  other  cats  were  given  a  rat  as  com- 
panion from  an  early  age  on.  Of  those  raised  in  isolation,  nine  killed  prey 
(=  25  per  cent);  of  the  second  group  eighteen  killed  prey  (85  per  cent); 
but  of  those  raised  with  rats,  only  three  killed  prey  and  then  only  of  a 
type  to  which  they  were  not  accustomed.  Towards  their  rat-companions 
the  latter  individuals  showed  peaceful  and  positive  reactions.  They  licked 
and  defended  them  and  searched  for  them  persistently  if  they  were  taken 
away.  Kuo  thus  clearly  showed  that  experience  influences  the  behaviour 
of  the  cat  towards  prey,  even  though  the  difference  in  the  percentage  of 
killing  in  the  first  two  groups  might  be  explained  as  a  result  of  a  different 
state  of  health  due  to  deprivation.  Kuo  expresses  the  opinion  that  the 
concept  of  instinct  has  been  proved  useless  by  his  experiments.  The  bodily 
structures  alone  explain  why  a  cat  behaves  like  a  cat  and  not  like  an  ape : 
one  does  not  need  to  have  recourse  to  instincts,  based  on  special  structures 
of  the  central  nervous  system.  What  the  animal  actually  does,  within  the 
potentiality  given  by  its  body,  is  learned  during  ontogeny.  'The  behaviour 
of  an  organism  is  a  passive  affair.  How  an  animal  or  a  man  will  behave  in  a 
given  situation  depends  on  how  it  has  been  brought  up  and  how  it  is 
stimulated'  (Kuo,  p.  37). 

It  seems,  nevertheless,  that  Kuo  did  not  realize  where  the  problem 


60  BRAIN    MECHANISMS    AND    LEARNING 

actually  lies.  Such  a  complex  behaviour  pattern  as  prey  hunting  is,  of 
course,  not  fully  innate  or  learned  as  a  whole,  and  we  agree  with  Kuo  that 
to  pose  such  an  alternative  is  a  mistake.  But,  like  Riess,  Kuo  did  not  see 
that  the  complex  functional  unit  in  any  animal's  behaviour  is  formed  by  a 
number  of  smaller  behavioural  patterns.  In  his  paper,  no  single,  particulate 
behaviour  pattern  is  described.  We  investigated  the  prey-hunting  be- 
haviour of  the  polecat,  asking  it  there  were  any  fixed  motor  patterns  or 
innate  orientation  movements  involved  in  the  pattern,  and  if  so  where  and 
how  experience  enters. 

Every  adult  polecat  kills  rodents  which  are  able  to  defend  themselves,  by 
biting  them  in  the  neck  or  occipital  region.  Prey  in  flight  is  often  grasped 
{{^raspiii'^)  on  another  part  of  the  body,  but  after  the  polecat  has  thus 
stopped  the  prey's  flight,  it  immediately  releases  its  preliminary  hold  to 
grasp  the  neck.  Often  it  turns  the  prey  on  its  back  and  shakes  it  torcetully 
{shakiiii^),  in  the  way  employed  by  many  other  carnivorous  animals.  The 
polecat  furthermore  loosens  and  fastens  its  grip,  in  rapid  succession,  sinking 
its  teeth  repeatedly  in  exactly  the  same  spot,  thus  gradually  perforating 
the  skull  {hillino  hitc)  (Eibl-Eibesfeldt,  1956a). 

Studying  the  ontogeny  of  this  technique  in  non-deprived  animals,  one 
finds  that  they  show  little  skill  in  their  first  attempts  to  kill  a  prey,  prob- 
ably partly  due  to  the  lack  of  bodily  strength.  At  the  age  of  3  months, 
however,  a  polecat  is  a  skilful  killer. 

Twenty  polecats  were  raised  under  deprivation.  They  were  not  con- 
fronted with  living  prey  until  the  test,  but  were  fed  with  meat  and  even 
dead  rats  to  keep  them  in  a  good  state  of  health.  Eight  of  the  polecats 
remained  with  their  mother  and  litter  mates.  Twelve  were  isolated  at  the 
age  of  21  days  from  members  of  their  own  species.  Six  of  the  polecats 
raised  in  isolation  and  eight  of  those  raised  with  their  litter  mates,  but  also 
never  being  confronted  with  living  prey,  were  given  an  adult  rat  when 
they  were  5  months  old.  One  of  those  raised  in  isolation  was  tested  at  10 
months,  and  five  raised  in  isolation  were  2  years  old  when  first  given  a 
prey.  The  latter  were  given  chicks. 

Those  tested  at  the  age  of  5  months  behaved  as  follows.  It  the  rat 
remained  motionless  on  the  spot,  the  polecat  approached  slowly,  sniflmg 
with  curiosity  at  the  prey  and  touching  it  with  the  paws.  Some  licked  or 
carefully  tried  to  bite,  but  they  did  not  attack.  If  the  rat  ran  towards  the 
polecat,  the  latter  retreated.  But  as  soon  as  the  rat  showed  flight  reactions 
by  running  away,  the  polecat  attacked  it  vigorously,  trying  to  grasp  and 
bite  it.  It  did  not  direct  its  attack  towards  a  special  part  of  the  rat's  body,  as 
an  experienced  polecat  does,  but  just  bit  into  what  it  grasped,  the  tail,  the 


IRENAUS   EIBL-EIBESFELDT  6 1 

shoulder  or  a  leg.  Then  the  rat  immediately  turned  in  defence,  and  the 
polecat,  evidently  surprised,  released  its  grip,  normally  attacking  again  and 
again.  The  more  anterior  the  hold  on  its  prey,  the  more  difficult  was  it  for 
the  latter  to  defend  itself.  If  the  polecat  was  successful  in  grasping  the 
rat's  neck,  then  it  could  kill  the  rat  easily.  The  polecats  learned  the  right 
grip  quite  rapidly.  One  killed  its  first  prey  within  20  seconds,  with  only 
three  attacks.  Others  needed  1-15  minutes,  depending  on  the  behaviour  of 
the  rat.  After  having  killed  four  to  six  rats,  one  each  day,  a  polecat  was  a 
skilful  hunter  and  its  killing  bite  was  always  directed  towards  the  neck  of 
the  prey.  One  female  that  was  bitten  by  the  rat  showed  fear  and  on  the 
following  3  days,  avoided  the  rat  which  had  been  left  with  her.  The  rat 
slept  in  the  polecat's  nest,  which  the  polecat  avoided.  When  awake  the 
polecat  restlessly  ran  up  and  down  in  the  cage.  On  the  fourth  day  it  killed 
the  rat.  It  became  a  good  hunter  from  then  on. 

The  one  polecat  tested  at  an  age  of  10  months  got  bitten  too,  and  it 
avoided  the  rat  even  i  month  later.  Unfortunately  this  polecat  escaped. 

There  were  no  differences  between  the  behaviour  of  those  seven  raised 
in  isolation  and  that  of  those  left  with  their  litter  mates.  In  both  groups, 
the  first  attack  was  released  by  the  fleeing  prey,  and  both  had  to  learn  the 
correct  orientation  of  the  killing  bite.  There  arc,  however,  indications 
that  those  raised  with  litter-mates  learned  this  orientation  faster,  probably 
as  the  result  of  experience  while  playing.  Four  succeeded  within  i  minute. 

The  movements  described  above,  such  as  shaking,  killing  bite  and 
turning  the  prey  on  its  back,  were  observed  at  the  first  encounter. 

Five  polecats,  at  2  years  of  age,  were  confronted  with  young  chicks  of 
the  domestic  fowl.  They  were  previously  fed  with  dead  chicks.  Neverthe- 
less, none  of  the  experimental  animals  attacked  the  chicken  as  long  as  it  did 
not  move.  They  sniffed  at  it  and  only  when  it  ran  away  did  three  of  the 
polecats  follow  and  grasp  it.  Two  of  them  killed  it  within  a  few  seconds 
by  bites  in  its  back,  one  that  had  not  got  a  very  good  hold  released  the 
grip  when  the  chicken  started  struggling,  but  killed  it  with  the  next  bite. 
All  three  killed  thereafter  without  hesitation,  but  they  did  not  aim  their 
bites  towards  the  neck  of  the  prey,  very  probably  because  these  animals, 
not  capable  of  self-defence,  did  not  demand  the  development  of  a  special 
killing  technique.  They  were  equally  easily  killed  by  bites  m  the  back,  side, 
chest,  or  neck. 

The  other  two  polecats  also  showed  great  interest  in  the  chicken.  They 
sniffed  and  licked  it,  meanwhile  uttering  the  low  sounds  (muttering)  that 
normally  express  readiness  for  social  contact  (Eibl-Eibesfeldt,  1955). 
After  some  minutes  they  turned  away,  but  returned  after  a  while  to 


62  BRAIN    MECHANISMS    AND    LEARNING 

explore  the  chick  agahi.  When  it  tried  to  escape,  both  chased  and  caught 
it,  but  they  showed  a  very  strong  inhibition  to  bite.  They  just  seized  the 
chicks,  without  causing  injury,  and  carried  them  into  their  nesting  box. 
After  5  hours  the  chicks  were  still  alive  there.  I  took  them  away.  On  each 
of  the  following  7  days  I  offered  one  chick  to  each  of  these  polecats. 
During  that  time  they  were  fed  only  with  very  little  meat  every  third  day. 
Until  the  fourth  day,  the  behaviour  of  the  polecats  towards  the  chick 
remained  nearly  the  same.  After  a  short  investigation  they  grasped  the 
chick  and  carried  it  home,  uttering  the  call  of  social  contact.  In  one  of  the 
polecats  a  little  hostility  was  observed  on  the  third  day;  it  hissed  when  it 
met  the  chick,  but  soon  started  muttering.  On  the  fourth  day  I  left  the 
chicks  with  the  polecats  over  night.  Next  morning  polecat  {b)  had  killed 
and  partly  eaten  its  chick,  while  the  other  chick  was  sitting  in  the  warm 
nest  without  showing  the  slightest  damage.  A  newly  offered  chick  was 
attacked  by  the  polecat,  grasped  in  the  neck  but  with  inhibition  to  bite, 
and  carried  alive  to  the  nest,  where  it  was  killed  and  eaten  half  an  hour 
later.  Polecat  ((7)  however,  hissed  a  little,  then  carried  the  new  chick  to  its 
nest,  where  I  found  it  still  ahve  next  morning.  After  I  killed  it,  the  hungry 
polecat  immediately  started  eating.  On  the  same  afternoon,  both  were 
given  chicks  again;  both  carried  them  in  alive.  After  3  hours  the  chicks 
were  found  to  be  still  ahve.  This  time  polecat  {a)  killed  the  chick  during 
the  night,  whereas  polecat  (/>)  left  it  undamaged.  The  experiments  are 
not  fmished  yet. 

The  experiments  have  shown  that  learning  plays  an  important  role  in 
the  development  of  prey-hunting  behaviour,  but  also  that  there  are  some 
important  inborn  reactions.  What  is  learned  is  the  orientation  of  the 
killing  bite  towards  the  neck  of  the  prey,  a  learning  process  which  takes 
place  only  if  the  prey  proves  difficult  to  kill  otherwise.  The  polecat  has, 
furthermore,  to  learn  that  a  quietly  sitting  rat  or  chick  is  prey,  even  when 
it  has  eaten  dead  rats  or  chicks  before.  The  first  attack  is  released  by  a 
fleeing  object,  this  reaction  of  chasing  and  biting  fleeing  prey  is  iimate, 
as  well  as  those  behaviour  patterns,  like  shaking  or  killing  bite,  described 
above.  The  inhibition  of  the  two-year-old  polecats  to  kill  chicks  is 
secondary  and  probably  due  to  social  frustration.  I  got  the  impression  that 
the  chicks  became  substitutes  for  a  social  companion. 

The  different  evaluation  of  the  results  of  the  experiments  by  Kuo, 
Lehrmami,  Riess  and  the  author  might  first  be  due  to  the  fact  that  the 
former  were  interested  only  in  the  final  outcome  of  the  experiments. 
They  noted  only:  'prey  killed  or  not  killed',  'retrieving  or  no  retrieving', 
'nest  building  or  no  nest  building'  but  did  not  care  very  much  about  the 


IRENAUS    EIBL-EIBESFELDT  63 

behaviour  of  the  animal  in  the  test  situation.  It  the  author  had  followed  the 
same  line  when  studying  the  prey-killing  behaviour  of  the  polecat,  he,  too, 
would  have  come  to  the  conclusion  that  this  specific  technique  is  learned, 
since  the  animals  need  several  trials  before  killing  efficiently.  But  the 
crucial  point  is  that  it  does  not  need  to  learn  the  shaking  movements  and 
it  does  not  need  to  learn  to  attack  and  grasp  a  fleeing  object.  If  one  observes 
the  behaviour  one  finds  that  a  number  of  movements  are  there  from  the 
moment  the  first  reaction  towards  prey  is  released.  Kuo's  (1930)  experi- 
ments on  cats  do  not  contradict  our  experiments,  but  simply  fail  to  give 
information  on  certain  important  questions.  The  results  of  Riess,  on  the 
other  hand,  clearly  contradict  our  observations,  due  to  the  fact  that  Riess 
made  the  methodological  mistake  of  testing  his  animals  in  a  surrounding 
strange  to  them.  The  immediate  nest  building  of  our  inexperienced  animals 
can  hardly  be  explained  by  the  learning  hypothesis.  How  should  our  rats 
have  learned  that  nesting  material  keeps  the  animal  warm  if  collected 
and  formed  into  a  nest?  And  what  taught  the  mother  that  newborn  nest- 
lings need  to  be  covered  with  nesting  material,  and  that  straw  has  to  be 
split? 

3.    DISCUSSION  OF  THE  CONCEPTIONS 

According  to  Lorenz  (1952)  fixed  motor  patterns  are  sequences  of 
movements  which  can  appear  in  an  animal  without  previous  exercise  and 
experience.  Presumably  they  are  based  on  specific  central  nervous 
mechanisms,  which  are  inherited  in  the  same  way  as  other  morphological 
structures.  The  characteristics  of  fixed  patterns  are: 

(i)  They  are  constant  in  form. 

(2)  They  are  characteristic  for  the  species. 

(3)  They  appear  in  an  animal  reared  in  isolation  from  members  of  its 
own  species. 

(4)  They  develop  even  if  the  animal  is  prevented  from  exercising  the 
behaviour  pattern  in  question. 

(5)  They  are  hardly  ever  found  in  one  species  alone  at  least  if  closely 
related  species  are  in  existence,  but  are  characteristic  of  taxonomic  groups 
just  as  morphological  characters  are.  Thus  can  they  be  used  for  taxonomic 
purposes,  as  has  been  shown  by  Heinroth  (191 1),  Whitman  (1919), 
Lorenz  (1941)  and  others. 

Our  experiments  have  shown  that  in  every  case  in  which,  on  the  basis 
of  criteria  gained  by  comparative  observation  alone,  a  sequence  of  move- 
ments was  suspected  of  being  a  fixed  pattern,  the  co-ordination  in  question 


64  BRAIN    MECHANISMS    AND    LEARNING 

appeared  unchanged  in  the  animal  reared  in  a  deprivation  situation,  used 
hke  a  ready-made  tool  by  the  inexperienced  animal.  Conditioning  deter- 
mined the  way  of  their  application  only  (see  also  Eibl-Eibesfeldt,  1956b 
and  Eibl-Eibesteldt  and  Kramer,  1958). 

Fixed  patterns  or  instinctive  movements  as  defined  by  Hcinroth  and 
Lorenz  are  therefore  not  a  fiction  as  implied  by  the  'anti-instinctivists',  but 
something  real,  and  the  distinction  between  innate  and  acquired  is  of 
analytical  value.  The  learning  psychologist  who  docs  not  know  what  is 
genetically  determined  is  in  a  position  equivalent  to  a  geneticist  perform- 
ing modification  experiments  on  genetically  unanalyscd  material.  We 
know,  of  course,  that  we  abbreviate,  when  we  say  a  behaviour  pattern  is 
inherited  or  innate  instead  of  saying  that  its  anatomical  and  physiological 
conditions  are.  But  there  is  no  reason  for  not  using  the  term  this  way,  as 
long  as  we  remain  aware  of  the  fact  that  characters  always  develop  on  the 
basis  of  an  inherited  range  of  variation,  all  the  more  if  the  range  of 
modifiability  is  practically  nil. 

Although  we  do  not  know  yet  what  a  fixed  pattern  is,  a  number  of 
investigations  have  made  it  highly  probable  that  they  share  a  common 
physiological  basis.  Besides  the  peculiarities  already  mentioned,  the  fixed 
pattern  is  characterized  by  a  specific  spontaneity  (Lorenz,  1937),  which 
may  be  hypothetically  explained  by, the  assumption  of  neural  centres 
creating  impulses.  The  spontaneous  activity  of  the  central  nervous 
system  has  been  demonstrated  by  von  Hoist  (1935,  1936,  1937),  first  in  the 
earthworm  in  which  he  discovered  in  the  isolated  ventral  nerve  cord  salvos 
of  rhythmical  impulses,  corresponding  exactly  to  the  contraction  of 
segments  in  the  normal  creeping  movements.  Later  von  Hoist  found  that 
even  such  highly  complicated  inborn  motor  patterns  like  swimming  in 
fishes  are  based  on  a  central  nervous  system  automatism.  Von  Hoist 
explains  this  spontaneity  by  the  hypothesis  that  there  are  groups  of  cells  in 
the  CNS  creating  impulses.  These  groups  of  cells  influence  each  other, 
leading  to  certain  forms  of  co-ordinated  movements. 

Very  little  is  known  about  the  neuroanatomical  basis  for  fixed  patterns 
but  the  experiments  of  Hess  (1948),  Hess  and  Brugger  (1943)  and  the 
recent  investigations  of  von  Hoist  and  von  St.  Paul  (1959)  strongly 
indicate  that  fixed  patterns  are  based  on  an  inherited  neurophysiological 
mechanism. 

Experiments  have  shown  that  fixed  patterns  are  released  by  certain  key 
stimuli  which  characterize  simply  but  unmistakably  the  biologically 
adequate  situation,  and  release  the  behaviour  pattern  even  in  an  in- 
experienced animal.  In  other  words,  besides  the  innate  ability  to  perform 


IRENAUS    EIBL-EIBESFELDT  65 

certain  movements,  there  is  an  innate  ability  to  recognize  (Lorenz,  1942). 
Although  our  investigation  concentrated  on  the  motor  patterns  we 
found  that  a  certain  stimuli  situation  must  be  given  to  release  nest  building, 
retrieving  and  prey  hunting.  Ignorance  oi  this  caused  all  Riess's  errors. 
Wild  brown  rats  failed  to  build,  not  because  they  had  less  unlearned 
responses,  but  because  they  reacted  only  to  more  specific  stimuli.  They 
needed  a  more  covered  nesting  site  and  when  I  offered  them  little  tin 
huts  they  started  to  build  under  this  cover. 


4.    THE  VALUE  OF  THE  DEPRIVATION  EXPERIMENT 

Lehrmann  (1953)  is  right  in  his  critique,  when  he  says  that  in  every 
deprivation  experiment  one  has  to  answer  the  question:  Of  exactly  what 
has  the  animal  been  deprived?  But  we  cannot  follow  him  to  his  conclusion, 
that  all  actual  behaviour  of  an  organism  is  determined  by  the  animal's 
experience,  the  only  inherited  basis  being  the  bodily  structures  deter- 
mining potential  behaviour.  He,  as  well  as  Schneirla  and  Hebb,  insists  that 
it  is  practically  impossible  to  prove  that  experiences  during  ontogeny 
are  not  at  work.  An  animal  might  even  learn  ///  iifcro  or  in  the  egg.  To 
elaborate  this  line  of  thought,  Schneirla  (1956)  and  Lehrmami  (1956) 
define  as  experience  any  influence  of  external  stimuli  on  development 
and  behaviour.  According  to  this  definition  even  biochemical  changes  or 
stimuli  arising  from  growth  processes,  as  well  as  any  kind  of  external 
stimulation,  must  be  termed  experience.  Learning  is  only  one  form  of  it. 

The  way  in  which  such  experiences  may  enter  development  is  explained 
by  Schneirla  and  Lehrmama  on  the  basis  of  Kuo's  (1932)  experiment  with 
chicks.  Kuo  examined  the  ontogenesis  of  the  food-pecking  reaction  in  the 
domestic  fowl.  These  animals  are  able  to  peck  for  small  objects  immed- 
iately after  hatching,  a  behaviour  which  we  would  look  at  as  innate.  But 
Kuo  observed  that  in  the  three-day  old  embryo  the  neck  is  bent  passively 
as  a  result  of  the  heartbeat,  which  lifts  and  lowers  the  animal's  head 
resting  on  the  chest.  At  the  same  time  the  head  is  stimulated  tactually 
by  the  yolk  sac,  which  is  moved  by  contractions  of  the  amnion  that  are 
synchronous  with  the  heart  beat.  One  day  later,  the  chick  reacts  to 
external  stimulation  by  bending  its  head  actively,  and  at  the  same  time  it 
opens  and  closes  its  beak  during  nodding.  According  to  Kuo,  this  is  due 
to  irradiation  of  the  neural  excitation  caused  by  the  nodding.  At  the  age 
of  8  to  ID  days,  liquid,  forced  into  the  mouth  by  the  head  and  beak  move- 
ments, is  swallowed.  The  movements  get  more  and  more  stereotyped  and 
the  previously  more  independent  head,  bill  and  throat  movements  become 


66  BRAIN   MECHANISMS    AND    LEARNING 

integrated  into  one  functional  pattern.  According  to  Kuo,  this  is  due  to 
learning.  The  first  arousal  of  the  animal  by  visual  stimuli  is  explained  by 
a  diffusion  of  impulses  from  the  optical  region  in  the  midbrain  centres 
which  previously  released  the  discussed  behaviour  to  tactile  stimulation 
(Maier  and  Schneirla,  1935). 

Lorenz  (195X)  objects  that  this  hypothesis  completely  leaves  out  of 
consideration  one  fact  ot  the  greatest  importance:  'All  these  structures  of 
behaviour,  whether  they  function  on  the  receptor  or  on  the  motor  side, 
are  adapted  to  innumerable  environmental  data.  Unless  one  assumes  a 
mystical  "prcstabilizcd  harmony"  between  the  organism  and  its  environ- 
ment —  which  would  be  "preformationism"  indeed,  information  con- 
cerning all  these  environmental  data  must,  at  some  time,  have  been  "fed 
into"  the  organism  to  make  this  adaptation  possible.  This  acquisition  of 
information  can  have  occurred  only  in  the  interaction  between  the 
organism  and  its  environment,  either  during  the  evolution  of  the  species 
or  during  the  ontogeny  of  the  individual.' 

To  uphold  the  hypothesis  that  pecking  is  learned  in  the  egg  in  the  way 
suggested  by  Kuo  one  would  have  to  make  at  least  one  of  three  assump- 
tions: 

'The  tirst  ot  these  is  that  the  heartbeat  and  the  primarily  independent 
swallowing  movements  just  happen,  by  pure  chance,  to  teach  the  chick 
motor  co-ordinations  that  can  later  on  be  used  in  pecking  up  food.  The 
second,  equally  impossible  assumption  is  that  there  is  a  preformed  harmony 
between  what  the  chick  learns  inside  the  egg  and  the  environment  with 
which  it  is  to  be  confronted  later  on.  The  third,  improbable  but  not 
impossible,  is  that  the  heartbeat  and  the  other  conditions  inside  the  egg, 
have,  in  the  evolutionary  interaction  between  the  species  and  its  environ- 
ment, been  developed  into  a  highly  specialized  apparatus  whose  function 
it  is  to  teach  the  chick  just  those  well  adapted  motor  co-ordinations.  In 
other  words,  the  attempt  to  avoid  the  assumption  of  genetically  fixed 
movements  saddles  us  with  that  of  an  equally  genetically  fixated  teacher!' 
(Lorenz,  195S). 

Once  we  have  realized  the  adaptive  character  of  a  behaviour  pattern, 
we  can  deprive  the  animal  experimentally  of  the  specific  information 
concerning  the  data  to  which  the  behaviour  is  adapted.  If  the  animal 
nevertheless  shows  the  adaptive  behaviour  pattern  in  the  test  situation, 
then  we  call  it  innate,  despite  the  fact  that  learning  in  the  widest  sense,  e.g. 
exercise  of  single  muscle  units,  might  have  played  a  role  during  the 
ontogeny  of  the  individual.  This  does  not  explain  why  the  behaviour 
pattern  as  a  whole  later  fits  the  environment. 


IRENAUS    EIBL-EIBESFELDT  67 

The  distinction  between  innate  and  acquired  behaviour  patterns,  there- 
fore, is  not  at  all  an  artificial  one.  If  a  male  salticid  spider  needed  to  learn 
by  trial  and  error  his  complicated  courtship  display,  which  enables  him 
to  approach  the  cannibalistic  female,  he  woulci  get  eaten  before  copula- 
tion. A  newborn  baby,  unable  to  suckle,  would  starve  before  having 
learned  the  complicated  pattern  of  movements.  On  the  Galapagos 
Islands  no  carnivorous  land  mammal  exists  and  therefore  many  of  the 
endemic  birds  have  lost  their  escape  reaction.  They  are  tame,  with  just  a 
few  exceptions.  One  such  exception  is  the  little  endemic  Galapagos  Dove 
[Ncsopclia  (^alapai^ociisis)  which  shows  'injury  feigning'.  As  soon  as  one 
approaches  a  nest  with  nestlings,  the  adult  bird  flutters  from  the  nest  to 
the  ground.  There  it  runs  away  from  the  nest,  fluttering  its  widespread 
wings.  This  "injury  feigning'  is  well  known  in  birds  of  other  countries, 
where  its  function  is  to  attract  the  attention  of  a  predator  and  to  lead  him 
from  the  nest.  But  on  Galapagos  there  arc  no  carnivorous  mammals, 
and  the  behaviour  pattern  is  normally  not  used.  It  seems  rather  difficult, 
therefore,  to  explain  this  behaviour  on  the  basis  of  the  learning  hypothesis. 
From  where  might  the  animal  have  gathered  the  information  about 
predators,  to  which  its  behaviour  is  adapted  ?  Since  the  information  could 
not  have  been  acquired  during  the  ontogeny  of  the  individual,  the  only 
remaining  possibility  is  that  this  information  was  acquired  by  the  species 
during  the  course  of  evolution,  at  a  time  when  it  was  confronted  with 
predators;  this  'experience'  must  have  been  preserved  in  the  genoma  of  the 
species.  It  appears  in  the  Galapagos  Dove  as  a  behavioural  relict. 

In  the  normal  behaviour  of  an  animal,  innate  and  acquired  patterns  are 
closely  linked  together  into  functional  units,  so  that  it  is  very  often  rather 
difficult  to  distinguish  the  two  components  from  each  other.  Nevertheless, 
we  can  deprive  an  organism  of  special  information  and  thereby  prove  that 
certain  behaviour  patterns  are  innate.  Doves  (Grohmann,  1939)  and 
swallows  (Spalding,  1873)  for  example  have  been  reared  under  conditions 
that  made  it  impossible  for  them  to  use  their  wings  and  practise  flying 
movements.  Upon  being  released,  however,  these  animals  were  able  to  fly 
as  well  as  their  siblings,  who  had  not  been  deprived  of  the  opportunity  to 
learn  flying. 

How  independently  from  learning  processes  certain  behaviour  patterns 
develop,  can  also  be  seen  in  mallards  reared  in  isolation.  With  the  onset  of 
sexual  maturity  they  will  show  such  highly  differentiated  movements  as 
grunt  whistle  and  head-up-tail-up,  without  ever  having  seen  another 
mallard.  If  we  raised  a  tufted  drake  or  a  mandarin  drake  under  identical 
conditions  we  should  observe  them  performing  their  species  specific 

F 


68  BRAIN    MECHANISMS    AND    LEARNING 

courting.  In  short,  those  movements  arc  inherited:  they  mature  as  part  of 
normal  development  in  each  individual  of  the  same  species  in  an 
almost  identical  way.  While  this  paper  was  under  press  I  continued  my 
investigation  of  the  ontogeny  of  behaviour  patterns  in  mammals.  These 
will  be  described  in  detail  in  a  later  publication,  but  I  should  like  to 
mention  here  one  more  example  illustrating  very  well  a  behaviour 
pattern  in  a  mammal  which  is  extremely  little  influenced  by  learning. 
As  is  well  known,  squirrels  {Sciuriis  vtt\(^aris  L.)  hide  nuts  in  holes  which 
they  dig  in  the  ground.  They  deposit  the  nut,  stamp  it  into  the  ground  by 
repeated  blows  with  the  front  of  the  upper  incisors  and  afterwards  cover 
the  hole  with  earth  by  means  of  the  forepaws.  Squirrels  raised  in  grill 
cages  with  powder  food,  by  a  procedure  similar  to  that  described  in 
connection  with  the  rat  experiment,  were  given  open  nuts.  After  they  had 
eaten  some  nuts  these  animals  immediately  began  to  search  for  a  hiding 
place.  With  the  nut  between  their  teeth  they  moved  over  the  ground, 
and  wherever  the  nut  met  an  obstacle  they  started  to  scratch  as  if  digging 
a  hole.  In  many  instances  they  deposited  the  nut,  banged  it  down  with 
their  teeth  and  finally  made  covering  movements  with  the  forepaws,  as  if 
covering  the  nut  with  earth,  although  in  fact  there  was  no  earth.  Only 
rarely  is  such  a  comparatively  long  chain  of  reactions  innate  in  mammals. 
This  behaviour  of  the  squirrels  was  filmed  and  a  detailed  analysis  will  be 
presented  in  the  near  future. 

Some  drawbacks  of  the  deprivation  experiments  have,  nevertheless,  to 
be  considered.  First  of  all,  we  must  always  keep  in  mind  that  an  animal 
raised  artificially  may  not  show  its  normal  behaviour.  How  easily  an 
animal  is  disturbed  under  the  conditions  of  captivity,  is  well  known  to 
every  animal  keeper.  If  certain  behaviour  patterns  characteristic  for  the 
species  under  observation,  do  not  appear  in  the  deprivation  experiment, 
this  might  be  a  result  of  disturbance  and  not  of  lack  of  information.  Strictly 
speaking,  the  deprivation  experiment  is  conclusive  only  in  case  of  a 
positive  result.  If  a  specific  behaviour  pattern  comes  out  despite  the 
specific  deprivation  situation,  we  can  say  that  it  is  a  fixed  pattern.  But  if  it 
does  not  appear,  it  does  not  necessarily  indicate  that  the  animal  needs  to 
learn  it.  If  we  keep  the  animal  in  good  health  we  may  be  able  to  avoid 
such  disturbances.  That  a  certain  behaviour  pattern  does  not  appear  in  the 
experimental  situation  might,  furthermore,  be  due  to  lack  of  the  stimuli 
normally  releasing  it.  To  avoid  this  error  a  normally  raised  control  animal 
must  be  tested  under  the  same  conditions  as  the  experimental  animal  and 
the  experimental  animal  must  be  confronted  with  the  situation  in  which 
the  behaviour  pattern  normally  appears. 


IRENAUS   EIBL-EIBESFELDT  69 


GROUP   DISCUSSION 


EiBL-EiBESFELDT.  Wc  saw  that  learning  plays  an  important  role  in  the  integration 
of  innate  behavioural  elements  into  a  functional  whole.  If  we  study  such  learning 
processes,  we  find  that  many  animals  are  capable  of  learning  certain  tasks  very 
rapidly.  These  arc  supposed  to  be  of  biological  importance  to  them.  Is  tliis  rapid 
learning  a  specific  talent  based  on  central  nervous  structures  adapted  to  that  special 
task  during  evolution  or  is  it  due  to  a  special  high  motivational  pressure? 

Galambos.  Dr  Eibl-Eibcsfcldt  asks  if  this  is  the  result  of  prime  motivation  or  of  a 
special  adaptive  mechanism.  Would  you  please  elaborated 

EiBL-EiBESFELDT.  When  I  studied  the  prey-hunting  behaviour  in  the  common 
toad,  I  found  that  this  animal,  which  normally  does  not  learn  very  fast,  learns 
rapidly  to  distinguish  between  palatable  and  unpalatable  foods.  If  it  gets  stung  by  a 
wasp  or  if  it  receives  unpalatable  food  it  needs  only  very  few  experiences  to  avoid 
such  prey  in  the  future.  Is  this  rapid  learning  based  on  specially  adapted  structures 
of  the  C.N.S.  or  is  it  just  due  to  an  especially  high  motivational  pressure?  Would 
they  learn  other  tasks  just  as  fast  if  a  similar  pressure  was  put  on  them?  Are  there 
experiments  where  animals  learned  the  same  tasks  under  different  motivation? 

Olds.  We  have  experiments  where  certain  animals  learned  complicated  and 
unusual  behaviour  patterns.  We  worked  with  rodents  too.  Provided  the  animal  by 
its  behaviour  could  turn  on  an  electrical  stimulus  to  the  hypothalamus  —  the 
animal  learned  with  great  speed,  provided  the  stimulus  was  in  the  right  part  of  the 
hypothalamus.  The  same  animal  looked  very  stupid  if  we  turned  the  stimulus  down 
so  that  it  was  barely  above  threshold.  This  will  be  clarified  later  when  I  give  my 
paper. 

Hebb.  I  thought  Dr  Eibl-Eibestcldt  was  disagreeing  with  the  idea  that  there  is  any 
role  of  learning  in  the  instinctive  patterns  ot  behaviour.  The  experiments  he  has 
described  clearly  support  the  idea  that  learning  and  the  constitutional  structure  of 
the  animal  collaborate  closely,  and  that  we  are  not  dealing  with  two  different  and 
totally  unrelated  sorts  of  processes.  We  must  not  distinguish  instinctive  processes 
from  processes  influenced  by  experience. 

It  is  my  impression  that  we  have  agreement  in  principle  on  the  question.  I  have 
not  talked  to  Riess,  but  I  am  sure  that  Lehrmann  would  not  disagree  with  any  of 
your  propositions  today.  It  would  be  ridiculous  to  suppose  today  that  there  are  no 
innate  mechanisms,  no  laid-down  patterns  of  response.  What  I  add,  reinforced  by 
your  paper,  is  that  those  laid-down  patterns  are  what  are  modified  by  the  effects 
of  experience.  In  some  animals  little  modification,  in  others  much.  The  lower 
animal  particularly  is  built  to  learn  a  few  things  and  he  learns  them  quickly.  If  this 
is  the  essence  of  the  notion  of  instinct,  this  and  the  tendency  to  act  in  certain  direc- 
tions, I  suggest  that  man's  behaviour  also  is  essentially  instinctive.  We  are  so 
conscious  of  individual  differences  that  we  do  not  see  the  extraordinary  uniformities 
that  occur  through  all  human  cultures. 

Eibl-Eibesfeldt.  If  you  read  Lehrmann's  paper  you  will  sec  that  he  does  not 
agree  with  all  these  concepts.  There  are  certain  behaviour  patterns  which  are  innate 
in  the  sense  that  they  develop  in  the  animal  without  certain  types  of  learning  being 
involved.  We  do  not  imply  that  experience  plays  no  role  at  all.  Lehrmann  has 
defined  experience  as  every  impact  of  external  stimuli  on  the  development  of 
behaviour,  formative  processes  and  so  on.  We  agree  that  all  these  can  influence 


70  BRAIN    MECHANISMS    AND    LEARNING 

behaviour,  but  behaviour  is  adapted  to  certain  environmental  situations.  There  arc 
two  possibihties  to  explain  such  an  adaptation:  during  evolution  of  a  species,  or  bv 
learning  during  the  ontogeny  of  the  individual.  And  wherever  we  find  that  such 
highly  adapted  behaviour  comes  out  in  the  animal  in  spite  of  complete  lack  of 
previous  knowledge  of  the  specific  stimulus  situation  to  which  its  behaviour  is 
adapted,  we  speak  of  innate  behaviour.  If  a  male  spider  would  need  to  learn  its 
complicated  courtship  postures  it  would  get  eaten  by  the  female.  When  a  male 
mallard  raised  in  isolation  still  shows  its  highly  complicated  courtship  postures  at 
sexual  maturity  it  demonstrates  innate  behaviour,  in  spite  of  the  fact  that  the 
animal  might  have  learned  something  in  addition  to  it.  How  our  opponents  argue 
is  demonstrated  in  Kuo's  paper.  He  observed  that  in  the  chick  embryo  the  head 
rests  on  the  heart  and  is  lifted  with  every  heartbeat.  Thus  nodding  movements,  a 
part  of  the  later  pecking  behaviour  —  get  induced.  Later  nodding  becomes  inte- 
grated with  the  previously  independent  swallowing  movements  into  food-pecking 
behaviour  which  every  newly  hatched  chick  shows.  Our  opponents  express  the 
opinion  that  this  behaviour  was  learned  within  the  egg.  (A  detailed  discussion  is 
given  in  my  paper.) 

Hebb.  No. 

EiBL-EiBESFELDT.  Yes  they  do.  Concluding  from  this  and  similar  experiments 
they  say  there  is  no  innate  motor  pattern :  everything  is  learned. 

Hebb.  There  is  no  support  for  that  extreme  view.  My  disagreement  is  with  the 
dichotomy  you  made  earlier,  between  learned  behaviour  and  instinctive  behaviour. 

Thorpe.  I  agree  with  Dr  Eibl-Eibesfeldt  on  this.  Dr  Lehrmann  does  not  now 
take  this  view,  but  he  certainly  did  appear  to  do  so  at  one  time.  I  am  glad  that  he 
seems  now  to  have  come  round  to  what  I  believe  is  the  only  reasonable  position  to 
take.  With  birds  you  get  the  same  sort  of  thing,  in  regard  to  this  interlacement  of 
learned  and  innate  behaviour  patterns.  It  depends  on  the  group  as  to  how  big  these 
innate  chunks  of  behaviour  are.  In  the  mammal  they  are  small  and  as  you  go  down 
the  zoological  scale  they  become  larger,  and  they  may  be  very  large  in  insects  or 
spiders.  One  other  point  I  would  like  to  mention  is  that  these  experiments  on 
birds  give  clear  evidence  that  the  learning  is  too  selective  to  be  'motivational'  in 
this  sense.  A  theory  which  relies  mainly  on  a  supposed  change  in  the  general 
motivational  level  would  not  carry  us  very  far  in  explaining  this  type  of  learning 
in  birds. 

EiBL-EiBESFELDT  (Added  later):  I  can  confirm  Dr  Thorpe's  statement  that  Dr 
Lehrmann  does  not  take  this  extreme  view  now.  I  discussed  the  matter  with  him 
in  Cambridge  at  the  Ethological  Conference. 

Grastyan.  I  would  like  to  know  in  more  exact  terms  what  is  meant  when  you 
say  that  the  animal  learns  quickly  —  How  many  trials  ? 

Eibl-Eibesfeldt.  It  has  to  kill  four  or  five  rats  to  learn  how  to  kill. 

Grastyan.  If  it  cannot  kill  the  first  time,  what  happens  in  the  next  trial? 

Eibl-Eibesfeldt.  He  tries  again.  If  he  receives  a  punishment  stimulus,  he  learns 
faster. 

Grastyan.  What  happens  if  you  work  with  a  satiated  animal? 

Eibl-Eibesfeldt.  It  kills  anyway.  It  was  shown  by  Kuo  that  in  cats  the  satiation 
has  no  influence  on  hunting  behaviour.  I  still  would  like  to  ask  why  Dr  Hebb  teels 
that  it  is  not  justified  to  speak  of  instincts  as  innate  behaviour  in  contrast  to  a 
learned  response? 


IRENAUS    EIBL-EIBESFELDT  7I 

Hebb.  My  objection  to  'instinct'  is  that  it  refers  to  a  mechanism  which  is  ciistinct 
from  what  enters  into  normal  learning  processes. 

EiBL-EiBESFELDT.  But  thcrc  are  differences,  for  example,  m  the  physiology  of 
these  innate  patterns.  I  would  like  to  mention  their  spontaneity.  Furthermore  they 
are  often  released  by  certain  key  stimuli  —  innately.  All  this  shows  that  we  are 
justified  in  distinguishing  innate  and  accjuired  behaviour  patterns. 

Hebb.  The  argument  against  that  is  exactly  the  evidence  that  you  have  in  your 
paper.  You  show  how  closely  the  two  collaborate.  The  implication  of  a  separate 
mechanism  is  that  some  behaviour  is  controlled  by  instinct,  some  by  intelligence 
and  learning.  It  seems  to  me  that  it  is  all  intelligence  or  all  instinct.  The  higher 
species  has  a  wider  range  of  situation  to  which  it  can  adapt,  innately.  The  operation 
of  intelligence  and  learning  is  within  the  scope  of  the  innate  aptitude,  hi  certain 
cases  we  see  the  deviation  from  the  species  pattern  clearly,  and  call  that  learning. 
But  learning  also  operates  in  the  things  which  are  characteristic  of  the  species.  My 
objection  to  instinct  as  a  term  is  the  suggestion  that  we  have  two  different  kinds  of 
mechanism  controlling  behaviour. 

Gerard.  There  is  a  continuity  from  growth,  through  heredity,  prebirth  experi- 
ence, to  youth  and  ageing  experience.  Only  in  the  fertilized  egg  have  you  heredity 
—  from  then  on,  the  chromosome  pattern  interacts  with  its  surroundings.  If  we 
find  it  useful  to  separate  innate  reflexes  from  conditioned  reflexes,  it  is  not  mean- 
ingless to  try  and  distinguish  other  different  levels;  some  higher  level  reflexes 
common  to  the  species  we  may  call  instinctive.  What  reallv  matters  in  any  given 
situation  is  whether  the  variance  normally  introduced  by  the  environmental 
experience  of  the  individual  is  relatively  important  compared  with  the  variance 
introduced  by  the  past  experience  of  the  race  and  put  in  the  genes. 

The  most  interesting  aspect  is  the  adaptive  one,  for  example,  the  rats  building 
nests  to  keep  their  young  warm.  The  pattern  seems  innate,  but  the  execution  of  the 
details  of  the  pattern  is  clearly  learned. 

As  an  illustration  of  the  innate  character,  the  behaviour  pattern  should  cease  if  a 
non-adaptive  situation  is  brought  about.  For  example,  it  you  put  the  rat  in  a  hot 
room,  where  the  young  might  become  overheated  would  it  still  make  a  nest? 

EiBL-EiBESFELDT.  Kinder  (1927)  has  studied  the  influence  of  temperature  on  the 
nest-building  activity  of  the  rat.  If  it  gets  too  warm,  the  animal  stops  nest-building. 
But  that  this  behaviour  is  controlled  by  temperature  and  thus  variable  to  a  certain 
extent  does  not  prove  that  it  is  not  innate  in  the  way  pointed  out  in  my  paper. 
Pregnant  rats,  by  the  way,  are  less  easily  influenced  by  temperature,  because  of  the 
secretion  of  progesterone. 

Gerard.  A  negative  result  does  not  disprove  it  but  if  you  have  an  instance  when 
an  animal  does  a  complex  act  despite  the  harmful  effects,  it  would  be  a  strong  case. 

Eibl-Eibesfeldt.  May  I  mention  two  examples.  Turkey  cocks  have  a  highly 
ritualized  way  of  fighting  with  rivals.  They  do  not  jump  in  the  air  and  hit  their 
opponent  with  the  spurs,  as  other  gallid  birds  do,  but  wrestle  with  their  necks, 
grasping  each  other  at  the  bill.  As  soon  as  one  wants  to  give  up  it  assumes  a  sub- 
missive posture,  by  lying  down  on  the  floor.  In  captivity  it  can  happen  that  a 
turkey  cock  and  a  peacock  get  involved  in  a  fight.  Both  closely  related  species  have 
a  similar  display  and  therefore  understand  the  expression  movements  of  the 
preliminary  display.  But  their  techniques  of  fighting  do  not  fit  together.  While  the 
turkey  cock  expects  wrestling  the  peacock  hits  him  with  his  spurs.  This  leads  to 


72  BRAIN    MECHANISMS    AND    LEARNING 

submissive  posture  in  the  turkey  cock  but  the  peacock  unable  to  'understand' 
continues  fighting  and  the  more  he  beats  the  turkey  cock  the  more  the  latter  gets 
latched  in  the  mechanism  of  the  submissive  posture.  He  does  not  run  away  and 
often  a  fatal  end  results.  Another  example  of  innate  behaviour  misleading  in 
artificial  circumstances  normally  not  occurring  in  nature  is  the  light  orientation  of 
mail)-  insects  which  leads  them  to  circle  around  lamps  and  burn  to  death. 

Concerning  the  previous  remark  of  Dr  Hcbb,  I  want  to  add  that  he  himself 
speaks  of  how  closely  'the  two'  collaborate,  referring  to  innate  and  acquired 
patterns.  Evidently  he  makes  a  distinction  and  only  avoids  the  terms  innate  and 
acquired.  We  use  them  as  we  feel  a  need  to  distinguish  those  behaviour  patterns 
which  show  adaptcdness  to  specific  environmental  situations  without  the  animal 
having  experienced  this  situation  before,  from  those  behaviour  patterns  which  are 
learned  by  the  animal  by  active  communication  with  the  environment  during 
ontogeny.  We  do  not  know  if  they  are  based  on  two  different  kinds  of  mechanisms 
and  our  term  does  not  imply  it.  It  is  probable  but  still  needs  to  be  analysed.  The 
separation  of  both  by  experiment  is  a  first  step  towards  such  an  analysis. 

LissAK.  The  other  side  of  the  question  is  the  humoral  or  hormonal  background. 
May  I  mention  that  well-known  experiment  of  Richter  and  the  mouse-killing  or 
frog-killing  test  of  the  lactating  animal.  The  maternal  aggressivitv  can  be  avoided 
by  a  simple  injection  of  ocstrone  or  by  destroying  the  amygdalate.  I  suppose  that 
the  hormonal  afterentation  must  have  a  very  important  role  in  such  aggressiveness 
or  killing  experiments. 

EiBL-EiBESFELDT.  There  exists  a  paper  published  by  Roller  some  years  ago,  dealing 
with  the  hormonal  control  of  nest-building  behaviour. 

LissAK.  His  method  is  very  convenient  for  studying  the  humoral  mechanism  too. 

Magoun.  Are  physiologists  making  an  effort  to  identify  activity  of  the  C.N.S. 
associated  with  such  behaviour? 

EiBL-EiBESFELDT.  Dr  vou  Holst  Studied  brain  mechanism  by  stimulating  certain 
areas  in  the  brain  of  the  domestic  fowl  —  and  he  released  several  highly  complicated 
behaviour  patterns.  He  will  present  a  paper  at  Cambridge  in  September. 

Thorpe.  I  would  like  to  comment  on  one  aspect  which  seems  important  in  this 
question  of  learned  and  instinctive:  that  is  the  complexitv  of  the  stimulation  to 
which  the  animal  is  exposed.  If  a  bird  is  raised  in  a  sound-proofroom  and  it  sings 
a  normally  elaborate  song  we  are  justified  in  saying  that  this  is  innate  because  there 
is  no  corresponding  complexity  in  the  environmental  situation  to  wliich  the  bird 
is  exposed  which  could  have  called  forth  the  behaviour.  One  must  assume  that  any 
observed  complexity  must  come  from  somewhere;  in  this  case  from  the  animal 
itself  If  on  the  other  hand  you  can  find  a  sufficient  complexity  in  the  sensory  input 
to  which  the  animal  has  been  exposed  you  are  inclined  to  put  it  down  to  the 
account  of  experience.  This  is  a  very  important  fundamental  distinction  between 
the  two  points  ot  view.  The  essential  point  is  the  origin  of  complexity  in  behaviour. 
In  so  many  examples  of  animal  behaviour  environmental  stimuli  may  be  acting  as 
triggers  to  set  off^  complex  behaviour  patterns  but  they  are  not  such  that  they  can 
be  regarded  as  the  full  'cause  of  the  behaviour;  the  complex  adjustment  of  it  must 
be  sought  elsewhere  and  in  such  circumstances  we  are  fully  justified  in  regarding  it 
as  internal  and  in  labelling  the  behaviour  as  innate. 

Hebb.  To  add  to  the  question  asked  by  Dr  Magoun,  I  think  that  it  is  relevant  to 
mention  the  extensive  neurolosiical  investitrations  b\'  Beach  made  on  instinctive 


IRENAUS    EIBL-EIBESFELDT  73 

patterns  in  the  rodent.  Instinct  in  behaviour  depends  on  the  cortex,  and  there  is  a 
close  correlation  between  problem-solving  capacity  and  sex  behaviour  in  the  male, 
and  problem-solving  capacity  and  maternal  behaviour  in  the  female. 

REFERENCE 
Loreiiz,  K.  (1937)  Uber  die  Bildung  dcs  Iiistinktbcgriftcs.  Die  Natuni'iss.  25,  289-300,  307-18, 
3:14-3 1- 


SOME   CHARACTERISTICS    OF   THE   EARLY  LEARNING 
PERIOD  IN  BIRDSi 

W.  H.  Thorpe 

In  the  last  3  or  4  years  much  new  work  on  the  early  learning  period  in 
birds  has  been  accomplished  so  I  propose  in  today's  talk  to  attempt  to 
survey  some  of  these  recent  advances  and  to  consider  what  lines  of 
investigation  now  appear  to  be  the  most  promising.  I  also  wish  to  discuss 
the  relation  of  modern  developments  in  the  study  of  bird  learning  to  the 
general  body  of  knowledge  and  theory  concerning  the  flexible  and 
individually  adaptable  behaviour  of  animals. 

The  acquisition  of  new  actions  and  the  development  ot  skills  by  the 
process  of  trial  and  error  learning  has  recently  been  the  subject  of  a  good 
deal  of  investigation.  A  type  of  behaviour  which  is  particularly  con- 
venient for  detailed  analysis  of  this  kind  is  the  feeding  technique  shown  by 
a  number  of  species  of  birds,  particularly  tits  [Paridav),  when  presented 
with  a  piece  of  food  suspended  by  a  thread.  Individuals  of  many  species  of 
birds  will  sooner  or  later  learn  to  pull  up  the  food,  the  pulled-in  loop  being 
held  by  the  foot  whilst  the  bird  reaches  with  its  beak  for  the  next  pull.  In 
goldfnichcs  {Carduelis  carducUs)  at  least  this  behaviour  has  been  known 
from  tunc  immemorial.  Goldfinches  are  so  adept  at  the  trick  that  they 
have  for  centuries  been  kept  in  special  cages  so  designed  that  the  bird  can 
subsist  only  by  pulling  up  and  holding  tight  two  strings,  that  on  one  side 
being  attached  to  a  little  cart  containing  food  and  resting  on  an  incline, 
and  that  on  the  other  a  thimble  containing  water.  The  keeping  of  birds  in 
this  type  of  cage  was  so  widespread  in  the  sixteenth  century  that  it  gave 
rise  to  the  name  'draw-water',  or  its  equivalent,  in  two  or  three  European 
languages.  Nor  was  this  type  of  aviculture  restricted  to  Europe.  Dr  Dillon 
Ripley  tells  me  that  Parus  variiis  in  Japan  is  kept  as  a  cage  bird  and  is 
taught  many  fancy  tricks,  such  as  the  solving  of  little  puzzles,  running  a 
betting  bank,  and  pulling  up  strings.  No  doubt  all  of  these  depend  upon 
trial  and  error  learning  of  the  kind  described. 

Those  of  us  who  have  seen  this  kind  of  performance  by  wild  birds  at  a 
bird  table,  as  can  so  easily  be  done  with  the  great  and  blue  tits  (P.  major 

^  Part  of  this  work  has  been  pubhshcd  in  Nature,  182,  554-7,  1958,  and  part  in  Ibis,  lOi: 
337-353.  1959-  Full  references  will  be  found  in  these  two  papers  and  in  "Current  Prohleim  oj 
Auiiihil  BclhU'iour"  cd.  W.  H.  Tiiorpc  and  O.  L.  Zangwill,  Canib.  Univ.  Press,  i960. 

75 


76  BRAIN    MECHANISMS    AND    LEARNING 

and  p.  caeriileiis)  in  Britain,  can  hardly  have  failed  to  have  been  impressed 
by  the  smooth  easy  certainty  with  which  the  complete  act  is  accomplished. 
Under  these  conditions  one  seldom  sees  anything  so  suggestive  of  trial 
and  error  learning.  On  the  contrary,  the  act  appears  at  first  sight  to  be  a 
real  and  sudden  solution  of  the  problem  from  the  start,  as  if  the  bird, 
before  responding  to  the  string  at  all,  had  seen  the  answer  to  the  problem, 
and  as  if  its  behaviour  was  the  planned  result  of  this  insight.  But  when  one 
comes  to  investigate  the  development  of  such  behaviour  in  the  nidividual, 
one  gets  a  very  different  picture.  Far  from  it  being  a  smooth  and  easy 
response,  one  fmds  instances  of  birds  which  learn  with  extreme  slowness 
and  difficulty,  acquire  some  part  of  the  response  only  to  lose  the  abihty 
again,  or  get  to  a  certain  point  in  the  acquisition  of  the  trick  and  arc  unable 
to  complete  the  learning. 

One  point  that  emerges  clearly,  however,  is  that  it  is  much  easier  — 
other  things  being  equal  —  for  a  bird  to  take  food  from  a  short  string 
than  a  long  one ;  and  that  an  essential  stage  in  the  training  of  birds  to  feed 
by  pulhng  up  strings  is  to  get  them  to  take  food  from  a  short  string,  say 
2  inches  long,  where  the  seed  is  reached  without  the  necessity  of  actually 
pulling  in  the  string.  Once  this  has  been  achieved,  the  problem  posed  by 
an  increase  of  length  to  2|  inches,  which  must  then  be  pulled  in  before  the 
seed  can  be  eaten,  is  a  relatively  easy  one;  although  it  of  course  imme- 
diately brings  in  a  new  movement,  that  of  holding  the  string.  Once  the 
string  has  been  held  and  the  bait  secured  in  this  manner,  a  gradual  increase 
in  the  length  of  string  can  very  often  be  made  without  causing  the  bird 
any  great  further  difficulties  or  setbacks. 

Prehminary  observations  at  the  Madinglcy  Field  Station  for  the  study 
of  Animal  Behaviour,  Cambridge  University,  with  captive  wild-caught 
and  hand-reared  tits  and  finches,  gave  puzzling  irregularities,  uncertainties 
and  differences  in  individual  and  specific  behaviour.  It  was  clear  that 
many  more  factors  were  coming  into  the  process  of  acquiring  this  rather 
striking  new  feeding  technique  on  the  part  of  the  birds  and  that  a  careful 
experimental  study  of  it  might  be  expected  to  give  results  not  merely 
of  interest  to  the  ornithologist,  but  of  wide  application  to  problems  of 
animal  learning  in  general;  and  possibly  even  to  bear  on  problems  of 
human  learning.  Miss  M.  A.  Vince  of  the  Cambridge  Department  of 
Experimental  Psychology  and  of  the  Madingley  Field  Station  accordingly 
took  up  this  study  which,  although  far  from  complete,  has  already 
yielded  results  of  remarkable  interest  (Vince,  1956-59  and  in  press).  First 
experiments  with  adult  wild-caught  great  tits  showed  that  the  bird's 
first  response  to  the  experimental  set-up  was  to  keep  away  from  it,  but 


W.    H.    THORPE  77 

that  with  further  trials  the  bird's  positive  response  to  bait  and  or  string 
tended  to  increase  over  a  period  of  time.  Subsequently  the  bird's  response 
to  both  might  tend  to  decrease  and  even  birds  which  were  learning  well, 
or  in  which  the  string-pulling  habit  had  been  completely  mastered,  might 
be  set  back,  or  the  habit  lost,  when  the  experimental  situation  was  changed 
or  the  bird  was  moved  to  a  new  cage. 

Further  tests,  not  only  with  wild  and  hand-reared  blue  and  great  tits 
but  also  with  greenfmches  {ChIori<;  chloris),  chaffmchcs  [Friti'^iUa  coelebs) 
and  canaries  [Serimis  c.  canarius),  have  thrown  a  good  deal  of  light  on 
what  is  evidently  a  very  complex  situation.  It  seems  clear  that  juvenile 
birds  tend  to  be  superior  to  adults  in  the  string-pulling  situation  and  that 
this  success  can  be  correlated  with  the  amount  of  time  spent  responding 
to  the  string  aiid/or  the  bait.  This  amount  of  time  responding  could  be 
due  to  a  higher  level  of  activity,  and  in  tasks  requiring  a  high  level  of 
activity  (requiring,  in  fact,  large  persistence  and  many  trials)  juveniles  — 
which  are  at  their  maximum  of  exploratory  activity  at  about  13  weeks  — 
are  likely  to  be  more  efficient  than  adults.  But  positive  response  is  not  the 
whole  of  learning,  and  in  such  a  task  as  string-pulling  it  is  necessary  also 
for  the  bird  to  learn  to  refrain  from  responding  to  situations  in  which 
reinforcement  is  absent  or  withdrawn.  This  ability  to  refrain  is,  as  Vincc 
shows,  dependent  on  something  similar  to  what  Pavlov  called  internal 
inhibition.^  It  is  weak  in  very  young  birds,  develops  as  a  result  of  age,  and 
as  a  result  of  experience  during  the  juvenile  stage,  is  still  being  strengthened 
at  an  age  when  positive  responsiveness  is  well  past  its  peak  and  later 
weakens  sHghtly  again.  Consequently  tasks  which  depend  less  on  the  level 
of  activity,  and  more  on  the  ability  to  control  behaviour  by  precisely 
timed  inhibition  are  more  likely  to  be  mastered  quickly  and  efficiently  by 
older  birds  than  by  younger  ones.  Other  experiments  in  which  great  tits 
were  required  to  obtain  food  by  opening  dishes  covered  with  white  lids 
and  refrain  from  opening  dishes  covered  with  black  lids  gave  further 
confirmation  of  this  view.  These  studies  also  suggest  that  internal  inhibi- 
tion is  unstable  in  young  birds  and  that  the  process  of  development  from 
the  unstable  type  of  inhibition  found  in  younger  birds  to  the  more  stable 
type  found  in  older  birds,  depends  not  only  upon  age  but  also  on  experi- 
ence. 

In  another  experiment,  great  tits  were  first  trained  to  feed  from  a  blue 
dish.    When   they   had   become   habituated  to  the  blue  dish,  a  white 

^  A  full  discussion  of  the  relationship  between  Habituation  and  Internal  Inhibition  would 
be  out  of  place  here;  those  interested  will  find  it  dealt  with  at  some  length  in  my  book 
(Thorpe,  1956,  57-62). 


78  BRAIN    MECHANISMS    AND    LEARNING 

cardboard  lid  was  placed  over  it.  The  number  of  trials  (i.e.  the  reinforced  or 
training  trials)  needed  for  the  consistent  removal  of  the  white  lid  was  then 
recorded.  Unreinforced  trials  consisted  of  empty  dishes  with  black  lids. 
When  hand-reared  birds  were  compared  in  this  test  with  wild-reared  ones 
caught  asjuveniles  over  a  period  of  8-20  weeks  after  fledging,  both  groups 
showed  internal  inhibition  (indicated  by  the  ability  to  refrain  from  remov- 
ing the  black  lid)  rising  as  a  function  of  age  and  later  falling  slightly.  But 
there  are  indications  that  a  richer  and  more  varied  experience  may 
change  the  slope  of  the  curve,  giving  a  sharper  rise  to  a  higher  level.  It 
seems  as  if,  at  any  rate  in  this  experimental  situation,  richness  of  early 
experience  is  an  important  factor  in  contributing  to  the  perfect  mastery  of 
a  task.  Thus  in  a  task  primarily  requiring  superabundant  activity  (as,  for 
instance,  does  maze  learning,  where  a  large  number  of  different  cues  have 
to  be  investigated),  younger  animals  arc  more  likely  to  excel.  On  the 
other  hand,  a  task  which  requires  activity  directed  to  a  particular  feature 
of  the  environment  may  well  be  learned  better  by  older  animals.  Both 
these  features  arc  shown  in  the  studies  of  bird  learning  which  I  have  been 
describing. 

To  sum  up,  there  are  four  aspects  of  development  which  have  emerged 
from  such  experiments.  Firstly,  there  is  the  question  of  responsiveness; 
this  appears,  in  the  hand-reared  great  tit,  to  increase  with  age  and  then 
decrease.  Secondly,  there  are  changes  in  a  different  type  of  responsiveness, 
namely  habituation  or  internal  inhibition.  Here  again  there  appears  to  be  a 
rise  and  also  probably  a  slight  subsequent  fall  with  age,  but  the  rates  of 
the  first  and  second  changes  may  be  quite  different,  and  so  the  variation  in 
these  two  factors  couJd  well  give  rise  to  the  puzzling  differences  in  learning 
ability  which  the  earlier  experiments  revealed.  Thirdly,  there  is  the 
question  of  the  hunger  drive.  The  birds  in  this  work  were  kept  under 
conditions  such  that  approximately  the  same  measure  of  food  deprivation 
was  experienced  by  all.  Fourthly,  the  effects  of  early  experience  or 
environment  on  behaviour  are  clearly  shown  and  it  seems  that  internal 
inhibition  may  develop  more  rapidly  and  more  completely  in  a  more 
varied  environment,  presumably  as  a  result  of  greater  activity,  greater 
stimulation  and  perhaps  greater  opportunity  for  adaptation  and  so  on.  It  is 
plausibly  assumed  that  aviary  rearing  is  a  richer  experience  than  hand- 
rearing  and  that  rearing  in  the  wild  is  a  richer  experience  still. 

hiipriiitiin^.  The  phenomenon  of  imprinting  is  now  so  well  known  to  the 
student  of  bird  behaviour  that  a  definition  is  hardly  necessary.  Recent 
experiments  have  confirmed  that  the  period  during  which  young  birds 
can  tirst  learn  to  follow  moving  objects  is  strictly  limited.  But  once  a 


W.    H.    THORPE  79 

bird  has  learnt  to  follow  models,  the  ability  to  transfer  from  one  type  to 
another  can  be  demonstrated  in  birds  as  young  as  3  days  and  as  old  as 
60  days;  although  when  first  presented  with  a  new  model  they  will  show 
a  slight  initial  diminution  in  response,  indicating  that  they  perceive  a 
difference  and  that  the  new  model  is  not  at  first  quite  as  acceptable  as 
the  old.  With  coot  and  moorhen,  Hinde,  Thorpe  and  Vince  (1956)  found 
that  in  the  early  days  of  life  the  following-response  is  stronger  than  the 
tendency  (which  is  also  present)  to  flee  from  strange  objects.  The  result  is 
that,  in  the  course  of  the  following  experiments,  the  younger  bird  gets 
used  to  a  number  of  strange  objects  and  so  its  fleeing  tendency  is  weakened 
by  habituation.  But  the  bird's  response  is  always  ambivalent  in  some 
degree  and  later  the  fleeing  drive  becomes  stronger,  and  more  difficult  to 
habituate;  and  consequently,  with  age,  a  strange  object  becomes  less 
likely  to  elicit  following.  In  the  coot,  practically  all  the  waning  of  a 
following  response  with  age  can  be  attributed  to  this  growth  in  the 
fleeing  drive  and  in  these  species  no  evidence  was  forthcoming  for  any 
permanent  effect  able  to  influence  instinctive  behaviour  patterns  which 
are  to  mature  later.  In  some  species,  however,  including  some  duck  such 
as  the  mallard  (Weidmann,  1955,  1958)  and  also  geese,  there  seems  little 
doubt  that  the  tcrnunation  of  the  imprinting  period  cannot  be  due  solely 
to  the  development  of  a  competing  fleeing  drive  but  there  that  is  an 
internally  controlled  waning  of  the  tendency  to  follow,  independent  of 
ihe  development  of  fear  responses  (jaynes,  1957). 

It  is  clear  that,  in  the  kind  of  experiment  which  I  have  just  described,  the 
foUowing-reponse  can  be  said  in  some  way  to  be  'its  own  reward'.  All 
that  the  bird  is  doing  in  the  first  instance  is  giving  rein  to  a  need  to 
maintain  itself  by  its  own  efforts  in  constant  spatial  relationship  with  a 
moving  object.  This  moving  object  can  be  almost  anything  which  is  not 
too  large  or  too  small,  and  which  does  not  move  too  fast  or  too  slowly. 

To  sum  up  this  work  on  imprinting  to  visual  stimuli,  we  can  say 
tentatively  that  the  imprinting  period  is  initiated  primarily  by  the  matura- 
tion of  an  internally  motivated,  appetitive  behaviour  system  which  is  in 
readiness,  at  the  time  of  hatching  or  very  soon  after,  to  express  itself  in  the 
following-response.  The  time  during  which  this  internally  controlled 
tendency  can  find  its  first  expression  in  action  is  limited,  to  a  matter  of  a 
few  hours  or  at  most  days,  by  internal  factors;  but  during  this  time  the 
response  is  ready  to  appear  as  soon  as  the  circumstances  permit  it  to  do  so. 
The  termination  of  the  ability  to  make  that  first  response  is,  as  we  have 
seen,  very  largely  influenced  by  the  development  of  competing  fleeing 
responses.  Nevertheless,  the  evidence  remains  very  strong  that,  in  some 


80  BRAIN    MECHANISMS    AND    LEARNING 

species  at  least,  an  internal  change  directly  reduces  the  appetitive  following- 
drive  with  age.  Conversely,  once  the  following-behaviour  has  had  a 
chance  to  establish  itself,  it  will  continue  towards  those  models  which 
have  become  associated  with  the  achievement  of  the  consummatory 
situation  resulting  from  successful  following,  and  may  be  yet  further 
generalized  to  others. 

It  is  clear  that  the  broad  nature  of  the  stimulus  to  which  following 
animals  respond  represents  a  difference  only  of  degree  from  other  instinc- 
tive responses,  especially  those  of  young  animals.  Not  only  does  the 
following-tendency  itself  become  primed  through  exercise  and  so  more 
firmly  established,  but  the  following  gives  opportunitv  for  the  animal  to 
become  conditioned  in  various  ways  to  the  characteristics  of  the  object 
which  has  elicited  the  response  in  the  first  place. 

Imprinting  can  occur  in  response  not  only  to  visual  stimuli  but  to 
auditory  ones  also.  Thus  an  animal  with  an  initially  weak  tendency  to 
respond  to  both  objects  and  sounds  within  a  wide  range  may  learn  to  pay 
attention  to,  and  ultimately  to  follow,  certain  sounds  which  have  been 
associated  with  the  visual  stimuli  first  releasing  the  following  response. 
This  may  work  both  ways.  Auditory  stimuli  may  be  conditioned  to 
visual  characteristics  of  the  object,  and  vice  versa.  The  recent  studies  of  Dr 
Klopfer  at  Madinglcy  and  in  the  United  States  have  given  particularly 
good  examples  of  this.  In  the  first  place  certain  surface-nesting  species  of 
waterfowl,  chiefly  mallard  and  redhead  [Aytliya  aimricana),  were  examined 
and  it  was  found  that  they  were  able  tc^  learn  appropriate  sound-signals 
involved  in  the  maintenance  of  the  brood-parent  relationship  as  a  con- 
sequence of  visual  imprinting.  No  unlearned  preferences  for  any  particular 
auditory  signals  seem  to  exist;  they  tended  to  approach  most  rhythmic 
repetitive  signals  without  distinguishing  between  them.  Nor  could 
auditory  imprinting  to  a  particular  one  occur  in  the  absence  of  visual 
stimulation.  When  Dr  Klopfer  came  to  investigate  the  wood  duck  (^4/.v 
sponsa)  which  is  a  hole-nesting  species,  the  situation  was  found  to  be 
reversed:  they  did  not  initially  tend  to  approach  the  repetitive  signals,  but 
exposure  to  a  sound  signal  alone  could  produce  a  subsequent  preference 
for  that  sound,  thus  demonstrating  auditory  imprinting.  Further,  the 
imprinted  response  was  not  reinforced  or  altered  in  any  way  by  following 
or  by  a  visual  stimulus.  This  fact  can  be  explained  by  the  nesting  habit  of 
wood  ducks,  which  require  that  the  young  duckling's  first  response  to  the 
mother  be  based  on  auditory  stinauli.  In  surface-nesting  birds,  visual  cues 
can  play  a  larger  role  from  the  start,  and  thus  assume  paramount  import- 
ance. The  quackless  muscovy  duck  [Cuiriiia  niosclmra)  was  shown  to  be 


W.    H.    THORPE  8l 

incapable  of  auditory  learning  under  the  conditions  oi  the  experiment,  and 
this  striking  failure  in  a  species  whose  wild  ancestors  arc  closely  related  to 
the  wood  duck  is  supposed  to  be  a  consequence  of  domestication.  Klopfer 
(1959)  then  studied  the  following-responses  of  European  shelduck 
[Tadorua  tadoriia).  Young  oi^  the  species  hatched  and  reared  in  sound- 
proof rooms  showed  no  tendency  to  approach  repetitive  sound  signals 
when  tested  at  18-26  hours  of  age.  In  this  they  were  similar  to  wood  ciucks 
and  domestic  muscovies,  and  unlike  any  species  of  surface-nesting  water- 
fowl. However,  with  the  shelduck,  exposure  to  repetitive  sound  signals  in 
early  life  produced  no  change  in  the  response  pattern,  whereas  in  the  wood 
duck  it  did  so.  Nevertheless,  associating  the  sound  signals  with  an  object  or 
person  which  the  ducklings  were  allowed  to  follow  for  short  periods 
enabled  a  highly  specific  preference  for  sound  to  be  developed,  and  in  this 
shelducks  resembled  several  species  of  surface-nesting  waterfowl,  particu- 
larly of  the  genus  Auas.  Of  course  this  work  does  not  prove  that  there  are 
no  sounds  to  which  these  birds  would  respond  in  the  absence  of  visual  and 
motor  experience,  but  it  does  appear  that  a  preference  can  be  established 
for  sounds  which  are  linked  to  a  visual  model.  As  in  the  surface-nesters, 
one  can  suppose  that  the  following-response  serves  as  a  necessary  rein- 
forcement in  the  learning  of  particular  sound  signals.  Thus  the  behaviour 
of  the  young  shelduck  does  not  show  the  pattern  which  would  seem  to  be 
most  appropriate  for  hole-nesting  species,  for  whom  auditory  stimuli 
should  be  of  much  greater  importance  than  visual  ones.  Moreover,  hole- 
nesting  species  should  either  be  endowed  with  response  tendencies  to 
specific  auditory  stimuli  at  the  time  of  hatching,  or  else  highly  susceptible 
to  auditory  imprinting.  That,  for  instance,  seems  to  be  true  of  the  wood 
duck.  It  would  thus  seem  likely  that  newly  hatched  shelducks  emerge 
from  their  burrows  in  response  to  visual  or  perhaps  tactile  stimuli,  with 
auditory  cues  assuming  a  secondary  importance.  The  fact  that  shelduck 
will  nest  in  thickets  above  ground  when  burrows  arc  not  readily  available 
also  suggests  a  possible  explanation  tor  this  difference  in  behaviour.  Here 
is  an  interesting  opportunity  for  a  held  investigation  which  will  be 
essential  before  the  whole  matter  can  be  completely  understood. 

In  nidicolous  birds  this  particular  type  of  following-response  cannot,  of 
course,  operate.  Nevertheless  there  is  in  certain  song  birds  good  evidence 
for  something  very  suggestive  of  imprinting  in  the  process  of  learning 
characteristic  song,  and  indeed  the  vocalizations  of  birds  can  be  regarded 
as  offering  particularly  crucial  problems  concerning  the  acquisition  of 
complex  behaviour  patterns  as  a  result  of  individual  learning. 

The  normal  song  of  the  chaffinch  is  an  elaborate  integration  of  inborn 


82  BRAIN    MECHANISMS    AND    LEARNING 

and  learned  components,  the  former  constituting  the  basis  for  the  latter. 

A  good  example  of  a  normal  song  of  Friin^illa  coclchs  qciiojcri  is  given  in 
Fig.  I.  The  inborn  component  of  the  chaffinch  song  can  be  revealed  by 
hand-rearing  the  young  birds  from  early  nestling  life  either  in  acoustic 
isolation  or  at  least  out  of  contact  with  all  chaffinch  song.  Six  birds  thus 
individually  isolated  produced  songs  of  an  extremely  simple  type  (Figs. 
2-4)  consisting  of  a  song-burst  of  approximately  the  correct  length  (2-2.5 
seconds)  made  up  of  about  the  right  number  of  notes.  The  pitch,  or  funda- 
mental frequency,  of  these  notes  was  somewhat  lower  than  normal  and 
the  songs  produced  by  these  isolates  lacked  the  division  into  the  three 
phrases  so  characteristic  of  the  normal  chaffinch  song.  Moreover,  the  final 
flourish  and  all  the  other  tme  details  by  which  the  chaffinch  song  is 
normally  recognized  as  such  were  also  absent.  Of  all  the  hundreds  of  wild 
and  aviary-kept  birds  which  have  passed  through  our  hands  during  the 
course  of  these  experiments,  none  has  produced  songs  of  such  extreme 
simplicity  as  these  six  birds,  although  such  undeveloped  songs  are  known 
to  occur  in  the  wild  at  times. 

In  contrast  to  the  simple,  restricted  song  produced  by  the  isolated  birds, 
we  find  that  if,  after  babyhood,  two  or  more  such  birds  are  put  together 
in  a  room  but  still  without  the  opportunity  of  hearing  experienced 
chafhnches,  they  will  develop  more  complex  songs.  It  seems  that  the 
attempt  to  sing  in  company  produces  mutual  stimulation  which  en- 
courages the  development  of  complexity.  The  members  of  each  group  of 
hand-reared  birds  thus  kept  together  will,  by  mutual  stimulation,  build 
up  a  distinctive  community  pattern.  The  birds  conform  so  closely  to  this 
pattern  that  it  is  sometimes  barely  possible  to  distinguish  the  songs  one 
from  another  even  by  electronic  analysis.  The  song  of  such  birds  may  be 
quite  as  complex  as  that  of  a  normal  wild  chaffinch,  but  its  complexity 
tends  to  be  of  a  different  kind  and  a  song  thus  produced  may  bear  little 
resemblance  to  the  characteristic  utterances  of  the  species.  From  further 
experiment  it  is  clear  that,  in  the  wild,  young  chaffinches  learn  some 
features  of  the  song  from  their  male  parents  or  from  other  adults  during 
the  first  few  weeks  of  life.  But  most  of  the  finer  details  of  the  song  are 
learned  by  the  young  bird  when,  in  its  first  breeding  season,  it  first  comes 
to  sing  in  competition  with  neighbouring  territory-holders.  There  is  little 
doubt  that  this  is  the  way  in  which  local  song  dialects  are  built  up  and 
perpetuated.  In  addition  to  this  true  song,  the  chaffinch,  like  many  other 
species,  has  what  has  been  called  a  sub-song,  which  is  a  much  quiet  and 
less  aggressive  affair  than  is  the  full  song.  It  is,  however,  not  merely  a  song 
of  low  intensity:  it  is  of  an  entirely  different  pattern  from  the  true  song  and 


W.    H.    THORPE 


83 


/.     n 


m\ 


Fic;.  I 
'Normal'  song  of  British  chaffinch  {Friiii;illa  coclchs  (.'t'/zsj/rn')  Vertical 
scale:  frequency  in  kc./s.  Horizontal  scale:  time  m  seconds  (Similarly 
Figs.  2-1 1). 


'i     k     '1     I 


WWWs 


10  15  2  0  2-5 


^^WM'^iw««\iWrti\ 


05 


l-O  15  20  2  5 


MhVVVUsv 


Figs.  2-4 
Song  of  three  hand-reared  isolates.  GW,  lune  24th,  1954;  B/BkY, 
May  25th,  1957;  and  BkW/W,  June  24th,  1955. 


84  BRAIN    MECHANISMS    AND    LEARNING 

may  be  described  cis  a  long  succession  of  chirps  and  rattles  (Thorpe,  1955, 
1958;  Thorpe  and  Pilcher,  1958).  It  seems  to  have  no  communicatory 
function  and  is  most  frequently  heard  in  the  early  spring,  when  it  is 
produced,  so  far  as  we  know,  much  more  by  tirst-year  birds  than  by  older 
ones  —  the  latter  seeming  to  come  into  full  song  with  much  less  of  this 
preliminary  sub-song.  There  seems  little  doubt,  however,  that  the  sub- 
song  provides  in  some  degree  the  raw  material  out  of  which,  by  practice 
and  by  the  elimination  of  unwanted  extremes  of  frequency,  the  full  song 
is  'crystallized'.  The  chaffinch  has,  of  course,  like  other  species,  a  number 
of  call  notes  which  arc  in  the  main  signals  for  co-ordinating  the  behaviour 
of  the  flock,  mate  and  family;  some  of  these  may  be  used  as  components 
of  both  sub-song  and  full  song.  It  is  interesting  that  call  notes  are  much 
more  in  evidence  as  components  of  the  songs  of  isolated  birds  than  they 
are  in  the  songs  of  normal  ones.  This  is  presumably  because  the  isolated 
birds  have  had  a  greatly  restricted  auditory  experience  to  draw  upon  as 
compared  with  normal  wild  individuals. 

Chaffinches  are  not  imitative  birds,  in  that  they  do  not  normally  copy 
anything  but  sounds  of  chaffinch  origin.  Once  a  chaffinch  has  heard  a 
chaftinch  song  as  a  young  bird  in  the  wild,  it  appears  to  have  learned 
enough  about  it  to  refuse  to  copy  any  sound  pattern  which  departs  far 
from  the  normal  chaffinch  song;  that  is,  it  will  learn  only  the  finer  indivi- 
dual variations  of  the  song  of  other  chaftmches.  So,  in  the  wild,  chaffinches 
practically  never,  in  their  full  songs,  imitate  anything  but  other  chaffinches. 
Hand-reared  isolated  birds  will  learn  songs  of  far  greater  abnormality, 
however,  provided  always  that  the  tonal  quality  is  not  too  far  different 
from  that  of  a  chaffinch  song.  Voices  as  'abnormal'  as  that  of  a  domesti- 
cated canary  may  be  learned  by  hand-reared  birds  (Thorpe,  1955),  and  very 
occasionally  by  wild  birds;  but  when  this  happens  the  alien  notes  are  kept 
as  components  of  the  non-communicative  sub-song  only;  the  full  song  is 
not  contaminated  with  them. 

If  one  catches  wild  chaffinches  in  their  first  autumn  and  keeps  them 
until  the  following  spring  with  other  chaffinches,  the  song  of  which  is 
already  fixed,  one  gets  clear  evidence  that  the  young  birds  have  modelled 
their  songs,  in  some  respects  at  least,  on  those  of  their  associates,  which 
have  probably  come  into  song  first  as  the  spring  season  comes  on,  and 
which  they  thus  hear  before  they  themselves  have  got  very  far  along  the 
path  of  song  production.  Similarly,  if,  instead  of  exposing  such  wild- 
caught  first-year  birds  to  the  songs  of  other  chaffinches,  one  plays  such 
songs  to  them  by  means  of  a  repeating  tape  machine  which  we  may  call  a 
'song  tutor',  a  clear  positive  effect  is  manifest.  An  experiment  carried  out 


W.    H.    THORPE 


85 


ill  1954-55  with  iour  wild-caught  birds  given  such  tuition  in  the  winter 
(January  6th-20th)  and  with  three  birds  similarly  treated  in  February- 
March  showed  clearly  the  effect  of  the  'song  tutor',  there  being  correct 
articulation  of  the  phrases  and  a  good  approximation  in  pitch  and  quality, 
although  there  were  abnormalities  in  length  and  emphasis.  If,  however, 
under  these  conditions  one  exposes  the  young  birds  to  highly  abnormal 
songs,  no  result  is  obtained.  Thus  in  experiments  in  1955-56  such  birds 
were  given  tuition  with  a  reversed  chaffinch  song  during  March.  The  fact 
that  no  definite  effect  was  obtained  suggested  that  enough  of  the  song  had 


^/■//'/' 


25 


Figs.  5  and  6 
Two  sons  of  a  hand-reared  auditory  isolate  after  having  been 
exposed  to  normal  song  on  the  'song  tutor'  for  lo  days  only  during 
November  of  its  first  year.  GY/BW,  April  24th,  1956. 


already  been  learned  in  the  autumn  for  the  reversed  song  to  be  ineffective 
even  with  visually  isolated  birds.  In  1956-57  a  similar  experiment  was 
done  using  six  wild-caught  autumn  males  and  exposing  them  in  this  case 
not  to  a  reversed  song,  which  was  thought  to  be  perhaps  too  abnormal, 
but  instead  to  three  different  're-articulated'  songs  (these  are  songs  in 
which  the  position  of  the  three  phrases  has  been  interchanged).  In  this 
experiment  the  birds  were  isolated  in  a  sound-proof  room.  Two  birds 
had  exposures  in  September  and  October,  repeated  in  January,  two  had 
exposures  in  mid-  to  late-October  and  late  January  and  early  February, 
and  two  were  similarly  exposed  in  November  and  February.  On  the 


86 


BRAIN    MECHANISMS    AND    LEARNING 


whole,  this  experiment  also  had  little  effect,  conhrming  the  tests  with  the 
reversed  song  and  suggesting  even  more  strongly  that  the  natural  training 
which  the  bird  had  already  received  by  the  time  it  has  reached  the  fnst 
winter  moult  has  equally  been  sufficient  to  prevent  it  from  learning  after- 


FiG.  7 
Re-articulatcd  model  with  'end  in  middle'. 

wards  the  rather  large  abnormalities  characteristic  of  these  re-articulated 
songs. 

When  we  come  to  similar  experiments  with  hand-reared  birds,  very 
different  results  are  obtained.  It  was  found  that  a  hand-reared  visual  isolate 
can  be  taught  features  of  a  normal  song  from  the  tape  by  being  exposed  to 
it  during  November  only  of  its  tu'st  winter  for  a  period  of  lo  days.  Figs.  5 


Fig.  8 
Song  of  hand-reared  auditory  isolate  B/BkP  after  having  been  exposed 
to  this  model  for  12  days  January-February  and  12  days  February-March. 
March  25th,  1958. 

and  6  give  the  two  songs  developed  in  1956  by  such  a  bird  treated  in  1955. 
The  first  song  shows  clearly  the  influence  of  the  'tutor'  in  that  it  has  three 
phrases  otherwise  unknown  in  the  hand-reared  isolate,  having  a  clear 
stepwise  descent  but  no  end-phrase.  The  second  song  is  of  the  isolate  type 
plus  two  end-notes.  These  experiments  thus  produce  evidence  that  tutor- 


W.    H.    THORPE  87 

ing,  even  for  a  short  period  in  November,  can  effect  the  same  kind  of 
result  as  the  normal  song  experience  of  a  wild  bird  in  the  field  during  the 
autumn.  Similar  positive  results  were  obtained  in  similar  experiments 
with  re-articulated  songs  carried  out  in  1956-57  and  1957-58.  Figs.  7  and 
8  show  such  a  re-articulated  model  and  its  effect  on  the  song  of  a  hand- 
reared  isolate.  Hand-reared  birds  show  similar  differences  from  the  wild- 
caught  ones,  in  that  if  given  a  reversed  song  a  considerable  amount  of 
copying  is  achieved.  Similar  experiments  with  other  birds  provide 
further  evidence  for  a  previous  conclusion  that  although  a  hand-reared 
isolate  is  incapable  by  itself  of  producing  anythhig  approximating  to  a 
normal  ending,  yet  if  once  it  hears  a  normal  end-flourish  on  the  'song 
tutor'  (even  though  in  the  rearticulated  song  on  the  tape  it  occurs  at  the 
beginning  or  in  the  middle  of  the  song)  it  will  recognize  it  as  appropriate 
for  an  ending  and  will  attempt  to  place  it  properly  in  its  own  song. 

In  experiments  in  1954-55  ^-i^  attempt  was  made  to  indoctrinate  hand- 
reared  isolate  chaffinches  with  the  song  of  the  tree  pipit  {Ainliiis  trivialis) 
(Fig.  9),  this  being  chosen  because  the  spectrograph  reveals  that  the  tonal 
quality  of  the  notes  is  similar  to  that  of  the  chaffinch.  The  i:irst  experiment 
gave  a  doubtful  result,  but  a  repeat  in  1956  resulted  (Fig.  10)  in  the 
achievement  of  a  remarkably  good  copy  by  such  a  chaffincli  of  the  song 
of  the  tree  pipit,  producing  a  chaffinch  song  entirely  unlike  any  other 
uttered  in  my  experience  by  a  wild  or  hand-reared  bird.  It  is  of  interest  to 
note  that  the  rather  long  song  of  the  model  has  been  condensed  to  conform 
to  the  standard  length  of  chaffinch  song  by  condensing  the  middle  phrase 
of  the  tree  pipit  song  to  two  notes  instead  of  tour.  This  song  became  still 
further  'tightened  up'  and  shortened  by  the  beginning  of  May  (Fig.  i  i). 

The  reason  why  chaffinches  do  not  imitate  and  acquire  songs  from  other 
species  in  the  wild  now  seems  fairly  evident.  There  is  little  doubt  that  they 
restrict  their  imitativeness  to  the  right  models  as  a  result  of  being  respon- 
sive only  to  notes  of  approximately  the  right  tonal  quality.  It  is  interesting 
that  the  imitation  of  the  tree  pipit  song  just  referred  to  is  the  best  copy  of  an 
alien  song  so  far  obtained.  Here  the  tonal  quality  of  the  model  was  right, 
although  the  song  itself  was  much  too  long  and  the  phrasing  of  the  notes 
of  the  model  abnormal  from  a  chaffinch  point  of  view. 

To  summarize  this  work  with  the  'song  tutor',  it  can  be  said  that  in 
eleven  experiments  carried  out  over  the  years  1955-57  a-i^d  involving 
thirty-four  wild  autumn-caught  first-year  males,  the  only  positive  effect 
obtained  (in  the  sense  of  a  significant  similarity  between  model  and 
mimic)  occurred  in  two  experiments  (seven  birds)  only,  and  in  these  two 
the  model  was  a  normal  chaffinch  song.  Of  the  remaining  ones  (nine 


BRAIN    MECHANISMS    AND    LEARNING 


experiments,  twenty-seven  birds)  the  models  were  always  abnormal  — 
the  songs  being  artificial,  re-articulated  or  reversed  —  and  the  results  were 
always  negative.  The  contrast  when  hand-reared  isolated  birds  are  used  is 


AAA  A 


\ 


3-0 


Fig.  9 
Song  of  Continental  tree  pipit  {Aiithtis  trividlii)  used  for  tutoring 


Fig.  10 

'Copy'  of  tree  pipit  song  produced  by  chaffinch  R/R  after  tuition 

on  'song  tutor'.  Apnl  21st,  1956. 


mxnt 


Fig.  II 
'Improved'  tree  pipit  copy.  R/R,  May  3rd,  1956. 


Striking.  Thus  during  1954-59,  thirteen  experiments  involving  sixteen 
hand-reared  birds  were  carried  out  using  similar  song  models.  Of  these, 
ten  experiments  (eleven  birds)  were  positive,  in  the  sense  of  yielding  a 


W.    H.    THORPE  89 

iignihcant  effect.  The  remaining  three  experiments  (tive  birds)  gave  a 
negative  result. 

The  counter-singing  that  occurs  between  birds  in  adjacent  territories  is 
an  important  factor  in  stimulating  and  restricting  the  imitative  abilities  of 
chaffinches.  When  a  chaffinch  has  acquired  more  than  one  song-type,  each 
song-burst  consists  of  a  sequence  of  one  song-type  followed  by  a  sequence 
of  another.  When  songs  are  played  back  to  a  chatiinch,  we  find  that  those 
songs  which  it  uses  most  frequently  itself  arc  the  most  effective  in  evoking 
song  (Hinde,  1958).  A  chaffinch  in  the  wild  will  thus  tend  to  reply  to  a 
neighbour  with  that  song  of  its  own  repertoire  which  most  nearly 
resembles  the  song  of  its  rival. 

It  is  suggested  that,  with  the  more  'imitative'  finches,  such  as  the  bull- 
finch [Pynhuhi  pyrrliiila),  hawfinch  [Coccothratistcs  coccotliriiiistes)  and  to 
some  extent  greenfinch  [Cliloris  cliloris),  the  song,  while  functional  in  co- 
ordinating the  breeding  cycle  and  behaviour  of  the  mated  pair,  is  of  less 
importance  as  a  territorial  proclamation.  Thus  in  some  respects  it  re- 
sembles the  sub-song  rather  than  the  full  song  of  the  chafimch;  similarly, 
contamination  with  alien  notes  can  be  tolerated  to  an  extent  which  might 
be  very  disadvantageous  in  a  strongly  territorial  song  that  must  maintain 
its  character  as  a  reliable  specific  recognition  mark.  A  preliminary  study  of 
a  number  of  species  of  buntings  shows  that  many  of  the  species,  for 
example  reed  and  corn  buntings  [Embcriza  schociiichis  and  E.  calaiidrn), 
have  songs  which  arc  highly  stereotyped  and  completely  innate.  The  song 
of  the  yellow  bunting  (R  citriiiclla)  appears  to  consist  of  an  integration  of 
innate  and  learned  components  much  as  in  the  chaffinch.  The  buntings  as 
a  whole  appear  to  have  strongly  territorial  songs  corresponding  to  that  of 
the  chaffinch  in  function. 

Apart  from  a  very  few  and  partial  exceptions,  chatiinches  can  learn  song 
patterns  only  during  the  first  1 3  months  of  life,  and  towards  the  end  of 
this  time  there  is  a  peak  period  of  learning  activity  of  a  few  weeks  during 
which  a  young  chaffinch  may  learn,  as  a  result  of  singing  in  a  territory,  the 
fine  details  of  as  many  as  six  different  songs.  This  special  period  of  high 
learning  ability  is  brought  to  an  abrupt  close  by  internal  factors.  It  matters 
not  whether  a  chaffinch  has  learned  one  or  six  songs  by  the  time  it  is 
13  months  old,  it  can  afterwards  learn  no  more,  and  so  remains  with  its 
one  song  or  its  six  for  the  rest  of  its  life.  This  restriction  of  learning  ability 
to  a  particular  type  of  object  and  to  a  sharply  defined  sensitive  period 
recalls  the  phenomenon  of  imprinting. 

The  inborn  recognition  and  performance  of  its  specific  song  by  the 
chaffinch  involves  (a)  duration  of  approximately  2^  seconds,  (h)  interval 


90  BRAIN    MECHANISMS    AND    LEARNING 

between  songs  of  between  6  and  20  seconds,  (c)  tonal  quality  (though  this 
last  may  have  been  learned  by  the  experience  of  the  bird  of  the  qualities 
of  its  own  voice).  The  readiness  with  which  the  bird  learns  to  divide  its 
song  into  three  sections  and  learns  to  attach  a  simple  flourish  at  the  end  as 
an  appropriate  termniation  shows  that  there  must  be  an  imperfectly 
inherited  tendency  to  respond  to,  and  perform,  tlie  features  of  the  normal 
song  as  soon  as  the  singer  is  stimulated  by  hearing  another  bird.  Such  an 
inherited  tendency  would  explain  the  basic  similarity  of  the  songs  of  the 
species  throughout  its  range. 

In  conclusion,  I  believe  that  recent  studies  of  bird  behaviour  have  added 
a  considerable  body  of  evidence  in  support  of  the  view,  now  being 
advanced  from  many  quarters  (sec  Thorpe  &  Zangwill,  i960)  that  in 
regard  to  both  learned  and  innate  behaviour  patterns  the  organism  is  to  be 
regarded  as  'searching'  largely  for  cues  and  stimuli,  consummatory 
situations  in  fxct,  rather  than  for  the  release  of  consummatory  acts.  This 
is  to  say  that  the  'goal'  of  the  behaviour  is  not  solely  or  even  primarily  the 
discharge  of  a  specific  motor-nicchanism  but  the  achievement  of  a 
specific  sensory  stimulation.  Moreover,  in  this  connection  we  must 
remember  that  the  animal  perceives  its  own  consummatory  acts  primarily 
through  its  own  interoceptors  and  proprioceptors,  and  that  in  the  majority 
of  cases  at  least  it  is  again  a  special  pattern  of  sensory  stimulation,  a  re- 
afference,  which  is  the  effective  reward  and  not  simply  the  general  level  of 
well-being  or  activity  resulting  from  the  concomitant  adjustment  of 
nutritional  or  endocrine  balance. 


GROUP   DISCUSSION 

Magoun.  1  am  trying  to  relate  this  behaviour  to  mechanisms  ot  the  brain.  It  is 
possible  in  the  cat  and  in  the  inonkey  to  introduce  electrodes  into  the  peri-aqucductal 
grey  or  the  tegmentum  of  the  midbrain  and  by  repetitive  stimulation  to  evoke 
flicio  vocal  responses  which  are  identical  with  the  normal  expression  of  emotion  by 
these  animals.  These  can  be  elicited  when  the  brain  stem  is  transected  just  ahead  of 
this  region,  so  evidently  one  is  not  exciting  an  ascending  pathway  to  some  higher 
level.  After  this  region  of  the  cephalic  brain  stem  is  destroyed  elcctrolytically,  the 
cat  no  longer  vocalizes  in  response  to  an  adequate  environmental  stimulus.  This 
suggests  that  there  is  built  into  this  part  of  the  brain  a  mechanism  for  faciovocal 
performance  in  the  expression  of  emotions,  to  be  differentiated  from  the  speech- 
mechanisms  that  have  developed  in  the  association  cortex  in  the  dominant  hemi- 
sphere of  man.  This  had  led  me  to  wonder  whether  it  would  be  possible,  by  intro- 
ducing electrodes  into  the  midbrain,  to  evoke  those  patterns  of  vocal  performance 
which  you  point  out  as  being  so  specific  for  individual  birds.  Have  experiments 
along  those  lines  been  tried?  Do  you  think  they  might  be  feasible; 

Thorpe.  Yes,  stinnilation  experiments  are  being  performed,  but  not  so  tar  with 


W.    H.    THORPE  91 

song  birds  which  arc,  ot  course,  very  active  and  mostly  small.  We  have  started 
some  ablation  experiments  with  song  birds,  but  these  have  not  got  very  far  yet.  It 
is  as  yet  very  difficult  to  stimulate  the  brain  of  a  very  small  bird  so  that  it  will  behave 
in  a  fairly  normal  fashion  and  still  sing.  I  think  it  will  be  some  rime  before  the 
technique  is  developed  to  the  point  at  which  signihcant  results  will  begin  to  accrue. 

Fessard.  What  about  parrots  f 

Thorpe.  Parrots  should  certainly  be  easier  to  investigate  but,  although  they  have 
of  course  an  astonishing  facility  for  vocal  mimicry,  would  not  be  much  good  tor 
the  study  of  the  innate  sounds.  In  this  matter  of  vocal  imitation  the  Indian  hill 
mynah  excels  even  the  parrots.  But  perhaps  the  most  puzzling  feature  is  that 
neither  parrots  nor  mynahs  appear  to  use  their  power  of  mimicry  in  the  wild  at  all 
(Thorpe,  1959).  They  have  stereotyped  cries  and  calls  which  seem  to  serve  tor 
co-ordinating  the  movements  oi  the  tiock  but  show  no  sign  of  mimicry.  From  the 
point  of  view  of  the  study  of  vocal  learning  these  species  would  be  admirable;  but 
not  for  studying  mechanisms  tor  innate  sound  production. 

BusER.  It  might  be  of  interest  to  mention  here  observations  made  in  Paris  by 
Dr  Rougeul  and  Dr  Assenmacher,  studying  the  electrical  activity  of  deep  brain 
structures  in  unanacsthetized  ducks  by  stereotaxic  methods:  each  time  when  simply 
introducing  or  moving  up  and  down  the  Horsley-Clarke  electrode,  the  animal 
would  start  quacking  whenever  a  certain  level  was  reached.  King  in  the  tegmental 
midbrain.  Electrical  stimuli  were  not  systematically  tried  and  the  mechanical 
excitation  produced  h\  the  electrode  appeared  actualK'  surticient  to  produce  the 
described  effect. 

KoNORSKl.  I  would  like  to  make  two  comments.  The  tirst  one  is  this:  As  far  as  I 
know,  only  birds,  and  among  mammals  only  man,  have  the  ability  ot  reproducing 
sounds,  i.e.  they  possess  what  mav  be  called  acoustic-vocal  reflexes  of  a  specitic 
kind.  This  ability  seems  to  indicate  that  in  these  animals  direct  connections  exist 
between  the  acoustic  area  and  the  part  of  motor  area  concerned  with  vocalization. 
We  know  that  in  man  such  connections  in  fict  exist  between  anterior  temporal 
area  and  frontal  opercular  region.  If  the}-  are  destroyed  the  peculiar  torm  of 
asphasia  ensues.  The  patient  understands  what  is  said  to  him  and  is  even  able  to 
verbalize  his  thoughts,  but  he  is  not  able  to  repeat  exactly  the  words  he  hears.  It  is 
much  easier  for  him  to  say  something  spontaneously  than  to  repeat  it.  It  would  be 
very  interesting  to  know  whether  such  an  acoustic  vocal  system  exists  in  birds,  and 
if  so,  to  study  it  both  from  anatomical  and  physiological  points  ot  view. 

The  second  point  concerns  the  problems  of  imprinting.  We  know  trom  exten- 
sive experimental  data  (the  literature  is  given  in  a  paper  by  Konorski  and  SzweJ- 
kowska,  1952)  that  classical  conditioning  shares  one  important  property  with 
imprinting,  namely  its  partial  irreversibility.  By  the  way,  this  is  why  I  do  not  like 
the  term  'temporary  connections'  because  these  connections,  once  established,  are 
not  temporary  but  stable,  and,  as  I  shall  discuss  later,  they  are  not  obliterated  by 
'disuse'.  If  you  elaborate  an  alimentary  conditioned  reflex  to  some  stimulus,  it  is 
much  more  difficult  to  transform  it  afterwards  into,  say,  a  detensive  conditioned 
stimulus  b}'  changing  the  reinforcement  trom  tood  to  shock,  than  to  elaborate  the 
defensive  conditioned  reflex  to  quite  a  new  stimulus.  Even  after  a  long  defensive 
training  of  the  alimentary  conditioned  stimulus,  its  previous  alimentary  role  may 
be  detected.  We  explain  these  facts  by  saying  that  the  old  conditioned  connections 
established  between  the  central  representation  of  the  conditioned  stimulus  and 


92  BRAIN    MECHANISMS    AND    LEARNING 

feeding  centre  are  by  no  means  removed  by  the  new  training  but  the  new  connec- 
tions are  formed  independently  of  them. 

This  suggests  a  form  of  continuity  between  the  inborn  reflexes,  imprinting  and 
normal  conditioning  and  shows  that  there  arc  perhaps  no  sharp  limits  between 
these  phenomena.  Experiments  made  long  ago  in  Pavlov's  laboratory  by  Citovitch 
are  also  relevant  here.  This  author  found  that  the  alimentary  reflex  to  the  smell  of 
tood  is  not  inborn  but  conditioned  because  it  appears  only  after  a  few  reinforce- 
ments of  the  stimulus,  but  this  reflex  is  established  very  rapidly  and  is  then  very 
stable.  I  think  that  we  could  label  this  phenomenon  either  as  conditioning  or  as 
imprinting. 

Thorpe.  Some  experiments  have  been  done  with  deafened  birds  by  Schwartakoft 
and  Messmer.  The  production  of  the  essential  elements  in  an  innate  song  is  not 
fundamentally  affected  by  being  deafened  but  there  may  be  a  change  in  the  overall 
'pitch'  of  the  song.  This  seems  to  provide  a  sharp  distinction  from  conditioning. 

EsTABLE.  In  certain  species  of  birds,  males  sing  more  and  more  and  differently 
when  exliilarated  by  the  presence  of  the  female  or  when  after  being  in  the  neigh- 
bourhood of  the  female  the  latter  is  removed  from  his  sight.  Hormonal  influences 
have  been  mentioned  as  possible  explanation  of  this,  but  though  they  are  probably 
necessary,  they  cannot  be  suflicient  to  explain  the  production  ot  such  a  variety  oi 
songs.  Besides,  an  exclusively  endocrine  mfluence  cannot  explain  the  flict  that  the 
male  sings  better  than  the  female;  the  nervous  system  and  tlie  sound-producing 
apparatus  must  necessarily  participate. 

When  the  male  bird  is  in  the  presence  of  the  female,  it  sings ;  if  the  latter  is  removed, 
it  sings  even  more.  When  the  female  is  absent  it  stops  singing.  What  happens  in 
the  brain  of  the  male  bird  would  be  interesting  to  know.  Is  there  some  endocrino- 
logical influence  in  the  mechanism  of  the  brain  which  conditions  this  behaviour ; 
For  example,  the  problem  of  the  gestalt  theory  if  the  conditioned  reflex  is  the 
cause,  if  it  is  first  or  second.  I  have  talked  on  this  subject  with  Kohler,  who  was  a 
pioneer  in  this  field.  He  believes  that  the  gestalt  structures  precede  conditioning. 

Segundo.  To  complement  the  observation  of  Dr  Baser  I  would  like  to  note  that 
we  have  implanted  electrodes  in  the  mesencephalon  of  the  Tero  bird  [Beleuopterus 
chilciisis).  Electrical  stimulation  with  threshold  voltage  produced  investigation  or 
orientation  movements;  with  higher  voltages,  the  bird  stretched  its  wings,  started 
to  fly  and  in  addition,  squawked  loudly.  (Silva,  Estable  and  Segundo,  unpublished 
observations.) 

Grastyan.  a  marked  following  reaction  could  be  observed  in  some  oi  our 
experiments  by  stimulating  the  hypothalamus  in  cats.  This  behaviour  seemed  to  be 
also  in  close  correlation  with  the  function  of  the  rhinencephalon.  You  say  that 
there  is  a  limited  period  of  the  animal's  life  when  this  reaction  can  occur  naturally. 
In  which  stage  of  maturation  of  the  central  nervous  system  does  this  reaction  occur? 
Which  structures  are  responsible  for  its  integration  in  the  birds? 

Doty.  I  have  seen  this  following  reaction  consistently  in  cats  deprived  of  all 
visual  cortex  in  infancy.  They  will  approach  and  follow  moving  acoustic  stimuli 
and  persist  in  this  activity  for  minutes. 

Grastyan.  l^r  Adey  has  made  similar  observations,  after  the  destruction  ot  the 
cntorhinal  cortex  in  the  marsupial  phalanaen. 

Adey.  After  a  limited  reaction  of  the  hippocampus  cortex  which  forms  the 
entorhinal  area.  The  animal  was  tamed  and  at  the  same  time  would  follow  anv 


W.    H.    THORPE  93 

moving  object.  This  was  not  accompanied  by  any  aggressive  behaviour  towards 
the  object  they  were  following.  They  normally  attack  with  jaws  or  teeth  objects 
that  come  within  the  visual  field.  This  ceases  after  ablation  of  the  entorhinal  cortex. 

Magoun.  I  am  glad  to  hear  reference  to  the  rhinencephalic  or  limbic  brain  in 
this  connection  because  I  think  attention  should  be  called  to  the  generalizations  of 
Paul  Maclean  that  this  part  of  the  C.N.S.  is  concerned  with  these  types  of  behaviour 
which  preserve  the  individual  on  feeding  or  aggression  or  defence,  and  which 
preserve  the  race  by  managing  sexual  behaviour. 

Hernandez-Peon.  The  curves  that  Dr  Thorpe  showed  us  concerning  the  rate 
ot  development  of  internal  inhibition  may  explain  the  great  individual  variation 
observed  during  experimentally  induced  habituation.  I  wonder  if  he  could  elabo- 
rate the  matter  further  and  tell  us  what  is  the  presently  available  evidence  obtained 
by  using  a  systematic  approach.  Wliat  kind  of  responses  have  been  tested  and 
which  animals  have  been  studied  f 

Thorpe.  The  subjects  were  all  birds  ot  tlie  following  species:  Canary  {Scriiiiis  c. 
caiiariiis).  Greenfinch  {Cliloris  chloris)  and  Great  Tit  [Pants  itiajor).  These  curves  refer 
to  string-pulling  behaviour  and  to  learning  to  take  food  from  two  types  of  dishes, 
one  with  a  black  lid  and  one  with  a  white  one.  In  the  string  pulling  the  wild  bird, 
it  it  learns  the  trick  at  all,  often  behaves  with  extreme  precision  and  the  whole 
movement  appears  highly  organized.  In  experimental  studies,  however,  the  birds 
present  very  varied  behaviour.  This,  we  hope,  will  be  explained  in  the  future  as  a 
result  of  this  discovery  of  the  diiferent  rates  of  change  of  these  factors,  namely  the 
level  of  responsiveness  and  of  internal  inhibition,  which  arc  themselves  partly  an 
expression  of  the  previous  experience  of  the  bird. 


SOME  ASPECTS  OF  THE  ELABORATION  OF 

CONDITIONED  CONNECTIONS   AND   FORMATION  OF 

THEIR  PROPERTIES 

E.    A.    ASRATYAN 

Much  in  the  field  of  conditioned  reflexes  was  achieved  by  Ivan  Pavlov 
and  his  pupils  and  by  his  other  followers  ni  many  countries  of  the  world. 
Nevertheless,  many  aspects  of  this  problem  have  not  yet  been  satisfactorily 
investigated  and  require  further  experimental  study  and  theoretical 
elaboration.  At  present,  many  scientists  in  the  U.S.S.R.  and  elsewhere 
are  studying,  as  Pavlov's  scientific  heritage,  the  elaboration  of  conditioned 
reflexes,  the  formation  of  their  properties,  their  preservation,  anc^  the 
significance  of  various  factors  acting  favourably  on  these  processes.  My 
collaborators  and  myself  are  among  them. 

At  present  the  main  trend  of  our  experimental  and  theoretical  investiga- 
tions in  this  field  is  the  study  of  the  role  of  the  strength  of  stimuh  and 
their  sequence  in  the  elaboration  of  conditioned  reflexes  and  the  formation 
of  their  properties.  The  purpose  of  this  paper  is  to  report  our  findings  and 
present  our  interpretation  of  them. 

The  important  role  played  by  the  relative  strength  of  the  excitatory 
processes  which  take  place  in  nervous  structures  and  especially  in  the  cor- 
tex, is  generally  known.  Pavlov  has  stated:  'Prime  importance  must  be 
ascribed,  of  course,  to  strength  relations  in  the  activity  of  the  cortex.'^  He 
also  repeatedly  emphasized  the  great  importance  of  the  pattern  of  com- 
binations of  stimuli  in  time  for  the  elaboration  of  conditioned  reflexes.  He 
stated  that  'since  conditioned  stimuli  play  the  role  of  signals,  they  must 
become  effective  only  wlien  they  precede  the  signalized  physiological 
activity. '- 

Our  collaborators  investigated  these  problems  in  dogs  in  the  usual 
semi-soundproof  chambers  designed  for  the  study  of  conditioned  reflexes. 
In  order  to  elaborate  conditioncc^  reflexes  with  definite  functional  pro- 
perties, we  combined  in  various  ways  either  two  so-called  'indifferent' 
stimuli,  or  two  different  unconditioned  stimuli,  or  one  'indifferent'  and 
one  unconditioned  stimulus.  The  characteristic  feature  of  our  experiments 

^  I.  P.  Pavlov,  Complete  Works,  vol.  Ill,  1949,  p.  382. 
- 1.  P.  Pavlov,  Complete  Works,  vol.  Ill,  1949,  p.  381. 

95 


96  BRAIN    MECHANISMS    AND    LEARNING 

was  the  attempt  to  select  and  apply  only  those  'indifferent'  stimuli  which 
provoke  in  experimental  animals  reflex  reactions  which  can  be  objectively 
observed  and  graphically  recorded. 

I.  In  1958,  our  collaborators  Varga  and  Pressman  pertormed  a  scries 
of  experiments  in  dogs  in  which  they  combined  two  so-called  'indifferent' 
stimuli,  namely,  a  sound  and  a  passive  lifting  of  the  animal's  leg.  In  some 
of  these  experiments  stimuli  were  always  applied  in  the  same  stereotyped 
sequence,  m  others  in  a  variable  sequence.  The  advantage  of  a  passive 
movement  of  the  leg  as  one  of  the  'indifferent'  stimuli  is  that  it  gives 
direct  and  immediate  indication  of  a  connection  between  the  combined 
stimuli  when  the  movement  of  the  leg  or  the  electromyogram  of  its 
muscles  is  observed.  In  addition,  with  these  indicators  the  investigators 
were  able  to  study  directly  the  whole  process  of  formation  of  conditioned 
connections  when  these  stimuli  are  combined  from  the  very  beginning  of 
the  connections  to  any  subsequent  stage  of  their  evolution. 

((?)  In  experiments  by  previous  investigators  of  this  problem  (Podko- 
payev  and  Narbutovich  (1936),  ZeHony  (1928),  Oreshuk  (1950),  Roko- 
tova  (1952),  Karmanova  (1955),  Bregadzc  (1956),  Sergeyev  (1957)  and 
others,  this  was  not  possible.  The  reason  was  that  they  used  only  the 
method  of  intermediated  and,  besides,  sporadic  indication  ot  the  process 
of  elaboration  of  connections  between  'indifferent'  stimuli.  Data  obtained 
by  Varga  and  Pressman  clearly  show  that  between  the  brain  points  of 
these  stimuli  a  double  (or  two-way)  'associative  connection',  i.e.  actually 
a  conditioned  reflex  connection  is  established.  This  occurs  not  only  when 
sound  and  passive  lifting  of  the  animal's  leg  are  combined  in  a  variable 
sequence,  but  also  when  they  are  combined  in  a  stereotyped  one.  (Fig.  i) 
Further,  in  the  course  of  their  experiments,  Varga  and  Pressman  also 
obtained  data  which  on  the  one  hand  corroborate  facts  previously  estab- 
lished by  other  workers,  and  on  the  other  are  new.  For  example,  they  have 
shown,  in  conformity  with  the  findings  of  other  authors,  that  the  connec- 
tions between  'indifferent'  stimuli  are  characterized  by  extreme  fragility 
and  instability.  After  being  established,  they  rapidly  begin  to  weaken  and 
soon  disappear  after  a  period  of  more  or  less  regular  function.  They 
recover  again  for  a  very  short  time  but  only  after  a  certain  interval, 
during  the  experiment,  or  when  an  alimentary  conditioned  reflex  has  been 
elaborated  in  response  to  one  of  the  combined  stimuli. 

(/;)  At  the  same  time  the  experiments  of  Varga  and  Pressman  established 
other  facts  which  illustrate  the  great  signiticancc  of  a  detnntc  sequence  in 
combining  stinndi.   Their  experimental   data  show  that  although   the 


E.    A.    ASRATYAN  97 

above-mentioned  properties  —  fragility  and  instability  —  are  characteristic 
for  both  conditioned  connections  between  the  brain  points  of  two  stimuli, 
they  are  not  inherent  in  these  reflexes  in  an  equal  measure.  When  sound 
and  passive  lifting  of  the  animal's  leg  are  combmed  in  a  variable  sequence, 
the  conditioned  connections  arising  between  them  are  almost  equivalent 
in  their  rate  of  formation,  consolidation,  stability,  resistance  to  extinction, 
etc.  But  when  these  stimuli  are  combined  in  a  stereotyped  sequence,  the 
resulting  conditioned  connections  essentially  difi^er  from  each  other  in  all 
of  the  above-mentioned  criteria.  A  direct  or  forward  conditioned  connec- 
tion, i.e.  a  connection  leading  from  the  preceding  stimulus  (P)  to  the 


/  iii»iw>h>i)iiit"'i ^.i^M>^^  *>iiit->41ii4»>iHi 

Z  ZZZ^ZZI 


I 

Fig.  I 
Conditioned  connections  resulting  from  various  combinations  of  a  sound  and  a  passive  lilting 
of  the  dog's  leg.  (a)  Active  lifting  of  the  leg  (indicated  by  the  rarefiction  or  disappearance  of 
electrical  potentials  in  the  extensor  of  the  leg,  i.e.  in  the  gastrocnemius  muscle)  in  response  to 
the  application  of  a  tone  after  its  thirty-seven  combinations  with  a  passive  lifting  of  the  leg  in 
the  stereotyped  sequence:  'tone  —  passive  lifting  of  the  leg' ;  (fo)  reaction  to  a  tone  after  twenty- 
eight  combinations  of  a  passive  lifting  of  the  leg  with  this  tone  in  experiments  with  a  reverse 
sequence,  i.e.  'passive  lifting  of  the  leg  —  tone'. 

I.  —  clectromyogram  of  the  gastrocnemius  muscle;  2.  —  mark  of  conditioned  stimulation. 

subsequent  one  (S)  becomes  elaborateci  more  easily  and  is  more  powerful 
and  resistant  to  extinction  and  other  altering  factors,  than  a  reverse  or 
backward  conditioned  ct^nnection,  i.e.  a  connection  leading  from  S  to  P. 
Further,  a  direct  connection  recovers  more  rapidly  than  a  reverse  one 
after  an  acute  extinction  or  when,  following  their  natural  disappearance, 
a  break  is  made  in  the  experiment,  or  when  one  of  the  combined  stimuli 
turns  into  an  alimentary  conditioned  signal.  Essentially  similar  results 
were  obtained  by  Varga  and  Pressman  in  a  series  of  experiments  on  other 
dogs  in  which  they  combined  passive  lifting  of  the  animal's  leg  with  the 
blowing  of  air  into  the  animal's  eye  which  evoked  the  blink  reflex.  The 
advantage  of  the  combination  of  these  two  stimuli  over  those  applied  in 
the  previously  described  experiments  was  that  both  stimuli  (and  not  only 


BRAIN    MECHANISMS    AND    LEARNING 


one  of  them)  called  forth  effects  which  could  be  recorded  objectively. 
Moreover,  as  shown  in  the  course  of  the  experiments,  the  new  stimulus,  a 
puff  of  air  in  the  animal's  eye,  applied  in  the  given  combination,  proved 
to  be  stronger  than  the  stimulus  (sound)  applied  in  the  previous  combina- 
tion. With  this  technique,  it  proved  possible  to  demonstrate  the  elabora- 
tion of  direct  and  reverse  connections  in  a  more  distinct,  graphic  and  what 
is  particularly  important,  direct  form.  This  was  possible  both  when  one 
of  the  combined  stimuli  was  applied  first  in  stereotyped  sequence,  and 


/  mmm 


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28.  U 3. 5 9 


m 


ff4'**.y^'y)l»  ^i|ii^pMi»^^l§ii^ 


Fig.  2 
A  two-way  connection  resulting  from  the  combination  of  a  passive  lifting  of  the  leg  with  the 
blowing  of  air  into  the  eye.  {a)  A  conditioned  motor  reflex  arising  when  the  combination  is 
applied  in  the  stereotyped  sequence  —  'blowing  of  air  into  the  eye  —  passive  lifting  of  the  leg'. 
In  response  to  the  blowing  of  air  into  the  eye  [d)  the  dog  blinks  and  lifts  the  leg  which  is 
testified  to  by  the  disappearance  of  action  potentials  in  the  gastrocnemius  muscle.  The  lifting 
of  the  leg  (p.p.)  is  again  accompanied  by  blinking  which  testifies  to  a  reverse  connection; 
(/))  A  conditioned  eyelid  reflex  arising  when  the  combination  is  applied  in  the  stereotype 
sequence  'passive  lifting  of  the  leg  —  blowing  of  air  into  the  eye'.  In  response  to  the  passive 
lifting  of  the  leg  (p.p)  the  dog  blinks.  After  the  blowing  of  air  into  the  eye  ((/)  there  is  observed, 
along  with  the  blinking,  a  disappearance  of  action  potentials  in  the  gastrocnemius  muscle, 
which  testihes  to  a  reverse  connection. 

I.  —  action  potentials  of  the  gastrocnemius  muscle;  i.  —  movement  of  the  eyelids;  3.  — 
marks  of  stimulation  (long  line  —  passive  lifting  of  the  leg;  short  line  —  blowing  of  air  into  the 
eye). 

when  the  other  stimulus  was  applied  first  (Fig.  2).  As  a  puff  of  air  in  the 
animal's  eye  proved  to  be  a  stronger  stimulus  than  sound,  the  direct 
conditioned  connections  were  much  more  stable  than  when  sound  was 
combined  with  a  passive  lifting  ot  the  animal's  leg.  To  some  extent  this 
also  applies  to  reverse  conditioned  connections. 

II.  New  facts  related  to  this  problem  were  established  by  Lyan-Chi-an, 
who  continued  the  investigation  of  a  very  pressing  problem  which 
Varga  (1953)  had  previously  studied  in  our  laboratory. 

Using  dogs,  Varga  combined  in  a  strictly  alternating  sequence  two 


E.    A.    ASRATYAN  99 

classical  unconditioned  stimuli  of  moderate  intensity,  namely,  presentation 
of  food  and  electrical  stimulation  of  the  leg.  She  established  the  possibility 
of  elaborating  a  stable  double  (or  two-way)  conditioned  connection  be- 
tween cerebral  nervous  structures  corresponding  to  these  two  stimuli.  It 
should  be  noted  that  under  standard  experimental  conditions  (strictly 
alternating  sequence  of  combination  of  stimuh,  relative  equality  of  their 
intensity,  observance  of  the  routine  conditions  of  maintenance  of  the 
experimental  animal,  etc.)  these  conditioned  connections  are  practically 
equivalent  as  regards  sign,  strength,  stability  and  so  on. 

On  the  contrary,  in  the  experiments  of  Lyan-Chi-an,  two  unconditioned 
stimuli  were  combined  in  a  stereotyped  sequence.  In  other  words,  he 
combined  in  a  stereotyped  sequence  a  defensive  motor  reflex  of  a  fore-leg, 
evoked  by  applying  an  electric  shock  of  moderate  intensity,  with  an 
alimentary  reflex  to  the  presentation  of  a  moderate  portion  of  powdered 
meat  and  bread.  In  certain  series  of  experiments,  performed  on  one  group 
of  dogs,  application  of  the  electric  shock  preceded  presentation  of  food, 
while  in  other  series,  performed  on  another  group,  presentation  of  food 
preceded  application  of  the  electric  shock.  Both  series  of  experiments 
yielded  essentially  similar  results  which  agree  in  some  respects  with  the 
data  of  Varga  and  of  Pressman  and  Varga,  but  differ  in  some  essential 
points.  In  the  experiments  of  Lyan-Chi-an,  double  (or  two-way)  con- 
ditioned reflex  connections  between  the  brain  points  of  the  combined 
unconditioned  stimuli  were  also  formed.  This  is  shown  in  Figs.  3  and  4. 
However,  here  also,  as  in  the  similar  Varga  and  Pressman  experiments, 
direct  and  reverse  conditioned  comiections  between  these  points  were  far 
from  being  equivalent.  In  comparison  with  Varga  and  Pressman's 
experiments  those  of  Lyan-Chi-an  showed  a  considerably  more  pro- 
nounced difference  in  the  rate  of  elaboration  of  conditioned  connections 
leading  from  the  preceding  (P)  to  the  subsequent  (S)  stimulus,  than  from 
(S)  to  (P).  In  both  scries  of  Lyan-Chi-an's  experiments,  the  direct  condi- 
tioned reflex  connection  between  the  combined  unconditioned  stimuli  is 
formed  sHghtly  more  rapidly  than  the  reverse  conditioned  reflex  connec- 
tion. This  connection  is  also  of  much  greater  strength  and  stability  and  is 
characterized  by  a  considerably  greater  regularity  than  the  reverse  connec- 
tion. In  contradistinction  to  a  direct  connection  between  two  indifferent, 
i.e.  physiologically  weak  stimuli,  a  direct  connection  between  two  un- 
conditioned, i.e.  physiologically  strong  stimuli,  forms  easily,  consolidates 
increasingly  from  day  to  day  and  persists  if  the  conditions  which  have 
given  rise  to  it  are  maintained;  namely,  when  these  stimuli  are  combined 
in  the  given  sequence. 

H 


100 


BRAIN   MECHANISMS    AND    LEARNING 


-J i i 


JLJil.7wt^vvlc/--VL. 


~13         V 


Fig.  3 

An  alimentary  conditioned  reflex  to  an  electric  current.  A  dog  to  which  an  electric  current 
and  the  presentation  of  food  were  applied  in  the  stereotyped  sequence  'electric  current  — 
food'.  (<i)  A  conditioned  salivary  alimentary  reflex  to  the  application  of  electric  current 
(direct  connection) ;  (/))  movements  of  the  leg  during  the  presentation  of  the  food  receptacle 
(reverse  connection). 

From  top  to  bottom:  i.  —  mcchanogram  of  movement  of  the  left  foreleg;  2.  —  mechanogram 
of  masticating  movements;  3.  —  salivation  in  drops;  4.  —  mark  of  electro-cutaneous  stimula- 
tion; 5.  —  mark  of  presentation  of  the  food  receptacle;  6.  —  time  in  seconds. 


/LAjL_4L-/iLJL 


i 


Fig.  4 

Electro-defensive  motor  reflex  to  presentation  of  food.  A  dog  to  which  presentation  of  food 
and  electrical  current  were  applied  in  the  stereotyped  sequence  'food  —  electric  current'. 
((7)  A  conditioned  motor  defensive  reflex  to  the  end  of  the  act  of  eating  (direct  connection); 
(/))  a  conditioned  alimentary  reaction  to  the  electric  current  (reverse  connection). 

From  top  to  bottom:  i.  —  mechanogram  of  movements  of  the  left  foreleg;  2.  —  mechanogram 
of  movements  of  the  right  foreleg;  3.  —  mechanogram  of  masticating  movements;  4.  —  saliva- 
tion in  drops;  5.  —  mark  of  electro-cutaneous  stimulation;  6.  —  mark  of  presentation  of  the 
food  receptacle;  7.  —  time  in  seconds. 


E.    A.    ASRATYAN  lOI 

The  matter  is  entirely  different  with  a  reverse  conditioned  reflex  connec- 
tion between  unconditioned  stiniuh.  They  greatly  resemble,  especially 
in  their  fragility  and  irregularity,  conditioned  connections  between  in- 
different stimuli.  It  must  be  pointed  out  that  a  reverse  connection,  is  so 
feeble,  so  unstable,  multiphasic  and  diverse  in  its  manifestations  and 
depends  on  so  many  factors  for  its  functioning  that  initially  we  even 
doubted  its  conditioned  reflex  nature. 

Some  of  the  peculiar  features  revealed  by  the  experiments  of  Lyan- 
Chi-an  in  the  functioning  of  reverse  conditioned  reflex  connections  are 
of  special  interest.  For  instance,  (S)  evokes  more  easily  the  reflex  corres- 
ponding to  (P)  if  the  strength  of  (P)  has  been  increased  or  if  the  excitability 
of  the  central  nervous  structures  is  raised.  By  strengthening  (P)  or  by 
an  increase  in  the  excitability  of  the  relevant  nervous  apparatus  it  becomes 
possible  to  revive  and  activate  the  reverse  conditioned  connections  even 
when  under  usual  experimental  conditions  they  cease  to  manifest  them- 
selves. A  similar  result  is  obtained  if  (S)  is  weakened,  or  the  excitability 
of  the  corresponding  nervous  structures  is  lowered.  For  example,  in  an 
experiment  in  which  stimuli  are  applied  in  the  sequences  'electrical  shock 
—  food',  the  presentation  of  food  evokes  a  conditioned  reflex  lifting  of 
the  animal's  leg  more  frequently  and  more  distinctly  if  the  leg  was 
previously  stimulated  by  a  stronger  shock  than  usual,  or  if,  prior  to 
the  experiment,  the  dog  was  deliberately  fed  to  satiety.  The  feature 
common  to  these  two  different  preliminary  experimental  manipulations 
is  that  they  both  lead  to  the  same  picture  of  relative  excitability  or 
excitation  of  the  central  nervous  structures  corresponding  to  these  two 
stimuli. 

In  contrast  to  this,  a  prehminary  strengthening  of  (S)  or  increase  in 
excitability  of  the  nervous  structures  corresponding  to  its  reflex  leads  to 
inactivation  of  the  nervous  connection  even  when  under  usual  experi- 
mental conditions  they  function  regularly  and  satisfactorily.  Similar 
results  are  obtained  by  a  preliminary  weakening  of  (P)  or  by  a  preliminary 
decrease  of  the  excitability  of  the  relevant  nervous  structures.  Let  us,  for 
example,  take  again  the  type  of  experiments  thoroughly  studied  by  Lyan 
Chi-an  in  which  stimuli  were  applied  in  the  sequence:  'electric  shock  — 
food'.  Here  the  presentation  of  food  evokes  no  conditioned  lifting  of  the 
leg  if  the  animal  is  in  a  state  of  fasting  before  the  experiment,  or  if  it  is 
given  appetizing  food  at  the  beginning  of  the  experiment,  or  if  its  leg  is 
first  stimulated  by  a  weak  electric  shock.  It  may  be  noted  that  although 
these  preliminary  experimental  manipulations  are  different,  they  have 
something  in  common:  in  different  ways  they  lead  to  the  creation  of  the 


102  BRAIN    MECHANISMS    AND    LEARNING 

same  picture  of  relative  excitability  or  excitation  of  the  central  nervous 
structures  of  these  two  stimuli. 

III.  New  and  interesting  data  obtained  by  our  collaborator  Struchkov 
(1958)  also  relate  to  the  problem  under  discussion.  While  elaborating 
conditioned  reflexes  in  dogs,  he  combined  'indifferent'  stimuli  with  an 
unconditioned  stimulus.  This  special  method  is  known  in  the  literature  as 
the  method  of  'covering'.  In  this  method  the  'indifferent'  stimuli  are 
applied  against  a  background  of  action  of  the  unconditioned  stimulus. 
Struchkov  used  food  as  an  unconditioned  stimulus  and  chose  only  those 
'indifferent'  stimuli  which  by  themselves  evoke  in  the  organism  specific 
reactions  that  can  be  objectively  observed  and  recorded.  For  example,  in 
one  series  of  experiments  he  applied  a  passive  lifting  of  one  of  the  dog's 
hind  legs  and  in  another  a  momentary  cooling  of  a  limited  area  of  the  skin 
on  one  side  of  the  animal's  body,  which  evokes  a  local  vasomotor  reaction. 
This  sequence  of  stimuli  was  applied  systematically  in  all  experiments  of 
each  scries.  The  following  very  interesting  facts  were  brought  to  light. 
After  repeated  combination  of  an  alimentary  reflex  with  one  of  the 
'indifferent'  stimuli,  presentation  of  food  alone  began  to  evoke  reactions 
peculiar  to  these  stimuli.  In  one  series  of  experiments  the  reaction  was  an 
active  lifting  of  the  leg,  and  in  another  a  local  vasomotor  reflex.  This  is 
shown  in  Fig.  5.  In  other  words,  in  Struckhov's  experiments  the  classical 
unconditioned  stimulus  —  food  —  played  the  role  of  a  conditioned  or 
signalling  stimulus,  while  the  so-called  'indifferent'  stimuli  —  passive 
movement  of  the  leg  or  local  cooling  of  the  skin  —  appeared  as  reinforcing 
stimuli.  These  remarkable  experiments  show  that  it  is  precisely  the 
position  in  time  of  the  preceding  stimulus  (P)  which  determines  the 
acquisition  by  the  food  of  a  signalling  significance  in  relation  to  other 
reflexes,  that  is,  the  formation  in  one  case  of  a  somato-motor  conditioned 
reflex  to  the  presentation  of  food,  and  in  the  other  case  a  vasomotor 
conditioned  reflex.  It  may  be  assumed  therefore  that  this  is  the  consequence 
of  the  formation  of  a  direct  conditioned  reflex  connection  between  central 
nervous  structures  of  the  alimentary  reflex  and  corresponding  structures  of 
the  somato-motor  or  vasomotor  reflexes.  It  was  subsequently  established 
that  in  these  experiments  there  also  arises  a  double  (or  two-way)  con- 
ditioned connection  between  the  unconditioned  and  indifferent  stimuli 
which  are  combined  in  a  definite,  stereotyped  sequence.  This  means  that 
with  the  direct  conditioned  reflex  connection  there  exists  a  reverse  connec- 
tion which  conducts  excitation  from  the  nervous  structures  corresponding 
to  (S)  (i.e.  to  the  movement  of  the  leg  or  local  coohiig  of  the  skin)  to  the 


E.    A.    ASRATYAN 


103 


nervous  structures  corresponding  to  (P)  (i.e.  the  alimentary  stimulus). 
This  is  clear  from  the  fact  that  passive  lifting  of  the  leg  or  local  cooling 
of  the  skin  also  acquire  a  signalling  significance  (i.e.  the  faculty  of  evoking 
an  alimentary  reaction  in  a  conditioned  reflex  way  when  repeatedly 
combined  with  food,  according  to  the  method  of  'covering'  applied  in 


^    -nrr 


luiiiiiiiiiiniumiiniimminminiiiuimiiiiiimi 


197(20) 


nj\JiJi_AJi_n_n_n-JuriJv-n_n_a_rLJLruvn_n_n_n_rij^^ 


a 


6 


Fig.  5 

{a)  A  motor  conditioned  reflex  evoked  in  the  dog  by  the  act  of  eating  (direct  connection); 
(/))  an  ahmentary  reflex  evoked  by  the  passive  lifting  of  the  leg  (reverse  connection). 

I.  —  Mark  of  masticating  movements;  2.  —  mark  of  placing  the  leg  on  a  bench;  3.  —  mark 
of  movements  of  the  same  leg;  4.  —  mark  of  salivation ;  5.  —  mark  of  passive  movement  of  the 
leg ;  6.  —  mark  of  presentation  of  food  (figure  indicates  the  number  of  combinations) ; 
7.  —  mark  of  time  —  in  seconds. 


the  experiments  discussed  above.  This  is  demonstrated  in  Fig.  6.  The 
data  obtained  from  these  experiments  show  that  here  too  there  is  a 
considerable  difference  between  the  specific  features  of  direct  and  reverse 
conditioned  connections,  and  that,  furthermore,  it  is  the  same  kind  of 
difference  as  is  observed  when  two  'indifferent'  or  two  unconditioned- 
reflexes  are  combined.  Thus,  in  a  given  case  the  direct  conditioned  reflex 
connection  is  formed  more  rapidly  than  the  reverse  conditioned  reflex 
connection  and  is  much  more  powerful,  stable  and  effective. 

The  fact  demonstrated  by  Struchkov  that  only  weak  and  unstable 
conditioned  reflexes  become  indifferent  stimuli  when  'covered'  by  un- 
conditioned reflexes,  has  been  known  since  the  work  of  Pimenov  (1908), 
Krepa  (1933),  Pavlova  (1933),  Vinogradov  (1933),  Petrova  (1933)  and 
others;  but  these  authors  regarded  it  as  an  indication  of  the  elaboration  of 
an  ordinary  one-way  conditioned  reflex  connection  possessing  certain 
specific  features.  In  Struchkov's  experiments  this  fact  appears  in  quite  a 


104  BRAIN    MECHANISMS    AND    LEARNING 

different  light,  namely,  as  a  particular  case  of  the  general  phenomenon  of 
elaboration  of  a  reverse  conditioned  reflex  connection  (along  with  the 
direct  connection)  when  two  stimuli  are  combined  in  a  stereotyped 
sequence.  The  transitory  character  of  this  connection,  which  was  pointed 
out  long  ago  by  many  workers  and  was  regarded  by  Pavlov  as  an  enig- 
matic phenomenon  in  conditioned  reflex  activity,  may,  to  a  considerable 
degree,  be  interpreted  as  a  result  of  its  systematic  non-reinforcement 
during  the  periodic  application  of  a  stimulus  for  the  purpose  of  testing  a 
conditioned  reflex  to  it. 


// 


Fig.  6 
Conditioned  and  unconditioned  refle.x  local  changes  in  the  skin  temperature. 

A.  Decrease  of  skin  temperature  in  the  dog  under  the  action  of  food  during  60  seconds  and 
subsequent  application  of  cold.  I.  Record  of  skin  temperature.  II.  Time  —  12  seconds;  (a)  back- 
ground; (/>)  decrease  of  temperature  during  the  process  of  eating  and  application  of  cold; 
(f)  recovery  of  skin  temperature  after  the  process  of  eating  and  action  of  cold.  i.  —  mark  of 
presentation  of  food  and  beginning  of  the  act  of  eating;  2.  —  mark  of  application  of  cold; 
3.  —  mark  of  the  end  of  eating  and  application  of  cold. 

B.  Conditioned  reflex  decrease  of  skin  temperature  during  the  process  of  eating,  (ci)  —  back- 
ground ;  (/))  —  decrease  of  skin  temperature  during  the  process  of  eating;  (c)  —  recovery  of  skin 
temperature  after  the  process  of  eating,  i.  —  mark  of  presentation  of  food  and  beginning  of 
the  process  of  eating;  2.  —  mark  of  the  end  of  eating. 


IV.  The  significance  of  a  definite  sequence  in  the  combination  of  stimuli 
for  elaboration  of  new  conditioned  reflex  connections  and  for  preservation 
of  existing  ones  is  graphically  shown  in  the  experimental  data  obtained  by 
our  collaborator  Pakovich. 

From  the  earlier  investigations  of  American  psychologists,  Schlosberg 
(1928),  Hilgard  (1937),  Wolflc  (1930),  Bernstein  (1934)  and  others,  which 
were  carried  out  on  human  beings,  it  was  known  that  when  the  indifferent 
stimulus  precedes  the  unconditioned  stimulus  by  o.i  second  and  less,  the 
elaboration  of  a  conditioned  reflex  is  impeded,  and  sometimes  even  be- 
comes impossible.  In  recent  years,  Pakovich  has  made  a  thorough  investi- 
gation of  this  question  in  dogs,  on  motoi  reflexes  which  can  be  objectively 


E.    A.    ASRATYAN  IO5 

recorded  with  a  sensitive  mechanographic  device,  and  in  some  experi- 
ments also  by  electromyography.  His  data  show  that  when  a  combination 
of  a  sound  of  moderate  intensity  with  an  electrical  stimulation  of  the 
animal's  legs  is  used,  a  motor  conditioned  reflex  is  not  elaborated  if  both 
stimuli  begin  and  cease  to  act  strictly  simultaneously  within  a  period  of 
I  to  5  seconds.  According  to  Pakovich's  fmdings,  hundreds  of  combina- 
tions of  these  stimuli  do  not  lead  to  the  formation  of  the  conditioned 
reflex  even  when  sound  precedes  the  electric  current  within  a  limit  of 
about  100  msec,  and  when  they  cease  to  act  simultaneously.  The  picture 
does  not  change  if  the  intensity  of  the  stimulating  current  is  considerably 
increased.  A  conditioned  reflex  becomes  elaborated  only  when  the 
interval  between  the  onset  of  the  sound  and  that  of  the  electrical  stimula- 
tion of  the  skin  exceeds  this  time-limit.  This  is  illustrated  in  Fig.  6.  Other 
data  obtained  by  Pakovich  show  that  the  time  fictor  expressed  in  such 
micro-values  makes  itself  felt  also  at  a  certain  distance  from  the  above- 
mentioned  peculiar  demarcation  line.  Pakovich  established  in  particular 
that  the  latent  period  of  the  newly  formed  conditioned  reflex,  as  well  as 
its  strength,  duration,  stability  and  other  properties,  depends  to  a  con- 
siderable degree  on  the  interval  between  the  onset  of  action  of  the  two 
stimuli,  the  indifferent  and  the  unconditioned. 

Pakovich  established  another  very  interesting  fact:  a  firmly  established 
and  regularly  evoked  clcctro-detensive  motor  reflex  disappears  in  the  dog 
if  the  conditioned  stimulus  is  applied  synchronously  with  the  uncondi- 
tioned one  in  the  course  of  a  series  of  experiments.  The  same  occurs  also 
when  the  interval  between  onset  of  the  conditioned  and  of  the  un- 
conditioned stimulus  is  reduced  to  less  than  lOO  msec.  The  conditioned 
reflex  reappears  only  when  these  conditions  of  combined  action  of  both 
stimuli  arc  changed  and  when  the  interval  between  the  onset  of  the  two 
stimuli  again  exceeds  lOO  msec.  The  restoration  of  the  conditioned  reflex 
proceeds  more  rapidly  and  is  more  complete  when  this  interval  is  some- 
what higher  than  its  threshold  value. 

Recently,  Pakovich  carried  out  an  experimental  analysis  of  the  dis- 
appearance of  the  established  conditioned  reflex  when  conditioned  and 
unconditioned  stimuli  were  applied  synchronously. 

He  found  that  this  phenomenon  is  due  to  the  sporadic  application  in  the 
course  of  his  experiment  of  the  conditioned  stimulus  alone  for  the  purpose 
of  testing  its  conditioned  effect.  It  seems,  therefore,  that  simultaneous 
application  of  the  conditioned  and  unconditioned  stimuli  leads  to  such  a 
weakening  of  the  conditioned  reflex  that  it  disappears  even  after  a  few 
extinction  trials. 


io6 


BRAIN    MECHANISMS    AND    LEARNING 


The  following  fact  is  noteworthy.  Although  a  strictly  simultaneous 
action  of  both  stimuli  or  a  certain  minimal  precedence  of  action  of  one  of 
them  creates  such  conditions  that  the  cerebral  nervous  structures  cannot 
elaborate  new  conditioned  connections,  or  even  abolishes  all  previously 
conditioned  reflexes,  this  does  not  preclude  the  possibility  of  a  negative 
anci  even  positive  interaction  between  the  cerebral  structures  which 
correspond  to  these  stimuli.  Pakovich  demonstrated  that  even  in  conditions 
of  a  synchronous  action  of  sound  and  electrical  current  there  may  take 


a 


6 


Fig.  7 
Motor  reflexes  arising  from  different  combinations  in  time  of  two  stimuli  —  a  tone  and  an 
electric  current.  (17)  —  a  motor  reaction  resulting  from  a  strictly  simultaneous  action  of  the 
stimuli;  (fo)  —  absence  of  a  conditioned  reflex  to  the  tone  after  582  strictly  simultaneous 
applications  of  it  in  combination  with  an  electric  current;  (c)  —  emergence  of  a  conditioned 
reflex  to  the  same  stimulus  after  fourteen  applications  of  it  in  combination  with  an  electrical 
current  delayed  for  2  seconds. 

I.  —  record  of  movements  of  the  leg;  2.  —  mark  of  conditioned  stimulation;  3.  —  mark  of 
unconditioned  stimulation;  4.  —  time  in  seconds. 


place  both  a  reciprocal  inhibition  and  a  summation  of  excitation  provoked 
by  each  of  these  stimuli  in  corresponding  central  nervous  structures.  The 
reciprocal  inhibition  is  observed  predominantly  in  the  first  period  of  the 
combined  action  of  the  stimuli,  when  the  orienting  reaction  to  sound  is 
still  strong.  As  to  summation  of  excitation,  it  is  observed  predominantly 
following  the  combined  action  of  the  stimuli.  During  these  periods  a 
subthreshold  excitation  evoked  by  an  electro-cutaneous  stimulus  applied 
separately  turns  into  an  above-threshold  excitation  when  an  electric  current 
of  similar  intensity  is  applied  in  combination  with  a  sound.  In  the  same 


E.    A.    ASRATYAN  IO7 

conditions  of  combined  action  ot  both  stimuli  a  weak  above-threshold 
excitation  evoked  by  a  weak  electric  current  becomes  considerably  intensi- 
fied, etc.  Finally,  it  must  be  noted  that  according  to  these  findings,  the 
phenomena  described  above  and  the  determining  factors  observed  in  the 
formation  of  conditioned  reflexes  are  not  connected  to  any  appreciable 
degree  with  typology,  age  or  other  features  of  the  experimental  animals; 
it  follows  that  they  belong  to  the  category  of  basic  phenomena  and 
determining  factors  which  are  characteristic  of  the  conditioned  reflex 
activity  of  higher  parts  ot  the  central  nervous  system. 

How  are  all  these  fmdings  to  be  interpreted  and  generalized? 

Experimental  psychologists,  neurophysiologists  and  animal  trainers  have 
for  long  known  a  number  of  facts  which  prove  the  formation  of  a  tw^o- 
way  nervous  connection  and  have  provided  a  basis  for  the  formulation  of 
corresponding  theories  on  this  question  (Goltz,  1884;  Bekhtercv,  1887; 
Ebbinghaus,  1911-13;  Kahsher,  1912-14,  Savich,  1918;  Zeliony,  1929; 
Beritov,  1932;  Konorsky  and  Miller,  1936;  Narbutovich  and  Podkopayev, 
1936;  Rosenthal,  1936;  Petrova,  1941;  Kupalov,  1948;  Fiodorov,  1952; 
Voronin,  1952,  and  others).  In  this  connection  special  mention  must  be 
made  of  the  theories  of  Pavlov  (1949)  concerning  double  (or  two-way) 
conditioned  connections,  advanced  by  him  in  recent  years  and  based  on 
original  facts  brought  to  light  in  his  laboratories.  Pavlov  stated  that  'when 
two  nervous  points  are  connected,  or  associated,  the  nervous  processes 
developing  between  them  proceed  in  both  directions'.^  At  that  time, 
however  the  founder  of  the  theory  of  conditioned  reflexes  was  of  the 
opinion  that  the  important  question  of  two-way  conditioned  connection 
was  still  not  sufficiently  elaborated,  experimentally  or  theoretically,  and 
that  it  required  further  investigation.  It  appears  to  us  that  the  facts  recently 
obtained  in  our  laboratory  increase  to  some  degree  our  knowledge  of  this 
problem.  They  reveal  new  aspects  of  direct  and  reverse  connections,  and, 
in  particular,  new  aspects  of  the  role  played  in  this  process  by  the  physio- 
logical strength  of  the  stimuli  and  by  the  sequence  of  their  combination. 

All  these  facts,  in  addition  to  the  previously  known  data  of  other  investi- 
gators, lead  to  the  assumption  that  the  formation  of  a  double  (or  two-way) 
conditioned  comiection  is  not  a  limited  phenomenon  peculiar  only  to  a 
certain  group  of  conditioned  reflexes,  but  is  widespread,  if  not  universal 
for  this  class  of  reflexes.  This  creates,  so  to  speak,  a  structural  basis  tor  a 
two-way  tunctional  connection  and  for  a  circular  conditioned  reflex 
interaction  between  the  comiected  nervous  points,  approximately  in  the 

1 1.  P.  Pavlov,  Complete  Works,  1949,  vol.  Ill,  p.  452. 


io8 


BRAIN    MECHANISMS    AND    LEARNING 


same  manner  as  was  assumed  by  Lorente  de  No  (1934,  1938)  and  his 
followers  for  the  activity  of  the  central  nervous  system  in  general.  In  any 
case,  there  are  sufficient  grounds  for  this  assumption  during  the  stage  of 
formation  of  conditioned  reflexes  and  for  the  initial  period  of  their  func- 
tioning. Subsequently,  depending  on  a  number  of  circumstances,  evolu- 
tionary development  leads  to  different  results:  to  the  inhibition  of  both 
conditioned  connections,  to  the  inhibition  of  one  of  them,  and  some- 
times to  the  preservation  of  both  connections  in  a  state  of  stability  and 
efficiency.  In  this  case  a  usual  one-way  conditioned  coiuiection  can  be 
regarded  as  a  derivative  of  a  double  conditioned  connection,  as  resulting 
from  the  subsequent  inhibition  of  one  of  the  paired  connections. 


Fig.  8 


Schematic  representation  of  a  conditioned  reflex  arc. 


I  should  like  also  to  point  out  that  all  the  factual  material  described  in 
this  communication,  as  well  as  the  appraisal  of  its  scientific  significance, 
may  also  be  regarded  as  corroborating  the  proposition  we  advanced  many 
years  ago,  that  the  primary  conditioned  reflex  results  from  the  synthesis 
of  combined  inborn  reflexes  evoked  by  both  unconditioned  and  'in- 
different' stimuli  (Fig.  8). 

Of  course,  at  present,  we  arc  far  from  a  satisfactory  interpretation  ot 
these  facts.  Nevertheless,  some  purely  hypothetical  statements  can  be  made. 
In  particular,  we  are  inclined  to  believe  that  the  elaboration  of  a  double 
conditioned  connection  may  be  accounted  for  by  the  relative  equality  of 
intensity  of  the  excitations  which  arise  in  the  corresponding  central 
nervous  structures  under  the  influence  of  the  combined  stimuli.  It  goes 


E.    A.    ASRATYAN 


109 


without  saying  that  this  basic  condition  can  be  observed  best  when  two 
stimuh  of  ahnost  equal  physiological  strength  are  combined  (for  example, 
two  'nidifterent'  stimuli,  two  unconditioned  stimuli,  or  one  'indifferent' 
and  one  unconditioned  stimulus).  This  is  also  possible  when  two  paired 
stimuli  are  combined  in  a  variable  sequence.  Such  a  combination  of  these 
two  factors  can  secure  the  formation  and  existence  of  double  conditioned 


a 


p' 


F[G.  9 

I.  Diagrammatic  representation   of  a   double   conditioned   connection 
with  equivalent  components. 

II.  Diagrammatic  representation  alter  development  of  non-equivalence. 


connection  with  absolutely  equivalent  components  (Fig.  9  I).  But  when 
these  paired  stimuli  are  combined  in  a  stereotyped  sequence,  the  basic 
condition  is  not  fulhlled,  which,  in  our  opinion,  leads  to  the  development 
of  non-equivalence  in  the  direct  and  reverse  conditioned  connections 
(Fig.  9  II).  We  explain  it  in  the  following  way.  When  the  (P)  and  (S) 
stimuli  are  applied  in  a  stereotyped  sequence,  the  central  nervous  structures 


no  BRAIN   MECHANISMS    AND    LEARNING 


corresponding  to  (S)  become  more  excited  after  the  emergence  of  condi- 
tioned connections  than  the  central  nervous  structures  corresponding  to 
(P).  This  is  due  to  the  fact  that  the  structures  corresponding  to  (S)  are  in 
this  case  excited  by  two  sources  —  by  (P)  in  a  conditioned  reflex  way  and 
by  (S)  in  an  unconditioned  reflex  way.  There  does  not  exist  the  initial 
relative  equality  in  intensity  of  excitation  of  the  central  nervous  structures 
which  corresponds  to  the  combined  stimuli.  The  excitation  of  the  nervous 
structures  of  (S)  prevails  to  a  great  extent  over  the  excitation  of  the  nervous 
structures  corresponding  to  (P).  As  a  result  the  direct  conditioned  connec- 
tion begins  to  prevail  over  the  reverse  connection  in  all  characteristics. 
This  explanation  was  corroborated  by  Varga  in  a  series  of  experiments 
(1958)  in  which  she  demonstrated  that  the  transition  from  a  variable 
sequence  of  combined  stimuli  to  a  stereotyped  sequence  entails  a  con- 
siderable increase  in  the  excitability  of  the  central  nervous  structures 
which  correspond  to  (S)  and  prevalence  in  this  respect  over  the  one 
corresponding  to  (P). 

We  are  inclined  to  offer  a  similar  explanation  for  Struchkov's  findings 
concerning  the  conversion  of  food  to  a  signalling  stimulus  for  somato- 
motor and  vasomotor  reflexes.  In  the  first  phase  of  combining  food 
(which  is  the  preceding  stimulus  (P))  with  a  passive  lifting  of  the  paw  or  a 
local  cooling  of  the  skin  (which  is  the  .subsequent  stimulus  (S) )  the  central 
nervous  structures  corresponding  to  the  latter  stimuli  become  excited  to 
a  relatively  high  degree  on  account  of  the  novelty  of  the  stimuli  for  the 
experimental  animals.  Owing  to  this,  the  level  of  excitation  of  the  central 
nervous  structures  corresponding  to  these  stimuli  approximates  the  level 
of  excitation  of  the  central  nervous  structures  of  the  alimentary  reflex 
which  is  the  preceding  stimulus.  This  creates  favourable  conditions  for 
the  elaboration  of  the  double  conditioned  connection  between  these 
structures.  Subsequently,  after  elaboration  of  this  double  connection,  the 
above-mentioned  factor  comes  into  effect,  namely,  a  more  intense 
excitation  of  the  central  nervous  structures  of  (S)  coming  from  two 
sources  by  way  of  summation  —  at  first,  from  the  food  in  a  conditioned 
reflex  way,  and  then,  against  this  background,  from  adequate  stimuli  of 
the  nervous  structures  (a  lifting  of  the  paw  or  cooling  of  the  skin)  in  an 
unconditioned  reflex  way.  This  maintains  the  previously  created  relative 
equality  in  levels  of  excitation  of  the  nervous  structures  corresponding  to 
the  combined  stimuli,  i.e.  the  precondition  necessary  for  maintaining  the 
double  conditioned  connection  is  preserved. 

Facts  concerning  relatively  different  duration  of  efficiency  for  the  condi- 
tioned comiections  arising  after  combination  of  various  stimuli  of  different 


E.    A.    ASRATYAN  III 


biological  significance  (two  'indifferent'  stimuli,  two  unconditioned 
stimuli,  or  one  'indifferent'  and  one  unconditioned  stimulus)  can  be  best 
understood  when  considering  the  important  role  of  the  concrete  physio- 
logical strength  of  the  corresponding  stimuli.  There  are  grounds  for 
assuming  that  this  factor  plays  an  important  role  in  the  further  fate  of 
the  conditioned  connections,  whereas  the  relative  strength  of  excitation  of 
the  central  nervous  structures  corresponding  to  these  stimuli  and  the 
sequence  of  application  play  an  outstanding  role  in  elaborating  these 
connections  and  forming  some  of  their  properties.  If  we  assume  that  the 
level  of  excitation  of  the  central  nervous  structures  originating  conditioned 
reflex  comiections  expresses  approximately  the  number  ot  functional 
units  which  come  into  activity,  and  that  the  strength  of  the  conditioned 
reflex  connection  is  its  derivative,  the  following  conclusion  may  be 
drawn :  for  maintenance  and  functioning  of  conditioned  connections  it  is 
necessary  that  they  should  possess  a  certain  threshold  strength,  i.e.  consist 
of  a  definite  'threshold'  number  of  functional  units.  Weak  conditioned 
connections,  that  is,  connections  consisting  of  a  small  number  of  functional 
units,  become  rapidly  fatigued  and  exhausted  even  after  moderate  activity; 
a  protective  inhibition  occurs  which  blocks  them.  At  present  we  arc  unable 
to  explain  satisfactorily  why  such  inhibition  develops  in  structures  corres- 
ponding to  weak  conditioned  connection.  We  can  point  out,  however, 
with  some  justification,  that  there  is  a  similarity  between  this  phenomenon 
and  the  rapid  development  of  inhibition  during  a  protracted  action  of  weak 
conditioned  and  even  indifferent  stimuli.  This  phenomenon  was  known  a 
long  time  ago,  trom  numerous  investigations  carried  out  by  Pavlov  in  his 
laboratories.  Moreover,  the  development  of  inhibition  in  coimection  with 
a  protracted  action  of  weak  stimuli  seems  to  belong  to  the  category  of 
phenomena  which  are  common  to  all  nervous  structures. 

For  the  time  being  we  cannot  give  a  satisfactory  explanation  for  the 
facts  obtained  by  Pakovich,  which  show  that  a  conditioned  reflex  cannot 
be  formed  when  two  combined  stimuli  act  synchronously.  Nor  can  we 
explain  the  disappearance  of  an  existing  conditioned  reflex  when  a 
conditioned  stimulus  and  an  unconditioned  one  are  combined  in  a  similar 
way,  although  in  this  case  the  possibility  of  a  positive  and  negative 
interaction  of  these  stimuli  remains.  It  is  possible  that  a  certain  role  in  this 
respect  is  played  by  mutual  inductive  inhibitory  influences  of  the  simul- 
taneously excited  cerebral  structures  upon  each  other.  These  influences, 
however,  do  not  preclude  the  summation  of  excitations  that  have 
originated  in  them. 


112  BRAIN    MECHANISMS    AND    LEARNING 


GROUP   DISCUSSION 


KoNORSKi.  The  problem  investigated  by  Professor  Asratyan  and  his  group  is 
very  important,  and  has  not  been  solved  as  yet,  although  it  has  been  studied  for 
many  years.  This  is  the  old  problem  whether  the  so-called  backward  conditioning 
exists,  or  not.  Both  in  Russia  and  in  America  there  were  authors  strongly  support- 
ing the  idea  of  backward  conditioning,  as  well  as  strong  opponents  of  this  view. 
While  the  first  group  of  authors  claimed  that  any  association  between  stimuli 
(both  forward  and  backward)  leads  to  the  formation  of  connections  between  them, 
the  second  group  argued  that  the  phenomena  of  backward  conditioning  were  only 
pseudo-conditioning  due  to  sensitization.  In  fact,  while  the  biological  role  of 
forward  conditioning  is  obvious,  the  biological  significance  of  backward  condi- 
tioning could  hardly  be  understood. 

Professor  Asratyan  has  brought  out  more  extensive  material  concerning  this 
problem  than  any  other  author.  According  to  his  data  backward  conditioning  does 
exist,  although  the  connections  formed  in  the  direction  from  the  subsequent 
stimulus  to  the  preceding  one  are  much  weaker  than  those  established  in  the 
opposite  direction.  This  is  also  in  agreement  with  the  results  obtained  by  Czech 
authors  on  chimpanzees,  and  recently  by  Mrs  Budochovska  in  the  Psychological 
Department  of  the  Nencki  Institute  on  man. 

Chow.  I  would  like  to  ask  Professor  Asratyan  how  these  very  interesting 
experimental  results  are  to  be  incorporated,  if  they  are  to  be  incorporated,  in  the 
concept  of  reinforcement  during  the  formation  of  the  conditioned  reflex. 

Asratyan.  These  conditioned  reflexes  also  need  reinforcement.  If  one  of  the 
stimuli  is  applied  without  any  other,  this, leads  to  the  extinction  of  the  reflex  in 
every  case.  But  in  cases  where  we  have  a  weak  stimulus,  the  so-called  'indifferent 
stimulus'  —  I  say  so-called  because  I  think  that  these  indifferent  stimuli  are  only 
relatively  indifferent  —  indeed  if  they  evoke  a  reaction  at  all  in  the  organism  they 
cannot  be  indifferent.  They  are  indifferent  in  relation  to  another  reaction  evoked  by 
another  stimulus  but  by  themselves  they  also  originate  reflexes  like  unconditioned 
stimuli,  althoush  their  histological  sia;n  and  their  strength  are  different.  When  we 
combine  two  indifferent  stimuli,  or  weak  stimuli,  in  these  cases  absence  of  reinforce- 
ment leads  to  a  more  rapid  extinction  than  in  the  case  of  strong  stimuli.  Reinforce- 
ment is  necessary. 

Naquet.  How  do  you  explain  the  limit  oi  loo  msec? 

Asratyan.  I  am  afraid  we  cannot  answer  this  question  in  a  satisfactory  manner. 
It  may  be  a  question  of  mutual  influences,  facilitation  and  inhibition,  not  elaborated 
connections.  I  really  don't  know.  But  it  should  be  pointed  out  that  tacilitation  alone 
is  not  sufficient  for  the  elaboration  of  conditioned  connections. 

Fessard.  I  believe  that  new  connections  within  the  central  nervous  system 
cannot  be  formed  unless  the  associated  afferent  messages  converge  towards  common 
neurones  so  that  the  limit  of  lOO  msec,  might  be  explained  by  the  recovery  period 
of  these  neurones,  at  least  of  those  having  discharged  aiter  the  first  of  the  afferent 
signals  reaching  them. 

Naquet.  I  think  loo  msec,  represents  the  recovery  time  of  the  reticular  excitability 
and  you  may  have  some  facilitation  which  permits  the  establishment  of  condition- 
ing. 

Hebb.  I  have  been  very  interested  for  a  long  time  in  the  problem  of  the  sequential 


E.    A.    ASRATYAN  II3 

aspect  of  cerebral  function.  It  may  tnid  its  simplest,  its  most  experimentally 
attackable  form  in  the  apparent  ordering  in  time  of  the  conditioned  stimulus  and 
unconditioned  stimulus.  I  was  going  to  ask  Professor  Asratyan  what  speculations 
he  was  making  about  possible  neuronal  action  that  might  explain  this.  It  seems  to 
me  that  Protcssor  Fessard's  point  is  excellent  but  yet  there  is  the  turther  problem 
that  conditioning  is  not  good  unless  there  is  some  overlap.  It  is  as  it  the  line  had  to  be 
busy  to  a  certain  extent,  or  in  certain  circumstances. 

I  would  like  to  say  also  that  I  found  the  paper  very  interesting  in  the  study  of 
relatively  unimportant,  biologically  unimportant,  stimulations.  So  much  of  human 
behaviour  is  composed  of  reactions  to  biologically  neutral  stimuli,  or  very  nearly 
neutral. 

Asratyan.  First  of  all  I  should  like  to  remind  you  that  we  are  quoting  from  our 
data.  In  the  case  of  stereotyped  sec]uences  ot  application  ot  the  stimulus  the  signifi- 
cance of  these  two  conditioned  connections  is  different.  Dr  Konorski  also  men- 
tioned this  in  his  remarks  that  direct  conditioning  in  all  cases  is  much  stronger  and 
steadier  and  more  regular  than  backward  conditioning.  This  illustrates  the  bio- 
logical differences  between  these  connections  and  the  significance  of  the  sequence 
of  combination.  How  does  one  explain  thisf  Originally  both  nervous  points  of 
both  stimuli  are  equally  stimulated,  however  once  the  connection  is  established 
and  the  stimuli  inverted,  one  point,  namely  the  second  point,  receives  stimuli  from 
two  sources,  whereas  the  other  receives  only  its  original  stimulus.  This  is  the  reason 
for  the  reinforcement  of  forward  conditioning  and  the  difficulty  of  backward 
conditioning. 

In  answer  to  vour  second  question,  in  cases  ot  biologically  weak  stimuli,  as  tor 
example  in  cases  when  we  combined  two  so-called  indifferent  reflexes,  giving  rise 
to  the  elaboration  of  weak  two-wav  conditioned  reffex,  these  reflexes  disappear 
very  rapidly.  Occasionally  in  our  cases  we  have  been  able  to  prolong  their  duration. 
Why  these  conditioned  weak  reflexes  disappear  we  don't  know.  Our  theory,  our 
'fantasy',  is  that  it  is  due  to  the  lower  threshold  level  of  excitation,  to  the  small 
number  of  cells  activated  in  both  coupled  nervous  points  during  the  elaboration  of 
reflexes.  As  a  result  of  the  activation  of  such  reflexes,  their  weak  connections  easily 
become  exhausted  and  fatigued  and  soon  disappear.  A  strong  stimulus  would  call 
into  play  a  larger  number  ot  cells  and  consequently  a  steady  conditioned  reflex  is 
elaborated. 


THE   PHYSIOLOGICAL   APPROACH  TO   THE  PROBLEM 
OF  RECENT  MEMORY 

Jerzy  Konorski 

It  is  a  striking  fact  that  the  investigations  of  higher  nervous  activity  of 
animals  carried  out  both  in  physiological  laboratories  by  methods  of 
conditioned  reflexes,  and  in  psychological  laboratories  by  use  of  such 
other  methods  as  maze  learning,  discrimination  box,  etc.,  have  been 
almost  exclusively  concerned  with  the  problem  of  stable  memory.  In 
fact,  in  all  these  investigations  the  animal  is  routinely  trained  to  perform  a 
particular  task  or  a  set  of  tasks  and  then  various  properties  of  the  acquired 
reactions,  or  the  very  process  of  their  acquisition,  are  studied.  But  it  is 
easy  to  conceive  that  the  performance  of  the  more  or  less  firmly  estab- 
lished conditioned  responses,  in  the  broadest  sense  of  the  word,  and,  of 
course,  unconditioned  responses,  does  not  exhaust  the  whole  behaviour 
of  the  animal.  We  know  from  everyday  observation  of  animals  and  man 
that  a  large  part  of  this  behaviour  is  often  based  on  transient  memory 
traces  which  persist  for  some  time  and  then  are  partially  or  even  totally 
abolished.  Recently  the  clear  realization  of  a  probable  difference  between 
the  mechanisms  of  stable  and  transient  memory  traces  has  turnec^  the 
attention  of  investigators  to  the  latter  category  of  phenomena  and  has 
given  an  impetus  to  their  studies. 

I  intend  in  the  present  paper  to  present  a  brief  review  of  the  methods 
used  so  far  in  the  study  of  phenomena  of  recent  memory,  to  propose  some 
new  methods  which  may  be  applied  in  this  field,  to  examine  the  relations 
between  stable  and  recent  memory  and  to  discuss  the  problems  of  a 
probable  physiological  mechanism  of  recent  memory,  versus  that  of 
stable  memory. 

I.    TRACE    CONDITIONED    REFLEXES 

As  a  matter  of  fact,  the  phenomena  of  recent  memory  have  been 
implicated  for  a  long  time  in  some  conditioned  reflex  (CR)  studies, 
although  their  significance  in  this  respect  was  not  clearly  understood.  I 
have  in  mind  the  so-called  trace  CRs  which  were  studied  by  several 
research- workers  of  the  Pavlov  school  (Pimenov,  1907;  Grossman,  1909; 
Dobrovolskij,  1911;  Feokritova,  1912;  Pavlova,  1914)  in  the  first  decade 

I  115 


Il6  BRAIN    MECHANISMS    AND    LEARNING 

of  the  work  in  this  field.  These  workers  estabhshed  that  if  a  given  'in- 
different' stinaukis  is  reinforced  not  during  its  action  but  some  time  —  of  a 
range  of  seconds  or  minutes  —  after  its  cessation  it  is  possible  to  establish  in 
a  dog  the  CR  not  to  the  stimulus  itself  but  to  a  short  period  of  time  just 
preceding  the  moment  of  reinforcement.  Thus,  if  for  example  a  dog 
repeatedly  receives  food  3  minutes  after  the  cessation  of  the  conditioned 
stimulus  (CS),  he  learns  to  salivate  not  earlier  than  about  half  a  minute 
before  the  moment  of  feeding.  In  a  variation  of  such  experiments  the 
animal  receives  food  simply  at  constant  intervals  and  learns  to  expect  it  at 
the  proper  moment  —  'the  CR  to  time'.  The  end  of  the  act  of  eating 
plays  in  this  experiment  a  role  of  a  trace  CS. 

Facts  of  this  kind  mean  that  (i)  the  CS  produces  some  changes  in  the 
CNS  which  persist  some  time  after  its  cessation,  and  (2)  that  the  animal 
is  able  to  'measure'  somehow  the  time  elapsed  after  it. 

The  process  of  elaboration  of  a  trace  CR  is  such  that  tu'st  both  the  CS 
itself  and  the  whole  period  between  the  stimulus  and  the  reinforcement 
evokes  salivation  and  then  gradually  the  conditioned  reaction  is  more 
and  more  postponed.  This  shows  that  first  there  is  a  generalization  of  the 
CR  to  all  moments  following  the  CS  and  then  differentiation  of  these 
moments  occurs. 

A  peculiar  property  of  trace  CRs  is  that  they  arc  very  widely  generalized : 
even  the  application  of  new  stimuli,  much  different  from  the  original  CS, 
produces  salivation  in  the  appropriate  moment  after  their  cessation;  for 
example,  when  the  original  trace  CR  was  elaborated  to  a  tactile  stimulus 
applied  to  one  spot  of  the  skin,  it  is  produced  by  tactile  stimuli  applied  to 
quite  different  spots  and  also  in  response  to  auditory  stimuli.  This  property 
of  trace  CRs  seems  to  suggest  that  they  are  formed  not  to  the  traces  of  the 
given  exteroceptive  stimulus  itself,  but  rather  to  some  of  its  consequences 
which  are  common  for  various  sorts  of  stimuli.  As  any  external  stimulus 
elicits  an  orientation  reaction  it  may  be  that  the  proprioceptive  stimuli 
generated  by  this  reaction  form  the  true  basis  for  elaboration  and  occur- 
rence of  trace  CRs.  We  shall  return  to  this  question  in  a  later  section. 

2.    DELAYED    RESPONSES 

Nearly  at  the  same  time  Hunter  (19 13),  according  to  the  suggestion  of 
Carr,  introduced  into  behaviouristic  psychology  another  method  of 
investigation  of  recent  memory  based  upon  the  so-called  delayed  responses. 
The  general  principles  of  this  method  are  roughly  these:  the  animal  is 
taught  to  receive  food  in  two  or  more  different  places  (or  run  to  the  food 


lERZY   KONORSKI 


117 


through  several  different  ways).  When  the  animal  is  restrained  in  the  cage 
or  attached  on  the  starting  platform,  a  signal  heralding  that  the  food  is 
presented  in  a  particular  place  is  given;  in  many  experiments  such  a 
signal  is  provided  simply  by  baiting  one  of  the  bowls  in  front  of  the 
animal.  Then  after  a  number  of  seconds  or  minutes  the  animal  is  released 
and  if  he  remembers  which  signal  was  given,  he  will  go  to  the  correspond- 
ing place  and  be  reinforced  there. 

After  the  first  paper  by  Hunter  appeared,  a  number  oi  authors  studied 
the  delayed  responses  in  various  species,  attempting  to  tnid  the  maximal 
delay  periods  which  can  be  achieved,  the  cues  which  are  used  by  the 


^^-^B^  L,\^ 

c^-^ 

F2 

0 

^^^^ 

'.'-y- 

^ 

c 

\ 

0 

^^C 

^ 

N     m     ^ 

^ 

Fic.  I 
Experimental  setting  used  in  our  study. 
Fi-  ^2.  F3'  ''•"ff-  iniddle,  and  right  food  tray.  The  bowls  are  auto- 
matically moved  into  position  by  the  experimenter  using  an  electro- 
magnetic device.  E,  table  and  seat  for  experimenter.  S,  starting 
platform.  Bj,  B.,,  B3,  buzzers,  Lj,  L,,  L3,  lamps  situated  on  the  respective 
food  trays.  (After  Konorski,  J.  and  Lawicka,  W.,  1959.  Acu\  B'\o\og\ae 
E.xperiiiieiiriilis,  19,  175-198). 


animals  to  solve  the  task,  and  the  way  in  which  the  delay  period  is 
'bridged'  by  the  animal  (Walton,  1915;  Yarborough,  1917;  Cowan, 
1923;  Yerkes  and  Yerkcs,  1928;  Tinklepaugh,  1928;  McAllister,  1932). 
This  form  of  experimentation  grew  in  importance  in  the  'thirties  of  this 
century  when  Jacobsen  (1936)  showed  that  delayed  responses  are  dramati- 
cally impaired  or  abolished  by  prefrontal  lesions  in  monkeys  and  apes. 
The  results  of  these  studies  will  be  discussed  in  a  later  section. 

The  delayed  responses  have  been  recently  studied  in  our  laboratory  by 
Lawicka  and  Konorski  (Lawicka,  1957,  1959;  Konorski  and  Lawicka, 
1959;  Lawicka  and  Konorski,  1959)  in  dogs  and  cats  by  using  the  experi- 
mental setting  presented  in  Fig.  i .  The  animal  was  on  the  leash  or  in  the 
cage  on  the  starting  platform  and  a  signal,  visual  or  auditory,  which  we 


Il8  BRAIN    MECHANISMS    AND    LEARNING 

shall  call  a  'preparatory  stimulus',  from  one  of  three  food  trays  was  given. 
When  after  being  released  the  animal  ran  to  the  proper  food  tray,  the 
bowl  with  food  was  automatically  presented.  In  certain  series  of  experi- 
ments the  source  of  preparatory  stimuli  was  situated  not  on  the  food  trays 
but  at  the  starting  platform,  and  the  animals  had  to  learn  by  trial  and  error 
which  signal  denoted  food  in  which  food  tray. 

Here  are  some  results  of  these  experiments  (Lawicka,  1959). 

1.  In  response  to  the  preparatory  stimulus  the  animal  as  a  rule  displays 
an  orienting  reaction  (of  the  whole  body,  of  the  head  or  only  of  the  eyes) 
towards  the  corresponding Jood  tray.  This  is  true  even  in  those  experiments  in 
which  the  source  of  the  preparatory  stimulus  is  not  situated  in  the  direc- 
tion of  the  goal. 

2.  As  shown  earlier  by  other  experimenters,  the  preservation  of  the 
bodily  orientation  towards  the  given  food  tray  during  the  delay  period  is, 
as  far  as  normal  animals  are  concerned,  not  at  all  necessary  for  the  correct 
reaction  after  release.  In  fact,  during  this  period  the  animals  nearly  always 
change  their  position  many  times  and  take  different  attitudes  which  does 
not  in  the  least  affect  their  post-delay  reaction. 

3.  During  the  delay  period  normal  animals  may  be  distracted  in  many 
different  ways,  by  presentation  of  extra-stimuli  from  different  places,  by 
screening  the  food  trays,  by  giving  the  animals  food  on  the  starting 
platform,  or  by  taking  them  out  of  the  experimental  room,  and  in  the 
majority  of  trials  these  measures  will  not  prevent  them  from  running  to 
the  correct  food  tray. 

4.  If  in  the  triple-choice  delayed  response  method  two  preparatory 
stimuli  arc  given  one  after  another  in  the  same  trial,  the  animal,  after 
being  released,  is  able  to  go  to  both  food  trays  and  ignore  the  third  one. 

These  data  seem  to  suggest  that  the  'locating'  of  the  food  tray  in  space 
during  the  action  of  the  preparatory  stimulus  constitutes  the  cue  the 
animal  uses  in  the  post-delay  run.  Since  the  bodily  orientation  is  not 
maintained  during  the  delay  period  —  the  animal  may  even  have  been 
removed  from  the  room  —  the  memory  of  this  cue  is  based  purely  on  the 
intracentral  nervous  processes  going  on  m  the  brain  during  the  delay 
period,  which  processes  are  precisely  responsible  for  those  forms  of 
phenomena  which  are  called  recent  memory. 

3.    RECENT    MEMORY    TESTS    FOR    VARIOUS    SORTS    OF    STIMULI 

From  what  has  just  been  said  about  the  delayed  response  test  it  can 
easily  be  seen  that  this  test  concerns  a  particniar  kind  of  recent  memory. 


JERZY   KONORSKI  II9 

namely  the  recent  memory  of  directions  in  space.  Although  we  do  not 
know  exactly  which  sorts  of  stimuli  are  involved  in  determining  these 
directions  (labirinthine,  proprioceptive,  or  a  compound  of  them)  we  do 
know  that  these  stimuli  were  acting  when  the  preparatory  signal  was 
applied  and  the  animal  remembers  them  during  the  delay  period.  But 
obviously  not  only  these  kinds  of  stimuli  but  also  exteroceptive  stimuli 
and  their  various  modalities  can  leave  their  transient  memory  traces 
which  may  be  easily  detected  in  human  beings,  by  use  of  introspection. 
However,  as  far  as  animals  are  concerned,  the  methods  for  examination  of 
recent  memory  of  these  stimuli  are  not  so  obvious  because  we  must  be 
sure  that  the  given  test  really  concerns  the  stimuli  in  question  and  not 
their  proprioceptive  effects.  We  have  seen  for  example  in  Section  i  that 
even  in  trace  CRs  we  cannot  be  sure  that  the  animal  remembers  the 
exteroceptive  stimulus  itself  and  we  have  some  reason  to  believe  that 
rather  its  proprioceptive  counterpart  constitutes  the  basis  of  this  form  of 
reflexes.  In  order  to  study  the  recent  memory  of  various  modalities  of 
exteroceptive  stimuli  the  following  test  has  been  devised  (Konorski, 

1959). 

We  choose  a  certain  group  of  stimuli  S^,  Sg .  .  .  Sn  whose  recent  memory 
we  wish  to  examine  —  e.g.  tones  of  various  pitch,  lights  of  various  inten- 
sity, tactile  stimuli  applied  to  various  places  of  the  body,  etc.  —  and  apply 
them  according  to  the  following  schedule:  the  compound  composed  of 
the  same  stimulus,  whatever  it  is,  repeated  twice  (SxSx)  is  reinforced,  while 
the  compound  composed  of  two  different  stimuli,  whichever  they  are 
(SxSy),  is  not  reinforced,  or  vice  versa.  And  so  when  the  first  component 
of  the  compound  is  applied,  the  animal  does  not  'know'  whether  he  will 
get  reinforcement  or  not  because  this  depends  on  comparison  with  the 
second  component  which  is  presented  several  seconds  after  the  first  one. 
Consequently,  the  animal  has  no  possibility  of  preparing  himself  before- 
hand for  a  particular  kind  of  reaction,  and  thus  to  make  use  of  propriocep- 
tive cues,  as  is  the  case  in  delayed  responses  or  in  some  other  tests  in  which 
the  first  clement  of  the  compound  determines  by  itself  the  character  of 
the  conditioned  reaction.^ 

The  test  described  was  applied  by  Chorcjzyna  (1959)  in  dogs  for  the 
study  of  recent  memory  of  tones,  and  by  St^pieii  and  Cordeau  (personal 
communication)  in  monkeys  for  the  study  of  recent  memory  of  rhythms 
of  acoustic  and  visual  stimuli. 

^  For  instance,  in  conditioned  inhibition  the  CS  alone  is  reinforced,  while  the  same  stimulus 
preceded  by  another  stimulus  (conditioned  inhibitor)  is  not  reinforced.  In  this  case  already 
during  the  action  of  the  conditioned  inhibitor  the  animal  takes  the  negative  attitude  towards 
the  food  tray  and  preserves  it  —  or  remembers  it  —  during  the  action  of  the  CS. 


T20  BRAIN    MECHANISMS    AND    LEARNING 

4.    ON    THE    PHYSIOLOGICAL    MECHANISM    OF    RECENT    MEMORY 

It  is  now  almost  generally  accepted  that  recent  memory  is  based  on  the 
activity  of  reverberating  circuits  of  neurones  which  are  connected  with  a 
group  of  neurones  excited  by  the  actual  operation  of  a  given  stimulus. 
Such  activity  causes  this  group  to  continue  to  be  excited  for  some  period 
after  the  cessation  of  the  stimulus  itself  (Hcbb,  1949),  and  either  dies  out 
spontaneously  within  a  lapse  of  time  or  is  knocked  out  by  some  inhibitory 
influence  arising  from  other  foci  of  antagonistic  excitation  (the  so-called 
external  inhibition). 

In  order  to  develop  this  hypothesis  a  little  further  and  make  it  more 
precise,  the  following  well-known  facts  from  the  field  of  CR  studies 
should  be  taken  into  account. 

1.  If  a  CS  is  suddenly  discontinued  before  the  moment  of  its  usual 
reinforcement,  the  conditioned  response  proceeds  uninterruptedly  almost 
with  the  same  intensity  as  if  the  CS  were  still  acting  (Kupalov  and  Lukov, 
1932).  On  the  contrary,  if  the  reinforcement  is  usually  presented  several 
seconds  after  the  CS  is  discontinued,  the  conditioned  response  appears 
already  during  its  operation.  This  shows  that  a  high  degree  of  generaliza- 
tion exists  between  the  actual  action  of  a  stimulus  and  its  traces. 

2.  If  an  actual  stimulus  is  not  reinforced,  but  the  'trace  stimulus'  is,  then 
dift'erentiation  of  the  two  stimuli  is  'gradually  established.  As  a  result  the 
animal  always  displays  the  conditioned  response  only  after  the  cessation 
of  the  stimulus. 

3.  The  animal  is  also  able  to  differentiate  early  traces  from  late  traces  of 
the  stinuilus  (cf  section  i).  This  differentiation  is,  however,  much  more 
difficult  than  that  between  the  stimulus  itself  and  its  traces. 

If  we  hold  the  view  developed  in  detail  elsewhere  (Konorski,  1948) 
that  generalization,  or  similarity,  of  stimuli  is  due  to  the  overlapping  of 
their  central  representations,  while  differentiation  of  them  is  possible  when 
in  at  least  one  of  these  representations  there  are  elements  which  do  not 
belong  to  the  other  one,  then  the  above  facts  can  be  understood  as 
follows : 

According  to  the  vast  evidence  of  facts  concerning  the  responses  of 
various  nerve-cells  to  the  incoming  impulses  on  all  levels  of  the  nervous 
axis,  we  may  admit  that  the  central  representation  of  a  given  stimulus 
consists  of  the  following  types  of  neurones:  Neurones  which  are  activated 
only  at  the  beginning  of  the  operation  of  the  stimulus  (pure  on-clements, 
group  la);  neurones  which  are  activated  during  the  whole  action  of  the 
stimulus   but  not   after  its  cessation  (group    ib);   neurones   which  are 


JERZY    KONORSKI  121 

activated  not  only  during  the  operation  of  the  stimuhis  but  also,  by  virtue 
of  reverberating  circuits  connected  with  them,  some  period  after  their 
cessation  (group  2) ;  neurones  which  are  activated  only  after  the  cessation 
of  the  stimulus  (pure  oft-elements  (group  3)).  This  is  illustrated  in  Fig.  2. 


Fig.  2 

Diagrammatic  representation  of  the  physiological  structure  of  a  trace  stimulus. 

The  X  axis  represents  time,  t,,  is  the  beginning  of  the  operation  of  the  particular  stimulus, 
tj,  its  termination. 

Along  the  y  axis  arc  represented  three  groups  of  neurones:  (i)  a  group  of  neurones  activated 
during,  and  only  during  the  operation  of  the  stinuilus;  (2)  a  group  of  neurones  activated  both 
during  the  operation  of  the  stimulus  and,  owing  to  the  reverberating  circuits  of  neurones,  for 
some  time  after  its  termination;  (3)  a  group  of  neurones  activated  niter  the  cessation  of  the 
stimulus  (off-neurones).  All  off-neurones  are  represented  as  acting  for  some  time  after  the 
cessation  of  the  stimulus  by  way  of  reverberating  circuits.  On  the  left  the  respective  type  of 
neurones  of  each  group  is  indicated.  The  horizontal  lines  represent  the  periods  of  excitation  of 
each  particular  neurone.  The  whole  group  I  is  activated  only  during  the  operation  of  the 
stimulus,  some  quickly  adapting  on-elemcnts  being  also  shown.  Group  2  is  activated  during 
the  operation  of  the  stimulus  and  after  its  cessation,  gradually  becoming  less  active  in  the 
course  of  time.  The  v.'hole  group  3  is  activated  by  the  cessation  of  stimulus  and  then  becomes 
gradually  less  active  as  in  the  case  of  group  2.  Further  explanations  in  text.  (After  Konorski 
and  Lawicka,  1959.  Acta  Biologiae  Experitnentalis,  19,  175-198.) 

As  we  sec  the  neurones  of  group  i,  being  activated  only  during  the 
operation  of  the  stimulus,  but  not  after  its  cessation,  are  responsible  only 
for  its  actual  ei^ccts;  group  la  — i.e.  the  pure  on-neurones  group  — 
causes  the  beginning  of  the  stimulus  to  have  a  greater  reflexogenic 
strength  than  its  continuation  —  a  well-known  fact  from  CR  experiments. 
On  the  other  hand  neurones  of  group  2  continue  to  be  activated  after  the 
cessation  of  the  stimulus  and  thus  form  a  basis  of  the  recent  memory  traces 
of  that  stimulus.  As  far  as  neurones  of  group  3  are  concerned  —  pure  off- 
elements  —  they  account  for  the  active  role  played  by  the  cessation  of  a 


122  BRAIN    MECHANISMS    AND    LEARNING 


Stimulus  (again  well  known  from  the  CR  experiments)  and  also  for  the 
recent  memory  traces  of  this  cessation.  And  so  while  neurones  of  group  2 
account  for  comiiioii  features  of  a  stimulus  and  its  traces  and  provide  a 
basis  for  their  mutual  generalization,  neurones  of  group  3  account  for 
diversity  of  the  stimulus  and  its  trace  and  form  a  basis  for  their  possible 
differentiation.  Various  moments  of  the  trace  of  the  stimulus  differ  among 
themselves  in  that  with  a  lapse  of  time  fewer  and  fewer  elements  of 
groups  2  and  3  arc  activated.  And  so  the  more  remote  the  trace  of  the 
stimulus,  the  less  its  refiexogenic  strength,  a  fact  which  is  again  supported 
by  much  experimental  evidence. 

We  have  a  strong  inclination  to  believe  that  the  'sense  of  time'  of  men 
and  other  animals,  i.e.  the  sense  of  the  varying  durations  of  time  which 
have  elapsed  since  a  defmite  event,  is  based  on  nothing  else  than  the 
strength  of  traces  left  by  this  event  at  various  moments  after  its  cessation. 
The  weaker  these  traces  the  more  remote  in  time  the  given  event  seems 
to  be. 


5.  THE  PROBLEM  OF  LOCALIZATION  OF  REVERBERATING  CIRCUITS 

If  the  above  hypothesis  is  correct  then  the  problem  arises  as  to  where  the 
reverberating  circuits  responsible  for  recent  memory  are  situated.  The 
simplest  assumption  is  that  they  are  localized  in  the  associative  areas  of  the 
cerebral  cortex  —  as  decorticated  animals  possess  hardly  any  recent 
memory  —  in  close  vicinity  to  the  respective  sensory  projection  areas.  In 
consequence  we  may  expect  that  the  destruction  of  these  associative  areas 
should  lead  to  the  abolition  of  recent  memory  for  stimuli  in  the  given 
sensory  modality. 

Let  us  analyse  from  this  point  of  view  the  functions  of  the  prefrontal 
area,  i.e.  that  associative  area  which  was  first  recognized  as  having  to  do 
with  recent  memory  in  the  classical  experiments  by  Jacobsen  (1936).  As  is 
well  known  this  author  demonstrated  that  after  bilateral  ablations  of  the 
prefrontal  area  in  monkeys  delayed  responses  are  abolished  and  he 
attributed  this  defect  to  the  loss  of  'immediate  niemory',  as  contrasted 
with  the  full  preservation  of 'stable  memory'.  The  results  of  Jacobsen  were 
afterwards  confirmed  by  many  authors,  but  his  interpretation  was  sub- 
jected to  much  criticism.  It  was  argued  that  the  impairment  of  delayed 
responses  is  due  not  to  the  lack  of 'immediate  memory'  but  to  the  enhanced 
distractability  of  prefrontal  animals  (Malmo,  1942;  Wade,  1947;  Harlow 
et  al.,  1952),  to  their  hypermotility  (Wade,  1947)  or  to  the  impairment  of 
associative  functions  (Nissen  et  al,  1938;  Finan,  1942). 


JERZY   KONORSKI 


123 


In  our  experiments  on  delayed  responses  with  dogs  (Lawicka  and 
Konorski,  1959)  we  used  an  experimental  setting  (Fig.  i)  which  allowed 
us  to  observe  and  analyse  the  changes  in  animal's  behaviour  after  operation 
more  clearly  than  was  possible  in  the  Wisconsin  apparatus.  We  have 
found  that  after  ablations  of  the  frontal  poles  rostral  to  the  presylvian 
sulcus  (Fig.  3)  the  animals,  completely  or  almost  completely,  lose  their 


Fig.  3 
The  cerebral  cortex  of  dog  represented  in  two  dimensions  (it  the  sheet  ot 
paper  is  bent  along  the  longitudinal  axis,  the  three-dimensional  picture  of  the 
cortex  is  obtained).  The  prefrontal  associative  areas  and  temporal  associative 
areas  removed  in  corresponding  experiments  are  stippled. 


capacity  to  remember  in  which  direction  they  have  to  go  in  the  delayed 
response  test.  Being  released  after  the  delay  period  they  'follow  their 
nose',  i.e.  go  to  that  food  tray  to  which  they  are  just  turned.  If  the  delay 
period  is  short  and  no  distracting  stimulus  has  mtervencd,  the  dogs  are 
able  to  preserve  their  bodily  orientation  towards  that  food  tray  which  was 
signalled  and  then  they  are  able  to  react  correctly;  we  have  called  this  type 
of  reaction  a  'pseudo-delayed  response'  since  it  is  due  not  to  the  recent 
memory  of  the  cue  but  to  the  actual  direction  of  the  body  and  head.  But 
if  the  animals'  attention  is  diverted  for  a  moment,  so  that  they  change  their 


124  BRAIN    MECHANISMS    AND    LEARNING 

bodily  orientation,  then  they  will  go  either  in  the  other  direction  or  will 
not  go  anywhere.  Of  course  they  are  also  not  able  to  go  to  the  proper 
food  tray  after  receiving  food  on  the  starting  platform,  or  after  being 
taken  out  of  the  room.  When  two  signals  are  given,  one  after  the  other, 
the  dog  after  release,  if  not  distracted,  goes  correctly  to  the  last  signalled 
food  tray  and  does  not  go  to  the  other  one.  In  other  respects  the  general 
behaviour  of  our  prefrontal  dogs  does  not  differ  from  that  before  opera- 
tion, in  particular  they  do  not  display  any  hyperactivity  or  exaggerated 
reactions  to  new  stimuli. 

Our  experimental  data  seem  to  support  the  original  idea  of  Jacobsen 
that  the  impairment  of  delayed  responses  in  prefrontal  animals  is  due  to 
the  loss  of  recent  memory.  However,  this  statement  requires  one  substan- 
tial qualification,  namely,  that  not  all  kinds  of  recent  memory  are  impaired 
after  prefrontal  lesions  but  only  recent  memory  of  directional  cues.  In  fact 
we  have  so  far  no  evidence  to  show  that  other  sorts  of  recent  memory  are 
also  affected  by  these  lesions  and  we  have  already  some  evidence  that  it  is 
not  so.  One  bit  of  it  is  provided  by  Mishkin  and  Pribram  (1956)  who 
have  found  that  delayed  responses  in  simple  go-no-go  tests  were  not 
impaired  in  prefrontal  monkeys.  Another  one  will  be  presented  later. 

The  important  problem  arises  as  to  why  it  is  that  only  the  recent 
memory  of  directional  cues  is  destroyed  after  prefrontal  lesions.  We  think 
that  a  tentative  answer  to  this  question  can  be  given. 

The  extensive  study  made  recently  by  Soltysik  in  our  laboratory  (in 
preparation)  concerning  the  effects  of  caudate  lesions  on  delayed  responses 
revealed  that  these  lesions  produce  striking  disorciers  of  orienting  reactions. 
The  animals  either  do  not  visibly  pay  any  attention  to  the  auditory  stimuli, 
or  are  not  able  to  locate  correctly  the  source  of  the  stimulus  even  during 
its  operation.  When  after  some  time  this  deficit  is  compensated  the 
delayed  responses  are  as  much  destroyed  as  in  prefrontal  animals.  These 
animals  arc  also  severely  impaired  in  all  locomotor  CRs,  not  being  able  to 
find  their  way  to  the  familiar  places  they  ran  to  hundreds  of  times  before 
operation. 

Although  premotor  cortex  was  not  specially  studied  from  this  point  of 
view,  nevertheless  as  observed  by  I.  Stg pien  et  al.  (in  preparation)  premotor 
lesions,  and  even  more  so  premotor-prefrontal  lesions,  also  produce 
striking  defects  in  the  animal's  orientation  in  space  and  orienting  reactions. 
The  connections  between  caudate  nucleus  and  pericruciate  region  were 
emphasized  by  several  authors  (cf  Purpura  et  al.). 

All  these  data  show  that  both  premotor  area  and  the  rostral  part  of 
caudate  nucleus  play  an  important  part  in  general  orientation  of  animals  in 


JERZY    KONORSKI  I25 

space,  i.e.  in  reacting  correctly  to  directional  cues  and  in  formation  and 
retention  of  locomotor  CRs.  Therefore,  it  is  quite  reasonable  to  believe 
that  the  prefrontal  area,  or  rather  some  yet  undehned  part  of  it,  is  closely 
functionally  connected  with  these  regions  supplynig  the  reverberating 
circuits  responsible  for  recent  memory  of  those  cues  which  subserve  this 
orientation. 

But  It  seems  that  much  more  precise  analysis  of  the  relations  between 
projection  areas  and  adjacent  associative  areas  can  be  carried  out  with 
respect  to  the  recent  memory  of  exteroceptive  stimuli  on  the  basis  of  the 
test  described  in  section  3.  The  corresponding  experiments  were  performed 
by  Chonjzyna  and  L.  St^pieh  in  our  laboratory  (unpublished).  After  the 
dogs  were  trained  to  differentiate  between  pairs  of  identical  tones  (SxSx) 
and  different  tones  (SxS>),  the  areas  situated  ventral  to  the  auditory  projec- 
tive area,  namely  gyrus  sylviacus  anterior  and  posterior  (Fig.  3),  were 
bilaterally  removed.  After  this  operation  the  dogs  lost  completely  and 
irreversibly  the  ability  to  differentiate  such  pairs,  although  not  only  simple 
differentiations,  but  even  conditioned  inhibition  (see  footnote  on  page  6) 
was  fully  preserved  (Fig.  4).  In  other  words,  the  animal  was  able  to  differ- 
entiate between  the  auditory  stimulus  S  —  positive  CS  —  and  the  auditory 
compound  SnS  —  inhibitory  CS  —  because  stimulus  So  elicited  a  negative 
attitudiual  reaction  which  was  retained  or  remembered  during  the  action 
of  S. 

On  the  other  hand  ablation  of  the  prefrontal  area  did  not  impair  the 
performance  of  our  test.^  This  shows  that  the  prefrontal  area  has  probably 
nothing  to  do  with  recent  memory  of  auditory  stimuli.  It  is  of  interest  to 
note  that  partial  bilateral  ablations  of  the  auditory  projection  area  also  did 
not  affect  this  test. 

Similar  results  were  obtained  by  Goldberg  ct  al.  (1957)  in  cats.  After 
bilateral  removal  of  ventral  parts  of  the  temporal  region  discrimination 
between  groups  of  tones  which  differed  only  in  temporal  patterning  was 
lost,  although  simple  tonal  discriminations  were  preserved. 

Even  more  convincing  experiments  were  recently  performed  by 
St(t^pieh  ct  al.  (personal  communication).  These  authors,  as  mentioned 
before,  used  our  test  for  investigating  visual  and  auditory  recent  memory 
in  monkeys.  After  the  animals  were  trained  to  differentiate  between 
pairs  of  identical  and  different  rhythmical  stimuli,  both  acoustic  (clicks) 
and  visual  (flashes),  different  parts  of  the  temporal  lobes  were  bilaterally 

1  After  prefrontal  ablation  the  animal  was  disinhibited  for  several  weeks  (Brutkowski  et  al., 
1956)  and  therefore  displayed  a  positive  reaction  to  both  excitatory  and  inhibiting  stimuli, 
but  this  defect  was  soon  totally  compensated. 


126 


BRAIN    MECHANISMS    AND    LEARNING 


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JERZY    KONORSKI  I2J 

removed.  After  ablation  of  the  anterior  parts  of  the  first  and  second 
temporal  gyri  the  differentiation  of  the  pairs  of  auditory  stimuli  was  lost, 
while  the  performance  of  the  same  test  with  visual  stimuli  was  preserved. 
The  opposite  was  found  after  the  ablation  of  the  posterior  parts  of  the 
second  and  third  temporal  gyri  and  gyrus  fusiformis. 

6.    RELATIONS    BETWEEN    RECENT    AND    STABLE    MEMORY 

It  is  now  generally  accepted  that  recent  memory  is  based  on  the  activity 
of  reverberating  chains  of  neurones,  whereas  stable,  or  permanent  memory 
is  due  to  some  structural  changes  produced  in  the  brain.  The  kind  of 
changes  with  which  wc  have  to  do  here  has  been  a  matter  of  much  specula- 
tion. One  of  the  possible  hypotheses  is  that  put  forward  long  ago  by 
Tanzi  (1893),  Ramon  y  Cajal  (191 1),  Ariens  Kappers  (1917),  Child  (1921), 
Coghill  (1929)  and  others,  and  recently  adjusted  to  the  CR  experimental 
evidence  by  Konorski  (1948).  According  to  this  hypothesis  when  an 
indifferent  stimulus  is  reinforced  by  an  unconditioned  stimulus,  the 
'potential  connections'  established  in  ontogenesis  between  the  correspond- 
ing groups  of  neurones  are  transformed  into  'actual  connections'.  This  is 
accomplished  by  growing  and  multiplication  of  synaptic  contacts  between 
the  axons  of  the  neurones  representing  the  CS  and  bodies  and/or  dendrites 
of  neurones  representing  the  UCS. 

Without  going  more  deeply  into  that  problem  one  must  notice  that 
all  structural  theories  of  conditioning  have  so  far  encountered  one  major 
difficulty :  it  is  well  known  that  quite  often  a  CR  is  formed  and  proves  to 
be  stable  even  after  a  single  reinforcement,  the  so-called  'one  trial  learning'. 
This  means  that  a  few  seconds'  simultaneous  operation  of  the  two  stimuli 
would  be  sufficient  for  the  formation  of  stable  connections  between  the 
respective  groups  of  neurones. 

Fig.  4 
The  effects  of  cortical  lesions  on  acoustic  recent  memory  in  dogs. 

Each  graph  represents  the  percentages  of  negative  (correct)  responses,  i.e.  lack  of  movement 
for  each  dog  to  the  inhibitory  CS-i  in  successive  blocks  often  inhibitory  trials. 

IT,  infratemporal  ablation,  EM,  ablation  of  gyrus  ectosylvius  mcdius,  F,  prefrontal  ablation. 
Continuous  lines,  responses  to  inhibitory  compound  stimuli,  S^Sy  (acoustic  recent  memory 
test).  Dashed  lines,  responses  to  inhibitory  stimulus  in  simple  acoustic  differentiation.  Dashed- 
dottcd  lines,  reactions  to  inhibitory  compound  of  conditioned  inhibition,  SoS. 

Arrows  in  the  course  of  tone-relation  differentiation  (SxSx  vs.  SxSy)  denote  the  end  of 
preliminary  training  in  which  only  particular  pairs  of  tones  were  applied. 

In  the  first  three  dogs  tone-relation  differentiation  was  totally  abolished  after  infratemporal 
lesion.  Both  differentiation  and  conditioned  inhibition  were  easily  established  after  operation. 
In  the  fourth  dog  bilateral  removal  of  middle  ectosylvian  gyrus  did  not  affect  the  tone- 
relation  differentiation;  the  removal  of  prefrontal  areas  caused  the  general  syndrome  of 
disinhibition  which  was  soon  compensated. 


128  BRAIN    MECHANISMS    AND    LEARNING 

This  difficulty  can  now  be  overcome  if  we  take  into  account  the  fact 
that  each  of  the  stimuh  taking  part  in  conditioning  leaves  transient  traces 
in  the  nervous  system  such  that  the  respective  central  representations  of 
the  stimuli  are  excited  for  a  much  longer  time  than  the  duration  of  the 
stimuli  themselves. 

If  the  proposed  mechanism  of  the  transformation  of  recent  memory 
traces  into  stable  memory  traces  is  correct,  then  one  should  predict  that 
cutting  the  first  ones  short  in  some  way  or  other,  for  instance  by  electro- 
convulsive shock,  would  lead  to  slowing  down  or  even  preventing  the 
process  of  conditioning. 

Such  experiments  were  in  fact  performed  by  a  number  ot  authors  and 
gave  clear  positive  results.  Duncan  (1949)  was  the  first  to  apply  ECS  after 
each  conditioning  trial  in  rats  and  he  showed  that  the  closer  the  application 
of  the  shock  is  to  the  trial,  the  stronger  is  its  disrupting  effect  upon  learn- 
ing. Later  the  co-workers  of  Gerard  (1955)  and  Thompson  and  Dean 
(1955)  applied  ECS  at  various  times  after  a  single  session  of  discrimination 
learning  and  again  proved  that  the  shorter  the  interval  between  the 
learning  session  and  the  shock,  the  poorer  is  the  animal's  retention  after 
24  hours. 

All  these  data  show  that  after  the  termination  of  the  learning  trial,  or  a 
massed  series  of  trials,  the  consolidation  of  the  CR  continues  and  that  this 
phenomenon  depends  on  some  on-going  process  in  the  nervous  system. 
It  is  quite  reasonable  to  believe  that  this  is  exactly  the  same  process  which  is 
involved  in  the  recent  memory  phenomena  described  in  earlier  sections. 

The  important  role  played  in  the  formation  of  CRs  by  recent  memory 
may  explain  some  other  facts  connected  with  learning  which  would 
otherwise  be  difficult  to  understand.  It  has  been  shown  by  Chow  (195 1), 
Mishkin  and  Pribram  (1954)  and  others  that  the  ablation  of  posterior 
ventral  parts  of  the  temporal  lobes  in  monkeys  abolishes  or  greatly 
impairs  visual  discriminations  established  before  operation.  However, 
Orbach  and  Faiitz  (1958)  found  recently  that  if  before  operation  the 
animals  were  given  prolonged,  post-criterional  overtraining,  then  the 
discrimination  habit  suffered  little  or  no  decrement  after  inferotemporal 
lesions.  If  we  assume  that  the  'learning  to  criterion'  of  a  visual  discrimina- 
tion is  largely  based  on  recent  memory,  i.e.  that  the  animal  remembers 
from  trial  to  trial  and  from  day  to  day  which  figure  is  positive  and  which 
negative,  then  this  would  explain  why  after  a  partial  destruction  of  the 
visual  association  area  the  habit  is  greatly  impaired.  On  the  other  hand  if 
with  long  training  the  habit  becomes  based  on  stable  memory,  then  no 
post-operative  deficit  would  ensue.  It  is  worth  while  to  stress  that  the 


JERZY    KONORSKI  129 

ablation  of  the  same  area  in  monkeys  produced  a  total  abolition  of  recent 
memory  of  visual  stimuli  tested  by  our  method  in  recent  experiments  by 
Stfpieii  ct  ill. 

To  sum  up,  we  believe  that  the  inferotemporal  area  in  monkeys  contains 
reverberating  chains  of  neurones  connected  with  the  visual  projection  area 
and  therefore  lesions  in  this  area  produce  the  deficit  of  recent  memory 
observed  either  directly  by  using  our  test,  or  indirectly  by  using  not  very 
firmly  established  visual  discrimination  habits. 

To  end  this  section  it  is  necessary  to  draw  attention  to  the  striking 
deficits  of  recent  memory  found  in  recent  years  in  humans  after  hippo- 
campal  lesions  (Milner  and  Penticld,  1955;  Scoville  and  Milner,  1957;  and 
others).  Similar  results  were  recently  obtained  after  hippocampal  lesions  in 
monkeys  by  St^pieii  et  al.  with  respect  to  both  visual  and  auditory  stimuli. 
The  physiological  mechanism  of  these  deficits  seems  to  us  so  far  not  clear 
and  they  require  more  detailed  investigation. 

SUMMARY 

In  this  paper  the  general  review  of  the  existing  experimental  material 
concerning  recent  memory  in  animals  is  presented  and  possible  mechan- 
isms of  this  phenomenon  are  discussed. 

It  has  been  shown  that  recent  memory  is  involved  in  trace  CRs  (section  i ) , 
in  delayed  responses  (section  2)  and  in  those  forms  of  CRs  in  w^hich,  in 
order  to  display  a  correct  response  the  animal  has  to  compare  two  succes- 
sive stimuli  (section  3).  It  has  been  assumed  that  the  mechanism  of  recent 
memory  depends  on  throwing  into  activity  reverberating  circuits  of 
neurones,  connected  with  neurones  engaged  in  perception  of  a  given 
stimulus,  and  probably  situated  in  the  so-called  association  areas  surround- 
ing the  given  projection  area  (section  4).  As  delayed  responses  appear  to  be 
based  on  the  recent  memory  of  directional  cues,  it  is  understandable  that 
they  are  destroyed  after  lesions  in  prefrontal  cortex  situated  in  the  vicinity 
of  premotor  area  and  caudate  nucleus,  structures  directly  concerned  with 
the  animal's  orientation  in  space.  Similarly  acoustic  recent  memory  is 
destroyed  by  lesion  in  gyri  sylviaci  in  dogs  and  cats  and  anterior  parts  of 
temporal  gyri  in  monkeys;  visual  recent  memory  is  destroyed  after 
inferotemporal  lesions  in  monkeys  (section  5). 

Recent  memory  plays  a  prominent  role  in  the  consolidation  processes  of 
conditioning,  since  it  causes  a  much  more  prolonged  activation  of  groups 
of  neurones  concerned  in  a  given  conditioning  than  is  provided  by  the 
actual  operation  of  the  corresponding  stimuli  (section  6).  Therefore,  the 


130  BRAIN    MECHANISMS    AND    LEARNING 

more  powerful  is  the  reverberating  system  of  neurones  within  a  given 
analyser  in  a  given  species,  the  more  perfect  and  long  lasting  is  the  recent 
memory  of  the  corresponding  stimuli  and  the  more  rapid  is  the  process  of 
consolidation  of  the  respective  CRs. 


GROUP  DISCUSSION 

RosvoLD.  I  would  like  to  ask  Dr  Konorski,  from  the  point  of  view  of  the  position 
put  forth  in  his  paper,  how  he  would  account  for  the  fact  that  in  the  literature  there 
are  many  papers  that  deal  with  the  impairment  of  sensory  discrimination  following 
frontal  lobe  lesions. 

Konorski.  As  we  have  established  in  our  laboratory,  prefrontal  ablations  produce 
two  different  sorts  of  impairment:  one  is  that  discussed  in  this  paper,  namely  the 
loss  of  recent  memory  of  directions  involved  in  delayed  response  tests ;  the  second 
is  the  impairment  of  inhibitory  conditioned  reflexes.  While  the  first  one  is, 
according  to  our  data,  irreversible,  the  second  one  is,  on  the  contrary,  compensated 
with  further  training.  It  is  clear  that  the  symptom  described  in  Rosvold  and 
Mislikin's  paper  belongs  to  the  second  category.  We  suppose  that  both  these 
symptoms  are  of  different  origin  and  mechanism,  and  we  try  now  to  check  this 
supposition  by  experiments. 

Rosvold.  With  reference  to  the  permanence  of  these  deficits,  I  would  say  that 
contrary  to  Jacobsen's  earlier  statements,  in  the  chimpanzee  the  deficit  is  not 
permanent.  Instead  with  training  the  animals  gradually  recover  their  ability  to 
perform  very  well  on  tests  of  recent  memory.  The  chimpanzee  tells  us  another 
thing:  a  subjective  thing  to  be  sure,  but  we  can  see  in  watching  the  animals  no 
evidence  that  orientation  is  a  critical  factor  for  those  tests.  In  fact  it  is  not  unusual 
for  the  animal  to  be  standing  on  his  head  when  looking  at  the  stimulus,  and  then 
turn  completely  over  and  respond  correctly.  Thus,  even  though  this  notion  of 
proprioceptive  recent  memory  being  the  unique  function  of  the  frontal  lobes  is 
intrigunig,  I  am  not  entirely  convinced  that  it  is  the  answer  to  delayed  response 
deficit.  As  Dr  Konorski  stated,  we  simply  do  not  know  what  the  stimulus  factors 
in  the  delayed  response  problem  really  are.  We  have  assiduously  tried  to  determine 
what  it  is  in  this  problem  that  the  animal  is  responding  to  or  by  what  means  he  is 
responding.  We  have  not  been  able  to  demonstrate  definitely  what  it  is  in  the  test 
situation  that  the  animal  uses  as  the  basis  for  his  solution  of  the  problem.  This  is 
why  there  is  so  much  speculation  about  the  probable  function  of  the  frontal  lobes. 
Probably  the  only  resolution  is  the  development  of  a  test  method  in  which  the 
stimulus  and  response  variables  will  be  clearly  delineated. 

Hebb.  I  would  like  to  add  to  this  that  bilateral  total  removal  in  another  species 
produces  no  sign  of  defect:  even  better  than  in  the  chimpanzee. 

Konorski.  In  man,  yes. 

EsTABLE.  I  am  very  much  interested  in  Professor  Konorski's  communication 
that  gives  rise  to  so  many  problems.  Obviously  the  only  objection,  if  it  can  be 
called  that,  is  that  we  have  on  one  side  techniques  to  study  the  central  nervous 
system  and  on  the  other  side  techniques  to  study  psychological  problems,  and  the 
bridge  is  always  there,  but  it  is  hard  to  correlate  and  the  passage  from  one  to  the 
other  is  hard  to  interpret. 


JERZY   KONORSKI  I3I 

One  must  be  precise  with  terms  and  when  one  says  centre,  for  instance,  one 
must  not  think  that  the  centre  of  the  spoken  word  means  that  the  spoken  word  is 
venerated  there.  If  a  cortical  area  is  destroyed  and  the  spoken  word  is  perturbed  or 
disappears,  all  that  one  can  say  is  that  the  cortical  area  is  necessary  but  not  surticient 
for  the  reproduction  of  the  spoken  word. 

The  fact  that  neurones  are  incapable  ot  reproducing  themselves  is  perhaps  the 
price  we  have  to  pay  to  have  memories  and  habits  and  other  learned  capacities 
which  persist  throughout  life.  If  neurones  died  and  were  substituted  by  others,  it 
is  hard  to  conceive  how  these  functions  could  be  preserved. 

Reverberation  circuits  may  be  the  basis  of  learning  but  perhaps  they  are  not 
enough.  Do  vou,  Dr  Konorski,  conceive  as  diiferent  phenomena:  habits,  organic 
memory  and  memory  itself? 

Konorski.  As  far  as  I  know  in  dogs  and  in  monkeys  the  loss  of  recent  memory  of 
directions  after  prefrontal  ablations  is  irreversible.  JVIoreover,  in  some  of  our 
annuals,  there  was  only  a  partial  deficit  of  recent  memor)',  due  perhaps  to  smaller 
lesions.  Why  in  Dr  Rosvold's  chimpanzee  the  deficit  of  recent  memory  is  rever- 
sible, should  be  explained  by  further  experimentation.  As  far  as  patients  with  pre- 
frontal lesions  are  concerned,  they  are  able  to  solve  the  delayed  response  test  very 
well.  We  believe  that  it  is  so  because  their  memory  of  directions  is  supported,  or 
even  based,  on  visual  cues  and  also  on  verbal  recent  memory  which  in  man,  is  very 
powerful. 

I  agree  that  we  are  not  able  so  tar  to  state  definitely  which  sorts  ot  cues  are 
responsible  in  delayed  response  tests,  although  it  seems  that  this  problem  may  be 
solved  by  further  experimentation. 

To  answer  Professor  Estable,  I  would  like  to  stress  once  more  that,  according  to 
our  view,  conditioned  reflexes,  including  habits  as  a  particular  form,  are  chiefly 
based  on  stable  or  static,  or  organic  memory,  while  such  forms  of  behaviour  which 
are  involved  in  delayed  responses  are  based  on  transient  or  dynamic  memory. 

Olds.  I  wish  to  address  myself  to  the  experiments  where  the  so-called  auditory 
association  areas  were  removed,  and  where  Dr  Konorski  says  his  experiment  was 
on  recent  memor\-,  for  an  auditory  stimulus.  I  wish  to  suggest  the  possibility  that 
these  were  not  experiments  on  recent  memory  at  all,  but  possibly  on  the  animal's 
ability  to  compare  two  stimuli.  It  seems  to  me  that  the  way  this  could  be  tested  is 
to  have  the  stimulus  and  the  comparison  stimulus  (another  S^  or  Sy)  presented 
somehow  simultaneously.  If  the  deficit  is  hi  the  animal's  ability  to  compare,  he 
will  fail  this  test.  If  it  is  in  recent  memory,  he  will  pass.  One  might  also  ask  the 
question  of  the  delayed  response  technique  again  here  and  ask  if  it  is  really  fair  to 
reject  the  delayed  response  as  a  test  for  recent  memory  of  a  particular  (e.g.  auditory) 
stimulus.  One  might  develop  some  text  in  which  a  given  tone  Sx  would  not  signify 
a  direction  but  an  abstract  contingency  and  find  whether  excision  o(  the  auditory 
association  areas  prevented  an  auditory  memory  which  involved  no  comparison. 

Konorski.  As  to  the  first  question  of  Dr  Olds  I  agree  that  the  test  proposed  b)'  us 
is  based  on  comparison  of  two  stimuli,  wliich  is  rendered  impossible  by  the  loss  of 
recent  memor)-.  Whether  or  not  there  is  any  special  function  which  may  be  called 
'comparison'  —  I  do  not  know. 

As  to  the  second  question  I  would  remind  that,  as  shown  in  my  paper,  the 
removal  of  pre-frontal  areas  did  not  impair  the  recent  memory  of  particular 
auditory  stimuli,  as  proved  by  our  recent  memory  test. 

E 


132  BRAIN    MECHANISMS    AND    LEARNING 

Anokhin.  I  should  like  to  make  two  comments  on  Dr  Konorski's  very  interest- 
ing report.  The  brain,  as  a  specific  substance  has  two  possibilities  for  'remember- 
ing', each  of  which  can  be  related  to  what  Dr  Konorski  relates  to  'recent  memory'. 
There  is  first  of  all  the  ability  of  a  nervous  substance  to  associate  any  successive 
stimuli  coming  trom  the  inner  or  outer  world  ot  the  organism.  On  account  of  its 
ability  to  conduct  stimuli  rapidly  and  multilateralK'  and  oi  its  ability  to  retain  in 
the  synaptic  systems  the  molecular  changes  which  have  taken  place,  the  nervous 
tissue  'remembers'  any  succession  of  stimuli  brought  upon  it.  That  is  the  most 
direct  and  universal  memory  which  fits  under  the  name  of 'recent  memory'. 

Tliis  memory,  however,  represents  a  specific  advance  effected  by  the  nervous 
system  in  relation  to  the  acting  agents  of  the  outside  world. 

For  a  given  association  to  become  stable,  it  has  to  end  by  a  strong  emotional 
discharge,  i.e.  has  to  end  by  some  event  which  is  meaniiigtul  for  the  life  of  the 
organism. 

Thus  in  my  view,  to  study  the  physiological  mechanisms  of  'recent  memory' 
consists  basically  in  discovering  those  concrete  processes  which  occur  as  a  result  of 
emotional  discharges  and  spread  in  the  direction  of  the  cerebral  cortex,  retaining 
there  fleeting  temporary  associations. 

As  is  shown  by  the  unavoidable  extinction  of  desynchronization  when  training 
for  the  association  'sound-light',  a  final  consolidation  of  such  ephemeral  associa- 
tions is  indispensable. 

AsRATYAN.  Food  boxcs  are  very  important  factors  in  recent  memory.  Do  you 
think  the  rule  of  the  tonic  conditional  reflex,  as  we  name  it,  plays  a  role  in  this 
recent  memory? 

BusER.  I  wish  to  ask  Dr  Konorski  if  he  has  some  information  on  the  thalamic 
connections  of  the  cortical  areas  which  were  ablated  in  his  experiments. 

Konorski.  I  tliink  that  Asratyan's  'tonic  conditioned  reflexes'  are  based  on  the 
same  principles  as  ordinary  conditioned  reflexes,  i.e.  when  firmly  established,  they 
are  due  to  stable  memory  traces. 

Our  lesion  producing  the  loss  of  delayed  responses  comprised  gyrus  proreus, 
subproreus  and  the  anterior  part  of  gyrus  orbitalis.  The  vessels  in  presylvian  sulcus 
were  usually  spared.  These  lesions  produce  degeneration  in  dorso-medial  nucleus 
of  the  thalamus.  Other  desenerations  were  not  so  far  studied. 


CONDITIONED  REFLEXES  ESTABLISHED  BY  COUPLING 
ELECTRICAL  EXCITATION  OF  TWO  CORTICAL  AREAS^ 

R.  W.  Doty  and  C.  Giurgea 

Is  the  mere  coincidence  of  action  of  two  stimuli  sutiicient  to  form  a 
learned  association  between  them,  or  is  some  motivational  factor  also 
required?  This  has  been  a  persistent  question  in  psychology  (and  psy- 
chiatry) and  is  of  major  importance  in  any  attempt  to  solve  the  riddle  of 
the  neural  mechanisms  subserving  learning.  Human  experience  is  too 
complex  to  provide  an  answer  despite  the  long  history  of  'associationism' 
as  a  science.  In  animal  experimentation,  on  the  other  hand,  it  has  been 
difficult  to  demonstrate  learning  or  establish  conditioned  reflexes  when 
motivation  or  'drive  reduction'  have  been  unequivocally  absent. 

The  pertinent  evidence  has  been  reviewed  elsewhere  (Giurgea,  1953a). 
The  experiments  of  Loucks  (1935),  however,  are  of  special  interest  since 
they  are  the  direct  antecedents  of  our  own.  In  several  dogs  Loucks 
stimulated  the  'motor'  cortex  through  permanently  implanted  electrodes 
effecting  a  movement  of  one  of  the  animal's  limbs.  With  each  animal  on 
as  many  as  600  occasions  over  several  days  he  preceded  the  motor  stimula- 
tion with  an  auditory  conditional  stimulus  (CS).  The  CS  never  came  to 
evoke  the  movement  with  which  it  was  so  thoroughly  paired,  nor  any 
other  movements.  A  food  reward  was  then  introduced  to  follow  the  CS 
and  the  induced  movement.  Within  a  few  trials  the  animal  began  moving 
to  the  CS.  Loucks  drew  the  justifiable  conclusion  from  these  experiments 
that  the  motivational  element  was  essential  to  the  formation  of  conditioned 
reflexes  and  these  results  have  had  a  wide  and  well-deserved  influence  on 
psychological  theory  since  that  time. 

Louck's  position  was  apparently  conhrmed  by  Masserman  (1943)  who 
failed  to  obtain  any  signs  of  conditioning  when  stimulation  of  the 
hypothalamus  was  used  as  US.  However,  Brogden  and  Gantt  (1942)  were 
able  to  produce  movements  by  presenting  a  CS  alone  after  repeated  pair- 
ing of  CS  and  stimulation  of  the  cerebellum.  In  some  animals  the  'condi- 
tioned response'  (CR)  so  elicited  was  very  similar  to  the  movement 
induced  by  cerebellar  stimulation.  Motivation  seemed  to  be  absent  here. 

1  New  research  reported  here  was  supported  by  grants  to  R.  W.  Doty  from  the  Foundations' 
Fund  for  Research  in  Psychiatry  and  the  National  histitutcs  of  Neurological  Diseases  and  Blind- 
ness (B-1068),  and  by  a  travel  grant  to  C.  Giurgea  from  the  Academy  of  the  Rumanian 
Peoples  Republic. 


134  BRAIN    MECHANISMS    AND    LEARNING 

In  195  r,  while  working  in  the  laboratories  of  P.  S.  Kupalov  seeking  further 
confirmation  of  the  hypothesis  of 'shortened  conditioned  reflexes',  it  was 
discovered  that  conditioned  reflexes  could  readily  be  formed  by  pairing 
stimuli  at  two  cortical  points  (Giurgea,  1953  a,  b).  Stimulation  of  occipital 
cortex  w^hich  is  initially  without  apparent  effect  ultimately  produces 
movement  highly  similar  to  that  elicited  by  the  stimulation  of  the  sigmoid 
gyrus  with  which  it  is  paired.  This  direct  contradiction  of  the  results  of 
Loucks  seems  best  explained  by  differences  in  the  timing  of  presentation 
of  stimuli.  In  all  his  experiments  Loucks  (1935)  used  intertrial  intervals  of 
2  minutes  or  less,  usually  30-60  seconds,  whereas  an  intertrial  interval 
of  3-5  minutes  was  used  in  our  experiments.  If  the  intertrial  interval  is 
reduced  to  2  minutes  even  after  such  CRs  have  been  established,  the  CRs 
disappear  in  the  majority  of  dogs  tested  so  far  (Giurgea,  1953  a,  b), 
although  the  unconditioned  response  (UR)  is  unaffected. 

Continuing  these  studies,  it  has  been  shown  that  formation  of  CRs  by 
cortical  stimulation  is  not  dependent  upon  sensory  endings  in  the  meninges 
since  the  CR  may  be  readily  established  after  destruction  of  the  Gasserian 
ganglion  (Raiciulescu,  Giurgea  and  Savescu,  1956).  A  CR  established  to 
stimulation  of  parietal-occipital  cortex  as  CS  was  also  elicited  by  a  tonal  or 
photic  CS  (Giurgea  and  Raiciulescu,  1957).  In  two  animals  with  total, 
histologically  confirmed  section  of  the  corpus  callosum  CRs  were 
established  even  though  CS  and  US  were  applied  to  different  hemispheres 
(Raiciulescu  and  Giurgea,  1957;  Giurgea,  Raiciulescu  and  Marco vici, 
1957).  The  electrical  activity  recorded  from  the  US  area  does  not  appear 
to  be  changed  by  this  conditioning  procedure  and  is  within  normal  limits 
of  low  voltage,  fast  activity  very  shortly  after  the  US  is  applied  (Giurgea 
and  Raiciulescu,  1959).  In  none  of  these  experiments  does  the  behaviour  of 
the  dogs  indicate  even  the  slightest  element  of  motivation.  This  impres- 
sion has  now  been  conhrmed  objectively  in  the  experiments  reported 
below. 

TECHNIQUE 

The  experiments  at  Michigan  have  so  fir  been  performed  on  four  dogs, 
two  cats  and  two  cynomolgous  monkeys.  The  dogs  are  restrained  easily 
by  placing  their  legs  through  plastic  loops  (e.g.  Fig.  i).  Cats  are  held  by 
placing  their  heads  through  a  heavy  plastic  stock  leaving  their  limbs  free. 
Monkeys  are  kept  permanently  seated  in  a  Lilly-type  chair  (Mason,  1958). 
All  animals  are  adapted  to  restraint  prior  to  electrode  implantation. 
During  the  experiment  the  animals  are  isolated  and  observed  through  a 
'one-way'  glass. 


R.    W.    DOTY    AND    C.    GIURGEA  I35 

The  cortex  is  stimulated  through  platinum  electrodes,  usually  resting 
on  the  pial  surface  or  just  beneath  it  although  in  some  dogs  the  thickness 
of  the  skull  made  such  adjustment  difficult.  Two  of  four  electrodes  are 
carried  in  7  mm.  diameter  plastic  buttons  which  are  held  in  trephine  holes 
by  means  of  screws  (Doty,  Rutledge  and  Larsen,  1956).  Flexible  0.5  mm. 
diameter  polyethylene  insulated  wires  connect  the  electrodes  to  an  1 8  or 
34  contact  receptacle  permanently  secured  to  the  skull  by  stainless  steel 
posts  (Doty,  1959). 

Stimulation  consists  of  i  msec,  rectangular  current  pulses  at  a  frequency 
of  50/sec.  and  is  monitored  on  a  cathode-ray  oscilloscope  with  a  long- 
persistence  screen.  Great  care  is  taken  to  keep  the  stimulating  circuits  and 
the  animals  isolated  from  ground  and  to  avoid  any  other  possibility  of 
stimulation  outside  that  intended. 

Prior  to  pairing  CS  and  US  the  effects  of  stimulation  are  observed  for 
each  electrode  pair.  It  is  advantageous  to  have  several  pairs  of  electrodes 
in  'motor'  cortical  areas  so  that  the  chances  are  increased  for  procuring  a 
relatively  simple  movement  to  serve  as  an  UR.  By  means  of  automatic  and 
silent  control  the  CS  is  presented  for  3-4  seconds  and  is  slightly  overlapped 
by  the  US  of  1-1.5  seconds  duration.  Six  to  ten  combinations  of  CS  and 
US  are  made  daily. 

After  study  of  CS-US  coupling  is  complete,  the  animals  are  trained  in 
the  same  experimental  chamber  to  press  a  lever  to  obtain  food.  The  lever 
is  then  connected  to  administer  cortical  stimulation  with  each  press. 

RESULTS 

Doi^  Alplhi.  All  stimulatit)n  in  the  'motor'  cortical  regions  produced 
stiff,  complex  and  unnatural  movements.  That  finally  chosen  as  an  UR 
was  a  lifting  and  extension  of  the  right  hind  leg,  a  slight  lifting  and  curling 
of  the  tail,  and  a  rotation  of  the  head  to  the  midline  and  down  (Fig.  1). 
The  US  was  1.8  mA.  applied  just  posterior  to  the  left  postcrucial  sulcus. 
The  CS  of  r.i  niA.  was  applied  to  the  left  posterior  suprasylvian  gyrus.  It 
elicited  no  response  for  the  first  forty-two  CS-US  pairings.  The  CS 
current  was  then  increased  to  2.2  mA.  and  elicited  an  opening  of  the  eyes 
and  turning  of  the  head  to  the  right,  a  response  judged  to  be  inherent  to 
stimulation  of  this  area.  It  was  still  obtained,  when,  later  in  the  experiment, 
the  CS  was  again  reduced  to  i.o  mA.  The  first  distinct  CR  was  seen  on  the 
thirtieth  post-operative  day  after  108  CS-US  pairings.  It  was  a  turning  of 
the  head  to  the  midline  and  down,  a  movement  similar  to  the  head  move- 
ment seen  to  the  US  and  in  opposition  to  that  inherently  evoked  by  the 


136 


BRAIN    MECHANISMS    AND    LEARNING 


CS.  Movement  of  the  leg  or  tail  was  never  elicited  by  the  CS.  This  CR 
subsequently  occurred  up  to  lOO  per  cent  of  the  time  in  some  sessions  and 
had  a  threshold  of  about  0.3  mA.  It  could  also  be  elicited  by  0.4  niA. 
applied  to  a  second  pair  of  electrodes  about  2  mm.  distant  from  the 
original  CS  pair. 


Fig.  I 
Unconditioned  response  o(  Do^  Alpha  to  stimulation  just  posterior  to  left  postcrucial  sulcus. 


The  same  CR  was  evoked  by  a  CS  of  3  seconds  clicks  after  one  session 
(eight  trials)  combining  this  CS  with  the  UR.  A  second  UR  was  coupled 
with  9/seconds  clicks  as  CS.  This  at  first  produced  the  previous  CR  which 
gradually  became  modified  to  a  sidewise  oscillation  of  the  head  with  nose 
pointing  down.  This  new  'CR',  however,  had  nothing  in  common  with 
the  second  UR. 

It  was  very  difficult  to  teach  this  dog  to  eat  in  the  experimental  situation. 
Once  trained,  however,  the  animal  pressed  the  lever  repeatedly  despite 
accompanying  CS  or  US  stimulation  which  in  the  case  of  the  US  produced 
violent  movements.  In  contrast,  if  the  side  of  the  cage  was  tapped  gently 
each  time  the  lever  was  pressed,  two  or  three  taps  abolished  all  pressing 
for  the  rest  of  the  session. 


R.    W.    DOTY    AND    C.    GIURGEA  1 37 

Dog  Beta.  A  us  of  2.0  niA.  at  the  right  postcruciatc  gyrus  produced  a 
brisk,  well-integrated  flexion  of  the  left  hind  leg  as  its  only  apparent 
effect.  The  CS  at  the  right  marginal  gyrus  gave  no  overt  sign  at  intensities 
up  to  2.2  mA.  The  hrst  sign  of  movement  to  this  CS  occurred  during  the 
sixth  session,  forty-fifth  pairing.  The  slight  tossing  of  the  head  and 
indefniite  movements  such  as  stepping  or  shifting  posture  seen  then  sub- 
sequently became  very  common.  On  the  sixty-sixth  piairing  two  lo-cm. 
flexions  of  the  left  hind  leg,  held  for  about  i  second  each,  were  seen  as  the 
only  movement  to  the  CS.  This  was  the  first  CR.  This  type  of  CR  occurred 
seventy-four  times  in  171  subsequent  CS  presentations  (including  extinc- 
tion) and  had  a  threshold  of  0.95  mA.  It  was  not  extinguished  by  eighty- 
four  presentations  of  the  CS  alone  at  2-3  minute  intervals  for  eleven 
sessions.  These  CRs  were  also  obtained  to  stimulation  ofthe  right  posterior 
cctosylvian  gyrus  indicating  some  generalization  had  occurred. 

Technical  difficulties  prevented  testing  this  dog  in  the  lever-pressing 
situation.  However,  the  animal  was  extraordinarily  sensitive  and  yelped 
violently  even  when  grasped  gently  by  the  scruff"  of  the  neck.  Yet  there 
was  no  evidence  of  pain  or  emotion  during  the  training  sessions,  and  the 
animal  ran  each  day  to  the  experimental  room  and  jumped  into  the 
enclosure  to  be  harnessed. 

Dog  Gallium.  Stimulation  at  0.4  mA.  1.5  mm.  above  the  right  pyramid 
in  the  field  H^  of  Forel  was  used  as  US.  It  produced  a  forceful  extension  of 
the  neck  and  rotation  ofthe  head  over  the  right  shoulder,  wider  opening 
ofthe  eyes,  flaring  ofthe  nostrils  and  occasionally  a  lilting  ot  the  right  lip 
(Fig.  2).  This  response  was  elicited  sixty-eight  times  in  ten  sessions  with  no 
particular  alteration  in  the  animal's  behaviour.  Pairing  ofthe  US  with  a 
CS  of  3/second  clicks  was  then  begun.  A  CR  of  turning  the  head  up  and 
130°  right  was  elicited  by  the  CS  on  the  sixteenth  trial  and  similar  CRs 
occurred  on  forty-eight  of  ninety-six  subsequent  presentations.  The  CS 
also  evoked  great  agitation,  whining  and  yelping.  Both  the  CRs  and  this 
agitation  to  the  CS  were  extinguished  in  three  sessions  totalling  twenty- 
two  presentations  of  the  CS  alone. 

Lever-pressing  behaviour  was  little  altered  by  coupling  with  stimulation 
ofthe  postcruciate  gyrus  producing  a  hind-leg  left.  It  was  slowed  greatly 
by  the  click  CS  or  other  sounds,  and  abolished  immediately  by  the  US. 

Dog  Epsiloii.  Stimulation  at  right  or  left  postcruciate  gyri  produced  well 
co-ordinated,  maximal  flexions  of  left  or  right  forelegs  respectively. 
Stimulation  of  left  posterior  ectosylvian  gyrus  with  1.8  mA.  or  right  mid- 
marginal  gyrus  with  1.6  mA.  produced  no  response  when  tested  initially. 
Stimulation  at  the  latter  points  was  then  used  as  CS  and  at  the  former  as 


138 


BRAIN    MECHANISMS    AND    LEARNING 


US.  For  convenience  the  prefix  'R'  or  'L'  will  be  used  to  designate  to 
which  hemisphere  the  stimulus  was  applied,  e.g.  L-CS  with  R-US  means 
CS  applied  to  left  posterior  ectosylvian  gyrus,  US  to  right  post  cruciate. 
For  the  first  forty  pairings  of  R-CS  with  R-US  there  was  no  response  to 
the  R-CS.  During  the  next  few  sessions  the  R-CS  frequently  elicited  a 
lowering  of  the  head  and  flexion  of  the  right  foreleg  as  shown  in  Fig.  3, 
i.e.  the  limb  opposite  that  in  which  the  UR  was  induced.  The  first  left 


Fig.  2 

Unconditioned  response  of  Dog  Gainuui  to  stnnulation  in  right 

field  Hi  of  Forel. 

foreleg  CR  occurred  on  the  eighty-first  presentation  of  R-CS  and  in  the 
next  113  trials  occurred  hfty-cight  times.  These  CRs  were  discrete,  4-20 
cm.  elevations  of  the  left  foreleg  held  for  several  seconds  and  frequently 
returned  to  the  floor  prior  to  the  UR.  The  threshold  for  CR  elicitation  was 
0.5-0.7  niA.  Other  movements,  not  so  specific,  occurred  regularly,  so  that 
movement  now  occurred  95  per  cent  of  the  time  to  this  CS. 

L-CS  was  now  paired  four  times  with  R-US,  and  except  for  the  first 
presentation  produced  flexions  of  the  right  foreleg  (again  opposite  to  the 
UR)  each  time.  Two  sessions  later  differentiation  was  begun  and  continued 


R.    W.    DOTY    AND    C.    GIURGEA 
Table  I 

INITIAL    FAILURE    OF   DIFFERENTIATION    IN    DOG    EPSILON 


139 


Stiiuiiliis  location       Total  differentiation  trials 


LFL  CRs    RFL  'CRs' 


R-CS,  R-US 
L-CS,  no  US 


50 
44 


14 


for  twelve  sessions  with  results  as  shown  in  Table  I.  Obviously  no  differen- 
tiation occurred  under  these  conditions;  CRs  were  maintained  to  stimula- 
tion of  cither  area  though  the  percentage  of  occurrence  to  R-CS  may  have 
declined. 


Fig.  3 
One  of  the  first  conditioned  responses  of  Dog  Epsilon  to  stimulation  of  right  marginal  gyrus. 
At  this  time  the  CR  is  in  the  'wrong'  leg,  but  in  subsequent  trials  the  left  foreleg,  the  one  lifted 
to  the  US,  lifted  to  this  CS  (Doty,  1959). 


It  is  characteristic  of  these  animals  (Giurgea,  1953  a,  b)  that  just  prior  to 
the  appearance  of  the  first  CRs  and  frequently  thereafter,  movements  of 
the  affected  limb  occur  sporadically  during  the  intertrial  period.  This 
phenomenon  was  observed  in  Dogs  Beta  and  Epsilon.  These  movements 


140  BRAIN    MECHANISMS    AND    LEARNING 

might  possibly  arise  from  some  'irritative'  process  consequent  to  the 
repeated  presentation  of  the  US,  but  the  following  experiments  show  this 
is  not  the  case.  Using  the  usual  timing  and  parameters,  the  L-US  alone 
was  presented  lOO  times  in  twelve  sessions  producing  a  forceful  right  fore- 
leg flexion  each  time.  No  spontaneous  lifts  of  this  limb  occurred  in  this 
period.  Another  150  presentations  were  then  given  in  which  L-US 
preceded  L-CS  by  irregular  intervals.  Initially  L-CS  still  gave  some  left 
foreleg  CRs  or  other  movements,  but  these  reactions  were  extinguished  by 
this  procedure  since  for  the  last  seventy  presentations  there  was  no  response 
whatever  to  L-CS.  Orthodox  temporal  relations  for  L-CS  and  L-US  were 
then  used.  At  first  this  restored  the  nonspecific  movements,  then  left 
foreleg  CRs  and  ultimately  right  foreleg  CRs  occurred  about  50  per  cent 
of  the  time  to  L-CS  at  a  threshold  of  0.7  mA. 

The  R-CS  was  then  presented  for  the  first  time  in  79  days.  The  left 
foreleg  was  lifted  15  cm.,  flexing  at  the  wrist,  and  was  held  so  for  about 
5  seconds.  Ultimately  it  was  possible  to  obtain  right  leg  flexions  to  L-CS 
and  left  leg  flexions  to  R-CS. 

Coupling  L-CS,  L-US  or  R-US  with  the  animal's  lever-pressing  had 
no  effect,  whereas  auditory  stimuli  or  R-CS  completely  abolished  pressing. 
The  effect  of  R-CS  had  been  predictable  on  the  basis  of  behaviour  changes 
seen  as  soon  as  the  use  of  R-CS  was  resumed  (after  the  hiatus  described 
above).  Since  more  than  5  months  had  then  elapsed  from  time  of  electrode 
implantation  it  seems  likely  trigeminal  fibres  had  grown  into  this  medial 
electrode  location. 

Monkey  1.  The  CS  of  i.o  mA.  applied  to  the  left  occipital  pole  con- 
sistently produced  movement  of  the  eyes,  and  sometimes  the  head  down 
and  to  the  right.  At  any  time  during  this  stimulation,  however,  the  eyes 
might  be  moved  elsewhere  if  attention  was  so  directed.  The  0.2  mA.  US 
(300/second)  in  the  left  precentral  cortex  produced  a  smooth,  vigorous 
flexion  of  the  right  forearm  and  contraction  of  the  muscles  on  the  right  side 
of  the  neck  and  face  causing  the  mouth  to  open  (Fig.  4).  Coupling  of  the 
CS  and  US  was  begun  2  weeks  after  surgery  and  continued  for  4  weeks, 
200  trials  in  twenty-four  sessions.  In  these  200  trials  the  right  arm  made 
random  movements  during  the  CS  eleven  times.  Obviously  there  was  no 
conditioning.  During  the  next  25  weeks  the  animal  was  used  sporadically 
for  testing  various  lever-pressing  procedures  with  fruit  juice  rewards. 

Coupling  of  CS  and  US  was  then  resumed.  The  effects  of  these  stimuli 
were  still  exactly  as  they  had  been  7  months  earlier.  LJsing  a  two-minute 
intcrtrial  interval  for  the  first  fifty-one  trials  in  five  sessions  there  was  no 
sign  of  conditioning.  A  four-minute  interval  was  then  used  for  trials 


R.    W.    DOTY    AND    C.    GIURGEA 


14-1 


52  to  84.  The  first  CR  was  seen  on  the  sixty-seventh  pairing.  The  right 
arm  was  flexed  to  the  level  of  the  restraining  collar,  then  extended  along 
its  lower  surface  with  hngcrs  fluttering  as  though  seeking  an  object.  In 
the  next  forty-seven  trials  a  movement  similar  to  this  occurred  to  the  CS 
thirty-one  times.  At  the  threshold  current  of  0.55  mA.  or  during  the  later 
phases  of  subsequent  extinction  sessions  the  movement  was  more  likely  to 
be  a  simple  flexion  very  similar  to  that  evoked  by  the  US  (Fig.  4).  Even 
when  the  movement  was  vigorous,  it  often  terminated  prior  to  the  US. 


3     .? 


^^*SK 


Fig.  4 
Responses  o(  Monkey  1,  enlarged  from  a  16  mm.  colour  film  which  was  taken  through  a 
one-way  mirror.  Left  and  centre:  conditioned  flexions  of  right  forearm  to  CS  at  left  occipital 
cortex.  The  slight  inclination  of  the  head  to  the  right,  which  also  imitates  a  movement  of  the 
UR,  was  sometimes  seen  with  high  intensities  of  the  CS  before  conditioning  was  begun  and 
hence  cannot  accurately  be  considered  a  part  of  the  CR,  although  its  consistency  and  tiireshold 
of  elicitation  may  have  been  altered  by  the  conditioning  procedure.  The  CS  and  US  signal 
lights  were  used  only  during  photography.  Ri^ilit:  unconditioned  response  to  stimulation  of 
left  precentral  cortex.  Note  similarity  of  end  point  of  this  response  to  that  obtained  by  Dclgado 
from  stimulation  of  the  rhinal  fissure  (Delgado,  1959,  Fig.  i  top). 


In  ninety-one  presentations  of  the  CS  given  in  five  sessions  without  the 
US  this  CR  was  elicited  fifty-six  times.  One-minute  intervals  were 
frequently  employed.  In  two  sessions  after  repeated  presentations  of  the 
CS  without  the  US,  the  CR  was  absent  for  five  or  more  consecutive 
trials.  The  head  and  eye  movements  evoked  by  the  CS  were  still  present 
during  this  period  of  extinction.  On  several  occasions  it  was  noted,  how- 
ever, that  the  eyes  closed  at  the  onset  of  the  CS  and  the  animal  appeared  to 
drowse  even  though  the  eyes  could  be  seen  moving  beneath  the  lids. 

Stimulation  with  an  electrode  pair  within  1-}  mm.  of  those  used  as  CS 
gave  no  eye  movements  if  the  polarity  of  the  stimulus  was  negative  for  the 
electrode  separated  from  the  others  by  a  small  sulcus.  None  the  less  the 


142  BRAIN   MECHANISMS    AND    LEARNING 

CR  was  evoked  from  this  pair  with  this  pohirity  three  times  in  six  stimula- 
tions, never  using  the  US.  Stimulation  in  the  right  posterior  parietal  lobe 
elicited  eye  and  head  movements  which  were  almost  the  exact  counterpart 
of  those  elicited  by  the  CS  save  they  were  to  the  left.  No  CRs  were  elicited 
by  this  stimulation  in  nine  attempts  during  two  sessions. 

With  four-minute  intervals  and  the  same  US  there  was  no  CR  to  an 
auditory  CS  despite  no  pairings  in  nine  sessions.  After  this,  giving  the 
auditory  CS  simultaneously  with  the  CS  to  the  occipital  pole  often  pro- 
duced 'external  inhibition'  of  the  CR  to  the  latter  stimulus.  Seventeen 
tests  with  the  auditory  CS  alone  (plus  the  US)  elicited  no  CRs  even  though 
the  tests  were  given  randomly  throughout  twenty-four  presentations  in 
which  simultaneous  auditory  and  cortical  CS  (plus  US)  was  used. 

The  effect  of  coupling  various  stimuli  with  lever-pressing  was  then 
studied.  On  July  nth  the  animal  pressed  the  lever  forty-one  times  in  a 
fivc-minute  period  and  with  each  press  received  a  US  of  0.4  niA.  (double 
the  intensity  used  routinely)  which  produced  violent  movements,  and 
often  convulsive  after-discharges,  with  each  press.  There  was  no  hesitation 
whatever  in  lever-pressing  behaviour  beyond  that  attributable  to  the 
physical  handicap  consequent  to  the  induced  movement  (e.g.  Fig.  5). 
Coupling  with  cortical  CS  was  similarly  without  effect.  On  the  following 
day,  as  seen  in  Fig.  5,  a  novel  clicking  stimulus  completely  disrupted  the 
behaviour  when  coupled  with  each  lever-press. 

The  animal  was  then  taught  in  sessions  of  twenty  trials  per  day  to  press 
a  lever  to  avoid  a  shock  to  its  tail.  The  first  response  to  a  tonal  CS  occurred 
on  the  thirty-third  trial  and  a  criterion  of  twelve  avoidances  in  twenty  CS 
presentations  was  reached  in  128  trials.  Generalization  to  20/sec.  and  5/sec. 
clicks  as  CS  was  immediate.  The  cortical  CS,  however,  produced  the 
former  CR,  a  flexion  of  the  right  hand  towards  the  chin  rather  than  the 
extension  to  press  the  lever  at  the  level  of  the  abdomen.  After  twenty-five 
combinations  of  this  cortical  CS  with  the  tail-shock,  the  animal  began 
making  lever  presses  to  avoid  this  US.  It  took  more  than  100  trials,  how- 
ever, before  the  former  CR  was  fully  extinguished  under  these  conditions. 
The  threshold  for  the  shock-avoidance  response  to  cortical  CS  was  0.2 
mA.  which  is  significantly  less  than  the  0.55  niA.  threshold  at  the  same 
electrodes  for  the  flexion  CR  established  without  motivational  context. 

Monkey  2.  The  CS  and  US  elicited  responses  very  similar  to  those  seen 
in  Monkey  1  save  that  the  seizure  threshold  was  much  lower  in  this  animal 
and  the  UR  was  frequently  followed  by  a  few  clonic  movements.  The 
animal  struggled  almost  continuously  in  the  experimental  situation  (even 
when  being  given  fruit  juice)  and  no  CRs  were  ever  observed.  Using 


R.    W.    DOTY   AND    C.    GIURGEA 


143 


MONKEY  # 
12  JULY  59 


r        CLICKS        T 

14  JULY  59 


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15  JULY  59 


CLICKS       TONE 


Fig.  5 
Records  of  lever  pressing  for  grape  juice.  The  animal  is  rewarded  for  each 
press  and  this  is  recorded  by  an  upward  excursion  of  the  trace.  On  July  12th 
for  the  fivc-minute  period  labelled  'clicks'  between  the  arrows  each  lever- 
press  turned  on  a  clicking  sound  for  3  seconds  in  addition  to  operating  the 
solenoid  dispensing  the  juice.  No  tests  were  made  on  July  13th.  On  July  14th 
coupling  a  cortical  US  with  each  Icvcr-press  produced  no  disturbance  in  pressing 
behaviour  beyond  that  attributable  to  the  violence  of  the  UR.  On  July  15th  the 
same  clicking  sound  used  on  July  12th  now  no  longer  disturbs  pressing 
behaviour,  but  introduction  of  a  2000  cycle  tone  with  each  press  brought  this 
behaviour  to  a  halt.  Started  again  pressing  without  the  tone  by  administration 
of  several  'free'  millilitres  of  juice,  the  monkey  continues  to  press  with  only  a 
minor  slowing  of  rate  when  the  tone  is  presented  during  a  second  period. 


144  BRAIN    MECHANISMS    AND    LEARNING 

threc-niiiiute  intervals  nincty-onc  couplings  were  administered  in  twelve 
sessions.  Then  after  a  hiatus  of  25  weeks  another  116  combinations  were 
given  with  two-minute  intervals  in  three  sessions  and  eighty-five  com- 
binations at  four-minute  intervals  in  four  sessions.  Finally,  265  couplings 
were  given  automatically  at  four-minute  intervals  in  two  overnight 
sessions,  but  still  without  indication  of  conditioning. 

The  animal  was  then  conciitioned  to  avoid  a  shock  to  the  tail  by  pressing 
a  lever.  The  first  CR  to  a  tonal  CS  required  105  trials  and  238  trials  to 
attain  twelve  avoidances  in  twenty  CS  presentations.  Generalization  to 
other  auditory  conditional  stimuli  was  immediate  and  complete.  The 
cortical  CS  was  then  employed.  For  300  conabinations  of  this  CS  with  the 
tail-shock  US  there  was,  judging  by  the  animal's  general  behaviour  and 
visually  obscrveci  respiration,  no  anticipation  whatever  of  the  impending 
shock  during  a  four-second  CS.  Yet  on  every  presentation  the  CS  was 
patently  effective  since  the  eyes  moved  persistently  down  and  to  the  right 
during  each  stimulation.  The  first  CRs  occurred  after  the  CS  was  in- 
creased to  1.2  niA.  The  threshold  was  ultimately  determined  to  be  0.6 
mA.  for  the  elicitation  of  this  CR. 

Cat  ^2^.  Conditioning  with  cortical  stimulation  was  likewise  a  failure 
in  this  animal;  but  so  too  was  conditioning  using  an  auditory  CS  and 
foot-shock  as  US.  The  animal  was  also  seizure-prone.  A  total  of  345 
pairings  of  a  right  middle  ectosylvian  gyrus  CS  with  right  ansate  gyrus 
US  produced  no  CRs,  and  420  pairings  of  a  tonal  CS  with  foot-shock  US 
was  almost  equally  ineffective  although  a  few  CRs  were  seen. 

Cat  48g.  This  animal  has  been  thoroughly  studied  by  Allan  Minster. 
The  CS  applied  to  right  middle  ectosylvian  gyrus  usually  elicited  no  overt 
response  initially  at  the  currents  used.  At  higher  currents  the  animal 
looked  up  and  to  the  left.  The  US  in  the  right  ansate  area  produced  an 
abrupt  turn  of  the  head  to  the  left  and  flexion  of  the  left  foreleg.  The  first 
CR  occurred  on  tlie  thirty-ninth  pairing,  fifth  session.  These  CRs,  how- 
ever, never  became  consistent  from  one  session  to  the  next.  In  100  trials 
after  the  first  CR  there  were  a  total  of  only  thirty-two  and  fifteen  of  these 
were  made  in  three  of  the  fifteen  sessions.  At  first,  the  CR  was  a  vigorous 
lifting  and  extension  of  the  left  foreleg,  but  after  the  seventy-second  pair- 
ing the  right  foreleg  executed  this  same  movement  to  the  CS  more  often 
than  did  the  left.  The  threshold  for  CR  elicitation  by  stimulation  of  middle 
ectosylvian  gyrus  was  probably  about  0.8  mA.  Stimulation  of  the  right 
posterior  ectosylvian  gyrus  at  0.35  mA.  yielded  seven  right  and  one  left 
foreleg  CRs  in  eleven  presentations.  To  date,  ninety-seven  pairings  of  the 
right  ansate  US  with  a  CS  applied  to  left  middle  suprasylvian  gyrus 


R.    W.    DOTY    AND    C.    GIURGEA  I45 

produced  only  four  leg  lifts  that  could  equivocally  be  called  CRs,  yet  the 
current  for  this  suprasylvian  CS  has  been  kept  high  enough  that  head 
movements  initially  seen  to  this  stimulation  still  occurred  frequently. 

Ten-channel  EEG  records  taken  for  each  trial  in  this  cat  have  not 
yielded  much  new  information.  Conhrming  Giurgea  and  Raiciulcscu 
(1959)  there  is  rarely  any  electrical  abnormality  even  in  the  immediate 
vicinity  of  the  electrodes  following  either  CS  or  US.  No  changes  char- 
acteristic of  the  conditioned  state  could  be  detected  and  it  could  not  be 
predicted  from  the  electrical  record  whether  a  CR  would  or  would  not 
occur.  The  CS  in  middle  or  posterior  ectosylvian  gyrus  usually  produced 
immediate  electrocortical  arousal  whereas  slower  patterns  frequently 
persisted  through  most  of  the  middle  suprasylvian  CS.  The  arousal 
produced  by  CS  and  US,  however,  was  minimal  since  8-i2/sec.  rhythms 
returned  often  within  1-2  seconds  after  stimulus  cessation. 


INTERPRETATION  OF  RESULTS 

There  can  be  no  question  that  conditioned  reflexes  can  be  established 
with  cortical  stimulation  as  US.  To  the  thirty  dogs  successfully  contiitioned 
in  this  manner  in  the  laboratory  in  Bucharest  and  the  cats  observed  by 
Nikolayeva  (1957)  can  be  added  the  animals  of  this  study  extending  the 
phenomenon  to  the  monkey  and  to  a  wide  variety  of  cortical  electrode 
placements.  The  vagaries  in  the  appearance  of  this  phenomenon  un- 
doubtedly arise  not  only  from  its  complexity  but  from  ignorance  of  its 
nature  and  the  procedures  most  favourable  for  its  induction.  Such 
problems  are  not  unknown  in  the  study  of  more  usual  types  of  condi- 
tioning. 

With  equal  assurance  one  can  state  that,  in  the  usual  sense  of  the  word, 
there  is  no  motivation  involved  in  the  formation  of  CRs  by  coupling 
cortical  stimulations.  The  animals  tested  so  fir  have  remained  entirely 
insouciant  to  self-administered  cortical  stimulation  of  near  convulsive 
strength  inducing  violent  movement,  yet  were  profoundly  inhibited  by 
moderate  and  innocuous  auditory  stimuli.  There  is  little  reason  to  expect 
the  cortical  stimulation  might  be  rewarding,  and  there  was  nothing  in  our 
observations  to  suggest  this.  On  the  other  hand  where  motivational  factors 
were  expected  as  with  the  possible  meningeal  involvement  {Doi^  Epsiloii) 
or  in  the  held  of  Forel  {Doi^  Gamma),  the  method  readily  conhrmed  this 
impression.  It  is  of  some  interest  that  in  Dcn^  Gamma  the  presence  of  this 
aversive  factor  did  not  preclude  some  form  of  motor  conditioning. 

Besides  the  direct  evidence  gained  from  coupling  the  cortical  CS  and 


146  BRAIN    MECHANISMS    AND    LEARNING 

US  with  lever-prcssiug  there  is  equally  convincing  circumstantial  evidence 
for  the  absence  of  motivation  in  these  conditioning  procedures.  The 
extreme  brevity  of  electrocortical  arousal  follow^ing  the  CS-US  com- 
bination in  Cat  48g,  or  Monkey  1  closing  its  eyes  to  doze  with  onset  of  the 
CS,  is  scarcely  expected  from  motivational  stimuli.  Nor  are  these  CR 
movements  purposeful;  rather  they  are  physiological  absurdities.  They 
seldom  prepare  the  animal  posturally  for  the  ensuing  UR  and  more  often 
than  not  the  CR  is  terminated  before  the  UR  begins.  Watching  Monkey  1 
day  after  day  raise  its  arm  to  stimulation  of  its  'visual'  cortex  one  could  not 
escape  the  feeling  that  this  nonsensical  yet  persistent  movement  was  some- 
how analogous  to  the  compulsive  movements  of  neurotic  humans. 

The  work  of  Segundo  and  his  colleagues,  reported  at  this  meeting  and 
elsewhere  (Segundo,  Roig  and  Sommer-Smith,  1959),  in  which  a  tonal 
CS  evokes  movements  similar  to  those  elicited  by  electrical  stimulation  of 
centre  median  or  the  mesencephalic  reticular  formation  as  US,  provide 
excellent  confirmation  of  our  observations  —  movements  produced  by 
central  stimulation  can  be  conditioned.  Masserman's  failure  to  obtain  such 
results  from  hypothalamic  stimulation  (Masserman,  1943)  stands  in  sharp 
contrast  to  the  results  with  Doi^  Gaiiiiiia  and  the  work  of  Segundo  et  al. 
Obviously  the  hypothalamus  must  be  carefully  re-examined  in  this 
regard.  The  US  in  the  experiments  9f  Segundo  et  al.  probably  produced 
motivational  effects  in  some  of  their  animals,  but  in  others  it  appears  less 
clear.  In  any  event  it  would  be  difficult  to  ascribe  some  'biological 
significance'  or  appropriateness  to  the  movements  induced  by  the  CS.  It 
is  equally  difficult  to  find  a  motivational  basis  for  the  'backwards'  type  of 
conditioning  linking  the  US  with  the  CS  as  analysed  by  Asratyan  in  this 
volume. 

Since  CRs  can  be  established  without  a  motivational  factor,  there  is 
more  hope  that  the  basic  phenomena  of  learning  can  be  sought  in  neural 
systems  sufficiently  simple  for  meaningful  analysis,  perhaps  with  purely 
electrophysiological  techniques.  The  temporal  factor  appears  to  be  critical 
and  the  experiments  with  Doi^  Gaiiiiiia  and  especially  Doo  Epsilon  show 
the  conditioned  state  is  not  established  by  the  repeated,  randomized 
excitation  of  US  and  CS  systems. 

Several  observations  support  Sperry's  hypothesis  (1955)  that  the  signi- 
ficant alteration  is  to  be  sought  in  the  effector  system.  In  motivated  condi- 
tioning an  alteration  in  excitability  specific  to  the  limb  being  conditioned 
can  be  observed  some  time  before  any  CRs  appear  (Doty  and  Rutledge, 
1959)-  In  the  present  and  earlier  experiments  (Giurgca,  1953  a,  b)  move- 
ments similar  to  the  CR,  never  seen  previously  in  the  animal's  behaviour, 


R.    W.    DOTY    AND    C.    GIURGEA  147 

often  appeared  spontaneously  at  about  the  same  tune  that  CRs  were  first 
noted.  The  threshold  of  the  neural  heirarchy  controlling  the  complex  CR 
thus  seems  to  have  been  lowered.  The  frequent  generalization  of  these 
CRs  to  other  stimuli  supports  this  view  and  m  Doo  Epsiloii  and  Cat  48g 
it  was  observed  that  convulsions  induced  accidentally  by  high-current 
CS  began  with  remarkably  prolonged  CRs. 

Some  animals  seem  to  have  inherently  low  thresholds  for  particular 
movement  complexes  so  that  stimulation  at  widely  separated  points  with- 
in the  nervous  system  will  evoke  the  same  response.  For  instance  in  Cat 
^23  stimulation  in  sensorimotor  cortex,  posterior  ectosylvian  and  middle 
suprasylvian  gyri,  and  the  caudate  nucleus  produced  an  abrupt  turning  of 
the  head  which  was  Inghlv  similar  for  the  different  stimulus  points. 
Stimulation  in  middle  ectosylvian  gyrus,  ventral  anterior  and  ventral 
posterolateral  nuclei  did  not  produce  this  effect  but  a  convulsion  elicited 
from  middle  ectosylvian  gyrus  began  with  prolonged  turning  of  the  head 
r8o^  to  the  rear.  In  Cat  j,C\^  flexion  and,  at  higher  currents,  attack  move- 
ments of  the  foreleg  could  be  elicited  by  stimulation  in  the  anterior  portion 
of  the  caudate  nucleus,  septal  region,  ventral  hippocampus,  and  periaque- 
ductal grey.  This  motor  response  was  not  correlated  with  the  motivational 
effects  of  this  stimulation  since  caudate  and  septal  stimulation  increased 
lever-pressing,  periaqueductal  stimulation  was  avoided  and  hippocampal 
stimulation  was  'neutral'.  Stimulation  of  the  median  forebrain  bundle, 
pyriform  area  and  habenula  which  produced  aversive  effects  in  this 
animal  did  not  elicit  the  foreleg  attack  movement. 

The  data  are  too  limited  to  know  whether  electrodes  in  these  areas  in 
any  cat  would  give  these  responses.  The  impression  is  gained,  however, 
that  they  would  not  and  that  somehow  a  particular  type  of  movement  has 
in  a  given  individual  come  to  be  'prepotent'  over  others.  The  stimulating 
electrodes  may  thus  be  revealing  the  existence  of  'individually  acquired 
reflexes'  (Beritoff",  1924)  established  through  the  animal's  own  activities. 
At  least  they  are  not  different  from  the  individually  acquired  reflexes 
deliberately  given  the  animal  by  the  stimulating  electrodes  during  the 
course  of  our  experiments.  However,  the  relation,  if  any,  between  these 
phenomena  must,  as  so  many  questions  raised  by  these  experiments, 
await  further  experimental  analysis. 


GROUP   DISCUSSION 

Segundo.  I  shall  first  comment  on  the  finding  that  motor  cortical  stimulation  is 
relatively  'indifferent'.  It  agrees  with  other  observations,  for  excitation  ot  tlus 
region  in  the  sleeping  monkey  produced  no  arousal  unless  a  generalized  seizure 

L 


I4o  BRAIN    MECHANISMS    AND    LEARNING 

occurred  and,  under  the  latter  conditions,  one  should  doubt  whether  wakefulness 
derived  from  stimulation  itself  or  from  proprioceptive  'feed  back'  resulting  from 
clonic  movements.  The  same  'indifference'  was  shown  by  the  visual  area:  when  the 
animal  was  awake,  excitation  ^vith  few  volts  produced  investigation  movements 
directed  towards  the  contralateral  field;  when  the  animal  was  asleep,  stimulation  of 
up  to  80  volts  produced  no  effect.  A  different  result  occurred  when  excitation  was 
applied  to  temporal  pole,  cingular  cortex  or  hippocampus:  with  low  voltages, 
animals  were  immediately  aroused,  both  behaviourally  and  electroencephalo- 
graphically  (Scgundo,  Arana  and  French,  1955).  Therefore,  and  as  far  as  we  can 
infer  irom  the  influence  of  animal  brain  stimulation  upon  sleeping  state  or  tendency 
to  excite  itself,  certain  areas  are  'indifferent'  and  others  are  not. 

Dr  Doty  mentioned  that  stimulation  ot  subcortical  structures  may  be  condi- 
tioned, hi  our  laboratory,  brief  tones  have  been  reinforced  by  direct  excitation  of 
mesencephalic  reticular  formation,  centre  median,  basolateral  amygdala  or  head  of 
caudate  nucleus  and  learned  responses  to  tones  have  eventually  appeared,  hi  some 
cases  (centre  median,  mesencephalic  reticular  formation,  certain  amygdaloid  or 
caudate  placements)  conditioned  effects  were  practically  identical  to  the  absolute 
responses.  In  other  cases,  responses  from  different  pomts  in  caudate  or  amygdala, 
could  not  be  conditioned  //;  Mo;  some  of  their  components,  however,  could  and 
coiiset]uently  conditioned  responses  were  similar  to  a  part  of  the  absolute  response, 
hi  a  third  group  o(  animals  (also  caudate  or  amygdala)  the  conditioned  reaction, 
though  consistent,  was  completely  different  to  the  asbolutc  effect.  This  variable 
relationship  has  been  found  in  other  types  of  conditioning  and,  therefore,  though 
difficult  to  interpret  here,  is  not  altogether  surprising  (Hilgard  and  Marqtiis,  1940). 

To  summarize  we  can  say  that  stimulation  effects  of  certain  areas  of  the  brain  can 
be  conditioned.  The  latter  term  seems  justified  in  the  sense  that  the  process  has 
many  features  (technique,  effects,  inhibitions)  of  classical  conditioning.  These 
studies  may  help  to  understand  the  physiology  of  learning  and  that  of  tested  nuclei 
(Roig,  Segundo,  Sommer-Smith  and  Galeano,  1959;  Seguiido,  Roig  and  Somnier- 
Smith,  1959). 

Chow,  hi  your  monkey  work,  do  you  worrv  about  whether  vour  stimulus 
would  activate  the  pain  sensation  in  your  animal  f 

Doty.  We  are  very  much  aware  that  the  factor  of  meningeal  stimulation  must 
be  considered.  Dr  Rutledge  and  I  have  shown  that  stimulation  of  the  dura  mater  of 
the  saggital  sinus  in  the  cat  can  serve  as  a  conditional  stimulus  and  is  undoubtedly 
also  a  nocuous  stimulation.  However,  I  feel  satisfied  that,  as  outlined  in  the  text, 
this  factor  can  be  detected  by  the  self-stmiulation  procedure  employed  and  was 
present  only  as  stated,  hi  addition,  Dr  Girugea  has  established  these  responses  in 
dogs  after  destruction  of  the  Gasseriaii  ganglion. 

Hernandez-Peon.  The  conditioned  response  obtained  by  Dr  Doty  using  cortical 
stimuli  as  conditioned  and  unconditioned  stimuli  provides  a  method  for  testing 
defniitely  whether  there  might  be  some  cortico-cortical  connections  in  some  cases 
of  conditioning.  And  I  wonder  whether  he  has  done  transcortical  cutting  isolating 
the  respective  cortical  areas  and  testing  whether  these  conditioned  responses  persist 
after  the  transection  or  not. 

Doty.  I  think  the  experiments  of  Girugea  and  his  colleagues  showing  these 
conditional  reffexes  to  be  established  after  callosal  section  when  the  conditional 
stimulus  and  unconditioned  stimulus  are  in  different  hemispheres,  indicate  that  a 


R.    W.    DOTY    AND    C.    GIURGEA  149 

subcortical  pathway  is  likely  to  be  involved  m  the  production  ot  this  phenomenon. 
Perhaps  pertinent  also  are  experiments  which  Dr  Rutledge  and  I  have  been  doing 
using  electrical  stimulation  of  marginal  gyrus  in  the  cat  as  conditional  stimulus  and 
shock  to  the  foreleg  as  unconditioned  stimulus.  If  the  stimulated  cortical  zone  is 
circumsccted  so  that  most  of  the  pathways  available  for  intracortical  elaboration  of 
the  excitation  are  severed,  conditioned  reflexes  still  occur  to  the  cortical  conditional 
stimulus.  If,  on  the  other  hand,  the  stimulated  cortical  zone  is  undercut  for  a  total 
length  of  more  than  about  8  mm.  the  conditioned  reflexes  are  lost.  They  often 
return,  however,  after  about  a  month  ot  training.  The  critical  factors  arc  not  fully 
determined  in  the  reappearance  of  conditional  reflexes  after  this  undercutting  of 
the  stimulated  cortex,  but  it  may  be  that  'U'  fibres  are  necessary.  It  is  also  not 
certain  whether  that  mere  passage  of  time  is  suflkient  or  whether  it  is  the  retraining 
which  is  critical. 

KoNORSKi.  Did  you  try  to  extinguish  these  reflexes  that  you  have  established 
and  how  did  you  obtain  the  extinction? 

Doty.  Dr  Giurgea  taught  me  a  lot  about  extinction.  Apparently  it  is  extremely 
dirticult  to  bring  about  a  total  extinction  of  a  salivary  conditioned  reflex. 
Those  'temporary  connections'  are  surprisingly  permanent.  Hence  a  technique 
of  'acute'  extinction  is  used  wherein  the  conditional  stimulus  is  presented 
as  one  might  expect  without  the  unconditioned  stimulus,  but  also  at  much  shorter 
time  intervals  than  employed  during  the  establishment  of  the  conditioned  state.  I 
objected  that  this  alteration  of  procedure  would  not  yield  a  proper  comparison  so 
we  tried  extinguishing  by  rather  long  intervals  between  conditioned  stimulus 
presentations.  In  Dog  Beta  we  got  no  extinction  in  eighty-five  presentations. 
Hence  in  Monkey  i  sliown  in  the  film,  we  used  shorter  intervals  of  1-2  minutes 
and  on  the  two  occasions  produced  'acute'  extension  in  which  the  conditioned 
reflexes  were  totally  absent  to  the  conditional  stimulus  and  in  five  or  more  con- 
secutive presentations  of  the  conditioned  stimulus,  although  the  animal  remained 
alert.  Giurgea  has  also  published  extinction  data  on  some  of  his  dogs.  Our  Dog 
Gamma  in  which  an  aversive  factor,  was  present  in  the  unconditioned  stimulus 
showed  rapid  extinction. 

Anokhin.  Much  of  the  recently  gathered  data  points  to  the  possibility  of  obtain- 
ing 'conditioned  responses'  by  an  association  between  the  most  distinct  points  of 
the  brain.  In  fact,  this  trend  of  thought  covers  also  some  of  the  better-known 
conditioned  reflexes,  as  the  one  induced  by  training  with  sound  and  light. 

Yet  a  question  comes  reasonably  to  our  mind:  what  aspect  of  the  activity  of  the 
brain,  taken  as  a  whole,  do  such  facts  reveal  ?  Dr  Doty's  interesting  experiments  may 
be  taken  as  instances  of  the  brain  tissue's  ability  to  act  as  a  specialized  substratum, 
and  to  establish  instant  links  between  any  two  stimuli  which  aftect  it 
simultaneously. 

Our  team  considers  that  such  aptitude  proves  the  capacity  of  the  nervous  tissue 
to  unite  any  separate  elements  during  stimulation.  This  capacity  is  the  basic 
physiological  ground  of  any  spontaneous  conditioned  response.  But  if  we  assume 
at  the  start  that  conditioned  responses  are  a  physiological  function  of  the  animal,  we 
must  consider  them  as  the  outcome  of  a  complex  physiological  system,  leading 
necessarily  to  an  adaptation  process  which  involves  the  organism  as  a  whole. 

Dr  Doty  tells  us  that  he  finds  it  diflicult  to  draw  objectively  a  difference  between 
the  leg-lifting  response  which  he  has  induced,  and  the  one  obtained  in  the  classical 


ISO  BRAIN    MECHANISMS    AND    LEARNING 

Pavlovian  test  by  direct  application  of  an  electric  shock  to  the  animal's  paw.  Yet 
to  us,  the  difference  seems  considerable,  hi  Pavlov's  test,  the  subject  draws  away 
the  paws  from  the  source  of  stimulation,  thus  displaying  an  adaptative  behaviour, 
which  terminates  in  a  reverse  afferent  drive,  in  our  sense  of  the  word,  indicating 
that  the  animal  has  avoided  the  impact  of  the  electric  current.  Besides,  Dr  Doty  in 
his  experiment  shows  the  movement  of  limbs  as  the  mechanical  effect  of  a  stimula- 
tion wliich,  after  having  been  subject  to  association,  is  now  conveyed  outwards 
onto  the  motor  system.  This  proves  admirabK'  the  capacity  of  the  brain  tissue  to 
register  any  sequence  of  induced  stimuli. 

I  wish,  in  concluding,  to  draw  your  attention  to  one  miportant  factor,  which  is 
of  particular  relevance,  to  Dr  Hernandez-Peon's  remark  on  the  possibility  of 
showing  pure  cortico-cortical  connections.  Our  laboratory  has  shown  that  the 
most  insignificant  stimuli,  as  well  as  lesions  of  the  cortical  tissue  will  instantly 
involve  subcortical  formations,  and  possibly,  reticular  ones.  Tliis  is  why,  by  the 
very  nature  of  the  process,  no  subsequent  effects  of  stimulation  can  be  only  cortical. 

Doty.  In  reply  to  Dr  Anokhin  —  I  think  we  must  simply  adopt  the  mechanistic, 
objective  approach  which  Pavlov  used  so  successfully.  If  I  form  a  conditioned  reflex 
by  using  an  avoidable,  painful,  'biologically  significant'  stimulus  to  a  forepaw  so 
that  the  animal  lifts  it  when  a  tonal  conditional  stimulus  is  sounded,  and  for  the 
other  paw  proceed  as  Giurgea  and  I  have  done  so  that  the  other  paw  is  hfted  when 
the  'auditory  anahser'  is  stimulated  directly  at  the  cortex,  you  would  be  unable  to 
tell  me  simply  by  looking  at  the  animal's  behaviour,  which  conditioned  reflex  was 
which.  True,  by  careful  analysis  I  suspect  you  would  find  great  differences  in  the 
autonomic  nervous  system  responses  to  the  stimuli  employed,  at  least  during  some 
stages  of  the  training.  But  their  absence  in  the  latter  case  only  proves  them  to  be  an 
unnecessary  complication  in  the  process  of  establishing  the  neural  alteration 
responsible  for  the  change  in  effect  of  the  conditional  stimulus.  Both  tone  and 
direct  electrical  stimulation  of  the  'auditory  analyser'  are  initially  without  effect  on 
somatic  musculature  save  possibly  for  an  'orientation  reflex'  which  is  soon  lost. 
Both  become  effective  on  the  same  motor  apparatus  in  approximately  the  same 
number  of  trials.  Both  states  are  subject  to  the  laws  of  conditioning,  i.e.  there  is  no 
apparent  backward  conditioning,  there  can  be  external  inhibition,  they  can  be 
extinguished.  Why  then  call  them  different  states  or  infer  for  them  different 
mechanisms  f 

We  have  shown  that  if  the  ventral  roots  are  crushed  and  an  animal  immobilized 
with  bulbocapnine,  it  can  still  be  conditioned  to  make  conditioned  reflexes  with  its 
hind  leg  even  though  the  leg  has  never  moved  during  conditioning.  Thus  we  can 
show  proprioceptive  feedback  from  the  unconditioned  reflex  to  be  unnecessary  for 
the  formation  of  conditioned  reflexes.  This  does  not  say,  that  such  factors  are  not 
normally  present;  only  that  they  need  not  be.  Such  experimental  simplification  ot 
the  situation  certainly  does  not  alter  significantly  the  process  we  desire  to  elucidate, 
nor  change  its  name.  In  similar  vein  the  elimination  of  motivational  factors  must 
not  be  construed  to  infer  qualitatively  different  processes  to  be  operative  in 
'cortical-cortical'  conditioning  as  compared  to  the  more  usual  procedures  which 
involve  such  unknowns  as  'biological  purpose'  or  unanalysable  emotional  and 
subjective  factors. 


R.    W.    DOTY    AND    C.    GIURGEA  I5I 

REFERENCES 

Doty,  R.  W.,  Rutledge,  L.  T.  and  Larsen,  R.  M.  (1956)  Conditioned  responses  established  to 

electrical  stimulation  of  cat  cerebral  cortex.  J.  Neuropliysiol.  ig,  401-15. 
Giurgea,  C,  Raiciulescu,  N.  and  Marcovici,  G.  (1957)  Reflex  condition  —  at  interheniisferic 

prin  excitarea  directa  corticala  dupa  sectionarea  corpului  calos.  Studiu  anatonio-histologic. 

Ret'istii  Fiziol.  Ncnii.  Potol.  4,  408-14. 
Doty,  R.  W.  and  Rutledge,  L.  T.  (1959)  Conditioned  reflexes  elicited  by  stmiulation  of 

partially  isolated  cerebral  cortex.  Fed.  Proc.  1$,  37. 
Beck,  E.  C.  and  Doty,  R.  W.  (1957)  Conditioned  flexion  reflexes  acquired  during  combined 

catalepsy  and  de-efferentation.  J.  comp.  Physiol.  Psychol.  50.  211-16. 


INTERFERENCE  AND  LEARNING  IN  PALAEOCORTICAL 

SYSTEMS^ 

J.  Olds  and  M.  E.  Olds 

Recent  stimulation  and  single-unit  studies  in  our  laboratory  have  con- 
vinced us  that  the  hypothalamus  with  its  projections  to  palaeocortical  and 
related  structures  bears  some  very  special  relation  to  mechanisms  of 
instrumental  learning,  and  possibly  to  associative  mechanisms  in  general. 

introduction 

In  one  sense  all  animal-learning  experiments  involve  response  learning, 
for  it  is  a  changed  response  that  signifies  to  the  experimenter  that  some 
learning  has  occurred.  Nevertheless,  it  is  possible  to  distinguish  between  a 
type  of  learning  that  is  mainly  response  learning,  and  another  type  that  is 
mainly  a  learning  of  associations.  The  former  is  evidenced  when  an  animal 
learns  how  to  get  food  in  a  problem  box;  he  has  learned  a  new  response, 
he  has  learned  what  to  do.  The  latter  is  evidenced  when  an  animal  learns 
to  salivate  when  a  bell  announces  the  present  arrival  of  food;  he  does  not 
salivate  to  get  food  but  because  the  bell  is  associated  with  food,  and  the 
animal  salivates  as  though  the  bell  meant  food. 

In  the  study  of  learning,  two  basic  procedures  have  been  used  with 
respect  to  these  two  types  of  learning. 

In  instrumental  conditioning,  response  learning  is  the  salient  feature  of 
the  procedure.  The  experimenter  has  only  one  stimulus  at  his  disposal  (a 
reward  or  punishment).  He  awaits  the  response  which  interests  him,  and, 
when  it  occurs,  proceeds  to  stimulate  or  to  withdraw  stimulation.  If  he 
stimulates  with  what  is  called  a  'reward',  the  response  in  question  has  its 
repetition  frequency  augmented,  and  if  the  animal  is  rewarded  again  and 
again,  the  response  may  quickly  come  to  dominate  the  animal's  repertory. 

In  Pavlovian  conditioning,  association  receives  the  emphasis.  The 
experimenter  imposes  first  an  'irrelevant'  stimulus  and  then  a  'relevant 
one.  Eventually,  the  irrelevant  response  makes  the  animal  'think'  of  the 
relevant  one,  or  at  least  perform  some  response  that  we  take  as  oblique 
evidence  of  such  a  thought.  Pavlovian  conditioning  is  thus  conceptualized, 

1  The  research  reported  here  was  supported  by  grants  from  the  Foundations  Fund  for 
Research  in  Psychiatry,  the  National  Institute  of  Mental  Health,  and  the  Ford  Foundation, 


154  BRAIN    MECHANISMS    AND    LEARNING 

usually  at  a  hidden  aud  unexpressed  level,  in  terms  of  the  association  of 
ideas.  A  new  association  in  the  environment  is  imprinted  on  the  animal,  and 
we  observe  the  conditioned  response  not  mainly  as  a  measure  of  the 
animal's  adaptive  behaviour  but  rather  as  a  measure  of  the  degree  to 
which  we  have  impressed  the  association  on  the  animal. 

Whether  there  is  one  basic  mechanism  with  two  aspects  or  two  or  more 
basic  mechanisms  is  still  almost  entirely  a  matter  to  be  decided  by  further 
experiments,  although  there  is  considerable  argument  pro  or  con  associa- 
tion or  response  learning.  At  any  rate,  our  experiments  have  taught  us 
something  rather  defniite  about  the  physiological  processes  underlying 
response  learning.  It  appears  to  us  that  our  studies  also  have  relevance 
to  the  broader  problem  of  associative  learning,  but  that  has  not  yet  been 
established.  Any  argument  that  there  is  only  one  basic  mechanism  with 
these  two  different  aspects  in  the  learning  process  will,  we  believe,  make 
it  even  more  likely  that  these  studies  involve  one  very  important  basis  of 
learning  in  general. 

I.    SELF-STIMULATION    EXPERIMENTS    ON    LEARNING 

Self-Stimulation  tests  (Fig.  i)  described  in  detail  elsewhere  (Olds,  iQS-S) 
indicate  that  electric  stimulation  in  medial-forebrain-bundle  regions  of 
the  hypothalamus,  or  in  related  structures  of  basal  ganglia,  paleocortex 
and  tegmentum  (Fig.  2),  causes  positive  reinforcement  of  learning  to  the 
degree  that  animals  will  spend  Ic^ng  times  turning  on  the  stimulus  to  the 
brain  in  preference  to  all  other  pursuits.  Animals  will  learn  to  run  in  a 
runway  (Fig.  3)  with  such  stimulation  as  the  only  reinforcement;  they 
will  cross  an  electrified  grid  (Fig.  4)  to  reach  a  pedal  and  stimulate  their 
brains;  and  they  will  learn  rapidly  to  perform  without  errors  in  a  multiple 
choice  maze  (Fig.  5)  (Olds,  1956)  with  the  electric  stimulus  to  the  brain  as 
the  only  incentive.  Both  acquisition  and  extinction  curves  on  all  these 
problems  compare  favourably  with  those  where  the  positive  reinforce- 
ment (or  unconditioned  stimulus)  is  a  food  object.  It  is  clear,  therefore, 
that  stimulation  in  these  regions  promotes  repetition  of  a  learned  response. 

II.    INTERFERENCE-STIMULATION    AND    LEARNING 

The  question  we  went  on  to  ask  was  a  question  that  has  troubled 
physiological  psychology  for  some  time:  is  there  any  sense  in  saying 
learning  mechanisms  are  somehow  localized  in  these  heldsf  Or  before  we 
ask  that,  is  learning  localized  at  alh. 


I.    OLDS    AND    M.    E.    OLDS 


155 


3V 
TRANSFORMER 


I  1000  Jl 

'^  POTENTIOMETER 


C   R   0 


Self-stimulation  experiment.  Animal's  lever  response  causes  i-second  cut-off  device  to  deliver 
60-cycle  current  as  long  as  lever  is  depressed  up  to  ^-second  maximum,  atter  v^'hich  the  animal 
must  release  and  press  again  for  more  current.  Current  causes  cumulative  recorder  to  register 
response  (thereby  converting  response  rate  into  the  slope  of  a  graph)  and  causes  via  transformer 
and  potentiometer  a  stimulus  to  the  rat's  brain  which  passes  on  the  way  through  a  constant 
resistor  across  which  it  is  measured  by  cathode-ray  oscilloscope.  Rats  respond  with  rates  up  to 
12,000  responses  per  hour  with  electrodes  in  medial-forebrain-bundle  regions. 


HPTH 

Fig.  2 
Map  of  self-stimulation  and  some  escape  points  in  rat's  brain.  The  former  arc 
indicated  by  cross  hatching,  the  latter  by  stippling.  Self-stimulation  region 
extends  from  baso-medial  areas  of  tegmentum  through  baso-lateral  hypotha- 
lamic areas  into  telencephalon  and  then  up  through  the  basal  ganglia  to  the 
whole  palaeocortical  system.  Escape  regions  plotted  here  include  the  dorsal 
posterior  hypothalamus  and  similarly  placed  points  in  the  gementum.  The 
escape  system  is  now  known  to  extend  forward  too. 


156 


BRAIN    MECHANISMS    AND    LEARNING 


o — o— o— o       S    group 
(8rats  ) 

»--*--»--*      F"    group 
(  7  ra1s  ) 


TRIALS 

Fig.  3 
Runway  experiment  in  which  animals  ran  faster  for  electric  reward 
(solid  line)  than  a  control  group  running  for  food  (dotted  line)  (Olds, 
1956). 


Fig.  4 
Obstruction  box  in  which  animals  were  required  to  cross  grid 
with  shock  to  feet  to  reach  pedal  to  stimulate  brain.  After  three 
self-stimulations  on  one  side,  pedal  became  inoperable  and 
animal  crossed  the  grid  again  to  get  three  more  selt-stimulations 
on  the  other  side.  Animal  continued  to  shuttle  as  shock  increased 
until  foot  shock  became  so  high  as  to  inhibit  further  self- 
stimulation  behaviour.  Foot  shock  of  60  laamp.  stopped  most  rats 
running  for  food;  however,  one  hungry  rat  took  almost  300 
namp.  for  food  reward.  Self-stimulating  rats  took  over  400 
ijamp.  for  hypothalamic  stimulus  as  reward. 


J.    OLDS    AND    M.    E.    OLDS 


157 


In  some  earlier  attempts  to  answer  this  question  following  the  example 
of  Lashley  (1929),  surgicallesions  were  used,  the  neocortex  was  the  prnnary 
locus  of  the  search,  and  each  animal  learned  only  once  so  he  could  not 
serve  as  his  own  control.  Very  often,  surgical  lesions  appeared  to  leave 
parallel  structures  to  do  the  job;  the  neocortex  seems  ipsoJiUto  a  narrow 
constraint  upon  the  search;  and  individual  as  well  as  surgical  differences 


FOUR  DAYS 
FIRST  RUNS 


EXTINCTION 


S  group 
(  8  rots  ) 


Fig.  5 
Multiple-choice  maze  in  which  animals  improved  performance  from  trial  to  trial  and  from 
day  to  day,  the  only  reward  being  an  electric  stimulus  below  the  septal  area  (solid  line). 
They  are  compared  with  a  control  group  running  for  food  (dotted  line).  Insert  shows  day-to-day 
improvement  m  terms  of  first  run  of  the  day  indicating  that  no  primer-stimulation  is  necessary 
to  get  rats  running  for  electric  reward. 


from  animal  to  animal  make  it  desirable  tor  animals  to  serve  as  their  own 
controls. 

Thus  we  turned  to  an  electric  stimulation  (ci.  Thompson,  1958; 
Mahut,  1957;  Stein  and  Hearst,  1958)  to  jam'  the  network,  to  cause,  that 
is,  a  temporary  disarrangement  of  pattern  which  is  believed  to  function  as 
a  temporary  (reversible)  lesion.  We  believe  this  has  three  advantages: 
(i)  it  is  reversible;  (2)  it  can  be  expected  to  project  to  parallel  structures 


158  BRAIN    MECHANISMS    AND    LEARNING 

and  thus  cause  a  diffuse  interference;  and  (3)  utilizing  penetrating  im- 
planted electrodes,  we  are  in  a  better  position  to  get  beyond  the  neocortex. 
Furthermore,  we  use  a  discrimination  reversal  experiment,  to  be 
described  below,  so  that  after  preliminary  training  the  animal  can  learn 
and  re-learn  the  same  problem  day  after  day,  eliminating  errors  each  day 
in  roughly  the  same  number  of  trials.  This  methodology  allows  us  to  test 
animals  one  day  on  rate  of  learning  under  the  electric  'lesion'  and  another 
day  to  test  the  same  animals  on  control ;  and  we  may  repeat  the  process  as 
often  as  we  choose. 


METHODS 

To  date,  150  rats  with  implanted  electrodes  have  been  tested  in  a 
problem  box  where  they  had  to  learn  over  again  each  day  which  pathway 
and  lever  would  activate  a  feeding  mechanism.  The  problem  box  is  shown 
in  Fig.  6.  A  red  plastic  lever  on  the  left  activated  the  food  magazine  one 
day,  and  a  white  metal  lever  on  the  right  activated  it  the  next.  Each  day  the 
rat  had  to  learn  anew  which  lever  worked.  This  took  a  small  number  of 
runs,  after  which  the  animal  would  run  only  to  the  correct  level.  After 
each  pellet  was  discharged,  the  animal  had  to  go  to  the  magazine  and  eat 
(thus  breaking  the  photo-beam)  befoi'e  the  magazine  would  work  a  second 
time.  Thus  animals  could  not  stay  at  the  pedal  discharging  several  pellets 
and  then  go  to  the  magazine  to  eat  them  all,  but  were  forced  to  run  the 
maze  both  ways  for  each  pellet.  Ten  consecutive  responses  on  the  correct 
lever  was  the  criterion  of  learning.  All  animals  were  put  through  extensive 
preliminary  training  (running  every  day  for  more  than  a  month)  before 
being  used  in  experiments.  By  the  end  of  this  training  period,  animals 
would  always  begin  each  day  by  distributing  runs  randomly  to  right  and 
left;  then  they  would  stabilize  on  the  lever  that  activated  the  food  maga- 
zine. Depending  on  the  animal,  this  would  take  from  three  to  twenty-five 
runs  each  day.  Animals  were  not  used  in  experiments  until  progressive 
improvement  in  this  daily  score  had  ceased.  During  training  and  tests, 
animals  were  maintained  on  a  feeding  schedule  with  23  hours  of  starvation 
and  I  hour  of  feeding  each  day.  They  were  tested  after  22  hours  of 
deprivation. 

The  data  were  plotted  in  terms  of  cumulative  response  curves  (see  Fig.  7). 
Solid  lines  were  used  to  indicate  correct  responses,  dotted  lines,  to  indicate 
errors.  The  slope  of  the  line  indicated  the  speed  of  responding  (on  the 
correct  or  error  pedal).  When  the  dotted  line  flattened  out,  this  indicated 


J.    OLDS    AND    M.    E.    OLDS 


159 


that  the  animal  had  stopped  making  errors.  Every  test  consisted  of  2  days, 
one  with  the  left  lever  correct  (indicated  by  graph  on  left),  the  other  with 
the  riglit  lever  correct  (indicated  by  graph  on  right),  to  rule  out  position 


WIDE    RED 
PLASTIC   LEVER 


LONG    WHITE 
METAL  LEVER 


RED   PLASTIC 
FLOOR  MARKER 


PHOTO 
CELL 


11 


x:i. 


WHITE    METAL 
FLOOR  MARKER 


^  LIGHT 

'source 


FOOD    TRAY 

Fig.  6 
Problem  box.  Response  on  correct  lever  causes  food  magazine 
to  operate.  Animal  must  retrace  steps  and  break  photo-beam  in 
order  for  correct  lever  to  work  a  second  time.  Correct  lever 
changes  from  side  to  side  from  day  to  day.  After  about  a  month 
of  preliminary  training,  each  animal  daily  achieves  criterion 
(ten  correct  runs  in  a  row)  in  about  three  to  twenty-five  trials. 


preference.  In  the  six  tests  shown  in  Fig.  7,  errors  level  off  in  all  cases, 
while  correct  responses  continue  to  cumulate. 

In  the  first  test,  there  was  no  stimulation.  Then  stimulation  was  intro- 
duced in  an  effort  to  interfere  with  the  learning  mechanism.  For  this 
purpose  a  series  of  i-second  trains  of  sine  wave  current  (60  o.p.s.)  was 
introduced  at  a  constant  rate  of  one  for  every  three  seconcis.  A  pair  of 


i6o 


BRAIN    MECHANISMS    AND    LEARNING 


tests  were  given  at  each  of  five  electric  current  levels,  lo,  20,  30,  40  and 
50  iJanip.  r.m.s.  It  is  believed  that  the  so-namp.  stimulus  sets  up  a  supra- 
threshold  electric  field  in  the  brain  of  about  i-inm.  diani.  (Olds,  i9.vS). 
The  stimulation  was  divided  into  ^-second  trains  separated  by  ih 
seconds  of  no  stimulation  because  it  was  found  that  such  a  discontinuous 


CONTROL 


SERIES 


CINGULATE        CORTEX 


Fk;.  7 
Daily  response  curves.  Slope  of  black  line  indicates  rate  of  correct  responding;  slope  of  dotted 
line  indicates  rate  of  incorrect  responding.  Cumulative  response  totals  are  plotted  along 
ordinate,  minutes  along  abscissa.  When  dotted  curve  flattens,  errors  have  been  eliminated  and 
only  correct  responding  continues.  Left  curve  in  each  pair  indicates  a  day  when  left  lever  is 
correct;  right  curve  indicates  a  day  when  right  lever  is  correct.  Large  numbers  above  each 
pair  indicate  electric  current  setting  in  microamperes  of  the  interference  stimulus.  In  this  scries 
with  cortical  stimulation,  the  stimulus  does  not  interfere  materially  with  animal's  ability  to 
learn. 


train  caused  few  seizures  and  caused  greater  stimulus  effects  in  other 
respects. 

Some  animals  were  also  given  a  series  of  special  tests  which  will  be 
described  in  more  detail  later.  These  were  (i)  a  selt-stimulation  test  tor 
positive  reinforcing  effects;  (2)  a  memory-performance  test  for  confusion 
after  criterion  is  reached  each  day;  (3)  a  reinforcement-confusion  test  to 
find  whether  confusion  persists  when  electric  stimulation  is  programmed 


J.    OLDS    AND    M.    E.    OLDS  l6l 

SO  as  to  reinforce  learning;  and  (4)  in  a  very  small  number  of  cases,  an 
escape  test  to  discover  negative  reinforcing  effects  of  stimulation. 

After  learning  experiments  were  complete,  each  animal  was  sacrificed, 
and  his  brain  was  sectioned  and  stained  to  determine  the  precise  location 
of  stimulation. 


RESULTS 

(r)  Differences.  —  The  results  indicate  a  dctmite  division  of  the  brain  into 

(1)  a  larger  set  of  regions  where  electric  stimulation  has  very  little  effect 
on  this  learning  behaviour,  (2)  a  smaller  (but  very  extensive)  region  where 
electric  stimulation  has  very  devastating  effects  and  (3)  a  region  where 
effects  are  ambiguous. 

First,  when  electrodes  are  implanted  in  the  neocortex  and  in  many 
parts  of  the  adjacent  cingulatc  cortex,  stimulation  from  10  to  50  namp. 
does  not  cause  any  major  deficit  in  behaviour  (Fig.  7).  Similar  effects  are 
often  seen  with  electrodes  in  the  thalamus  (left  of  Fig.  9).  In  all  these  cases, 
there  is  learning,  with,  of  course,  some  day-to-day  differences.  Stimu- 
lation may  cause  some  increment  in  errors,  but  it  does  not  prohibit 
perforniance  or  learning.  Animals  run  well,  eat  well,  and  learn  well 
whether  the  stimulus  is  going  or  not. 

Seconc^,  when  electrodes  stimulate  in  other  places,  quite  different  results 
are  obtained  (Fig.  8).  It  appears  totally  impossible  for  animals  to  reach 
criterion  with  the  stimulus  going  in  these  areas.  Except  for  confusion  of 
learning,  the  animals  perform  well.  They  run  almost  as  fast  as  usual;  that 
is,  the  total  number  of  runs  is  about  equal  for  the  stimulated  and  control 
series.  The  animals  eat  food  well  when  the  correct  response  activates  the 
food  magazine.  But  they  cannot  learn  to  eliminate  errors  on  days  when 
the  stimulus  is  going.  Because  the  animals  continue  to  run  and  to  eat,  it  is 
assumed  that  there  is  no  interference  with  behaviour  or  drives.  The  inter- 
ference has  to  do  only  with  the  ability  to  eliminate  errors.  The  stimulus  in 
these  cases  is  very  small,  interfering  usually  at  levels  of  20  laamp.  or  less. 
Finally,  it  should  be  noted  that  the  stimulus  does  not  merely  cause  or 
enhance  a  position  preference,  for  errors  on  right  or  left  levers  are  both 
caused  to  increase  greatly  by  the  electric  stimulus. 

Third,  there  are  sometimes  effects  which  make  it  impossible  to  make  a 
satisfactory  test:  (i)  animals  stop  running  when  the  stimulus  is  introduced: 

(2)  the  stimulus  produces  seizures  so  that  no  test  can  be  made;  (3)  the 
animal  stops  eating  so  that  it  is  no  longer  possible  to  assume  motivation 
for  learning ;  and  (4)  the  stimulus  causes  some  definite  confusion  which  is 


l62 


BRAIN    MECHANISMS    AND    LEARNING 


SO  mild  or  unstable  as  to  be  ambiguous  or  a  forced  position  habit  renders 
results  ambiguous  (sec  caudate  placement  in  Fig.  9). 

(2)  MappiiK^.  —  Mapping  these  effects,  we  tnid  the  surprising  result  that 


40n 


PERIAMYGDALOID 


ANT.   THAL. 


20-1         /   17^v 


ANT.   THAL 


U 


i  n  u  t  e  s 

Fig.  8 
Interference  effects.  Control  curves  (in  background)  show  errors  eliminated  (dotted  lines) 
correct  responses  cumulating  (solid  lines).  On  days  when  animals  run  under  ctTccts  of  stimula- 
tion (double  lines  in  foreground),  errors  are  not  eliminated. 


the  mcdial-forebrain-bundle  regions  of  the  hypothalamus,  its  extensions 
into  the  tegmentum  and  basal  ganglia,  and  the  relatcti  structures  of  the 
paleocortex  are  the  places  most  apt  to  yield  confusion  upon  electric 
stimulation.  Stimulation  in  the  neocortex,  sensory  thalamus,  and  large 


40 1 


J.    OLDS    AND    M.    E.    OLDS  I63 

CINGULATE  CAUDATE 


Minutes 

Fig.  9 
Stimulation  with  very  little  effect  (cingulate  and  posterior  thalamic  electrode,  left)  and  mild 
effects  (two  caudate  points,  right).  With  stimulation  in  cingulate  or  posterior  thalamus, 
responding  is  sometimes  slowed,  and  errors  sometimes  increase.  But  learning  is  not  prevented. 
In  two  cases  with  electrodes  in  the  caudate  nucleus,  results  are  ambiguous.  At  the  top,  the 
stimulus  causes  the  number  of  errors  to  double  (thus  stimulation  interferes  with  learning) ; 
but  errors  are  eventually  eliminated  (thus  learning  is  not  prevented  by  stimulation).  In  the 
other  animal  with  caudate  electrodes,  stimulation  sometimes  caused  such  a  great  decrement  in 
correct  responding  that  it  was  impossible  to  tell  whether  learning  occurred  or  not.  In  this 
case,  it  may  also  be  noted,  the  decrement  caused  by  electric  stimulation  seemed  to  involve  a 
position  habit  forced  by  stimulation,  so  that  the  animal  failed  when  the  left  lever  was  correct, 
but  succeeded  when  the  right  was  correct. 

parts  of  the  reticular  activating  system  cause  no  detrimental  effects  at  all. 
And  moderate  or  ambiguous  effects  are  yielded  in  the  borderline  structures 
such  as  the  caudate  (Fig.  lo).  And  this  is  practically  the  same  map  as  was 
obtained  for  self-stimulation  effects  (Fig.  2). 

Is  it  true,  then,  that  the  points  of  positive  reinforcement,  far  from  facili- 
tating learning,  actually  inhibit  it? 

M 


1 64 


BRAIN    MECHANISMS    AND    LEARNING 


Fig.  10 
Mapping  of  interference  effects.  Plus  marks  indicate  complete  interference  with 
learning,  i.e.  more  than  three  times  normal  number  of  trials  without  meeting 
criterion.  Open  circles  indicate  no  clfect  of  stimulation.  Closed  circles  indicate 
ambiguous  effects  as  noted  in  text.  Other  nictations  are:  S  —  seizure,  P  —  forced 
position  preference,  A  —  activation. 


J.    OLDS    AND    M.    E.    OLDS  I65 

(3)  Correlation  with  Sclf-Stiiinihnioii.  —  In  an  effort  to  test  for  such  a 
correlation,  forty-six  animals  with  electrodes  placed  diversely  throughout 
the  brain  were  tested  first  for  interference  and  later  for  the  self-stimulation 
effect.  The  result  was  a  most  remarkable  correlation.  Of  eighteen  animals 
completely  confused  by  the  electric  stimulus,  fifteen  were  self-stimulators. 
Of  seventeen  animals  unaffected,  fourteen  were  non-self-stimulators 
(Fig.  11).  Of  eleven  animals  moderately  impaired  by  the  stimulus,  seven 
were  self-stimulators.  All  told,  there  were  only  three  cases  of  definite 
impairment  that  were  non-sclf-stimulators;  and  there  were  four  cases  of 
ambiguous  impairment. 

A  first  answer  is,  therefore,  that  points  yielding  the  most  interference  in 
a  learning  experiment  are  the  points  which  also  cause  self-stimulation.  A 
question  arises,  however,  whether  the  points  which  cause  interference 
but  no  positive  reinforcement  occurred  by  chance,  or  whether  they 
follow  some  pattern.  Mapping  the  points  (Fig.  12),  we  see  that  there  is  a 
design.  Of  the  twenty-nine  points  yielding  complete  or  ambiguous 
impairment,  we  have  satisfactory  histological  localization  on  twenty-six. 
The  points  which  yield  both  confusion  and  self-stimulation  arc  scattered 
throughout  the  hypothalamic-palaeocortical  system,  but  the  points  which 
yield  only  confusion  are  clustered  along  the  hippocampus  proper  (that  is, 
as  distinct  from  the  dentate  gyrus),  plus  one  in  the  anterior  thalamus. 
We  may  guess,  then,  that  there  are  two  kinds  of  confusion  points:  (1)  the 
self-stimulation  points,  and  (2)  a  second  kind  located  mainly  in  the 
hippocampus  proper. 

(4)  Memory  Test.  —  A  further  difference  between  these  two  kinds  of 
points  appears  when  we  test  for  confusing  effects  of  the  stimulus  on  on- 
going performance,  after  criterion  has  been  reached  on  a  given  day.  We 
have  called  this,  perhaps  wrongly,  a  memory  test  because  we  introduce 
the  jamming  stimulus  after  learning  has  occurred,  and  we  look  to  see  if 
the  animal  can  still  'remember'  the  correct  way.  We  might  equally  well 
call  it  a  performance  test,  inasmuch  as  the  stimulus  might  interfere  with 
correct  performance  even  if  some  hypothetical  'memory'  were  intact. 

At  any  rate,  the  test  shows  up  a  striking  difference  between  two  kinds 
of  placement.  If  electrodes  are  in  placements  which  produce  avid  self- 
stimulation,  the  stimulus  causes  a  complete  relapse  to  errors  (and  errors 
continue  indefinitely)  when  stimulation  is  introduced  after  learning.  But 
if  electrodes  are  in  the  interference  points  where  this  is  dissociated  with 
self-stimulation,  the  result  is  different.  The  animal  may  make  a  few  errors 
upon  initial  introciuction  of  the  stimulus,  but  correct  performance  is 
readily  resumed  (Fig.  13). 


1 66 


BRAIN    MECHANISMS    AND    LEARNING 


X 

500 

" 

X 
X 

X 

5 

400 

X 

X 
X 

X 
X 

iOO 

-  X 

X 

X 

X 

X 

X 

200 

- 

5 

X 

100 

' 

X 
X 

X 
X 

0 

—   XXXXXXXXXXXXXX 

X  X  X  X 

XXX 

MODERATE    IMPAIRMENT 


LEARNING    DECREMENT 


COMPLETE    IMPAIRMENT 


Fig.  II 
Correlation  of  interference  with  self-stimulation.  Each  point  stands  for  one  electrode  pair. 
The  position  on  the  ordinate  indicates  the  self-stimulation  rate  for  an  8-minutc  test  period 
(current  set  at  optimal  level  in  lo-  to  50-pamp.  range).  Three  categories  on  abscissa  indicate  no 
interference,  ambiguous  interference,  and  total  interference. 

Self-Stimulotion  Test  of   26  Points  Which   Yield    Confusion 

s  =  5e/f  stimulation 


Basal  Ganglia 


*-  No  self  stimulation 
Hpc 


Points    where   self-stiniulatic 


electrodes   (S)    and  non-self-stimulation  electrodes  (#) 
yielded  confusion. 


J.    OLDS    AND    M.    E.    OLDS 


167 


Of  seventeen  self-stimulators  given  this  test,  fifteen  showed  total  failure 
to  regain  criterion;  the  other  tw^o  were  moderately  impaired.  Of  six  non- 
self-stimulators  given  the  test,  three  were  moderately  impaired,  and  three 
were  unaffected  (Fig.  14).  All  animals  were  significantly  impaired  on  the 
initial  learning  test.  This  suggests  that  the  points  where  impairment  is 
dissociated  from  self-stimulation  are  points  involved  in  learning  but  not  in 
later  memory  or  performance. 


M    EMORY 
PER  I  AMYGDALOID 


1/     .^ 


4        8       12      16     20     34     2B     32     3t      40 

H  I  PPOCAMPUS 


^--rr 

■!  20    30 


ANT.      T  HAL. 


/35//0 


.'-r 
-)—^ 


Fig.  13 
Memory  test.  Cumulative-error  curves  arc  shown  for  days  when  stimulation  started  at 
onset  of  test  (double  lines)  and  days  when  stimulation  did  not  start  until  after  criterion 
was  reached  (single  lines).  Vertical  dotted  line  indicates  onset  of  stimulation  for  latter  case. 
When  stimulation  starts  at  onset  of  test,  errors  are  not  eliminated  in  any  of  these  cases. 
When  stimulation  is  introduced  after  criterion,  it  causes  complete  relapse  with  electrodes 
in  periamygdaloid  cortex,  but  not  complete  relapse  with  hippocampal  or  anterior  thala- 
mic electrodes. 


Now  the  question  arises  whether,  in  places  where  self-stimulation  and 
confusion  are  associated,  the  confusion  results  from  the  extreme  reward 
(which  might  render  the  food  reward  unimportant),  or  from  some 
additional  pattern  disruption  over  and  above  this  reinforcing  effect. 

(5)  Reuiforcement-Jutcrfcreuce  Test.  —  To  attempt  an  answer  to  this 
question,  a  test  was  devised  in  which  the  'interfering'  stimulus  was  so 
correlated  with  the  correct  response  as  to  constitute  to  some  degree  an 


i68 


BRAIN    MECHANISMS    AND    LEARNING 


added  incentive.  This  was  accomplished  by  having  the  wrons;  lever 
terminate  the  series  of  stimulations,  and  the  correct  lever  re-start  the 
series.  Thus  the  animal  making  all  correct  responses  would  be  stimulated 
as  before,  i  second  on,  2^  seconds  oft.  But  during  learning,  each  day,  the 
sequence  would  be  interrupted  every  time  an  error  occurred,  and  restarted 
only  by  the  next  correct  response  (Fig.  15). 


EFFECT   OF  STIMULUS   AFTER    LEARNING 


SELF    STIMULATION    POINTS 


NO   SS 
PTS 


MAXIMUM    IMPAIRMENT 


MODERATE  IMPAIRMENT 


MINIMUM  IMPAIRMENT 


Fig.  14 
Memory  test  for  twenty-three  points,  all  of  which  yielded  impair- 
ment on  learning  test.  Seventeen  cases  were  self-stimulators.  Si-x  were 
non-self-stimulators.  The  figure  shows  that  fifteen  of  the  self-stimu- 
lation points  yielded  maximum  impairment  when  introduced  after 
learning;  the  other  two  self-stimulation  points  yielded  moderate 
impairment.  Of  the  non-self-stimulation  points,  three  yielded  moder- 
ate impairment,  and  3  yielded  almost  no  impairment. 


When  this  test  was  applied  to  the  confused  selt-stimulators,  those  with 
very  rapid  rates  of  self-stimulation  were  no  longer  confused.  Several  of 
the  slower  self-stimulators  appeared,  however,  to  be  still  confused 
(Table  I).  The  possibility  remained  that  those  still  appearing  confused  were 
in  fact  making  errors  to  terminate  negative  reinforcement;  i.e.  they  were 
receiving  both  positive  and  negative  reinforcement  from  the  same 
stimulus  (Roberts,  195 8).  To  test  for  this  in  a  very  preliminary  fashion 
three  of  them  were  given  tests  for  escape  responding  yielded  by  the 
electric  stimulus,  and  these  three  did  give  evidence  of  escape.  Thus  we 
cannot  find  from  these  tests  any  support  for  the  notion  that  the  self-stimula- 
tion points  cause  a  bona-fide  confusion.  Rather,  it  appears  that  the  large 
reinforcing  effect  of  the  electric  stimulation  somehow  overrides  the 
smaller  positive  reinforcing  effect  of  the  food.  When  food  and  electric 


J.    OLDS    AND    M.    E.    OLDS 


169 


reinforcement  pull  the  sanie  way,  the  animal  can  achieve  criterion,  and 
can  run  perfectly. 

There  is  still  room  for  doubt,  however,  because  (i)  the  animals  appear  to 
be  running  and  searching  for  food  during  stimulation  trials  in  the  learning 
and  memory  test,  and  they  cat  the  food  rapidly  when  they  get  it;  (2)  it  is 


Tadle  I 

REINFORCEMENT-INTERFERENCE  TEST  COMPARED 
WITH  SELF-STIMULATION  SCORE  AND  ESCAPE 
TEST.  POINTS  IN  THE  O  COLUMN  SHOWED  NO 
IMPAIRMENT  ON  THE  REINFORCEMENT-INTER- 
FERENCE TEST.  POINTS  IN  THE  PLUS  COLUMN 
WERE  COMPLETELY  IMPAIRED.  SELF-STIMULATION 
SCORES  ARE  RANK-ORDERED  FROM  TOP  TO 
BOTTOM  OF  THE  TABLE;  THESE  ARE  RATES  FOR 
AN  8-MINUTE  TEST  PERIOD.  THE  EVIDENCE 
SHOWS  THAT  POINTS  YIELDING  HIGH  SELF- 
STIMULATION  RATES  CAUSED  NO  INTERFERENCE 
IN  THIS  TEST.  THREE  POINTS  WHERE  INTERFERENCE 
OCCURRED  WERE  TESTED  FOR  ESCAPE,  AND  THESE 
TESTS  INDICATED  THAT  NEGATIVE  REINFORCE- 
MENT ACCOMPANIED  POSITIVE  REINFORCEMENT 
AT    THESE    POINTS 


0 

+ 

S.  St. 

S.  St. 

Esc. 

550 

soo 

468 

450 

370 

350 

+ 

3^.S 

300 

280 

270 

150 

100 

+ 

122 

+ 

not  clear  why  animals  which  have  reached  criterion  in  the  memory  test 
proceed  to  make  errors  upon  introduction  of  stimulation,  when  the  same 
animals,  having  reached  criterion  under  the  reinforcement-interference 
conditions,  can  run  and  eat  perfectly  under  the  same  electric  stnnulation; 
and  (3)  in  the  reinforcement-interference  test  the  added  incentive  of  the 
goal  might  cause  the  animal  to  override  the  confusing  effects  of  the 


1 70 


BRAIN    MECHANISMS    AND    LEARNING 


stinuilus,  rather  than  proving  there  were  no  confusing  effects  in  the  first 
place.  We  have  often  seen  animals  become  'brighter'  as  the  'reward' 
potentiometer  is  turned  upwards  in  maze  experiments. 


INCORRECT 


CORRECT 


STIM.  EVERY  3  SEC. 

NO  STIM. 

Fig..  15 
Reinforcement-interference  test. 
Interference  stimulus  starts  when 
animal  is  placed  in  box  and  con- 
tinues unless  error  pedal  is  pressed. 
At  that  point  it  is  terminated  and 
does  not  start  again  until  correct 
response  occurs. 


DISCUSSION 


At  the  end  of  the  first  set  of  experiments  we  were  well  aware  that  the 
hypothalamic-rhinencephalic  system  was  most  likely  the  central  core  of 
the  positive-reinforcement  mechanism.  And  wc  also  thought  in  terms  of 
positive  reinforcement  as  involving  (i)  some  close  relationship  to  learning 
(a  concept  we  still  hold)  and  (2)  some  peculiar  virtue  in  promoting  learn- 
ing, sharpening  the  wits,  oiling  the  course,  or  stamping  in  the  right 
response. 

The  second  set  of  experiments  surprised  us  at  first,  indicating  as  it  did 
that  the  most  efficacious  way  to  interfere  with  the  learning  mechanism 
was  to  hyperstimulate  the  same  system  which  we  had  formerly  thought 
to  promote  learning.  We  should  not  have  been  surprised,  of  course,  for 


J.    OLDS    AND    M.    E.    OLDS  I71 

this  finding  emphasized  what  we  should  have  known  at  first:  response 
learning  involves,  hrst,  cessation  of  wrong  behaviours,  secondly,  com- 
mencement of  correct  ones,  and  thirdly,  repetition  of  correct  ones.  A 
stimulus  causing  repetition  of  behaviour  would  only  promote  the  thu-d 
stage  of  the  process,  which  in  a  sense  is  not  learning  at  all  but  its  antithesis. 

But  again  there  was  still  room  for  doubt.  Our  stimulation  of  the  large 
hypothalamic  system  causes  repetition  and  inhibits  adaptive  changes  in 
behaviour.  In  a  sense,  this  is  one  and  the  same  thing;  by  repeating,  the 
animal  cannot  be  adaptive,  changing.  This  is  consistent;  but  we  must 
sometimes  beware  of  consistency. 

Our  animals  could  repeatedly  get  the  brain  stimulus  (which  is  all  the 
repetition  they  want)  and  yet  adcipt  the  correct  response  to  get  food  at  the 
same  time;  and  they  appear  to  be  trying  to  get  food.  Why  does  the 
response  fail  to  become  stereotyped  down  one  lane?  One  might  say  there 
is  a  reinforcement  ot  the  antecedent  so  per  cent  probability.  But  then  why 
in  the  memory  tests  where  the  learning  occurs  first  does  the  stimulus  cause 
return  to  50  per  cent  probability:  Or  even  more  strikingly,  why,  after  the 
animal  learns  in  reinforcement-interference  tests,  can  he  run  successfully 
under  stimulation,  to  food  and  back,  with  no  errors  even  though  the 
stimulation  continues?  The  same  animal  running  currently  in  the  memory 
test  starts  and  continues  to  make  errors  upon  introduction  ol  the  stimulus. 

The  possibility  we  want  to  suggest  is  this:  our  stimulus  might  cause 
some  confusion  in  addition  to  the  output  of  positive  motivation.  In  the 
reinforcement-interference  test,  the  strong  positive  motivation  emanating 
from  hypothalamic  stimulation  keeps  behaviour  in  line.  But  minor  prob- 
lems cannot  be  solved  because  of  confusing  effect.  It  might  be,  then,  that 
total  activity  in  this  hypothalamic-rhinencephalic  system  determines  the 
positive-reinforcement  function;  but  the  pattern  of  activity  in  the  same 
system  is  precisely  the  more  or  less  lasting  process  that  is  altered  by  learning. 

Giving  up,  then,  the  idea  that  positive  reinforcement  promotes  learning, 
we  are  left  with  alternative  notions:  either  it  is  a  simple  inhibitor  of 
learning  or  else  it  is  somehow  a  function  of  the  same  neural  aggregates 
which  are  chiefly  involved  in  learning;  but  quantity  is  most  important 
from  a  standpoint  of  reintorccmcnt,  the  patterning  most  important  from 
the  standpoint  of  learning. 

From  the  latter  point  of  view,  stimulation  of  the  system  could  be  said  to 
augment  the  positive  reinforcement  and  the  repetitiousness  of  the  whole 
system,  but  to  disrupt  the  patterns  formed  by  association  of  mild  cues. 

The  final  experiment  we  have  to  report  searched  for  ways  of  causing 
learned  changes  in  neural  patterns  by  operant-conditioning  techniques. 


172  BRAIN    MECHANISMS    AND    LEARNING 

III.    THE    OPERANT    CONDITIONING    OF    SINGLE-UNIT    RESPONSES 

A  most  important  contribution  of  behavioural  psychology  to  the 
brain  and  behaviour  field  is  the  conception  that  a  response  is  not  merely 
something  to  be  elicited,  observed,  characterized,  and  recorded.  In 
operant-behaviour  analysis,  a  response  is  more  than  that:  it  is  something 
to  be  conditioned.  The  single-unit  response  is,  on  the  face  of  it,  precisely 
the  type  of  categorical  and  clearly  defined  event  that  should  be  amenable 
to  operant-conditioning  techniques.  We  report  here  initial  successes  in 
this  endeavour. 


METHODS 

In  these  studies,  rats  were  prepared  first  with  self-stimulation  electrodes 
in  mcdial-forebrain-bundle  regions.  Preliminary  tests  established  that 
very  high  self-stimulation  rates  were  achieved,  and  no  tendency  to  escape 
from  stimulation  was  present.  Rats  which  failed  to  meet  these  requirements 
were  eliminated.  Each  rat  was  then  placed  in  a  stereotaxic  instrument 
under  barbiturate  anaesthesia.  A  hole  of  3-mm.  diameter  was  drilled  in  the 
skull,  usually  i  mm.  behind,  and  i  mm.  lateral  to  the  bregma.  The  dura 
was  pierced  repeatedly  with  a  sharp  instrument.  Then  tungsten  micro- 
electrodes  of  i-ii  diameter  (Hubel,  1957)  were  lowered  imni.  into  the 
cortex. 

As  the  animal  recovered  from  the  barbiturate  anaesthesia,  still  in  the 
stereotaxic  instrument,  he  was  given  repeated  doses  of  isopropyl  meproba- 
mate  (Soma,  Wallace  Laboratories).  Each  dose  was  80  mg./kg.  The  dose 
was  repeated  whenever  any  tendency  of  the  animal  to  try  to  escape  from 
the  instrument  appeared.  Previous  tests  had  shown  that  an  almost  paralys- 
ing dose  of  isopropyl  meprobamate  (100  mg.  kg.)  fails  to  block  self- 
stimulation  (Olds  and  Travis).  From  this  point  on,  the  electrode  was 
advanced  downwards  through  the  cortex,  hippocampal  formation,  thala- 
mus and  so  forth,  stopping  whenever  a  clear  spontaneous  response 
appeared.  Output  from  the  microelectrode  was  led  through  a  cathode 
follower  into  a  Grass  a-c  amplifier  and  thence  into  a  Dumont  cathode-ray 
oscilloscope.  Responses  of  single  nerve  cells  appeared  as  200-  to  500-|jv. 
negative  spikes,  lasting  about  i  msec.  They  were  identified  mainly  by 
their  duration,  by  being  repeated  responses  of  constant  amplitude,  and  by 
their  disappearance  upon  movement  of  the  microelectrode  by  about  200 
microns. 

Unit  responses  were  not  considered  satisfactory  for  these  experiments  if 
their  resting  frequency  was  more  than  about  2  per  second ;  and  they  were 


J.    OLDS    AND    M.    E.    OLDS 


173 


preferred  if  this  were  something  less  than  i  per  second.  When  such  a 
response  was  observed,  a  three-step  experiment  was  performed :  first,  after 
several  minutes  of  waiting,  a  30-second  record  was  made  on  moving 
photographic  paper  of  the  resting  rate  of  the  unit  response.  Second,  an 
elicitation  test  was  made.  A  scries  of  twenty  -j-second  trains  of  stimulation 
(sine  wave  60  c.p.s.,  50  namp.)  was  introduccci  via  the  medial-forebrain- 
bundle  electrodes  at  a  repetition  rate  of  i  every  2  seconds.  These  were  not 
correlated  with  single-unit  response.  Instead,  there  was  an  explicit  effort 


Fig.  16 

Schematic  diagram  of  single-unit  operant-conditioning 
apparatus.  Single-unit  response  is  amplified  and  fed  into 
amplitude  discriminator  which  disregards  all  lesser  signals, 
but  yields  an  output  whenever  the  single-unit  response 
occurs;  the  output  then  goes  to  a  counter.  The  counter  is 
preset  to  activate  a  stimulator  and  reset  whenever  it  reaches 
some  number  from  i  to  9.  At  this  point,  a  |^-second  train  of 
60-cycle  stimulation  (50  namp.  r.m.s.)  is  delivered  to  the 
medial-forebrain-bundlc  'reward'  point.  During  the  stimu- 
lation, the  counter  is  disengaged  so  that  it  will  not  count 
stimulus  artifact.  Immediately  afterwards,  it  commences 
to  count  again  until  the  preset  ratio  is  again  reached  at 
which  point  it  delivers  another  'reward'  stimulus. 


made  to  stimulate  only  in  the  absence  of  single-unit  responses.  Immediately 
after  this  test  a  second  30-second  record  of  activity  was  made  on  film.  In 
the  event  of  elicited  effects,  each  stimulation  produced  a  series  of  responses 
from  the  unit,  and  no  further  tests  were  made.  The  microelectrode  was 
then  advanced  until  a  new  unit  response  appeared.  In  the  event  that 
elicited  effects  were  not  found,  the  experiment  continued.  Third,  a 
reinforcement  test  was  made.  The  experimenter  awaited  a  single-unit 
response  and,  each  time  it  appeared,  immediately  delivered  a  stimulus  to 
the  hypothalamus.  When  this  was  done  by  hand,  reinforcement  could  be 


174  BRAIN    MECHANISMS    AND    LEARNING 

applied  after  one  appearance  or  after  several  appearances  of  the  unit 
response.  It  was  usually  applied  after  each  appearance  of  the  response  with 
a  delay  of  about  i  second  (this  was  the  experimenter's  response  tinae). 

The  design  of  the  experiment,  when  the  stimulus  was  presented  auto- 
matically, is  shown  in  Fig.  16.  The  output  from  the  oscilloscope  amplifiers 
was  led  into  an  amplitude  discriminator  circuit,  and  the  output  from  the 
circuit  activated  an  electronic  counter  which  could  be  preset  to  deliver 
stmiulation  after  a  preset  number  of  responses  from  i  to  9.  In  this  case,  the 
delay  of  reinforcement  was  about  3  msec.  Each  activation  of  the  stimulator 
was  recorded  on  a  cumulative  response  recorder,  so  that  the  response  rate 
was  retained  on  a  permanent  record. 

In  the  case  of  a  positive  experiment,  the  single-unit  response  rate  was 
greatly  augmented  by  either  the  hand  or  the  mechanical  reinforcement 
procedure.  The  increased  rate  outlasted  the  procedure  by  a  variable  period 
of  time.  Immediately  after  this  procedure,  a  third  record  of  the  unit's 
activity  was  made  on  film.  It  is  the  comparison  of  the  three  tilms  that 
comprises  our  data. 

In  the  event  of  failure  to  reinforce,  by  manual  techniques,  the  unit  was 
often  put  on  the  automatic  reinforcement  procedure,  and  sometimes 
positive  reinforcement  bypassed  by  the  former  procedure  was  discovered 
after  long  runs  with  the  latter  method.  Because  of  the  close  temporal 
relationship  between  the  control  picture  and  the  augmented  picture, when 
the  manual  technique  was  successful,  it  was  always  the  more  convincing. 

RESULTS 

The  first  point  to  emphasize  is  the  difference  between  the  neocortex  and 
the  palaeocortical  structures  studied.  Palaeocortical  units  often  appeared  to 
'learn  with  ease'.  Neocortical  units  never  yielded  any  similar  rapid  modi- 
fication when  subjected  to  reinforcement  techniques.  The  details  of  this 
difference  will  be  clarified  below.  Most  often,  stimulation  caused  neo- 
cortical unit  respc^nses  to  disappear,  never  to  return;  but  sometimes,  rein- 
forcement caused  slow  augmentation  of  response. 

Where  stimulation  had  any  effect  other  than  inhibition,  it  produced  one 
of  four  kinds  of  changes  in  the  pattern  of  single-unit  response:  (i)  conver- 
sion of  a  sporadic  grouped  response  to  a  continuous  response  by  the 
reinforcement  procedure;  (2)  augmentation  of  the  response  rate  of  a 
sporadic  response  by  reinforcement;  (3)  ehcitation  of  activity  imme- 
diately after  the  stimulus,  but  only  when  it  was  given  as  a  reinforcement; 
and  (4)  ehcitation  of  activity  by  the  stimulus  irrespective  of  its  use  as  a 
reinforcement. 


J.    OLDS    AND    M.    E.    OLDS  I75 

The  most  striking  cases  were  of  the  hrst  type  (Figs.  17  and  20  I,  II,  IV). 
They  were  recorded  mainly  from  areas  such  as  the  dentate  gyrus,  tmibria 
regions,  and  mammillo-thalamic  tract  regions,  which  appeared  to  be 
'seizure-prone'  in  our  previous  experiment  (Fig.  10).  In  these  cases,  the 
unit  was  originally  responding  in  a  sporadic  pattern  with  single  responses 
or  groups  appearing  at  less  than   one  per  second.    Stimulation   when 

-M'3  1/3  )0°P  Before  Stimulation  #1118  Dentate 

»  |i  1,4    iijiiiiiiiiX" i<»r»  iii^i 4»'''*"'4''' '4****'**'''*'**^^ 

^tftt^ nii<iwi4i  III  !»■' iiWMw«4«*«wlN4>'i«^«"y^ 

After    5'   Stimulation        No   RemforcemenI 

-A-  A ^    '  -  - 


ii»iAyi   4 I     t    ■»  nil     11*1  ■«    |>|     »  I'i     iiiifilii    |<'<>  MJiijiN 

'<|iiii^i4ii4 muiumm^immmmmmmmmmmmitt ifi  ii»iiii|iiili>i>iw>rt»iM«iiiii  1     ■inwi^iu 

After  5    Reinforcoment 

mimitm4'»tm^mmmtm$»tmmm*mi»^^  ^i:iiiiii4Mii«iiiii»iiii» #i 

iiiiiiii  |iwi  i^ii'i j'  iwii^ii  I'^m  'jiiii   iiiiiiiu I  I  Ai  li  \\i\n$\\i  «iii4iii 

Fig.  17 
E.xperimciit  on  single-unit  response  recorded  from  dentate  gyrus.  Small  unit  response 
(almost  lost  among  larger  slow  waves)  occurs  at  rate  of  approximately  one  per  second 
tefore  stimulation,  and  rate  is  not  greatly  increased  by  uncorrelated  stimulation. 
When  stimulation  is  correlated  as  reinforcement  for  unit  response,  however,  continuous 
firing  (at  rate  of  about  30  per  second)  ensues.  Time  base  as  in  Fig.  18. 

nitrociuced  during  silent  peru)ds  did  not  cause  any  elicited  tiring.  Such 
stimulation  could  be  continued  for  periods  of  5  minutes  or  more  without 
materially  augmenting  the  response  rate.  Then,  if  the  stimulation  was 
withheld  and  delivered  only  after  the  appearance  of  a  single  or  grouped 
response,  ten  to  twenty  reinforcements  would  often  suffice  to  cause  a 
sudden  burst  of  activity;  the  unit  would  respond  continuously  at  rates  as 
high  as  30  per  second.  This  burst  would  sometimes  last  for  a  period  of  only 


176 


BRAIN    MECHANISMS    AND    LEARNING 


K)62  Anterior  Rhirencepholo 


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Remloromeni   Proceedu 


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J.    OLDS    AND    M.    E.    OLDS 


177 


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1062  Anlenor  Rhinencepka 


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V 

Fig.  18 
Series  of  experiments  on  single-unit  response  recorded  from  anterior  rhinencephalon.  I.  Before 
stimulation.  II.  After  stimulation  without  reinforcement.  III.  After  reinforcement.  IV.  After 
waiting  for  unit  to  slow  down  (about  5  minutes),  reinforcement  procedure  is  undertaken  a 
second  time,  and  a  photographic  record  is  made  during  reinforcement;  large  Litticc-type 
artifact  indicates  60-cycle  sine  wave  stimulus.  V.  Still  later,  after  another  wait,  attempt  is  made 
to  correlate  stimulation  with  pauses,  but  this  is  unsuccessful.  Later  an  electronic  device  was 
made  to  correlate  stimulation  with  long  silent  periods,  and  the  procedure  caused  some  unit 
responses  to  cease  altogether. 


several  minutes,  with  response  amplitude  decreasing  in  an  orderly  fashion. 
Then  the  unit  response  would  disappear  for  a  period  of  some  minutes,  to 
return  at  the  original  amplitude.  At  other  times,  the  repetitive  activity 
would  continue  at  a  high  level  for  longer  periods.  One  might  suspect  that 
a  hippocampal  seizure  had  been  started  by  the  reinforcement  procedure, 
except  for  the  fact  that  movement  of  the  electrode  in  these  cases  reveals  no 
similar  activity  in  neighbouring  cells. 

The  second  type  of  changes  (Figs.  i8  and  20  III)  were  not  greatly 
different  from  the  first,  but  in  these  cases,  the  rapid  responding  caused  by 
reinforcement  seemed  much  more  like  the  original  sporadic  responding, 
although  its  frequency  was  far  greater.  There  was  no  tendency  for  the 
rapid  responding  to  be  accompanied  by  decrement  in  amplitude.   It 


IjS  BRAIN    MECHANISMS    AND    LEARNING 

appeared  to  follow  much  more  ordinary  acquisition  and  extinction 
patterns,  augmenting  at  each  reinforcement,  slowing  upon  cessation  of 
the  reinforcement  procedure,  often  coming  to  rest  at  a  higher  firing  rate 
than  the  original  rate,  but  lower  than  during  reinforcement. 

Changes  of  this  type  were  graded  along  a  dimension  of  rapid  or  slow 
conditioning.  With  units  in  the  anterior  rhincnccphalic  cortex,  condi- 


I  Betoo  S 


!092  ■  Hipptxompyi  Proper 

miiimmimmm'imim'itmt  m  i  nm  »■  n  iiiiii" 


in  Mm  Rl< 


fm0' 


V  [X...r.g  Si        No   Rft 


Fig.  19 
Expennieut  on  single-unit  response  recorded  from  hippocampus.  It  is  noteworthy  that  stimula- 
tion which  closely  follows  a  unit  discharge  (see  IV)  causes  a  burst  of  activity  which  is  not  seen 
when  stimulus  occurs  against  a  background  of  no-firing  (see  V). 

tioning  was  quite  as  fast  as  with  type  I  units  in  the  dentate  gyrus.  But  the 
response  was  more  moderate.  Some  'learning'  of  a  much  slower  order 
occurred  with  points  estimated  to  be  at  the  base  of  the  neocortex.  There 
was  never  any  possibility  of  augmenting  the  rate  by  manual  reinforcement 
with  electrodes,  here,  but,  left  on  automatic  reinforcement  for  long 
periods  of  time,  the  unit  response  rate  would  sometimes  increase 
gradually.  This  seemed  quite  like  the  conditioning  of  a  skilled  act  in  its 


J.    OLDS    AND    M.    E.    OLDS  179 

time  course,  an  idea  possibly  forced  on  us  by  the  fact  that  the  hnal  condi- 
tioned unit  activity  was  often  accompanied  by  some  minute  movement  of 
an  extremity.  One  animal  learned  to  move  his  tail  to  the  right  while 
remaining,  otherwise,  absolutely  still. 

In  contrast  to  the  conditioning  ot  cortical  units  which  sometimes  seemed 
like  conditioning  the  muscle  output  itself,  the  conditioning  of  subcortical 
units  often  led  us  to  teel  that  we  were  observing  the  basic  mechanism  of 
instrumental  conditioning  itself.  This  was  the  case  first  in  the  conversion 
of  dentate  responses  to  seizure-like  tempos  as  in  type  i.  But  also  the  type 
3  modification,  observed  in  the  hippocampus  and  diencephalon,  appeared 
to  involve  some  basic  mechanism  of  learning. 

With  microclectrodes  here,  the  stimulus  had  quite  different  effects  when 
given  immediately  after  a  unit  response  from  those  it  might  have  against 
a  background  of  silence  (Figs.  19,  and  20  IV).  When  it  followed  the 
unit,  the  stimulus  would  invoke  either  a  further  burst  of  response  in  the 
same  unit,  or  a  burst  of  very  high  potential  activity  not  easily  characterized. 
If  the  same  stimulus  was  applied  at  some  temporal  distance  from  a  single- 
unit  response,  there  were  no  similar  effects. 

It  may  be  relevant  that  stimulation  did  sometimes  elicit  in  hippocampal 
electrodes  a  high-voltage,  repetitive,  positive  discharge  of  somewhat 
longer  duration  than  the  single-unit  response. 

Finally,  there  is  of  course  the  type  4  modification:  the  stimulus  causes 
an  elicited  effect  so  that  reinforcement  cannot  be  tested.  It  is  hard  to 
estimate  how  frequent  this  occurrence  is  because  these  effects  have  been 
quickly  by-passed  in  our  experiments  in  search  of  areas  where  elicited 
effects  are  absent.  It  is  certainly  clear  that  these  cases  increase  in  number 
as  the  microelectrode  approaches  the  point  of  stimulation  in  the  posterior 
hypothalamus  (Fig.  20  V). 

SPECULATIONS 

It  is  certainly  tempting  to  speculate  at  this  point,  so  long  as  it  is  under- 
stood that  no  scientific  factual  import  should  be  attached  to  these  specula- 
tions. 

Ashby  (1953)  has  suggested  that  perhaps  each  neurone  is  in  itself  a 
negative  feedback  system,  at  least  a  system  that  modifies  its  output 
depending  on  the  feedback  it  gets  from  previous  outputs.  We  have  perhaps 
shown  something  of  this  kind  here. 

There  is  of  course  nothing  in  our  work  to  determine  that  the  unit  is  the 
conditioned  entity;  perhaps  it  is  simply  our  method  for  identifying  a 

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BRAIN    MECHANISMS    AND    LEARNING 

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J.    OLDS    AND    M.    E.    OLDS 


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Fig.  20 
Localizations  of  microclectrode  points  yielding  various  effects.  I.  Point  in  or  near  maninnllo 
thalamic  tract  yielding  reinforcement  to  contmiioiis  firing  (schematically  symbolized  by  unit- 
sinewave  pairings  followed  by  repetitive  vmit  discharge).  II.  Point  in  fimbria  yielding  rein- 
forcement to  continuous  firing,  plus  three  cortical  points  yielding  negative  results.  III.  Point 
in  anterior  rhinencephalon  which  augmented  firing  rate  greatly  during  reintorccment 
procedure.  IV.  Point  in  hippocampus  where  reinforcement  caused  firing  after  the  stimulus; 
and  point  in  mammillo-thalamic  tract  region  of  thalamus  where  reinforcement  yielded 
continuous  firing.  V.  Point  in  dorsal  posterior  hypothalamus  where  stimulation  elicited  unit 
firings. 


larger  integration  which  we  proceed  to  condition.  However,  wc  do  have 
anecdotes  which  suggest  that  a  unit  discharge  started  by  pressure  (as  our 
microclectrode  enters  an  area)  can  be  maintained  active  by  reinforcement. 
If  stimulation  with  the  microclectrode  can  be  performed  systematically,  it 
will  at  least  be  shown  whether  the  unit  response  needs  to  be  started  by 
some  afferent  system  to  be  conditioned. 


1 82  BRAIN    MECHANISMS    AND    LEARNING 

Supposing  for  a  moment  that  the  unit  itself  is  the  conditionablc  entity  in 
these  experiments,  we  would  then  be  provided  with  some  sort  of  a  trace 
system.  We  could  suggest  that  instrumental  conditioning  techniques 
leave  a  changed  pattern  of  repetitive  discharge  in  these  units,  a  suggestion 
which  someone  more  given  to  theorizing  than  we  might  inflate  into  a 
model  for  a  brain. 

SUMMARY 

Three  sets  of  experiments  have  been  reviewed  here,  suggesting  first 
obliquely  and  then  more  directly  that  the  hypothalamic-rhinencephalic 
system  is  more  intimately  related  to  instrumental  conditioning  than  the 
other  parts  of  the  brain. 

First,  self-stimulation  experiments  which  show  that  stimulation  in  this 
area  can  serve  as  a  strong  positive-reinforcement  or  unconditioned  stimulus 
in  Skinner  box,  runway,  obstruction  box,  and  maze  experiments  were 
cited.  These  suggested  that  somehow  a  good  deal  of  activity  emanating 
from  this  system  might  foster  at  least  the  repetition  of  preceding  responses, 
if  not  the  learning  of  responses  themselves. 

Second,  interference-stimulation  experiments  were  conducted  to  find 
where  electric  stimulation  might  interfere  with  performance  in  a  T-maze 
type  of  test.  It  was  found  that  precisely  the  same  system  was  implicated. 
Stimulation  in  positive-reinforcement  points  appeared  to  cause  confusion 
because  of  the  prepotency  of  the  electric  brain-stimulus  'reward'  over  the 
food  reward  to  the  hungry  rats.  But  other  points  in  the  hippocampus 
proper  caused  confusion  without  any  accompanying  positive-reinforcing 
effects.  These  points  were  also  distinct  from  positive-reinforcement 
points  in  that  interference  occurred  only  during  learning  but  not  during 
later  performance. 

Third,  instrumental-conditioning  experiments  were  carried  out  on 
single-unit  responses  in  cortical,  palaeocortical  and  subcortical  regions. 
Units  in  subcortical  and  palaeocortical  structures  were  often  readily 
conditioned.  Only  rarely  and  with  great  difficulty  were  cortical  units 
conditioned.  Conditioning  in  lower  centres  often  appeared  to  suggest 
basic  mechanisms,  as  stimulation  after  a  unit  discharge  would  have 
different  effects  from  those  it  would  have  against  a  background  of  silence, 
or,  several  stimulations  after  a  unit  discharge,  would  cause  seizure-like 
repetitive  discharge. 

The  data  from  all  three  experimental  programmes  might  be  summarized 
by  the  hypothesis  that  the  quantitative  measure  of  activity  in  the  hypotha- 
lamic-palaeocortical  system  is  a  measure  of  the  positive  reinforcement,  the 


J.    OLDS    AND    M.    E.    OLDS  1 83 

tendency  to  repetitive  behaviour.  The  pattern  of  repetitive  firing  in  the 
units  of  this  same  system  is  the  residual  process  which  is  modulated  by 
instrumental-conditioning  techniques. 

As  to  whether  the  same  changing  pattern  of  residual  processes  might 
serve  as  a  model  for  associative  conditioning,  we  will  suspend  judgment. 

GROUP   DISCUSSION 

Gerard.  In  what  manner  are  your  experiments  different  in  principle  —  ob- 
viously they  are  more  elegant  in  degree  —  than  ones  using  any  other  kind  of 
effector  response?  Any  response  obviously  must  involve  the  discharge  of  some  unit 
somewhere  in  the  brain. 

Olds.  Two  answers.  In  the  case  of  the  cortical  unit  and  even  in  the  case  of  the 
anterior  rhincncephalic  unit  that  I  showed,  my  impression  is  that  there  is  no 
difference  m  principle  at  all.  My  feeling  is,  in  both  these  cases,  that  the  animal 
decided  that  doing  something  was  getting  him  reinforced  and  so  he  did  it.  In  the 
case,  however,  of  the  fimbria  and  dentate  gyrus  units  and  in  the  case  of  some  of  the 
liippocampals,  I  had  a  feeling  that  here  is  the  mechanism,  so  to  speak,  so  that  you 
would  say  'this  is  the  stuff  decisions  are  made  out  oC.  That  here  we  were  playing 
with  sornething  that  just  automatically  had  its  response  rate  augmented  if  we 
stimulated  the  hypothalamus  right  after  it  has  discharged. 

Gerard.  Did  you  say  that  stimulation  of  the  fornix  in  the  rat,  under  your  condi- 
tions, interferes  with  learning  f 

Olds.  No.  The  answer  is  that  in  the  hippocampus  proper  wc  interfered.  But  in 
the  fimbria  and  often  in  the  fornix  our  stimulation  usualK*  produced  seizures  before 
we  could  get  any  experimental  tests. 

Gerard"  I  raised  the  point  only  because  of  the  recent  report  of  an  unfortunate 
operation  on  man,  in  which  the  fornix  was  cut  bilaterally.  Recent  memory  was 
completely  abolished. 

Olds.  I  have  a  hunch  that  response  Icarnnig  and  recent  memory  are  somehow 
very  closely  related.  And  that  if  we  said  response  learning  and  recent  memory 
involve  palaeocortical  and  hypothalamic  systems  we  might  be  on  to  something,  and 
the  more  structured  memory  might  be,  it  seems  to  me,  in  the  neocortex  and  the 
classical  thalamic  system. 

Grastyan.  Bv  stimulation  of  the  hippocampus  we  got  similar  observations  in 
somewhat  different  experiments.  On  the  background  of  already  established  condi- 
tioned reflexes  we  obtained  always  an  inhibition.  The  interpretation  of  these 
observations  was,  however,  always  very  problematic.  It  is  well  knowii  that  the 
hippocampus  is  one  of  the  structures  that  has  the  lowest  threshold  for  eliciting  after- 
discharges.  I  see  that  you  disregard  the  experiments  in  which  you  elicited  after- 
discharges.  I  am  still  not  absolutely  convmced,  however,  that  by  stimulating  the 
liippocampus  you  did  not  get  any  after-discharge  in  the  hippocampus  itself 
Sometimes  when  recording  in  various  parts  of  the  hippocampus  we  got  after 
discharges  when  we  did  not  see  any  sign  of  after-discharge  in  other  structures.  I  am 
not  convmced  that  these  effects  represented  a  physiological  inhibition.  I  have  to 
admit  at  the  same  time  that  we  had  some  observations  m  wliich  we  did  not  elicit 
any  after-discharge  in  the  hippocampus  and  we  still  obtained  inlnbition.  I  would  be 


l84  BRAIN    MECHANISMS    AND    LEARNING 

very  interested  to  know  what  might  be  the  physiological  meanijig  of  this  inhibition. 
According  to  our  supposition,  the  hippocampus  inhibits  the  orientation  reflex, 
which  is  a  necessary  step  in  the  development  of  the  conditioned  reflex. 

Olds.  Wc  found  that  if  we  were  on  the  surtace  of  the  hippocampus  itself,  so  that 
we  were  stimulating  the  hippocampal  cells  proper,  we  very  rarely  got  grand  mal 
seizure  perceptible  in  the  animal's  behaviour.  When  we  were  in  dentate  we  almost 
invariably  did  get  grand  mal  at  such  low  thresholds  that  it  was  impossible  to  do 
any  research  at  all.  Now  as  to  whether  our  results  in  the  hippocampus  proper  might 
be  from  hippocampal  seizure  which  could  be  recorded  although  not  observed  I 
certainly  would  not  be  at  all  surprised  if  that  were  true.  I  have  often  conceived  of 
these  experiments  in  the  light  of  trving  to  tind  the  place  where  localized  seizures 
would  have  the  same  effect  as  a  generalized  electro-convulsive  shock.  We  are  trying 
to  look  for  a  place  where  we  can,  so  to  speak,  jam  the  network  by  excessive  activity. 

Adey.  I  was  very  interested  in  Dr  Olds's  observations  of  the  role  of  the  anterior 
hippocampus  in  this  particular  type  of  activity.  I  wonder  whether  he  has  also 
examined  the  ventral  parts  of  the  hippocampus  arch  and  whether  he  has  come  to 
anv  conclusions  about  the  relative  significance  of  the  more  ventral  zones  ot  the 
hippocampus  as  opposed  to  the  dorsal.  My  reason  for  asking  this  is  primarily  that 
we  have  studied  quite  extensively  the  course  of  the  normal  wave  discharges  in  the 
hippocampus  in  the  course  of  various  learning  procedures.  I  would  mention  that 
there  does  not  appear  to  be  a  homogeneity  of  the  whole  aspect  of  the  hippocampus 
in  this  regard,  and  that,  briefly,  the  dorsal  hippocampus  and  the  entorhinal  cortex 
are  regions  which  appear  to  be  particularly  concerned  in  the  type  of  behaviour  in 
which  we  are  interested,  to  the  point  where  one  might  summarize  by  saying  that 
the  region  between  the  hippocampal  pyramidal  cells  and  the  dentate  gyrus,  where 
Dr  Olds  mentions  this  extreme  sensibility  to  seizure,  this  region  and  the  adjacent 
entorhinal  cortex  appear  to  be  concerned  in  what  we  might  term  the  execution  of 
planned  behaviour,  basing  that  opinion  on  certain  very  regular  slow-wave  dis- 
charges. If  I  might  raise  one  further  point,  that  is  the  question  of  these  curious 
polyphasic  discharges  which  Dr  Olds  saw  when  he  was  recording  from  the  vicinity 
of  the  dentate  gyrus.  I  wonder  whether  he  may  not  be  seeing  in  fact  a  muscle 
discharge  if  his  microelectrode  recording  set-up  is  the  typical  one  with  the  mono- 
polar method  of  recording.  The  absence  of  the  normal  muscular  paralysing  agents 
will  very  often  produce  volume  conducted  muscular  effects  that  may  be  extremely 
confusing  in  the  interpretation  of  the  micro-electrode  recording. 

Olds.  In  all  cases  that  we  have  reported,  in  which  are  found  this  special  pheno- 
mena of  peculiar  effects  immediately  after  the  stimulus  we  have  very  careful 
control  showing  that  we  do  not  get  these  effects  except  when  we  apply  the  stimulus 
immediately  after  the  unit  response.  In  all  other  respects,  I  assure  you  this  looks  like 
artefact.  And  it  is  only  because  it  has  this  physiological  significance,  namely  that  the 
proximal  unit  has  to  fire  before  we  apply  our  stimulus  in  order  for  us  to  see  this 
response,  it  is  only  for  that  reason  that  I  even  mention  it. 

Let  me  go  back  to  following  the  hippocampus  around  to  its  posterior  arch.  To 
me  it  looks  like  the  hippocampus  all  the  way  around  has  the  dentate  gyrus  facing  it. 
I  did  show  three  sagittal  sections  in  my  large  map  and  if  you  had  looked  carefully 
you  would  find  that  in  all  cases  if  the  electrodes  w^re  placed  just  above  the  arch  of 
the  hippocampus  proper,  we  got  the  rather  total  inhibitory  effect  without  self- 
stimulation.  Finally,  as  to  your  notion  that  the  dentate  might  be  involved  particu- 


J.    OLDS    AND    M.    E.    OLDS  185 

larly  in  planned  behaviour,  I  had  very  much  a  similar  notion  after  this  work 
because  we  interfered  completely  with  stimulation  in  hippocampus  and  I  felt  that 
the  hand-in-glove  arrangement  between  hippocampus  and  dentate  cannot  be  for 
nothing,  hi  the  single  unit  studies  we  tound  the  most  remarkable  mechanism-like 
effects  in  the  outflow  from  the  dentate  itself  where  we  could  give  two  or  three 
stimulations  in  a  reinforcing  position,  that  is  following  the  response,  and  then 
multiple  firing  would  suddenly  ensue. 

Magoun.  Stimulating  ascending  pathways  to  the  rabbit's  hippocampus  evokes 
an  undulating  slow-wave  discharge  whose  frequency  is  around  5  to  7  a  second. 
Unit  recordings  from  the  hippocampus,  by  Dr  John  Green,  often  show  firing  in 
some  relationship  to  this  ryhthm.  Did  you  elicit  such  a  rhythm  from  stimulating 
reinforcing  sites?  if  so,  could  you  correlate  unit  tiring  with  the  slow  waves? 

Olds.  We  do  not  have  fair  data  to  answer  that.  Because  wherever  we  got  an 
elicited  effect  we  went  on  very  rapidly  to  another  unit.  Quite  often  units  would 
respond  on  slow  waves,  this  being  rather  hard  to  see  when  you  have  a  lot  of  filters, 
but  still  it  was  rather  obviously  there  and  it  made  the  unit  an  unlikely  one  for 
further  recording.  We  did  not  spend  much  time  with  units  that  were  associated 
clearly  with  slow  waves.  Thus  in  a  sense  we  have  worked  out  of  our  population 
a  lot  of  material  which  you  would  like  to  have  and  we  will  certainly  go  back  and 
look  at  it  later. 

Segundo.  It  seems  opportune  to  mention  observations  performed  upon  human 
subjects  that  illustrate  contrasting  features  of  archi-  and  palaeo-cortices.  Firstly, 
excitation  effects  of  hippocampus  or  fornix  that  included  somnolence  or  even  slight 
blurring  of  consciousness,  a  result  has  that  not  been  encountered  in  extensive  explora- 
tion of  the  human  neocortical  mantle  (Pentield,  and  Rasmussen,  1950;  Segundo, 
Arana,  Migliaro,  Villar,  Garcia-Guelfi,  and  Garcia-Austt,  1955).  Secondly,  the 
report  by  Griinthal  of  dementia  produced  by  hippocampal  atrophy  (Griinthal, 
1947);  neocortical  lesions  of  comparable  size  do  not  provoke  dementia.  This 
material  stresses  the  manner  in  which  interference  with  hippocampal  mechanisms 
affects  behaviour,  thus  supporting  Dr  Olds's  observations. 

KoNORSKi.  Did  you  try  to  use  as  reinforcing  agent  self-punishing  points  instead 
of  self-rewarding  ones?  It  is  interesting  to  see  whether  in  this  case  the  units,  whose 
activity  you  observe,  will  behave  in  the  same  way  as  in  your  experiments  or,  on 
the  contrary  whether  they  will  stop  firing,  when  their  activity  is  negatively 
reinforced. 

Olds.  The  positively  reinforcing  points  interfered  with  learning.  Then  we  have 
anecdotes  on  the  negative  reinforcing  points  which  show  they  do  not  interfere  with 
learning  in  any  similar  fashion.  But  we  do  not  have  full  evidence,  just  anecdotes, 
which  make  us  sure  that  we  will  find  that  the  negative  reinforcing  points  do  not 
interfere  with  learning. 

As  for  slowins;  the  units,  I  believe  asain  on  the  basis  of  anecdotes,  the  answer 
will  be  yes.  In  the  early  days  of  tliis  experiment  we  had  animals  that  were  tested 
for  self-stimulation  but  we  did  not  find  whether  they  were  also  escaping  and  I  have 
had  an  animal  that  I  worked  on  for  a  period  of  almost  24  hours  and  every  unit  that 
I  ever  tried  to  reinforce  was  slowed.  Since  then  I  think  that  when  we  do  study  the 
negative  reinforcement  we  should  find  that  it  will  work. 

BusER.  I  wish  to  mention  here  some  observations  made  on  rabbits,  by  Dr 
Cazard    and    myself,    on    the    effect    of   repetitive    stimulation    of  the    dorsal 


1 86  BRAIN   MECHANISMS    AND    LEARNING 

hippocampus  on  ncocortical  evoked  potentials.  It  appeared  that  a  short  tetanization 
of  the  hippocampus  (subhminal  for  producing  any  hypersynchronic  or  paroxystic 
phenomenon),  was  toUowed  by  a  net  increase  (lasting  up  to  30  minutes)  of  the 
amplitude  of  cortical  sensory  responses  (primary  as  well  as  motor  irradiated 
evoked  potentials).  These  effects  were  obtained  on  acute  (chloralose  or  curarized 
unanacsthcthized)  as  well  as  chronic  preparations. 

Olds.  I  believe  that  that  sounds  extremely  pertinent.  Ot  course  under  anaesthesia 
the  evoked  potentials  are  also  augmented,  is  that  truef 

BuSER.  Yes,  under  anaesthesia  and  also  in  caudate  rabbits. 

Olds.  So  it  does  look  as  if  the  same  function  could  be  involved  in  both  of  our 
situations. 

RosvOLD.  I  was  wondering  whetlier  there  is  any  difference  in  your  results 
between  the  caudate  and  the  hippocampus  or  whether  you  think  they  are  very 
similar. 

Olds.  There  is  a  difference.  Of  course,  because  of  the  internal  capsule  it  is  very 
difficult  to  know  when  you  are  stimulating  caudate  and  not  internal  capsule  too. 
We  found  that  all  our  caudate  stimulators  produced  associated  movements  of  one 
sort  or  another.  Very  often  in  the  case  of  the  ambiguous  caudate  results  we  were 
quite  sure  that  the  animal  was  trying  to  do  one  thing  and  being  forced  to  do 
another  by  the  stimulus.  We  found  that  also  inevitably  with  caudate  stimulation 
the  running  ceased,  that  is,  the  animal  simply  would  not  run  at  all.  It  looked  more 
like  total  disruption.  I  might  even  be  tempted  to  say  that  even  long-term  memory 
was  disrupted  in  these  cases. 

RosvoLD.  Do  you  suppose  that  the  stimulation  of  the  hippocampus  jams  the 
function  of  the  hippocampus  or  excited  it? 

Olds.  I  think  it  is  interfering.  I  find- it  hard  to  think  of  a  stimulation  in  a 
learning  experiment  of  doing  something  to  organize  a  pattern,  though  stimulation 
of  certain  places  of  the  reticular  formation  has  been  shown  to  augment  certain 
kinds  of  perceptual  tasks,  but  I  regard  this  as  an  exception. 

Myers.  What  proportion  of  your  attempts  to  condition  rhinencephalic  neurones 
has  resulted  in  failure; 

Olds.  We  have  never  had  a  failure  of  the  sort  we  have  had  with  cortical  units 
with  rhinencephalic  units.  We  have  had  a  failure  of  the  experiment  either  because 
we  reinforced  too  soon ;  its  activity  remained  high  and  we  could  not  use  it  further, 
because  we  could  not  find  whether  we  had  elicited  it  or  not.  Similarly  we  have  had 
cases  where  we  thought  we  had  something  to  work  with  but  after  trying  to 
reinforce  silence,  the  response  did  not  come  back.  But  this  cannot  be  said  to  be  a 
failure  to  reinforce.  With  cortical  units,  we  have  had  the  unit  going  for  periods  of 
5,  10,  15  minutes,  reinforcing  regularly  and  failed  to  augment  its  firing  rate.  This 
has  happened  many  times  with  ncocortical  units  but  never  with  palaeocortical 
units  so  far. 

Myers.  Have  you  seen  evidence  that  the  conditioning  of  one  unit  has  any 
influence  on  the  conditioning  of  other  units  in  the  neighbourhood. 

Olds.  Yes.  This  is  a  definite  thing.  Quite  surprising  and  I  don't  know  quite  how 
to  put  sufficient  constructions  on  the  situation  to  explain  it.  We  found  some  situa- 
tions where  we  had  one  unit  in  an  area,  and  reinforced  it.  Eventually  it  went  into 
continuous  firing.  Its  amplitude  decreased  and  it  finally  disappeared  and  it  sub- 
sequently was  replaced  and  we  reinforced  the  other  one,  and  those  two  then 


J.    OLDS    AND    M.    E.    OLDS  187 

alternated.  Another  thing  has  happened,  we  seemed  to  be  reinforcing  a  slow  wave 
and  a  unit,  and  then  we  moved  the  electrode  and  then  we  found  that  now  for 
perhaps  a  milhmetre  we  could  not  get  rid  of  the  slow  wave,  and  other  units  firing 
on  it;  this  should  have  been  mentioned  in  connection  with  Dr  Magoun's  earlier 
question. 


A  NEW  CONCEPTION  OF  THE  PHYSIOLOGICAL 
ARCHITECTURE  OF  CONDITIONED  REFLEX 

P.  K.  Anokhin 

The  present  conception  has  taken  shape  over  a  period  of  more  than  30 
years  as  the  result  of  the  work  of  the  author  and  his  pupils  on  the  physio- 
logy of  higher  nervous  activity. 

The  conception  proposed  in  this  paper  eliminates  a  number  of  contra- 
dictions that  have  accumulated  in  the  physiology  of  the  conditioned  reflex 
in  recent  years;  it  opens  new  avenues  of  research  in  the  mechanisms  of  the 
conditioned  reflex  discovered  by  Pavlov,  who  revolutionized  the  study  of 
the  behaviour  of  annuals  and  man. 

The  generally  accepted  view  of  the  mechanism  of  the  conditioned 
reflex  rests  on  Descartes's  reflex  theory  expressed  in  the  concept  of  the 
'reflex  arc'.  According  to  this  view,  the  excitation  evoked  by  a  condi- 
tioned stimulus  constitutes  the  afferent  part  of  the  conditioned  reflex  arc. 
In  the  central  part  of  the  arc  the  excitation  is  transferred  from  the  analyser 
to  the  effector  part  of  the  reflex  and,  hnally,  the  excitation  reaches  the 
efferent  part  of  the  reflex  arc  where  it  stimulates  some  working  organ  or 
combination  of  organs  to  action. 

This  classical  concept  has  three  characteristic  features. 

1.  In  the  reflex  arc  the  excitation  spreads  according  to  the  lincar- 
translational  principle:  at  each  successive  moment  it  spreads  to  new- 
neural  elements  and  never  returns  to  the  course  already  traversed. 

2.  The  reflex  arc  ends  in  an  adaptive  action  which,  from  the  point  of 
view  of  these  ideas,  forms  as  an  entirely  new  phenomenon  in  tlic  padi  of 
the  linear-translational  spread  of  the  conditioned  excitation. 

3.  The  formation  of  the  reflex  action  in  the  peripheral  working  appara- 
tuses is  conceived  as  a  process  complctiuo  the  reflex  arc  and,  consequently, 
the  very  adaptive  result  of  the  reflex  action  is  not  the  decisive  factor  for 
the  dynamic  alternation  of  the  processes  of  excitation  and  inhibition  in  the 
reflex  arc. 

The  conception  proposed  below  does  not  exclude  the  reflex  as  a  prin- 
ciple of  the  organism's  activity  and  its  relation  to  the  external  environ- 
ment. The  reflex  invariably  constitutes  the  nucleus  of  our  new  ideas. 

189 


ipO  BRAIN   MECHANISMS    AND    LEARNING 

However,  this  nucleus  is  considerably  expanded  and  supplemented  by  new 
links  physiologically  conceived  as  components  of  an  integral  neurodyna- 
mic  and  not  linear  organization,  which  we  have  named  the  'functional 
system'. 

The  formulation  of  our  concept  became  possible  only  when  the  basic 
classical  method  of  investigating  conditioned  reflexes  had  been  supple- 
mented by  additional  techniques  which  enabled  us  to  reveal  the  other 
aspects  of  conditioned  reactions  and  their  physiological  substrate. 

The  'secretomotor  method',  the  method  of  studying  conditioned 
reflexes  proposed  by  us,  has  been  of  particular  importance  in  the  elabora- 
tion of  the  new  concept.  Owing  to  a  special  design  of  the  stand  this 
method  made  it  possible  to  record  simultaneously  the  secretory  and  motor 
components  of  the  conditioned  reflex,  the  motor  component  constituting 
not  a  mere  manitestation  of  movement  towards  food  but  a  movement  of 
choice  towards  one  of  the  two  or  four  feeding  troughs  connected  with  the 
given  conditioned  stimulus  (Fig.  i). 

The  special  design  of  a  two-sided  experimental  stand  made  it  possible 
to  connect  various  conditioned  stimuli  with  the  different  sides  of  the 
stand  and  to  compare  the  secretory  and  motor  coniponents  in  the  most 
diverse  experimental  situations. 

Since  by  the  classical  secretory  method  this  had  not  been  possible  on  a 
wide  scale,  the  first  experiments  conducted  in  our  laboratory  with  our 
method  revealed  new  aspects  in  the  physiological  architecture  of  the 
conditioned  reflex  (Anokhin,  1932,  1933).  All  the  results  of  our  investiga- 
tions were  published  in  detail  in  some  of  our  generalizing  papers  (Anokhin, 

1949,  1955,  1958). 

To  solve  the  problem  of  the  physiological  architecture  of  the  condi- 
tioned reflex  we  have  made  extensive  use,  since  1937,  of  the  clectro- 
enccphalographic  method.  A  method  of  recording  the  EEG  in  a  perfectly 
natural  environment  in  the  study  of  conditioned  reflexes  was  first  used  in 
our  laboratory  (Laptev,  1941,  1949).  Recently  these  aims  have  been  con- 
siderably furthered  by  the  numerous  investigations  of  the  physiological 
peculiarities  of  the  brain  stem  reticular  formation  so  brilliantly  begun  in 
the  laboratories  of  Magoun,  Forbes  and  Moruzzi  and  later  applied  to  the 
elaboration  of  conditioned  reflexes  in  the  laboratories  of  Jasper,  Hernan- 
dez-Peon, Morrell,  Gastaut,  and  our  own  (Jasper,  1957;  Morrell,  1958; 
Hernandez-Peon,  1958;  Gastaut,  1957,  loshii,  1956). 

Our  conception  of  the  general  physiological  architecture  of  the  condi- 
tioned reflex  is  best  considered  fragmentally,  so  that  at  the  end  of  this 
report  it  may  appear  before  the  reader  in  its  totality. 


p.    K.    ANOKHIN 


191 


i£ef^ 


Riaht 


38.235    '     Bett 


' 

~c0j7S      Ri-g^t 

Fig.  I 

A.  Two-sided  stand  with  two  feeding-troughs  making  it  possible  to  record  sinuiltaneously  the 
secretory  and  motor  components  of  the  conditioned  reaction  ('Secretomotor  method'). 
Pneumatic  transmission. 

B.  Sample  of  kymograph  record  showing  movement  to  the  left  (i)  and  right  (2)  and  the 
conditioned  secretion  of  saliva  in  drops. 


I.    CONCEPT    AND    MECHANISM    OF   AFFERENT    SYNTHESIS 


According  to  the  reflex  theory  the  role  of  the  aftercnt  influences  on  the 
central  nervous  system  consists  in  the  fact  that  the  external  stimulus 
usually  serves  as  the  impetus  for  the  beginning  of  some  reflex  action.  This 


192  BRAIN    MECHANISMS    AND    LEARNING 

conception  ascribes  the  decisive  role  to  an  isolated  stimulus,  something 
that  has  found  expression  in  the  evaluation  ot  the  conditioned  stimulus  as 
a  decisive  factor  in  determining  the  quality  and  strength  of  the  conditioned 
reflex  effect. 

However,  one  physiological  phenomenon  which  has  considerablv 
shaken  this  widespread  idea  was  described  in  detail  in  Pavlov's  laboratory. 
I  refer  to  the  phenomenon  of  the  dyitaiiiic  paneni  (Pavlov,  1932). 

As  is  well  known,  a  definite  and  precise  sequence  of  the  selfsame  con- 
ditioned stimuli,  trained  without  any  alterations  over  a  long  period  of 
time,  becomes  the  principal  factor  determining  the  quality  and  strength  of 
the  conditioned  reactions.  Conversely,  the  role  of  the  itidiviihial  condi- 
tioned stimulus  is  eliminated  and  the  latter  serves  only  as  a  noii-spccific 
iiiipetiis  for  the  appearance  of  the  conditioned  reflex,  whereas  the  quality 
and  nature  of  the  conditioned  reaction  does  not  depend  on  any  condi- 
tioned stimulus  in  particular.  This  stimulus  does  not  even  have  to  be  a 
conditioned  stimulus,  but  may  be  an  entirely  new,  i.e.  indifferent  (in 
Pavlovian  terminology)  stimulus.  Nevertheless,  it  will  evoke  the  condi- 
tioned reaction  characteristic  of  the  absent  conditioned  stimulus  which 
was  always  used  in  the  former  experiments  at  tiic  given  point  of  the  (dynamic 
pattern  (Pavlov,  1932). 

Thus  these  experiments  already  revealed  that  the  conditioned  reflex,  as 
regards  its  quality,  strength  and  time'of  appearance,  is  a  synthetic  result  of 
the  action  of  the  conditioned  stimulus  and  the  preceding  action  of  a 
greater  sum  of  af]:erent  stimuli  representing  the  conditions  of  the  experiment 
as  a  whole. 

A  direct  EEG  analysis  of  the  processes  of  the  cerebral  cortex  conducted 
in  our  laboratory  has  shown  that  a  sound  stimulus,  applied  at  the  point  of 
the  dynamic  pattern  where  light  was  always  used,  causes  a  desynchroniza- 
tion  of  cortical  electrical  activity,  although  applied  at  its  usual  place 
15  seconds  previously  it  did  not  produce  such  desynchronization  (Fig.  2) 
(Anokhin,  1956).  Thus  a  real  sound  cannot  alter  the  electrical  activity  of  the 
cerebral  cortex,  this  activity  alternating  according  to  the  preceding 
training  of  the  dynamic  pattern. 

This  dependence  of  each  conditioned  reflex  on  the  synthetic  nature  of 
the  external  afferent  influences  was  particularly  clearly  revealed  in  a 
special  experiment  conducted  in  our  laboratory.  The  selfsame  comhtioneil 
stinnihis  (bell)  was  reinforceti  by  food  in  the  morning  and  by  an  electro- 
cutaneous  pain  stimulus  in  the  evening  (Laptev,  1937).  In  the  end  the  dog 
elaborates  a  perfectly  clear  differentiation:  experimented  upon  in  the 
morning  it  responds  to  the  bell  with  pronounced  food  reflexes,  whereas 


p.    K.    ANOKHIN 


193 


in  the  evening  in  response  to  the  same  bell  in  the  saiiw  chamber  the  animal 
shows  a  pronounced  defensive  reaction. 

In  this  experiment  the  difference  in  the  reactions  clearly  does  not  depend 
on  the  conditioned  stimulus  which  has  retained  only  the  uoii-spccijic 
trigger  action  because  both  reactions  emerge  only  in  response  to  the  action 


^^ 


J9e<S^ 


J¥^ 


Fig.  2 

A.  EEG  of  the  dynamic  pattern  of  'Bell-Light-Siren'.  The  regular  light  (  +  )  is  suddenly 
replaced  by  a  bell,  but  a  desynchronization  corresponding  to  the  application  of  light  at  this 
place  is  evident  just  the  same. 

B.  Application  of  all  the  stimuli  of  the  dynamic  pattern  (  j  )  is  discontinued.  Further  develop- 
ment of  cerebral  activity  in  total  conformity  with  the  structure  of  the  pattern  can  be  seen. 
Complete  desynchronization  can  be  seen  in  place  of  the  absent  light  (+). 


of  the  bell,  whereas  in  the  intervals  between  the  conditioned  stimuli  the 
animal  sits  quietly. 

Nor  are  the  conditions  of  the  experiment  as  a  whole  a  differentiating 
factor  since  they  are  the  same  in  both  experiments  and  only  the  tunc  oj 
day,  as  one  of  the  components  of  the  conditions  of  the  experiment,  is  the 
determining  factor. 

If  we  take  into  consideration  the  fact  that  the  time  of  day  becomes  an 


194  BRAIN    MECHANISMS    AND    LEARNING 

active  factor  the  luomcnt  the  dog  is  placed  in  the  stand  and  the  reaction 
emerges  only  at  the  moment  the  bell  comes  into  play  it  will  become  clear 
that  the  time  of  day,  being  a  special  stimulus,  determines  the  quahty  of 
the  reaction  because  of  the  creation  of  a  specific  subthreshold  dommant 
state  ot  the  central  nervous  system  (according  to  Uchtomsky)  which 
spreads  to  the  working  apparatuses  owing  to  the  trigger  action  of  the 
conditioned  stimulus. 

The  synthetic  nature  oi  the  relations  between  the  conditioned  reflex 
and  the  external  conditions  ot  the  experiment,  both  as  a  whole  and  of  its 
individual  components,  may  also  be  revealed  under  the  usual  conditions. 
Suffice  it  to  transfer  the  animal,  that  until  then  had  responded  with  good 
conditioned  alimentary  reflexes,  to  other  surroundings  (for  example,  a 
lecture-hall  for  demonstration  to  students)  and  the  conditioned  stimulus 
loses  its  conditioned  reflex  effect.  In  this  case  the  synthesis  elaborated  from 
the  tonic  afferent  action  of  the  usual  experimental  situation  and  the  trigger 
action  ot  the  conditioned  stimulus  is  disturbed  and  the  conditioned  reflex 
disappears. 

The  following  question  arose  in  our  laboratory:  does  this  process  of  the 
synthesis  of  the  situational  and  trigger  afferent  influences  have  any 
preferable  localization  in  the  cerebral  cortex? 

The  experiments  of  our  associate  Shumilina,  conducted  over  many 
years  and  consisting  in  extirpation  of  the  frontal  lobes  in  dogs  who  had 
conditioned  reflexes  elaborated  in  the  two-sided  stand,  have  shown  that 
the  frontal  lobes  have  a  very  definite  relation  to  this  function  of  synthesis 
of  the  afferent  stimulations  of  different  quality.  During  the  experiment  all 
the  normal  intact  animals  in  the  two-sided  stand  behave  rather  mono- 
tonously, with  certain  insignificant  variations.  Since  the  different  condi- 
tioned stimuli  are  reinforced  by  a  single  portion  of  food  on  the  different 
sides  of  the  stand,  the  animals  elaborate  an  expedient  habit  of  sitting 
quietly  during  the  intervals  between  the  conditioned  stimuli  ///  the  niiddh' 
of  the  stand. 

After  removal  of  the  frontal  parts  (six  to  eight  according  to  Brodman) 
all  the  intact  animals  begin  to  behave  in  a  characteristic  way  immediately 
following  the  operation  —  they  keep  running  from  one  feeding  trough  to 
the  other  as  long  as  the  experiment  lasts.  We  have  named  these  movements 
'pendular'  (Fig.  3). 

It  might  be  assumed  that  these  movements  were  one  of  the  forms  of 
'motor  restlessness'  described  by  many  authors  after  they  had  removed  the 
frontal  areas  of  the  animals'  brains.  However,  a  direct  analysis  of  the 
mechanism  of  these  pendulous  movements  has  shown  them  to  be  directly 


p.    K.    ANOKHIN 


195 


\*(#f    In 


Seen 


\  \  \  \  « «< 


■*     f     I" 


-MT 


■■■ —1  wmmmmmWf'^im 


Fr;.  ,^ 

A.  Normal  discrimination  of  the  sides  of  the  stand  in  response  to  corres- 
ponding conditioned  stimuli.  Stable  movements  to  the  left  and  right  sides 
and  quiet  attitude  in  the  middle  of  the  stand  during  the  interval  between 
the  stimulations. 

B.  Continuous  'pcndular'  runs  to  the  opposite  sides  of  the  stand  alter 
removal  of  the  frontal  divisions  of  the  cerebral  cortex.  Stops  only  during 
feeding.  Conditioned  secretion  is  the  same  as  before  the  operation. 

dcpcudciit  o\\  the  nature  ot  the  aflerent  intiuences  suflered  by  the  animal 
under  the  conditions  of  the  given  experiment. 

For  example,  if  we  elaborate  in  the  animal  conditioned  reflexes  only  to 
one  side  of  the  stand,  i.e.  set  up  the  conditions  of  Pavlov's  classical  method, 

o 


jg6  BRAIN    MECHANISMS    AND    LEARNING 

after  the  removal  of  the  frontal  parts  of  the  cerebral  cortex  this  animal 
behaves  perfectly  quietly  during  the  intervals  between  the  applications  of 
the  conditioned  stimuli:  it  sits  on  oiiv  side  of  the  stand  and  performs  no  pendn- 
lar  nioi'cnieiits. 

However,  if  we  feed  this  quiet  animal  trom  the  opposite  feeding 
trough  but  once,  it  immediately  begms  to  perform  the  well-known 
continuous  pendulous  movements  to  both  sides  of  the  stand. 

These  experiments  suggest  that  the  'pendular'  movements  are  a  direct 
result  of  the  situation  stimulation  which  includes  conditions  of  alternate 
choice  and  behaviour. 

Why  then  does  the  intact  animal  sit  quietly  in  the  middle  ot  the  stand 
during  the  intervals  between  the  applications  ot  the  conditioned  stimuli? 

The  interest  of  this  phenomenon  consists  precisely  in  the  fact  that  the 
numerous  stimulations  of  the  experimental  conditions  (situational  afteren- 
tation)  affect  the  nervous  system  all  the  time,  whereas  the  conditioned 
reaction  manifests  itself  only  at  the  moment  the  conditioned  stimulus 
begins  to  act  (trigger  ali'erentation).  At  the  same  time  the  extreme  change 
in  the  experimental  situation  convinces  us  that  the  situational  stimuli  form 
an  organic  component  part  of  the  afferent  integral.  Thus  it  becomes  clear 
that  all  forms  of  afferent  excitations  affecting  the  animal's  nervous  system 
at  the  given  moment  undergo  a  synthetic  processing  and  that  only  after 
this  stage  does  the  efferent  complex  of  working  excitations  begin  to  form. 

In  recent  years,  neurophysiological  studies  have  convinced  us  that  all 
the  afferent  influences  on  the  organism  come  to  the  cerebral  cortex  along 
two  channels:  (i)  the  specific  or  lemniscus  pathway  and  (2)  the  non- 
specific, i.e.  the  brain  stem  reticular  formation.  The  latter  excitation  is  an 
indispensable  condition  for  any  interaction  and  interconnection  of 
specific  excitations  on  the  level  of  the  cerebral  cortex. 

Specially  for  the  physiology  of  the  conditioned  refiex  this  means  that 
any  form  of  association  of  stimulations  acting  on  the  organism  simul- 
taneously or  successively  becomes  possible  only  if  the  activating  effect  of 
the  reticular  formation  has  spread  to  the  substrate  of  the  cerebral  cortex. 
The  constant  mediator  between  the  new  external  conditions  and  the 
associative  activity  of  the  cerebral  cortex  and  subcortical  structures  is  the 
orienting-investigatory  reaction  of  the  animal  taking  place  under  an 
uncommonly  high  activation  of  the  apparatus  of  the  brain  stem  reticular 
formation  (Heniandez-Peon,  Shumilina,  Havlicck). 

The  physiological  and  biological  purport  of  the  orienting-investigatory 
reaction  was  very  well  revealed  by  Pavlov  himself  (Pavlov,  1925).  It  has 
now  been  shown  that  it  occurs  under  a  constant  excitation  not  only  of 


p.    K.    ANOKHIN  197 

the  cerebral  cortex  but  also  under  an  efferent  excitation  of  the  peripheral 
apparatus  of  the  sense  organs  (Granit,  Dell,  Livingston).  Owing 
to  the  rapid  alternation  of  this  efferent  stream  from  one  analyser  to 
another  the  afferent  synthesis  stage  precedmg  the  very  conditioned 
reaction  is  considerably  enriched  by  afferent  impulses,  something  that 
determines  a  finer  and  more  adequate  (for  the  given  conditions)  formation 
of  effector  processes  of  the  conditioned  reflex. 

Naturally,  after  the  stage  oi  elaboration  of  the  conditioned  reaction  this 
primary  period  of  the  multifarious  efferent  influences  on  the  sense  organs, 
increasing  the  excitability  of  the  latter,  is  in  large  measure  eliminated, 
owing  to  which  the  apparatus  of  the  very  conditioned  reflex  are  simplified 
during  the  stage  of  its  complete  automation  (see  Fig.  4). 

Electrophysiological  studies  of  the  orienting  and  investigatory  reaction 
have  shown  that  it  is  able  continuously  to  maintain  a  high  level  of  excita- 
tion in  the  cerebral  cortex  and  at  the  same  time  maintain  in  an  active 
state  the  newly  formed  temporary  bonds  (Anokhin,  1957;  Karazina, 
1957).  Recently  Professor  Lindsley  published  a  remarkable  paper  in  wliich 
direct  stimulation  of  the  brain  stem  reticular  formation  demonstrated  the 
tremendous  role  played  by  the  reticular  formation  in  the  discriminative 
function  of  the  cerebral  cortex  for  rhythmic  flashes  of  light  (Lindsley, 
1958). 

Thus  we  believe  it  completely  proved  that  the  power  basis  for  the  all- 
rouiui  synthesis  of  the  iiiiiiieroiis  external  and  internal,  situational  and  trio(^er 
afferent  influences  on  the  cerebral  cortex  is  the  ascendino  oenerali::ed  actiration 
of  the  brain  stem  reticular  formation. 

The  role  of  the  reticular  formation  in  refining  afferent  analysis  also 
manifests  itself  in  the  fact  that  at  this  moment  an  alternate  increase  in  the 
excitability  of  various  receptor  structures  at  the  periphery  takes  place 
(Granit,  1957;  Dell,  1957;  Snyakin,  1958). 

All  told  this  makes  it  absolutely  necessary,  in  analysing  conditioned 
reflex  adaptations,  to  set  apart  an  independent  stage  of  afferent  synthesis. 

The  significance  of  this  stage  consists  first  of  all  in  the  fact  that  before  its 
completion  the  flow  of  effector  excitations  to  the  functioning  organs 
cannot  be  formed.  The  composition  of  these  effector  excitations  and, 
consequently,  the  nature  of  the  adaptive  act  itself  are  directly  dependent 
on  the  way  in  which  this  stage  of  the  afferent  synthesis  is  completed. 

At  this  point  I  must  emphasize  that  the  decisive  role  of  the  afferent 
function,  as  a  'creative'  function  of  the  cerebral  cortex,  was  repeatecily 
indicated  by  Pavlov  (Pavlov,  1928).  The  proof  of  this  decisive  role  of  the 
afferent  function  o{  the  cerebral  cortex  is.  in  our  opinion,  the  afferent 


198 


BRAIN    MECHANISMS    AND    LEARNING 


synthesis  stage  which,  as  wc  shall  sec  below,  determines  all  the  subsequent 
stages  in  the  formation  of  the  behaviour  of  man  and  animals. 


Fig.  4 
General  scheme  illustrating  the  role  of  the  orienting-investigatory 
reaction  in  the  formation  of  the  conditioned  reaction,  i.e.  in  the 
establishment  of  the  chain  of  afferent  traces  from  the  stimulus  to 
the  acceptor  of  action. 

A.  At  each  stage  of  the  animal's  movement  towards  the 
reinforcing  factor  the  orientmg-investigatory  reaction  contributes 
to  the  production  of  return  afferentation. 

B.  Final  form  of  bonds.  The  conditioned  signal  aids  in  the  almost 
instant  spread  of  excitations  along  the  afferent  traces  fixed  in  the 
past  by  means  of  the  orienting-investigatory  reaction. 


2.    SPECIFIC  ACTIVATING  EFFECT  ON  THE   CEREBRAL   CORTEX   AND   PROCESSES 
OF   AFFERENT    SYNTHESIS 

The  specific  activating  function  of  the  brain  stem  reticular  formation 
plays  a  special  part  in  the  processes  of  afferent  synthesis  (Anokhin,  1958). 


p.    K.    ANOKHIN 


199 


There  is  a  widespread  opinion  that  the  activating  effect  of  the  reticular 
formation  on  the  cerebral  cortex  is  of  a  non-specific  nature.  According  to 
this  view,  the  non-specitic  influence  on  the  cerebral  cortex  is  always  of  the 


.,4hiHH#WV^^ 


-1  '\i-.y  v- 


B 


iiiililiiiiitiiililTiiiiniiiiiiiiiiiiiiiiiiiiiiiiiimiint,,,,, 


'r^^^-rf,j"^ff(rW 


Fig.  5 

A.  Normal  EEG  of  the  rabbit  in  an  experiment  without  a  pain  reiiiforceiiwnl. 

B.  EEG  of  the  same  rabbit  after  application  of  sereral  pain  reinforcements  durintj  elaboration  of  a 
conditioned  defensive  reflex.  Very  strong  desynchronization  of  electrical  activity  can  be  seen 
not  only  at  the  moment  of  application  of  the  conditioned  stimuli  but  also  during  the  intervals 
between  them. 

C.  After  chlorpromazin  injection. 

same  physiological  nature  regardless  of  the  reactions  of  the  integral 
organism  taking  place  in  the  given  situation  (Moruzzi  and  Magoun,  1949; 
Magoun,  1952;  Magoun,  1958;  ct  ah). 


200  BRAIN    MECHANISMS    AND    LEARNING 

This  point  of  view  undoubtedly  fnids  justification  in  the  facihtating 
effect  which  develops  in  the  cortical  cells  for  the  excitations  coming  to  the 
cortex  along  the  specific  lemniscus  system.  This  conclusion  is  also  favoured 
by  the  phenomenon  of  'awakening'  or  desynchronization  of  the 
cortical  electrical  activity  which  is  always  of  a  generalized  nature  and 
seems  to  be  independent  oi  the  biological  quality  of  the  unfolding 
reactions. 

However,  along  with  these  remarkable  generalizations,  our  laboratory 
has  obtained  tacts  attesting  that  the  non-specific  activating  effect  of  the 
brain  stem  reticular  formation  on  the  cerebral  cortex  is  or<^iviical]y  connected 
with  the  hioh\i^ical  specificity  of  the  (^ii'en  conditioned  reaction.  It  proved 
possible  to  block  by  means  of  chlorpromazinc  (amuiasinc)  the  activating 
effect  of  the  reticular  formation  for  the  conditioned  defensive  reaction,  at 
the  same  time  retaining  the  activating  effect  on  the  cortex  for  the  alinien- 
tary  reaction,  i.e.  for  a  reaction  of  another  biological  quality.  At  this 
moment  the  animal  can  greedily  eat  the  food  offered  to  it  (Gavlichck, 
1958)  (Fig.  5). 

Similarly  blocking  the  defensive  activation  of  cortical  electrical  activity 
by  chlorpromazinc  fails  to  eliminate  the  animal's  waking  state  which,  as  is 
well  known,  is  also  maintained  by  the  activating  effect  of  the  brain  stem 
reticular  formation  on  the  cerebral  cortex  (Fig.  6). 

Thus  it  was  demonstrated  beyond  all  doubt  that  there  arc  several 
activating  influences  on  the  cerebral  cortex  and  that  each  of  theni  may  he 
hhuked  indii'idnally  because  of  the  different  chemical  specificity  of  the  nerrous 
substrate  on  iidiich  each  of  these  bioh-x^ically  different  reactions  occur. 

What  is  the  significance  of  this  varying  biological  specificity  of  the 
activating  influences  on  the  cerebral  cortex  occurring  during  the  afferent 
synthesis  which  precedes  the  formation  of  the  conditioned  reaction  itself  ■ 

In  the  first  place  it  contributes  to  the  sek-ctii'e  rise  in  the  excitability 
('facihtation')  of  the  neural  elements  in  the  cerebral  cortex,  which  in  the 
given  animal  were  historically  associated,  by  the  principle  of  conditioned 
coupling,  with  the  inborn  subcortical  reaction  of  the  given  biological 
quality  (positive  or  negative). 

Owing  to  this  selective  involvement  of  the  cortical  elements  the 
mobilization  of  the  numerous  cortical  systemic  connections,  which  help 
to  complete  the  stage  of  afferent  synthesis,  proceeds  much  faster  and  more 
efficiently. 

Our  view  of  the  specific,  i.e.  selective,  activating  influence  of  the 
reticular  formation  on  the  cerebral  cortex  with  the  perceptibk  oeiieralized 
desynchronization  of  its  eh'cfrical  activity  fits  in  with  the  remarkable  experi- 


p.    K.    ANOKHIN  201 


II        TON  iCO  I  X    ,/ 


-II        79  TONE  500 


^Aj^f^^llyVV^ 


B 


~A^^M-^J'fAA/\iW\/^Ar^W\^^  — 


'jy^V/^VVV/*VW\v-Vw^-^^Vs 


■'a        5J  TOKE  POOD 


f;     r^     ri     1]     a     fi     fi     fi     fi     1     f,     fi     f'  ^JL  fL  -  J ti — fi — fl — L  . 

Fig.  6 

A.  Shows  the  presence  in  the  reticular  formation  of  a  specific  rhythm  of  electrical  activity 
(4-6/scc.)  corresponding  to  the  animal's  defensive  state. 

B.  Elimination  of  the  specific  reaction  by  an  injection  of  chlorpromazine.  Application  of  the 
conditioned  defensive  stimulus  no  longer  produces  the  generalized  activation  of  the  EEC 

C.  Cortical  and  subcortical  BEG  of  the  food  conditioned  stimulus  (tone). 


202 


BRAIN    MECHANISMS    AND    LEARNING 


incuts  performed  by  Jasper,  Kogan  and  our  own  collaborator  Polyantsev 
(Jasper,  1957;  Kogan,  1958;  Polyantsev,  1959)  (Fig-  7)- 

These  authors  have  shown  that,  when  cortical  electrical  activity  is  in  a 
state  of  generalized  dcsynchronization,  the  various  individual  cortical 
elements  are  in  absolutely  different  states  of  activity.  Some  of  them  may  be 
excited,  others  inhibited,  while  still  others  may  change  the  form  ot  their 
activity  several  times  during  the  entire  desynchronized  state.  These  data 
can  be  understood  only  in  the  sense  that  each  activated  state  of  the 


500^^ 


ZOj^y 


vvy^^v^ 


B 


300/«v 


20;iy 


Fig.  7 

A.  Simultaneous  lead-oft"  with  the  same  electrode,  i.e.  from  the  same  point  of  the  cerebral 
cortex,  of  slow  EEG  activity  and  impulse  activity.  The  apparent  lack  of  coincidence  between 
the  two  forms  of  activity  shows  a  certain  independence  of  the  cellular  impulse  activity  on  the 
EEG. 

B.  An  even  more  demonstrative  lack  of  coincidence  is  revealed  by  leading  off^thc  two  indices 
from  the  same  point  of  the  reticular  formation.  Here  the  EEG  does  not  have  the  usual  desyn- 
chronization  at  all  but  the  cellular  impulse  activity  emerges  just  the  same. 


cerebral  cortex  (according  to  the  desynchronization  index)  has  a  corres- 
ponding system  of  selective  excitation  of  cortical  bonds.  It  is  just  this  that 
constitutes  the  physiological  basis  for  the  extensively  ramified  process  ot 
afferent  synthesis. 

This  first  stage  in  the  formation  of  the  physiological  architecture  of  the 
conditioned  refiex  may  be  represented  schematically  as  in  Fig.  cS. 

This  Figure  shows  that  the  afferent  synthesis,  as  a  physiological  process, 
draws  its  energy  from  the  ascending  activating  influences  of  the  brain 
stem  reticular  formation.  These  influences  reacli  the  cerebral  cortex  in  the 


p.    K.    ANOKHIN 


203 


form  of  facilitating  influences  both  at  the  moment  ot  the  action  oi  the 
external  stimulations  and,  especially,  at  the  moment  of  the  appearance  of 
the  orienting-invcstigatory  reaction. 


Fig.  8 
Schematic  representation  of  the  constituent 
processes  of  the  afferent  synthesis  stage.  The 
scheme  shows  the  constant  activating  influ- 
ence of  the  brain  stem  reticular  formation 
on  the  afferent  synthesis.  It  manifests  itself 
during  the  action  of  the  experimental  situ- 
ation as  a  whole  and  durmg  the  episodic 
action  of  the  conditioned  stimulus. 
A^,    A-.    Analysers    through    which    the 
situation  stimuh  produce  their  effect, 
a^.   Collateral  action  of  the  same  stunuli 
through  the  reticular  formation. 
A.  Analyser  of  the  conditioned  stinuilus. 
a.    Collateral    action    of  the    conditioned 
stimulus  throutrh  the  reticular  formation. 


3.    PHYSIOLOGICAL  MECHANISM.S  FORMING  THE  APPARATUS  OF  THE  ACCEPTOR 

OF   ACTION 

In  this  part  of  our  report  we  shall  describe  a  new  mechanism  ot  the 
conditioned  reaction  noticeci  and  claborateti  in  our  laboratory.  In  its 
physiological  essence  this  mechanism  is  the  end  result  of  the  afferent 


204  BRAIN    MECHANISMS    AND    LEARNING 

synthesis  stage,  like  the  subsequent  formation  of  the  effector  apparatus  of 
the  conditioned  reaction  itself  However,  it  forms,  in  large  measure  as  an 
independent,  physiological  formation  and  has,  as  we  shall  see  later,  a 
special  afferent  significance. 

hi  its  physiological  content  this  apparatus  consists  essentially  of  the 
afferent  excitations  which  in  their  totality  reflect  precisely  the  sum  of 
afferent  excitations  that  must  enter  the  cerebral  cortex  only  at  the  end  of 
the  reflex  action.  It  follows  that  the  acceptor  of  action,  as  an  afferent 
reflection  of  the  results  of  future  action,  is  a  physiological  apparatus  of 
so-called  'anticipation'. 

The  tremendous  importance  of  this  apparatus  in  the  behaviour  of 
animals  consists  primarily  in  the  fact  that  forming  immediately  after  the 
end  of  the  afferent  synthesis  stage  it  considerably  forestalls  the  process  of 
formation  of  the  reflex  action  as  well  as  the  completion  of  this  action. 

The  acceptor  of  action  makes  its  appearance  so  soon  after  the  end  of  the 
afferent  synthesis  that  it  may  be  argued  that  this  apparatus  is  a  direct  and 
immediate  result  of  precisely  the  afferent  synthesis  stage. 

From  a  psychological  point  of  view  this  moment,  i.e.  the  end  of  the 
afferent  synthesis  corresponds  to  the  emergence  of  the  'idea',  'intention'  or 
'aim'  to  perform  the  given  action. 

I  believe  it  is  necessary  to  observe  at  this  point  that  the  various  reports 
that  I  have  pubhshed  on  the  physiological  mechanisms  of  this  stage  in  the 
development  of  conditioned  reflex  actions,  have  shown  that  many 
investigators  do  not  as  yet  adequately  understand  that  m  a  psychological 
sense  the  emergence  of  an  'intention'  to  perform  some  action  /'.■;  an  abso- 
lutely indispensable  stage  which  antedates  the  action  itself  and  that,  con- 
sequently, we,  physiologists  of  the  nervous  system  and  higher  nervous 
activity,  must  strive  to  analyse  the  physiological  correlates  of  this  'intention'. 

The  physiological  content  of  this  apparatus  consists  of  the  entire  past 
afferent  experience  of  the  animal  or  man  concretely  related  to  the  given 
behaviour  pattern.  Basically  it  is  a  certain  integration  of  the  afferent 
impulses  w  hich  arise  from  the  results  of  some  reflex  action  or  act  of 
behaviour. 

For  example,  grasping  a  pitcher  of  water  is  connected  with  the  reception 
of  a  series  of  aftcrcnt  influences  of  a  varying  modality. 

Our  brain  receives  specific  tactile  impulses  reflecting  the  form  and 
mechanical  properties  of  the  pitcher,  temperature  impulses,  kmaesthetic 
impulses  suggesting  weight  and,  consequently  the  fact  that  the  pitcher  is 
filleci  with  water,  etc.  The  impulses  also  include  a  visual  afferentation 
suggesting  the  movement  of  the  hand  towards  the  pitcher. 


p.    K.    ANOKHIN  205 

The  aggregate  ot  all  these  afferent  impulses  arises  only  when  the  pitcher 
is  grasped  and,  consequently,  may  be  referred  to  as  affcrciitcitioii  oj  the 
results  of  the  action,  in  the  true  sense  of  these  words. 

From  the  morpho-physiological  point  of  view  such  an  aggregate  of 
afferent  influences  torms  in  the  cerebral  cortex  and  subcortical  apparatus 
a  system  of  strong  bonds  which,  by  virtue  of  a  number  of  repetitions  of 
the  given  act  acquires  properties  ot  an  organized,  integral  afferent  forma- 
tion. It  is  precisely  this  system  of  bonds  that  becomes  active  owing  to  the 
rapid  selective  spread  of  excitations  at  the  moment  the  afferent  synthesis 
stage  is  being  completed  and  that  constitutes  the  physiological  basis  of  the 
acceptor  of  action. 

At  this  point  we  are  consciously  leavnig  out  ot  consitieration  the 
aggregate  oi  the  internal  and  external  nitluences  which,  after  the  afferent 
synthesis  stage,  have,  on  the  whole,  conditioned  the  emergence  of  the  very 
intention  'to  grasp  the  pitcher'. 

It  stands  to  reason  that  this  intention  is  only  a  separate  stage  in  a  series  of 
other  'intentions'  which  are  tinally  completed  through  the  stage  of  a 
subjective  'quenching  ot  thirst'  by  a  drop  in  the  osmotic  blood 
pressure. 

At  this  point  it  is  important  to  inne  diat,  as  soon  as  the  afferent  synthesis 
stage  was  completed,  the  cerebral  cortex  immeciiately  exhibited  an  active 
excitation  ot  the  entire  system  of  the  aforesaid  afferent  bonds  which  had 
become  consolidated  on  the  basis  ot  the  past  experience  ot  the  afterent 
results  of  the  act  of  grasping  the  pitcher. 

In  other  words,  the  afferent  apparatus,  which  we  ha\'c  named  the 
acceptor  of  action,  torms  under  any  action  oi  a  condititMied  stimulus 
before  this  reflex  action  has  occurred  and  consequently  constitutes  an 
absolutely  integral  part  of  the  cyclic  architecture  of  any  conditioned 
reflex  action. 

It  may  be  assumed  that  the  anticipatory  formation  ot  the  acceptor  of 
action  has  become  the  decisive  factor  in  the  organization  ot  the  adaptive 
behaviour  ot  animals  because  it  eliminates  chaos  in  the  choice  and  elabora- 
tion ot  the  individual  acts  ot  this  behaviour  (Fig.  9). 

Containing  all  the  afferent  restiks  of  the  past  reintorcements,  i.e.  con- 
taining at  the  moment  ot  action  ot  the  conditioned  stimulation  the 
afferent  results  only  ot  the  tuture  (!)  action,  the  acceptor  ot  action  becomes 
a  peculiar  control  apparatus  which  establishes  a  physiological  correspond- 
ence between  the  completed  action  and  the  initial  "intention'  to  pertorm 
this  action. 

There  are  several  torms  oi  experimental  proot  ot  the  existence  ot  such 


206 


BRAIN    MECHANISMS    AND    LEARNING 


an  afferent  apparatus  which  forestalls  the  appearance  of  the  conditioned 
rellex  action,  as  well  as  its  afferent  results. 

The  first  and  most  demonstrative  form  of  experiment  consists  in  the 
fact  that  the  experiiiwiitcr  suddtiil)'  replaces  the  qtiality  of  the  uiicoiiditioiied 
alimentary  reiiiforceiiient. 

hi  conducting  these  experiments  we  reasoned  as  follows:  it  the  prepared 
conditioned  excitation  of  the  afferent  cells  in  the  cortical  representation  of 
the  unconditioned  centre  precisely  reflects  the  properties  ot  the  Jiitiire 


Fig.  9 


CS. 


Stage  of  formation  of  the  'acceptor  of  action'  consisting  of  the  afferent  traces  of  past  reinforce- 
ments. At  this  stage  the  reflex  action  itself  has  not  formed  as  yet. 


return  unconditioned  excitation  and  the  normally  elaborated  behaviour  of 
animals  is  based  on  this  adequacy,  the  latter  must  iniallibly  change  if  we 
replace  the  unconditioned  stimulus.  Owing  to  this  replacement  the 
anticipatory  conditioned  excitation  in  the  additional  afterent  apparatus 
would  be  of  one  quality  (on  the  basis  of  the  former  reinforcements)  while 
the  real  unconditioned  stimulus  would  suddenly  (!)  be  of  another  quality 
and,  consequently,  because  of  such  a  combination  of  the  conditions  the 
composition  of  the  nervous  impulses  of  the  return  afterentation  coming  to 
the  cerebral  cortex  from  the  real  unconditioned  stimulus  would  not 
correspond  to  the  conditioned  excitation  prepared  there.  What  will  the 
actual  behaviour  of  the  animal  in  this  case  be? 


p.    K.    ANOKHIN  207 

This  idea  was  applied  in  our  laboratory  (Anokhin  and  Strczh,  Soi'iet 
Journal  of  Physiolo(^y,  No.  5,  1933)  on  the  basis  of  a  bilateral  alimentary 
reinforcement  allowing  these  peculiarities  of  higher  nervous  activity  to 
be  demonstrated. 

The  experiment  was  conducted  in  the  followuig  manner.  Only  two 
conditioned  secretomotor  reflexes  were  elaborated  in  the  animal:  to  the 
tone  of 'A'  with  a  reinforcement  on  the  right  side  of  the  stand  and  to  the 
tone  of 'F'  with  a  reinforcement  on  the  left  side.  Both  reflexes  were  rein- 
forced by  20  g.  of  dry  bread  and  were  sufficiently  well  consolidated.  After 
a  brief  latent  period  the  animal  would  rush  to  the  corresponding  side  of 
the  stand  and  wait  there  for  the  unconditioned  stimulus.  At  this  stage  of 
the  experiments  the  annual  no  longer  exhibited  any  erroneous  motor 
reactions. 

At  the  beginning  ot  an  expernncntal  day  dried  meat  was  placed  in  one 
of  the  plates  on  the  left  side  and  thus,  against  the  background  of  the  usual 
dried-bread  reinforcements,  the  animal  was  to  receive  a  nieat  reinforce- 
ment to  one  of  the  regular  stimulations  with  the  tone  of 'F'.  On  the  basis 
of  the  aforementioned  peculiarities  of  the  afferent  apparatus  ot  conditioned 
excitation  we  niust  assume  that  tor  some  brict  space  ot  time  the  new  un- 
conditioned stimulations  ii'liicli  do  not  coincide  in  their  visnal,  olfactory  and 
qnstntory  qualities  with  the  already  enien^ed  conditioned  excitation  must  lead  to 
a  lack  ot  coincidence  in  the  two  excitations  and  then  to  the  development 
of  an  orienting-investigatory  reaction.  The  latter  shcnild  be  the  more 
strongly  pronounced  the  more  the  prepared  conditioned  afferent  excita- 
tions and  the  available  afferent  excitations  trom  the  true  unconditioned 
stimulus  tail  to  coincide. 

These  expectations  were  justified  by  experiment.  When  the  uncondi- 
tioned stimulus  is  thus  replaced  it  usually  gives  rise  to  an  orienting- 
investigatory  reaction  which,  depending  on  the  strength  ot  the  stimula- 
tory action  ot  the  suddenly  used  inadequate  unconditioned  stimulus, 
either  changes  to  an  active  alimentary  reaction  (when  bread  is  replaced  by 
meat)  or  retards  the  alimentary  reaction  and  the  animal  even  retuses  the 
food  (if  the  meat  is  replaced  by  bread). 

The  toregoing  experiment  enabled  us  to  observe  both  tonus  ot  the 
reaction. 

The  second  form  of  the  experiment  aimed  at  proving  the  existence  of 
the  acceptor  of  action  is  based  on  the  peculiarities  ot  the  experimental 
method  in  the  two-sided  stand  proposed  by  us  (sec  Fig.  1). 

Several  conditioned  secretomotor  reflexes  firmly  tixed  by  training  are 
elaborated  in  the  animal.  To  each  of  the  stimuli  used  at  any  given  moment 


208  BRAIN    MECHANISMS    AND    LEARNING 

the  animal  responds  with  a  positive  motor  ahmentary  reaction  to  a 
feeding-trough  either  on  the  right  or  left  side  according  to  the  side  on 
which  the  animal  was  fed  during  the  application  of  the  given  conditioned 
stimulus. 

Let  us  assume  that  with  a  flash  of  light  the  ciog  was  always  fed  from  the 
right-hand  trough,  whereas  \\'ith  the  sound  of  the  tone  of 'C  it  was  given 
food  in  the  left-hand  trough.  According  to  the  law  of  the  conditioned 
reflex,  the  animal  responds  to  this  form  of  experiment  by  elaborating 
precise  conditioned  motor  reactions  to  the  right  and  left  sides  of  the  stand. 

As  soon  as  these  conditioned  reactions  are  firmly  fixed  the  food  is 
suddenly  (!)  given  to  the  flash  of  hght  on  the  left  rather  than  on  the  right 
side  of  the  stand. 

hi  other  words,  an  operation  is  performed  or,  in  the  terminology  of  the 
Pavlovian  laboratory,  the  conditioned  reflex  is  'reshaped'. 

hi  this  form  of  experiment  it  is  possible  to  see  that  the  animal  frequently 
fails  to  take  food  from  the  trough  on  the  side  that  does  not  correspond  to 
the  conditioned  signal.  For  a  long  time  it  looks  alternately  to  the  right  and 
left  feeding-troughs  (orienting-investigatory  reaction)  and  begins  to  eat 
the  food  only  after  a  long  latent  period.  Additional  investigations  of  the 
animars  respiratory  component,  when  the  side  on  which  the  food  rein- 
forcement is  made  is  suddenly  changed,  show  the  animal  to  exhibit  an 
uncommonly  pronounced  oricntihg-investigatory  reaction  with  a 
strongly  marked  inspiratory  tonus  in  breathing. 

The  only  cause  that  could  be  tliought  of  for  this  pronounced  reaction 
was  the  lack  of  corrcspoiidciice  hctwccu  the  sudden  feediui^  {return  affereiitation) 
and  the  already  prepared  complex  of  afferent  excitations  in  the  cerebral  cortex  in 
accordance  with  the  place  of  the  old  and  usual  feedino  (acceptor  of  action).  Tlic 
same  conclusion  is  suggested  by  the  fact  that  both  food  reinforcements, 
on  the  right  as  well  as  on  the  left  sides,  are  essentially  of  the  same  signifi- 
cance to  the  animal,  the  distances  from  both  feeding-troughs  also  being 
the  same. 

The  only  remaining  cause  is  the  lack  of  correspondence  between  the 
already  prepared  acceptor  of  action  and  the  afferent  influences  emerging 
when  the  animal  is  fed  on  the  inadequate  side. 

The  method  of  sudden  replacement  of  the  rehiforccment  may  be  used 
in  most  diverse  variations,  especially  in  experiments  c:>n  human  adults  and 
children.  For  example,  by  showing  some  daintv  to  a  child  and  placing  this 
dainty,  so  that  the  child  sees  it,  in  a  'problem  box'  from  which  the  child 
extracts  it,  it  is  possible  finally  to  establish  adequate  correlations  between 
the  sight  of  the  daiiity  and  the  subsequent  reinforcement  wliich  occurs 


p.    K.    ANOKHIN  209 

when  the  child  opens  the  box.  However,  if  a  (laiiity  of  another  quality  is 
imperceptibly  placed  in  the  box,  upon  opening  the  box  the  child  imme- 
diately develops  a  reaction  of 'surprise'  ('What  is  it?',  according  to  Pavlov) 
which  occurs  with  different  variations  depending  on  a  number  of  condi- 
tions. The  child  may  carefully  examine  the  box  from  all  sides,  shake  it 
in  the  hope  of  receiving  the  expected  reini(n-ceinent,  etc.  It  is  perfectly 
clear  that  all  these  actions  are  a  direct  result  ot  the  lack  of  correspondence 
between  tlie  fixed  afferent  excitations  in  the  form  of  the  acceptor  of  actio)!  and  the 
afferent  iujiitences  coniino  to  the  central  nerrons  system  from  the  inadequate 
appearance  of  the  nen'  dainty  when  the  box  is  opened. 

The  third  way  of  proving  the  emergence  of  afferent  excitations  in  the 
acceptor  of  action  forestalling  the  formation  of  the  action  itself  is  the 
electroencephalographic  method.  As  stated  previously  the  systems  of 
afferent  excitations  forming  part  of  the  acceptor  of  action  are  mobilized 
much  more  rapidly  than  the  effector  part  of  action.  At  times,  a  very  com- 
plex reflex  action  is  formed.  It  follows  that  the  ascertainment  of  the  prepara- 
tory excitations  in  the  area  of  the  cerebral  cortex,  ndiicli  must,  in  the  future, 
receive  the  return  afferentation  from  the  results  of  the  action,  should  become  one 
of  the  methods  of  studying  the  physiological  mechanisms  of  tlie  acceptor 
of  action. 

A  typical  example  of  the  anticipatory  spread  of  excitations  over  the 
cerebral  cortex  is  the  generally  known,  so-called,  electroencephalographic 
'conditioned  reflex'  which  manifests  itself  when  sound  and  light  are 
combined.  As  is  well  known,  after  a  number  of  such  combinations 
the  sound  alone  causes  a  desynchronization  of  the  a-rhythm  in  the 
occipital  area  of  the  cortex  before  the  appearance  of  the  lioht.  Here  the 
sound  sets  off  a  chain  of  excitations  in  the  cerebral  cortex,  which  spreading 
rapidly  reaches  the  elements  in  the  visual  cortex  that  will  not  receive 
adequate  visual  excitation  from  the  periphery  until  a  few  seconds  later 
(Jasper,  1937;  Livanov,  1937;  Karazina,  1957;  and  many  others). 

Any  acceptor  of  action  for  any,  even  very  complex  acts  of  behaviour,  is 
formed  absolutely  according  to  the  same  type.  Any  act  of  behaviour  is 
represented  in  the  cortex  by  the  development  of  an  uninterrupted  chain  of 
afferent  excitations  received  from  the  individual  stages  of  this  act  to  the 
final  reinforcing  factor  inclusive.  It  is  precisely  this  chain  of  traces  of  the 
past  afferent  excitations  that  is  a  peculiar  'conductor'  for  the  rapid  spread 
of  the  excitations  from  the  conditioned  stimulus  to  the  system  of  excita- 
tions udiich  is  the  afferent  reflection  of  the  results  of  the  as  yet  forthcomino 
action. 

Exaniples  of  such  a  spread  of  the  afferent  excitations  may  now  be 


210 


BRAIN    MECHANISMS    AND    LEARNING 


obtained  from  most  diverse  papers  in  which  the  authors  themselves  did 
not  intend  to  study  precisely  this  problem. 

We  may  cite  data  from  the  work  oi  Jasper  who  points  out  that  in  a 
number  of  cases  the  secretomotor  area  of  the  cerebral  cortex  exhibits  a 
depression  of  its  rhythm  much  ahead  of  the  real  movement  of  the  arm, 
this  desvnchronization  sometmics  appearing  in  the  person  tested  at  the 
thought  of  the  forthcoming  movement  alone  ( lasper,  1958). 


A 


o — o 


o — o 


'il' 


8. 


• — o 

II 

• — o 

II 

•  --o 

--0 


1 


d' 

c' 

*-^' 


Fig.  10 
Schematic  representation  of  the  'anticipatory'  spread  of  excitation 
and  its  significance  in  the  formation  of  the  acceptor  of  action. 

A,  a,  h,  c,  d,  -^  successively  developing  action  of  the  external  stimu- 
lations of  which  d  is  the  reinforcement  with  food.  Orienting  reactions 
a^,  b^,  c^  and  d^  emerge  correspondingly. 

B.  Correlation  of  the  processes  after  training.  The  action  of  the  one 
initial  stimulus  a  is  enough  for  the  process  of  excitation  immediately 
to  spread  along  the  afferent  traces  to  d  which  is  the  'acceptor  of  action' 
in  this  case. 

We  fmd  indications  of  similar  facts  111  the  studies  oi  Gastaut  concerned 
with  depressing  the  rolandic  rhythm  (Gastaut,  1957). 

hi  his  recent  detailed  review  of  the  stuciies  of  the  reticular  formation 
O'Leary  also  cited  data  to  the  effect  that  the  'idea'  of  the  forthcoming 
movement  alone  may  lead  to  a  desynchronization  of  the  electrical  activity 
of  the  cerebral  cortex  (Fig.  10). 

All  the  data  culled  from  the  literature,  as  well  as  our  own  observations, 
indicate  that  after  the  application  of  a  stimulus  or  the  reading  of  instruc- 
tions  the   selective   impulse   process   of  excitation,    which   ensures   the 


p.    K.    ANOKHIN  211 


formation  of  the  conditioned  reflex,  spreads  with  uncommon  speed 
through  all  the  chains  ot  the  past  afferent  stimulations  which  reflected  the 
continuity  in  the  development  ot  some  act  ot  behaviour.  This  process  of 
the  anticipatory  propagation  of  afferent  excitations  until  the  moment  the 
acceptor  of  action  is  formed  may  be  shown  diagramatically  as  in  Fig.  9. 

4.    FORMATION     OF     THE     CONDITIONED     REACTION     EFFECTOR     APPARATUS 

The  stage  of  formation  oi  the  conditioned  reaction  effector  apparatus 
is  directly  dependent  on  the  course  or  end  of  the  afferent  synthesis.  The 
latter  is  always  an  integral  whole  and  contains  in  its  composition  both 
somatic  and  vegetative  components  (motor  component,  respiratory 
component,  cardiac  component,  vascular  component,  hormonal  com- 
ponent, etc.). 

The  characteristic  feature  ot  this  effector  integration  is  the  fact  that  each 
of  its  functioning  peripheral  components  is  harmoniously  related  to  the 
other  components  and  together  they  constitute  the  given  act  oi  behaviour 
or  the  conditioned  reflex. 

For  example,  the  respiratory  component  ot  the  conditioned  reflex  was 
subjected  to  systematic  analysis  fc^r  the  tirst  time  in  our  laboratory 
(Balakhm,  1930-35;  Polezhayev,  1952;  Makarov,  195(S;  ct  ah).  It  was 
shown  to  be  ot  an  entirely  specitic  character  corresponding  to  the  bio- 
Ic^gical  quality  of  the  animal's  given  reaction  as  a  whole.  In  the  defensive 
conditioned  reflex  the  respiratory  component  exhibits  a  high  inspiratory 
tonus  and  frequent  respiratory  movements  of  the  thorax. 

In  a  well-fixed  alimentary  conditioned  reflex  the  respiratory  rhythm  is, 
on  the  contrary,  quiet  and  only  at  the  moment  when  the  conditioned 
stimulus  is  applied  docs  the  orienting-investigatory  reaction  temporarily 
raise  the  activity  of  the  respiratory  component  (Fig.  11). 

A  comparative  evaluation  of  the  secretory,  motor,  respiratory  and 
cardiovascular  components  of  the  conditioned  reflex  shows  that  they  are 
all  harmoniously  adapted  to  the  biological  signiticance  of  the  whole 
reaction.  If  the  reaction  requires  general  activity  and  tension  (as,  for 
example,  the  conditioned  defensive  reaction)  all  the  vegetative  com- 
ponents, as  many  as  there  are,  unite  into  an  integrated  whole,  each  ot  them 
corresponding  to  the  tasks  ot  the  given  adaptive  act.  This  means  that  the 
intensity  of  the  vegetative  components  of  the  conditioned  reflex,  which 
provide  the  entire  reaction  with  power  resources,  is  directly  dependent  on 
the  degree  of  the  fortlicoiiiiin^  expenditure  of  these  resources. 

This  state,  revealed  particularly  clearly  as  early  as  1935  in  the  studies  of 

p 


212 


BRAIN    MECHANISMS    AND    LEARNING 


our  associate  Balakin,  was  recently  confirmed  by  special  forms  of  experi- 
ments. 

In  our  laboratory  Dr  Kasyanov  has  shown  that  the  respiratory  com- 
ponent of  the  conditioned  reflex  is  the  first  conditioned  reflex  component 
to  form  in  the  effector  pathways  (Kasyanov,  1950).  The  cardiovascular 
complex  reaches  the  effector  pathways  almost  simultaneously  with  the 
respiratory  component.  Gantt's  studies  have  show-n,  however,  that  the 
cardiac  component  of  the  conditioned  reflex  appears  somewhat  ahead  of 
the  respiratory  component  (Gantt,  I95-)- 


wvv>**iyv*^«-*«^ 


B 


A 


Fig.  II 
Dissociation  between  the  generalized  and  local  excitation  of  the  motor  apparatus  of  the  dog 
after  bilateral  extirpation  of  the  sensorimotor  areas  of  the  cerebral  cortex.  The  generalized 
reaction  (A)  is  on  hand,  while  the  local  raising  of  the  hind  limb  is  totally  absent  (B). 

The  recent  studies  conducted  by  Shidlovsky  in  our  laboratory  with  the 
aid  of  up-to-date  cardiographic  apparatus  ('Cardiovar',  'Barovar',  etc.) 
have  confirmed  our  former  observations  and  have  shown  the  respiratory 
component  to  reach  the  effector  pathways  somewhat  ahead  of  the  cardiac 
component  (Shidlovsky,  1959). 

It  should  be  noted,  however,  that  these  insignificant  differences  in  the 
appearance  of  the  vegetative  excitations  in  the  peripheral  organs,  where 
they  are  detected  by  suitable  apparatus,  are  of  no  fundamental  importance. 
They  may  be  due  to  different  lengths  of  the  pathways  the  excitations  must 
traverse  from  the  centres  to  corresponding  organs,  to  the  number  o'l 
synapses  in  these  pathways,  and,  lastly,  to  the  peculiarities  of  the  recording 
apparatus. 

But  some  aspects  of  this  phenomenon,  constant  for  all  types  of  condi- 
tioned reactions,  are  undoubtedly  important.  For  example,  the  vegetative 


V.    K.    ANOKIIIN  213 

components  in  general  reach  the  tei'uimal  effector  components  hi  the 
form  of  components  of  specific  quahties  (secretion  for  the  aUnientary 
conditioned  reaction,  movement  for  the  defensive  conditioned  reaction) 
before  the  conditioned  reflex  reaction  manifests  itself.  The  other  important 
aspect  of  what  we  call  Vegetative  outstripping'  consists  in  the  fact  that  all 
these  components  in  their  totality  are  of  a  conditioned  refiex  nature  and 
reflect  precisely  the  energy  requirements  of  the  forthcoming  conciitioned 
reflex  action. 

Shidlovsky  devoted  a  special  experiment  to  this  problem.  He  recorded 
the  cardiovascular  components  of  the  conditioned  alimentary  reaction  in 
two  different  situations:  in  one  case,  the  animal  had  to  overcome  a  small 
obstacle  to  get  at  the  food  received  as  reinforcement,  thus  exerting  a 
muscular  effort,  while  in  the  other  case  the  food  was  brought  directly  to 
the  animal's  muzzle.  Thus,  in  the  first  case,  the  conditioned  signal  warned 
the  animal  not  only  of  the  forthcoming  feeding  but  also  of  certain  uiiisciihv 
efforts  it  had  to  exert  before  receiving  the  food. 

hi  total  conformity  with  these  conditions  the  respiratory  and  cardio- 
vascular components  of  the  conditioned  reaction  are  vigorously  activated 
in  the  first  case.  Conversely,  in  the  second  case,  the  same  vegetative 
components  manifest  no  such  changes  and  deviate  but  slightly  from  the 
level  of  the  resting  state  (Fig.  12). 

All  the  experiments  performed  in  this  direction  clearly  show  that  the 
conditioned  reaction,  as  a  manifestation  of  the  integral  organism,  atlects 
the  periphery  through  very  numerous  terminal  neurones  involving  most 
diverse  somatic  and  vegetative  components. 

An  evaluation  of  the  physiological  composition  of  this  integral  etlerent 
formation  should  take  into  account  its  three  physiological  peculiarities: 

[a)  it  is  a  direct  result  of  the  afferent  synthesis  stage; 

[b)  it  forms  during  the  entire  course  of  elaboration  of  the  given  concii- 
tioned reflex  (see  below) ; 

(f)  it  has  a  vertical  physiological  architecture,  since  it  infallibly  includes 
cortical  and  subcortical  components. 

The  last  of  the  foregoing  propositions  is  clearly  demonstrated  by  the 
very  participation  of  vegetative  components  in  the  conditioned  reflex. 
Since  these  components  reflect  the  integral  character  of  the  total  reaction 
and  are  formed  through  the  terminal  pathways  of  the  hypothalamus  and 
the  brain  stem  reticular  formation,  it  is  possible  to  chart  the  general 
distribution  of  the  nervous  impulses  within  the  entire  efferent  stream  of 
excitations,  including  the  functioning  organs. 


214 


BRAIN    MECHANISMS    AND    LEARNING 


^. 


\rr^ 


~0.     TH.     ...^Y^^^^  ' 


F  O  R  E  L  I  M  B      E  M  G 


h*'  '  P'  ' — 1- 


Xfm 


Lji^ (  «^ni4^iiiiii  H«4"" 


RESPIRATION 


E  C  G      LEAD      1 


ART.      BLOOD      PRESSURE 


J}J),^t4)ll,^^^H^4^^wy**'**'^^ 


SALIVARY      DROP^ 


Mm 


AUDIT        S  T  I  M 


Ip 


AF  O  O  D 

Fig.  12A 
Illustration  of  the  dependence  of  the  vegetative  components  of  the  conditioned  reflex  on  the 
forthcoming  energy  expenditures  signalled  by  the  conditioned  stimulus. 
A.  Reaction  to  the  conditioned  stimulus  with  the  animal  in  close  proxnuity  to  the  food. 


p.    K.    ANOKHIN 


215 


E  C  G      LEAD      1 


^4||,l>#H)t>>>i*WHtll**lli 


ART       BLOOD      PRESSURE 


SALIVARY      DROPS 

|ll|MlllHilllHIIIIIIHllll 


B 


AUDIT       S  T  I  M 


»I 


ilL 


Fig.  12B 
B.  Reaction  to  the  conditioned  stimulus  when  overcoming  a  difficulty  before  taking  the  food. 
The  latter  case  shows  much  greater  activity  of  all  the  vegetative  components  of  the  conditioned 
reaction. 


2l6 


BRAIN    MECHANISMS    AND    LEARNING 

L.s.m. 


/^7'VVVv^/Vv^^wv^n(v>ft^^'VV^^vvw^«vv^^ 


o.i. 
n.v.p.L.L. 

n.v.p.L  r 
EKG 

2f]0/xl/1  bee 

Fig.  12C 
C.  Confrontation  of  dirtcrcnt  components  of  a  response  to 
direct  stimulation  of  the  brain  stem  reticular  formation. 
Abbreviations:  l.s.m. —  left  sensorimotor  cortex,  r.s.m.  —  right 
sensorimotor  cortex,  t.l.  —  left  temporal  cortex,  t.r.  —  right 
temporal  cortex,  o.s.  — occipitalis  sinistra,  o.d.  — occipitalis  dex- 
tra,  n.v.p.1.1.  —  n.  ventralis  posterior  lateralis,  left,  n.v.p.l.r.  — n. 
ventralis  posterior  lateralis,  right,  EKG,  respir. —  respiration. 


The  latest  data  on  the  representation  ot  vegetative  tunctions  in  the 
cerebral  cortex  once  more  emphasize  the  importance  of  precisely  the  verti- 
cal plan  in  the  structure  of  the  effector  complex  ot  excitations  in  the  condi- 
tioned reflex.  I  am  referrnig  primarily  to  Papez's  view  of  the  'visceral 
cortex'  and  to  the  studies  of  a  number  of  other  authors  directed  towards 
the  same  aspect  of  the  subject  (Papez,  ips.S;  Maclean,  1954;  Bard,  194^"^; 
Green,  1958;  Adcy,  1958). 

On  the  basis  of  authentic  facts  indicating  representation  of  vegetative 


p.    K.    ANOKHIN  217 

functions  in  the  limbic,  orbital,  girus  cinguli  and  other  parts  of  the  cere- 
bral cortex  it  might  be  assumed  that  the  whole  effector  part  of  the  condi- 
tioned reflex,  including  the  vegetative  components  is  elaborated  in  some 
form  at  the  level  of  the  cerebral  cortex. 

However,  the  manifestation  of  the  vegetative  components  durmg  the 
first  fractions  of  a  second  in  the  action  of  the  conditioned  stimulus  warrants 
the  assumption  that  this  tirst  reaction  of  the  well-tixed  conditioned 
reflex  forms  at  the  level  of  the  subcortical  apparatus. 

With  this  question  we  closely  approach  the  problem  of  localization  of 
conditioned  reflex  coupling.  On  the  basis  oi  electroencephalographic 
expermients  Fessard,  Gastaut  and  Yoshii  reached  the  conclusion  that  the 
coupling  of  the  conditioned  bond  occurred  primarily  in  the  area  of  the 
reticular  formation  and  that  only  later,  already  as  a  vertical  'projection', 
did  the  conditioned  reflex  process  became  cortical  (Fessard  and  Gastaut, 
1958;  Gastaut,  i95(S).  The  very  rapid  changes  in  the  respiratory 
component,  revealed  in  our  experiments,  also  seem  to  indicate  this 
localization  of  the  process  of  coupling  of  conditioned  bonds.  This  seems 
the  more  probable  since  the  brain  stem  reticular  formation,  which  receives 
along  collaterals  the  afferent  impulses  from  the  lemniscus-conditioncd 
excitations,  contains  all  the  fractions  of  the  respiratory  and  cardiovascular 
centres. 

Moreover,  the  unconditioned  excitations  also  come  to  the  reticular 
formation.  Thus  all  favourable  conditions  for  the  coupling  function  seem 
to  be  set  up  in  the  area  of  the  brain  stem  reticular  formation  whose  neural 
elements  liave  extensive  possibilities  for  the  convergence  of  afferent 
excitations  (Moruzzi,  1956;  Amassian,  1958;  Fessard,  1958).  Nevertheless, 
considering  the  particular  role  of  the  orientiiig-investigatory  reaction  in 
the  formation  of  the  conditioned  reflex,  it  is  difficult  to  agree  with  the 
idea  of  a  primary  subcortical  coupling  of  the  conditioned  bond  (Anokhin, 
1957;  Anokhin,  1958). 

The  question  of  the  composition  ot  the  effector  complex  of  the  condi- 
tioned reaction  came  particularly  clearly  to  the  fore  in  our  experiments 
during  the  studies  of  the  conditioned  motor  reflex,  hi  this  case  we  are 
referring  to  the  local  motor-defensive  conditioned  reflex  reinforced  by 
electric  current  and  manifesting  itself  in  lifting  the  hind  limb. 

In  our  laboratory  it  was  established  long  ago  that  this  'local'  reflex,  its 
seeming  simplicity  and  'localness'  notwithstanding,  is  a  result  of  extra- 
ordinarily complexly  integrated  effector  excitations  selectively  propagated 
to  the  peripheral  motor  apparatus  according  to  very  dehnite  stages  in  the 
formation  of  the  conditioned  reaction.  It  was  found  that,  before  the 


21 8  BRAIN    MECHANISMS    AND    LEARNING 

animal  lifts  its  corresponding  limb  in  response  to  the  conditioned  stimulus 
signalling  pain  stimulation,  the  excitations  are  rapidly  redistributed  along 
the  axial  musculature  of  its  body.  Owing  to  this  rapid  process,  the  animal 
assumes  a  new  posture  with  new  relations  between  the  points  of  support 
and  the  centre  of  gravity,  enabling  it  to  raise  the  corresponding  limb 
(Shumilina,  1939). 

An  electromyographic  analysis  of  the  antagonistic  muscles  in  the 
different  hmbs  of  animals  and  man  made  it  possible  to  show  that  this 
excitation,  which  we  have  named  'positional  excitation',  very  rapidly 
reaches  the  extensors  of  the  limbs,  and  the  entire  body  shifts  to  three 
points  of  support  within  several  fractions  of  a  second  before  the  limb 
previously  stimulated  by  electric  current  is  raised  (Shumilma,  1949; 
Kasyanov,  1950). 

hi  this  interesting  phenomenon  we  thought  it  possible  to  analyse  the 
composition  of  the  effector  complex  of  excitations  in  so  commonplace  a 
conditioned  motor  act  as  the  jerking  away  of  the  hind  limb. 

For  the  physiologist  interested  in  higher  nervous  activity  and  animal 
behaviour  this  phenomenon  of  the  dual  nature  of  excitations  in  the  motor 
conditioned  reflex  is  important  because  both  the  tirst  and  second  stages 
arc  dearly  of  a  couditiivwd  reflex  character  despite  their  different  central  localiza- 
tion. As  a  matter  of  fact,  the  rapid  redistribution  of  the  tonic  tensions  in 
the  axial  musculature  of  the  body  and  the  proximal  parts  of  the  limbs  is 
not  'diffuse'  in  the  ordinary  physiological  sense.  This  positional  excitation 
is  distributed  over  very  dcfniite  motor  neurones  which  shape  the  animal's 
posture  precisely  corresponding  to  the  future  raising  of  one  oi  the  limbs. 
From  the  biomechanical  point  of  view  we  know  very  well  that,  it  it  had 
not  been  for  this  preliminary  phase  of  shift  of  the  centre  of  gravity  in 
accordance  with  the  basic  points  oi  support,  the  dog  would  fall,  in 
attempting  to  raise  the  hind  limb,  as  a  bronze  statuette  falls  when  one  of 
its  legs  is  broken. 

A  conditioned  motor  reflex  may  be  elaborated  tor  any  of  the  dog's 
four  limbs  by  reinforcing  it  with  electric  current,  and  in  each  individual 
case  the  positional  excitation  will  be  distributed  over  the  body  segments 
anew,  i.e.  depending  on  the  limb  which  will  be  lifted  within  several 
fractions  of  a  second  after  the  application  ot  the  conditioned  stimulus. 
This  fact  is  the  best  proof  that  both  stages  in  the  development  of  motor 
excitations  are  ot  a  conditioned  reflex  nature. 

At  the  same  time  we  know  very  well  that  the  central  localization  of 
both  excitations  is  not  the  same.  Whereas  the  positional  excitation  forms 
at  the  level  of  subcortical  centres,  especially  in  the  neural  elements  of  the 


p.    K.    ANOKHIN 


219 


reticular  formation  (Magoun,  1952;  Moruzzi,  1956,  ct  al.),  the  local 
limb  lifting,  i.e.  the  local  conditioned  motor  act  is  cftcctcd  by  the 
pyramidal  tract  and  has  a  definite  cortical  localization. 

The  question  is:  how  do  both  these  organic  components  integrate  in  the 
animal's  integral  conditioned  motor  act?  We  endeavoured  to  answer  this 
question  by  means  of  a  number  of  variations  of  conditioned  reflex 
experiments. 

In  order  to  trace  the  very  fact  of  the  shift  in  the  centre  of  the  body's 
gravity  during  the  stage  of  formation  of  tlie  positional  excitation  we 


Fig.  13 
Stand   designed    with   four   separately   recorded   stages.   In 
addition  to  recording  the  spread  of  positiiinal  excitation  this 
stand  permits  of  recording  the  secretion  of  sahva  and  the 
vegetative  components. 


designed  a  stand  by  means  of  which  we  could  record  the  pressure  exerted 
by  each  of  the  four  limbs  (Fig.  13).  The  experiment  showed  that  the 
moment  the  conditioned  stmiulus  was  applied  there  was  a  rapid  and 
rather  complex  redistribution  of  muscular  efforts,  which  could  be  easily 
recorded  kymographically  and  elcctromyographically  (Koryakin,  1958). 
It  also  showed  that,  if  the  conditioned  motor  defensive  act  was  effected, 
say,  by  the  right  hinci  limb,  the  lifting  of  the  paw  was  always  preceded  by 
an  uncommonly  stable  complex  of  relations  in  the  excitations  of  the 
brain  stem.  Now,  if  both  sensomotor  areas  of  the  cerebral  cortex  are 
removed,  an  interesting  dissociation  between  the  positional  and  local 


220 


BRAIN    MECHANISMS    AND    LEARNING 


Stages  of  the  conditioned  motor  reaction  are  observed.  Whereas  in 
response  to  the  conditioned  stiniukis  the  positional  complex  is  retained  in 
total  conformity  with  its  former  nature,  the  local  motor  act  is  completely 
absent.  This  selective  injury  to  the  local  component  of  the  conditioned 
motor  act  indicates  that  positional  excitations  are  really  of  a  subcortical 
origin.  (Fig.  14). 


B 


'^^^m^i^'/''^^ 


V.    of 
•  limb 


yxfM^^^M^' 


l!*^ 


■iJHiiwiiiiiMiiiiiiiiiiiiiiiiiiiiiiiiHiBimmwwHHHiiHiiimiiiiiimiiiiii' 


Fig.  14 
Comparison  of  tlic  respiratory  component  of  two  conditioned  reactions  —  defensive  (A)  and 

aluncntary  (B). 


The  question  of  how  a  clearly  subcortical  complex  of  excitations  could 
acquire  a  conditioned  reflex  nature  cannot  be  dealt  with  at  present,  since 
It  would  lead  us  away  from  the  subject  under  consitieration.  Here  it  is 
important  only  to  note  that  our  various  experiments  with  the  oricnting- 
investigatory  reaction  have  convinced  us  that  the  coiuiirioiicd  reflex  iidtiirc 
of  the  subcortical  reactions  is  not  primary.  It  becomes  such  only  after  the 
active  interference  oi  cortical  control  at  the  stage  of  the  very  strong 
orientating  reflex  (Anokhin,   1949;  Livingston,   195H;  Hernandez-Peon, 

1958,  1959;  t'f^/-)  (Fig.  15). 

I  presume  that  this  part  of  my  report  illustrates  sufliciently  clearly  two 
propositions:  (i)  the  intricate  complex  c^f  the  effector  excitations  of  the 
conditioned  reflex  is  always  very  extensive  and  includes  the  cortex,  as 
well  as  subcortical  apparatus,  and  (2)  this  complex  can  be  understood  only 
by  assuming  the  existence  of  a  stage  of  synthesis  of  all  the  afferent  in- 
fluences affecting  the  animal  at  the  given  moment. 


p.    K.    ANOKHIN 


221 


5.  RETURN  AFFERENTATION  OF  THE  RESULTS  OF  CONDITIONED  REFLEX  ACTION 

The  conception  of  'return  affcrentation'  had  developed  hi  our  labora- 
tory long  before  the  cybernetic  trend  ot  thinking  led  to  the  formulation  of 
the  'feedback'  idea,  now  being  transferred  into  neurophysiology  and 
proposed  for  the  self-regulating  technical  systems. 

Studying  the  problem  of  compensation  of  organic  functions  after  the 
production  of  cross  anastomoses  we  came  to  the  conclusion  that  the 
creation  of  any  new  functional  system  of  the  organism  in  place  of  a 


Fig.  15 

Further  development  o(  the  conditioned  reflex  architecture,  hitegratcd  cflector  excitations 
reach  the  functioning  organs,  and  formation  of  the  aciaptive  action. 


previous  system  that  has  been  abolished  required  constant  interference  of 
return  afferent  impulses  from  the  results  of  the  performed  action  them- 
selves. 

The  physiological  meaning  of  return  atierentation  consists  in  the 
reflection  in  minutest  afferent  impulses  of  the  minutest  details  of  the  results 
of  a  given  action.  These  results  may  direct  the  information  to  the  central 
nervous  system  through  the  most  diverse  receptor  apparatus.  However, 
this  af^ercntation  as  a  whole  constitutes  a  peculiar  integral  which  reflects  in 
the  stream  of  afferent  impulses  the  aggregate  results  of  the  given  reflex 
action  (Anokhin,  1935;  Anokhin  and  Ivanov,  1933).  Since  it  is  directed 
back  to  the  central  nervous  system  to  the  neural  formations  just  activated 
we  found  it  most  convenient  to  name  it  the  'return  affcrentation'. 


222  BRAIN    MECHANISMS    AND    LEARNING 

In  the  existing  literature  afferent  impulses  of  this  type  are  ascribed 
mainly  to  proprioceptive  formations.  At  this  point  I  want  to  stress  the 
fact  that  this  conception  has  nothing  in  common  with  that  of  return 
afterentation.  Proprioceptive  signalling  is  also  of  a  return  nature,  but  it 
regulates  the  trend  of  the  very  action  in  the  sense  of  its  biomcchanical 
characteristics.  Proprioceptive  signalling  will  never  be  able  to  inform  the 
brain  of  the  results  of  the  adaptive  effect  obtained  by  means  of  the  given 
movement.  Asa  matter  of  fact,  we  cannot  assay  by  means  ofa  proprioceptor 
whether  we  have  grasped  a  knife  or  fork,  although  the  impulses  of  a 
tactile  nature,  suggesting  that  the  hand  has  touched  the  object  and  the 
visual  impulses  fixing  the  moment  of  grasping  the  object,  by  means  of 
return  afferent  impulses  together  ensure  exhaustive  information  of  the 
fact  that  the  movement  has  ended  in  a  certain  positive  result. 

Here  we  approach  the  most  critical  point  of  the  physiological  architec- 
ture of  the  conditional  reflex  from  which  all  the  new  adaptive  acts, 
yielding  more  perfect  results  of  action,  begin.  We  shall  ask  the  question  in 
the  following  manner:  where  is  the  return  afterentation  ot  the  results  of  the 
action  directed  to,  what  apparatus  of  the  central  nervous  system  perceives 
it  and,  so  to  speak,  'assays'  the  correspondence  of  the  result  achieved  with 
the  result  of  the  afferent  synthesis  performed  by  it  earlier  ? 

The  experiments  and  cc^nsiderations  discussed  above,  as  regards  the 
formation  of  the  afferent  apparatus  of  the  acceptor  of  action,  have  led  us  to 
the  conclusion  that  the  meeting  of  the  excitations  of  the  acceptor  of  action 
and  of  the  return  aff'erentation  from  the  results  of  the  performed  action  is 
the  moment  at  which  the  organism  is  always  informed  of  the  satisfactory 
precision  of  the  act  of  behaviour  that  has  taken  place.  It  is  precisely  at 
the  pcnnt  where  these  two  excitations  —  the  excitation  of  the  acceptor 
of  action  and  the  stream  of  return  afferentations  from  the  results  of  the 
action  —  meet  that,  in  our  opinion,  the  necessary  condition  for  any 
co-ordinated  and  regulated  relation  oi  the  animal  and  man  to  the  external 
environment  lies.  Only  when  these  two  streams  of  excitation  exactly 
coincide  do  the  effector  excitations  cease  to  reach  the  functioning  apparatus 
and  is  the  given  behaviour  stage  in  the  chain  of  individual  reflex  actions 
completed  (Fig.  i6). 

Conversely,  if  the  streams  of  return  afferentations  entering  the  brain 
along  different  analysers  fail  to  coincide  with  the  system  of  excitations, 
which  has  formed  at  the  end  of  the  afferent  synthesis  and  is  the  apparatus 
of  the  acceptor  of  action,  this  lack  of  coincidence  immediately  involves 
other  reactions,  primarily,  the  orienting-investigatory  reaction.  By  its 
very  essence  the  orienting-investigatory  reaction  leads  to  an  accumulation 


p.    K.    ANOKHIN 


223 


U  Stage 


Fig.  16 

Completion  of  the  conditioned  reflex  physiological  architecture.  The  figure 

slaows  the  successive  stages  in  the  development  of  the  architecture. 


124 


BRAIN    MECHANISMS    AND    LEARNING 


of  new  affcrcntations  from  the  external  environment,  to  a  repetition  of  the 
afferent  synthesis  stage  already  at  a  new  level  and,  lastly,  to  the  formation 
of  new  effector  complexes.  On  their  part,  these  latter  lead  to  some  new  act 
of  behaviom*  and  thus  determine  streams  ot  new  return  afferent  impulses 
which  usually  correspond  in  larger  measure  to  the  established  acceptor  of 
action,  hi  any  act  oi  behaviour  this  cyclic  process,  beginning  with  the 
afferent  synthesis  stage  and  ending  in  the  confrontation  of  the  return 
afferentations  and  the  excitations  ot  the  acceptor  of  action,  continues  until 


/f.af,r 


Cond. 
sum. 


Fig.  17 
Example  of  lack  of  correspondence  between  the  acceptor  of  actitm  and  the  return  affercntation 

'Discordance'. 


both  excitations  tuUy  coincide.  In  human  behaviour,  which,  in  our 
opinion,  unfolds,  even  in  its  higher  forms,  according  to  the  foregoing 
physiological  architecture  of  the  conditioned  reflex,  this  final  moment  may 
be  formulated  as  a  'coincidence  of  the  results  of  action  with  the  initial 
intention'.  It  is  in  this  that  the  definite  significance  of  the  conception 
proposed  by  us  for  the  physiological  understanding  of  a  number  of 
phenomena  of  a  psychological  nature  lies. 

An  analysis  of  most  of  the  experimental  situations,  especially  conducted 
in  the  way  of  the  integral  behaviour  of  the  animal  by  the  'free  runs' 


p.    K.    ANOKHIN  225 

method,  shows  that  very  many  forms  of  behaviour  are  elaborated  accord- 
iiii?  to  the  aforesaid  physiological  architecture  oi  the  conditioned  reflex 
(Fig.  16).  The  diagram  shows  the  completion  of  the  whole  stream  of 
excitations,  which  arose  as  a  result  of  the  afferent  synthesis  and  of  deter- 
mined and  particular  adaptive  effect.  Practically  every  act  ni  the  life  of 
man  develops  according  to  this  architecture.  Both  as  regards  erroneous 
actions  and  the  initial  period  of  learning  new  actions,  the  only  criterion 
of  the  correctness  of  the  action  is,  ni  our  opmion,  the  coincidence  of  the 
assigned  excitations  with  the  stream  of  the  return  afferent  impulses  which 
bring  information  of  the  results  of  the  action  performed  at  the  given 
moment.  This  is  particularly  well  seen  in  cases  in  which  some  erroneous 
act  is  performed.  How  do  we  detect  the  errors  of  an  action  if  the  latter 
has  ended  'safely'  from  the  point  of  view  of  all  the  demands  made  on  it 
by  the  classical  reflex  theory?  Everything  seems  to  be  on  hand  here:  the 
stimulus,  the  central  apparatus,  as  it  is  usually  understood,  and,  lastly, 
the  reflex  action.  By  means  of  what  additional  apparatus  then  does  man  or 
the  animal  discover  that  the  action  they  have  performed  is  inadequate  or 
erroneous?  (Fig.  17). 

The  physiological  architecture  oi  the  conditioned  reflex  proposed  by 
us,  like  that  of  any  'voluntary  action',  offers  a  sufficiently  objectively 
grounded  answer  to  all  these  questions.  At  the  same  time  it  offers  a  real 
basis  for  a  further  scientifically  objective  analysis  ot  the  complex  behaviour 
reactions  of  man  and  the  animals. 


CONCLUSION 

The  concept  discussed  above  is  an  attempt  to  unify  some  of  the  available 
information  on  the  physiology  of  the  central  nervous  system  and  to  com- 
bine it  with  the  facts  obtained  in  direct  studies  of  the  neurophysiological 
mechanisms  of  the  conditioned  reflex. 

It  is  but  natural  that,  with  such  a  synthesis  of  the  vast  number  of  facts, 
we  had  to  introduce  several  new  conceptions  which  correspond  to  certain 
mechanisms  discovered  by  us. 

To  begin  with  these  conceptions  include  that  of  the  a§crcut  synthesis. 
The  absence  of  stress  on  this  stage  of  the  complex  treatment  of  all  the 
multiform  and  numerous  afl'erent  influences  on  the  organism  by  the 
central  nervous  system  rendered  unintelligible  the  very  process  of  forma- 
tion of  the  efferent  complex  of  excitations,  always  of  an  integrative  nature, 
i.e.  always  harmoniously  combining  the  functioning  components  of  the 
whole  conditioned  reaction. 


226  BRAIN    MECHANISMS    AND    LEARNING 

To  be  sure,  on  the  basis  of  what  inechanisnis  docs  the  given  combina- 
tion, rather  than  any  other  out  ot  the  niilhons  of  possible  combinations  of 
excitations  developing  in  the  cellular  elements  of  the  central  nervous 
system,  become  integrated? 

On  the  basis  of  what  mechanisms  is  a  very  dehnite  end  effect  of  adapta- 
tion chosen  and  fixed  out  of  the  many  probable  end  effects  of  adaptation, 
this  end  effect  being  precisely  the  one  which  exactly  corresponds  to  the 
aggregate  of  the  afferent  influences  affecting  the  organism  at  the  given 
moment ; 

We  have  become  convinced  that  the  key  to  the  solution  of  these 
problems  lies  in  the  extremelv  fme  and  multihM"m  processes  of  accumula- 
tion of  afferent  information  from  the  external  and  internal  environments 
of  animals  and  man.  This  is  followed  by  a  dynamic  interaction  and 
synthesis  of  this  afferent  information  and,  on  the  basis  of  these  processes, 
one  of  the  most  intimate  processes  of  any  form  of  conditioned  behaviour 
—  the  formation  of  the  complex  integrations  of  the  effector  apparatus. 
This  process  truly  deserves  the  picturesque  designation  given  to  it  at  one 
time  by  our  teacher  Pavlov  who  named  the  afferent  tunction  of  the  brain 
the  'creative'  function. 

We  see  that  it  is  indeeci  'creative'  if  we  take  into  account  the  enormous 
number  of  qualitatively  heterogeneous  afferent  stimulations  acting  on  the 
organism  at  each  given  moment  and  if  we  adci  to  this  that  for  man  it 
infallibly  ends  in  what  may  be  psychologically  termed  the  formation  of 
the  'intention'  of  action. 

Many  physiological  factors  contribute  to  this  remarkable  process. 
Here  we  may  include  the  rule  oi  coiii'frociicc  of  heterogeneous  afferent 
stimulations  in  the  selfsame  element  of  the  stem  reticular  formation 
(Fessard,  1958;  Moruzzi,  1958;  Amassian,  1958),  the  activating  effect  of 
this  system  on  the  cortical  level  of  elaboration  of  the  afferent  signals 
(Moruzzi  and  Magoun,  1949),  the  integrating  action  of  the  frontal 
divisions  of  the  cerebral  cortex  on  this  synthetic  process  (Shumilina,  1944; 
Anokhin,  1949)  and,  lastly,  the  controlling  action  of  the  cerebral  cortex 
on  all  the  subcortical  and  spinal  entering  elements  for  the  afferent  impulses 
(Anokhin,  1949;  Livingston,  1958).  All  the  above,  put  together,  serves 
the  highest  synthesis  -  the  formation  of  the  conditioned  bond! 

Application  oi'  die  term  'creative'  to  this  process  does  not  exclude  the 
fact  that  all  its  details,  as  well  as  the  process  as  a  whole,  are  structurally  and 
physiologically  determined  and,  consequently,  may  become  the  subject 
of  a  strictly  objective  scientific  analysis. 

This  latter  proposition  is  illustrated  by  the  fact  that  it  is  precisely  the 


p.    K.    ANOKHIN  227 

physiological  methods  of  research  that  enabled  us  to  discover  the  existence 
of  a  special  apparatus  —  the  acceptor  of  action.  As  may  be  observed  it  co- 
ordinates behaviour  during  the  second  stage  of  the  conditioned  reflex, 
i.e.  during  the  formation  of  the  efferent  act  and  the  emergence  of  the 
return  afferentation  on  the  adaptive  results  of  this  act. 

The  entire  architecture  of  the  whole  conditioned  reflex  offered  for  your 
consideration  shows  that  this  physiological  analysis  may  be  continued.  It 
shows  how  living  nature  in  the  long  evolutionary  process  mastered  the 
future  and  fixed  in  material  forms  —  structural  and  dynamic  —  the  possibility 
of  the  animal's  adaptation  to  forthcomuig  ci'ciits  in  the  external  en- 
vironment. 

The  conditioned  reflex  is  the  expression  of  the  higher  aciaptation 
formulated  by  Pavlov  in  the  principle  of  signalling,  i.e.  the  possibility  of 
adaptation  of  the  animal  and  man  to  future  events  by  just  the  retnote  sij^iial 
of  these  forthcoming  events  alone. 

Of  course,  it  would  be  wrong  to  assume  that  the  foregoing  material 
exhausts  the  entire  content  of  the  physiological  architecture  of  the  condi- 
tioned reflex.  The  material  presented  is  undoubtedly  only  the  beginning 
of  its  study.  However,  it  is  important  that  its  features  be  outlined  precisely 
as  those  of  an  iiireoral  pliysioloi^ical  architecture  and  for  us  it  serves  as  the 
point  of  cieparture  for  further  analysis. 

Making  a  positive  evaluation  o{  our  concepts  of  the  physiological 
architecture  of  the  conditioned  reflex  in  one  of  his  recent  works,  Alfred 
Fessard  expresses  the  opinion  that  a  further  fine  neurophysiological 
elaboration  of  the  'main  points'  of  this  general  architecture  will  make  an 
essential  contribution  to  the  development  of  these  concepts  (Fessard,  1958). 

We  fully  agree  with  this  opinion  and,  as  may  be  judged  from  the  fore- 
going material,  we  are  doing  all  we  can  to  concretize  physiologically  the 
various  aspects  of  this  general  architecture. 

We  also  think  it  possible  that  further  analysis  and  accumulation  of  facts 
in  the  study  of  the  neurophysiological  bases  of  the  conditioned  reflex  may 
make  us  change  some  of  our  present-day  views  and  form  new  concepts 
concerning  the  concrete  physiological  mechanisms.  This  is  the  essence  of 
scientific  progress. 

We  beHeve,  however,  that  any  study  of  the  intimate  processes  of  the 
conditioned  reflex  by  means  of  analytical  and  very  fine  methods  and 
techniques  may  prove  much  more  successful  if  it  is  correlated  with  the 
general  physiological  architecture  of  the  conditioned  reflex.  And  it  is 
just  this  that  prompted  us  to  make  this  general  architecture  of  the  condi- 
tioned reflex,  as  we  conceive  it  today,  the  subject  of  discussion. 

Q 


228  BRAIN    MECHANISMS    AND    LEARNING 


GROUP   DISCUSSION 


Olds.  I  would  like  to  address  myseli  to  the  remarks  on  the  reticular  tormatioii 
and  its  differentiation.  We  also  found  differentiation  in  the  reticular  formation 
based  on  the  dichotomy  between  the  aversive  and  approach  behaviour.  We  find 
that  stimulation  in  the  dorsal  medial  tegmentum  produces  escape.  Stimulation  in 
the  ventral  lateral  tegmentum  produces  approach  of  the  self-stimulation  variety  — 
in  between  there  are  overlaps. 

First  —  the  type  of  electrical  activity  which  Dr  Anokhin  showed  as  typical  of 
aversive  stimulation  did  not  appear  in  the  ventral  lateral  placements  but  did  appear 
in  dorsal  medial  placements.  The  type  of  electrical  activity  which  he  showed  as 
characteristic  of  alimentary  stimulation  did  appear  in  the  ventral  lateral  place- 
ments, but  not  in  the  dorsal-medial  placements.  Mv  question  is  whether  the 
electrodes  used  by  Professor  Anokhin  were  in  the  same  parts  of  the  reticular 
formation  or  in  different  parts. 

My  second  question  is:  We  have  applied  chlorpromazine  and  we  have  obtained 
results  which  are  superficially  in  conflict  with  Dr  Anokhin's  results  and  we  have 
checked  our  data.  This  is  it:  Chlorpromazine  inhibits  the  self-stimulation  response 
rotally  in  the  rat  at  2  mg.  per  kilogramme  —  a  dose  which  has  very  little  effect  on 
the  escape  reaction  produced  by  stimulation  of  the  dorso-medial  tegmentum. 
This  is  different  from  Neprobamate  and  Nembutal  which  inhibit  the  escape  reaction 
and  have  little  efiect  on  the  self-stimulation  response. 

Anokhin.  I  suppose  that  the  difference  here  is  to  be  found  in  the  specific  localiza- 
tion of  the  stimulation.  A  given  reaction  may  be  induced  from  difl:erent  points  of 
the  functional  system ;  it  can  be  provoked  by  natural  stimuli,  as  by  electrical  ones. 
Yet,  if  electric  stimulation  is  applied  to'  a  given  spot  of  the  reticular  formation 
which  is  on  the  excitation  pathway,  after  synapses  which  have  been  made  sensitive 
to  chlorpromazine,  it  may  happen  that  the  drug  will  have  no  blocking  effect  on  the 
animal's  defence  reaction,  wluch  had  been  induced  by  direct  excitation. 

Grastyan.  I  am  in  perfect  agreement  with  Professor  Anokhin  about  the  concep- 
tion of  the  functional  specificity  of  reticular  activating  influences.  I  think  we 
also  obtained  in  our  own  experiments  evidence  confirming  this  supposition :  we 
found  that  the  stimulation  of  different  points  in  the  reticular  formation  in  the 
hypothalamus  had  always  a  specific  influence  in  the  sense  that  it  activated  only 
certain  behavioural  acts,  but  inhibited  others,  antagonistic  to  those  of  the  activated 
ones.  The  only  point  with  which  I  do  not  agree  is  the  interpretation  of  the  electrical 
activity  recorded  in  the  reticular  formation.  I  cannot  believe  that  it  represents  a 
specific  activity  of  the  reticular  formation  (I  refer  to  the  4-6  cycles  per  second 
activity  see  slides  6  (?;/(/  7).  It  must  be  recorded  very  close  to  the  substantia  grisea 
centralis  in  the  mesencephalon  and  in  my  opinion  it  reflects  a  special  projected 
activity  of  the  rhinencephalon  to  the  brain  stem  (hippocampus,  entorhinal  cortex). 
It  was  shown  by  Dr  Adey  that  abundant  connections  exist  between  these  two  areas. 
Moreover  I  have  seen  this  activity  to  appear  in  the  same  point  of  the  reticular 
formation  in  both  alimentary  and  defensive  conditioned  reflexes;  thus  in  my 
opinion  it  could  not  be  regarded  as  representative  of  a  specific  function  of  this 
reticular  subcentre. 

Anokhin.  I  can  give  Dr  Grastyan  the  following  answer:  Comparison  of  the 
slow  rhythms  of  the  reticular  formations  of  the  hippocampus  and  of  the  different 


p.    K.    ANOKHIN  229 

regions  ol:  the  cerebral  cortex  shows  that  the  specific  slow  rhythm  ot  4-7  per 
second  occurs  as  a  general  rule  in  connection  with  direct  paintul  stimuli  ot  either 
the  sciatic  nerve  or  the  skin  ot  the  foot.  With  other  torms  ot  stimuli,  tor  instance, 
stimuli  due  to  tood,  one  does  not  get  this  rhythm.  As  has  been  shown  by  simul- 
taneous recordings  ot  EEG  and  ot  nervous  impulses  ot  individual  nerve  cells  from 
one  and  the  same  point  ot  the  brain,  the  main  characteristic  of  this  rhythm  is  its 
persistence  and  its  regularity. 

As  soon  as  the  rhythm  changes  even  tor  a  traction  ot  a  second,  the  cell  impulses 
disappear  or  diminish. 

We  believe  that  this  rhythm  originates  in  the  reticular  tormation  and  atter  a  very 
short  time  (o,  i-o,  3  seconds)  spreads  to  the  corresponding  region  of  the  cortex,  the 
parietal  and  the  visual  region.  I  suppose  that  our  disagreements  with  Dr  CIrastvan 
are  basically  due  to  the  tact  that  under  normal  experimental  conditions  our 
laboratory  animals  are  always  under  some  painful  influence  or  in  a  state  ot  tear.  A 
specific  rh\thm  can  always  appear  on  the  electroencephalogram  according  to  the 
degree  of  fear.  In  normal  animals,  which  are  awake,  it  is  very  difticult  to  suppress 
this  rhythm  and  it  can  be  achieved  only  after  working  several  months  with  a 
pleasant  food  remtorcement.  It  mav  be  that  all  these  conditions  were  fulfilled  in  Or 
Grastyan's  experiments. 

I  think  that  in  the  future  we  also  shall  endeavour  to  bring  about  conditions  under 
which  this  rhythm  appears  more  often. 

Galambos.  The  data  from  Dr  Grastyan's  experiments  resemble  ours  closely.  I 
am  not  sure,  however,  that  the  term  'conditioned  response'  should  be  applied  to 
these  data.  Choice  ot  term  is  ot  course  merely  a  matter  of  definition,  and  since  a 
stimulus  followed  by  a  reinforcement  here  yields  a  changed  brain  response,  the 
brain  event  fits  the  usual  definition  tor  a  CR.  We  view  the  electrical  event,  how- 
ever, as  more  probably  indicating  an  elementary  process  in  a  chain  of  processes, 
that,  when  completed,  \ield  learning.  The  phenomenon  in  question  probably 
indicates  that  the  brain  is  being  prepared  for  the  specific  change  that  will  occur  and 
is  not  the  signal  of  the  actual  chana:e  itself. 


CHANGING  CONCEPTS   OF  THE  LEARNING 
MECHANISM 

Robert  Galambos 

general  considerations 

Animals  almost  invariably  learn  when  placed  m  a  situation  where  an 
opportunity  to  do  so  is  provided,  and  yet  they  can  learn  no  more  than 
their  capacities  permit  or  make  possible.  It  is,  in  other  words,  as  unprofit- 
able to  try  to  teach  an  animal  a  task  beyond  his  capabilities  as  it  is  to  try  to 
prevent  his  learning  it  when  he  has  been  prepared  by  nature  to  do  so. 
Such  essential  facts  as  the  inevitability  but  limited  scope  of  learned  responses 
were  well  known  to  Darwin  (e.g.  Descent  of  Man,  Chapter  3)  and  to  other 
astute  observers  before  and  since.  Herrick,  taking  this  broad  biological 
view,  has  comprehensively  summarized  the  more  recent  work  (1956)- 

In  the  analysis  of  how  animals  come  to  learn,  scientists  from  several 
disciplines  generally  agree  now  that  they  {a)  sense  environmental  events, 
(/))  react  'reflexly'  to  them,  and  (c)  modify  their  subsequent  behaviour  in 
the  light  of  those  experiences.  Much  study  and  an  enormous  literature 
have  developed  around  these  phenomena  and  current  work  on  the  brain 
events  occurring  during  learning  seems  to  be  directed  towards  answers  for 
the  following  three  major  questions: 

1.  What  IS  the  nature  oi  the  neural  organization  that  enables,  permits 
and  indeed  requires  the  organism  to  make  contact  with  the  environment 
through  its  senses  for  the  purpose  of  analysing  it?  Much  ei^ort  has  been 
spent  on  defining  the  physical  nature  of  the  energy  exchange  that  occurs  at 
the  sensory  end  organ  —  e.g.  the  transmutation  into  nerve  impulses  of 
mechanical  motion  in  the  inner  ear  and  of  electromagnetic  radiation  in  the 
eye.  Beyond  this  many  investigators  have  been  trying  to  specify  the 
analysis  performed  within  the  sensory  afferent  pathways;  much  of  this 
work  has  been  done  in  anaesthetized  or  otherwise  reduced  preparations. 
Besides  this,  effort  in  increasing  amount  is  being  devoted  to  uncovering 
the  basis  for  the  evident  ability  of  normal,  intact  organisms  to  respond 
preferentially  to  input  from  one  rather  than  another  of  its  sensory  inputs 
—  the  problem  of  'attention'  and  its  converse  'habituation'  if  you  will. 

231 


232  BRAIN    MECHANISMS    AND    LEARNING 

Finally,  there  arc  the  matters  of  how  different  'perceptions'  arise  merely 
because  the  input  energy  arrives,  say,  via  the  ear  rather  than  the  eye,  and 
how  it  can  be  that  these  perceptions  become  permanently  stored  as 
'memories'.  The  data  about  the  brain  needed  for  dealing  scientifically 
with  these  last  objective  behavioural  events  are  meagre  or  nonexistent, 
but  progress  in  the  development  of  new  and  relevant  information  is 
obviously  accelerating  and  inevitable. 

II.  What  is  the  essential  nature  of  the  neuronal  organization  which 
makes  the  innate  'reflex'  responses  inevitable  for  the  animal;  It  is  not  a 
chance  matter  that  dogs  breathe  and  swallow,  and  salivate  when  food  is  put 
into  the  mouth,  and  withdraw  the  paw  when  an  electric  shock  is  applied 
to  it.  Neither,  one  must  admit,  is  it  accidental  or  by  chance  that  they  learn 
when  exposed  to  the  world  about  them.  As  is  true  of  every  living  animal, 
dogs  come  naturally  equipped  to  do  things  of  this  sort.  There  are  many 
such  innate  behavioural  responses  displayed  commonly  throughout  the 
animal  kingdom,  and  in  addition  patterns  peculiar  to  each  species  are 
clearly  recognizable.  Thus  dogs  bark,  not  mew;  and  they  are  adapted 
behaviourally  to  do  many  other  things  not  in  the  repertoire  of  pigeons  and 
cockroaches.  Experimenters  on  brain  function  generally  assume  that 
comprehensible  neural  correlates  exist  for  both  the  species-specific 
behavioural  displays  and  for  the  ones  which  the  different  species  com- 
monly exhibit.  It  is  unnecessary  to  point  out,  however,  that  while  exact 
descriptions  of  such  behaviour  arc  available  from  many  sources,  satis- 
factorily comprehensive  neural  generalizations  for  dealing  with  them 
certainly  are  not. 

III.  What  is  the  new  neuronal  organization  created  within  the  animal  by 
an  experience  with  the  world  around  him;  The  dramatic  commonplace 
phenomenon  we  call  learning  must  be  explained,  it  would  appear,  as  a 
more  or  less  permanent  change  of  the  nervous  system.  An  astonishingly 
large  amount  of  searching  has  gone  into  attempts  to  specify  the  exact 
nature  of  that  change,  and  it  is  clear  that  physiologists,  rightly  or  wrongly, 
consider  this  process  of  learning  to  be  of  paramount  interest  and  import- 
ance to  an  understanding  of  brain  physiology.  The  scientific  analysis  has 
largely  proceeded  by  attempts  to  describe  where  in  the  brain,  and  when 
in  time,  the  brain  change  takes  place,  and  there  are  several  current  ideas  of 
the  essential  features  of  the  process.  Furthermore,  much  new  information 
is  being  developed,  as  this  Conference  will  demonstrate.  Some  ideas  seem 
to  be  growing  in  favour  while  others  decline,  and  it  is  towards  a  critical 
evaluation  of  both  the  ascendant  views  and  the  classical  ones  that  I  would 
direct  your  attention  in  what  follows. 


ROBERT    GALAMBOS  233 

CONCEPTS    ABOUT    THE    BRAIN    CHANCJE    IN    LEARNING^ 

The  classical  view  holds  that  the  neocortex  is  where  the  specific  changes 
accountable  for  new  learned  responses  occur.  I  shall  not  list  the  arguments 
in  favour  of  this  view ;  the  reader  will  instead  find  below  several  experi- 
ments that  raise  objections  to  this  generalization  and  others  that  may 
provide  concepts  for  our  possible  further  enlightenment. 

1.  There  seems  to  be  no  universally  accepted  definition  of  learning. 
'Learning'  is  common  to  octopus,  cat  and  bee  despite  the  large  differences 
in  their  neural  apparatus.  In  particular  the  mammalian  cerebral  cortex  is 
obviously  not  needed  since  animals  wholly  deficient  m  this  structure 
display  behaviour  that  by  any  reasonable  detinition  is  'learned'. 

2.  Some  mammalian  habits  can  be  abolished  by  decortication  and  then 
be  relearned.  The  pre-  and  post-operative  CRs  seem  to  be  the  same,  and  if 
we  make  the  plausible  assumptitm  that  the  cortex  participated  in  the 
original  habit  it  is  evident  that  the  second  one  is  mediated  by  extracortical 
structures. 

3.  The  cortex,  however,  is  clearly  the  site  of  a  durable  change  in  certain 
other  kinds  of  habits.  This  conclusion  emerges,  for  example,  from  the 
learning  experiments  in  which  the  corpus  callosum  is  sectioned  at  a 
crucial  state  (Myers).  These  studies  show  that  some  essential  event  does 
indeed  occur  in  the  cerebral  hemisphere  for  habits  involving  visual 
discriminations  at  least. 

4.  Different  amounts  of  neocortex  seem  to  be  required  according  to  the 
degree  of  complexity  of  the  learning  problem.  If  a  two-tone  pitch 
discrimination  and  a  three-tone  pattern  discrimination  are  taught  to  a  cat, 
removal  of  its  auditory  cortex  abolishes  both,  and  only  the  'simple'  pitch 
discrimination  can  be  relearned  (Neft  and  Diamond).  Some  neural  events 
responsible  for  the  'complex'  tone-pattern  CR  have  been  eliminated  by 
partial  decortication  but  the  necessaries  tor  a  'simple'  CR  remain.  (What 
is  meant  by  simple  vs.  complex  learning  has  not  to  my  knowledge  been 
adequately  defined.) 

5.  Recent  experiments  on  various  neuronal  aggregates  within  the  brain 
(e.g.  the  reticular  and  limbic  systems),  while  suggesting  remarkably 
distinctive  functions  for  each  of  them  (e.g.  attention,  emotion),  indicate 
also  that  these  separate  cellular  aggregates  combine  in  some  orderly  way 
to   create  the  brain  change  that   ultimately  yields  learned  behaviour. 

1  Tliis  section  closely  follows  a  portion  of  an  unpublished  niaiuiscript  by  R.  Cialanibos  and 
C.  T.  Morgan,  'The  Neural  Basis  of  Learning",  prepared  in  iyS7  for  Hiiiulhook  of  Physioloiiy, 
scheduled  for  publication  in  i960. 


234  BRAIN    MECHANISMS    AND    LEARNING 

Consideration  of  the  time  course  of  acquisition  will  illustrate  this  concept. 
A  monkey  learning  to  avoid  shocks  by  pressing  a  lever  at  a  signal  appears 
to  pass  through  a  series  of  behavioural  stages  in  the  process.  At  first  the 
signal  arouses  much  'emotional'  activity  such  as  pilo-erection  and 
vocalization.  Later,  when  learning  has  progressed  to  50  per  cent  correct 
responses,  this  'emotional'  behaviour  can  be  partly  replaced  by  an  'alert 
or  attentive'  attitude.  The  fully  trained  animal,  in  fnial  complete  com- 
mand of  the  situation,  seems  undisturbed  'emotionally'  by  the  signal  and 
sits  relatively  'inattentive'  as  he  delays  making  the  correct  response  until 
the  very  last  moment.  These  successive  behavioural  stages  presumably 
reflect  a  progressive  reorganization  of  brain  structures  or  processes  during 
acquisition.  If  this  is  true,  brain  events  measured  at  a  particular  place  in  the 
early  stages  of  learning  might  be  absent  there  later;  while  at  another  brain 
locus  characteristic  brain  events  might  appear  only  when  learning  has 
become  complete.  Evidence  accumulates  that  learning  is  just  such  a 
dynamic  orderly  march  of  events  that  involves  much  or  all  of  the  neural 
apparatus  the  organism  possesses. 

6.  There  is  reason  to  believe  that  there  are  different  kinds  of  learning, 
that  the  brain  changes  accounting  for  these  are  not  uniform  or  identical, 
and  that  what  happens  in  the  brain  during  solution  of  one  problem  need 
not  happen  in  the  solution  of  the  next  one.  As  has  been  adequately  shown 
(Brady  anci  Hunt)  a  rat  trained  both'(r7)  to  press  a  lever  to  get  a  drop  of 
water  (an  instrumental  or  Type  II  response)  and  (/))  to  'expect'  a  shock  at 
the  termination  of  a  signal  (a  classical  or  Type  I  response),  loses  only  the 
second  of  these  habits  after  experiencing  a  number  of  convulsive  seizures. 
Furthermore,  the  lost  habit  returns  after  a  time  without  retraining.  That 
convulsive  seizures  temporarily  abolish  one  CR  while  leaving  another 
entirely  intact  defines  a  large  and  presumably  highly  significant  difference 
in  the  neural  basis  of  the  two  CRs. 

7.  All  problems  are  not  equally  easy  for  animals  to  learn.  Teachers 
know  that  what  one  child  learns  easily  another  may  never  acquire,  and 
everyone  will  concede  that  speaking,  writing  and  reading  are  much  more 
readily  learned  by  man  than  by  any  other  species.  Besides  the  obvious 
species  and  individual  differences  in  learning  capacities  which  are  apparent 
upon  a  moment's  reflection,  there  is  the  fact  that  whereas  many  or  very 
many  combinations  of  CS  and  US  are  ordinarily  required  to  establish  a 
CR,  a  single  exposure  to  CS  alone  proc^uces  lifetime  retention  in  the  case 
of  imprinting  (Hess).  What  are  the  neural  events  in  this  exceptional 
instance,  where  for  only  a  few  hours  in  the  life  history  of  an  organism  its 
brain  is  prepared  to  make  a  particular  set  of  functional  connections  ?  The 


ROBERT    GALAMBOS  235 

answer  to  this  question  would  undoubtedly  provide  highly  useful  clues 
applicable  to  'ordinary'  learning  as  well. 

8.  Wholly  unlearned  complex  behaviour  like  that  of  newly  hatched 
birds  which  arc  said  to  scatter  for  cover  at  the  first  presentation  of  specific 
sounds  or  moving  shapes  may  represent  simply  the  ultimate  with  respect 
to  the  neural  processes  we  would  like  to  understand.  Reflexes  and  instincts 
emerge  because  some  neuronal  organization  is  handed  down,  like  body 
shape,  as  part  of  an  organism's  phylogenetic  heritage.  Conceivably  this 
neuronal  organization  has  much  in  common  with  or  is  actually  identical 
to  the  one  achieved  through  experience.  If  this  were  so,  the  same  physio- 
logical principles  would  suffice  equally  well  for  explaining  the  behaviour 
built  in  at  birth  and  that  acquired  during  life.  Darwin's  choice  of  the  term 
'inherited  habit'  for  the  unlearned  response  would  in  that  event  turn  out 
to  have  been  peculiarly  apt.  For  a  full  discussion  of  this  problem  by  the 
author  the  reader  is  referred  to  the  2nd  Macy  Conference  on  The  Central 
Neri'ous  Systei}!  and  Behavior,  where  the  neural  mechanism  of  vomiting 
was  considered. 


DATA    ABOUT   THE    BRAIN    CHANGE   IN    LEARNING 

For  reasons  of  convenience  or  of  convention  the  mammalian  brain 
seems  to  have  become  the  principal  object  of  study  and  the  facts  make  it 
increasingly  clear  that  within  it  the  neural  change  oi  learning  is  not  a 
single  event  occurring  at  a  single  point  in  time  but  rather  a  sequence  of 
events  occurring  over  a  more  or  less  prolonged  interval  in  widespread 
brain  locations.  Acquisition  of  the  learned  response  takes  time  (Duncan), 
and  not  only  is  the  appropriate  classical  analyser  system  activated  but  so 
also  are  the  reticular  core  of  the  brain  stem  and  the  limbic  system  as  well 
(e.g.  Anokhin,  Buser  and  Roger,  Galambos  et  al.,  Hernandez-Peon  er  ai, 
1958;  Trotimov  et  al.).  Within  the  anatomical  limits  of  a  classical  analyser 
system,  furthermore,  variation  in  response  to  the  conditioning  stimulus 
is  commonly  encountered  during  the  learning  process  not  only  at  the 
cortical  termination  but  also  at  the  first  synapse  (Galambos  et  al.,  Gersuni 
et  al.,  Hernandcz-Pcon  et  ai,  1956),  a  fact  presumably  related  to  action  of 
the  efferent  sensory  systems.  With  large  and  microelectrodes  new  electrical 
events  uniquely  related  to  learning  have  been  described  (Jasper  et  al., 
Kogan,  Livanov,  Morrell  and  Jasper,  and  Yoshii  et  al),  and  experimental 
evidence  is  even  being  marshalled  to  support  Coghill's  insight  (Herrick) 
that  it  is  'neuropile'  modification  that  produces  learning  (e.g.  Gastaut). 
Finally,  recent  observers  (e.g.  John  and  Killam)  have  begun  to  cast  some 


236  BRAIN    MECHANISMS    AND    LEARNING 

light  upon  the  dynamic  course  of  events  ckiring  acquisition  according  to 
which  responses  grow  and  fade  in  one  structure  after  another  until  at 
last  a  stable  pattern  of  brain  activity  associated  with  the  fully  elaborated 
CR  becomes  established.  Any  concept,  therefore,  that  holds  that  the 
essential  events  in  conditioning  and  learning  occur  at  a  particular  instant 
in  time  and  exclusively  in  the  cerebral  neocortex  struggles  against  an 
already  impressive  and  continuously  growing  body  of  contrary  facts. 

As  for  the  work  in  our  own  laboratory,  the  research  effort  in  which 
Drs  Shcatz,  Hearst,  Bogdanski,  Vernier  and  several  others  have  colla- 
borated has  been  directed  towards  a  descriptive  analysis  of  the  electro- 
physiological events  associated  with  acquisition,  retention  and  extinction 
of  learned  responses.  It  is  our  feeling  that  much  new  information  remains 
to  be  collected  before  we  can  comprehend  even  the  simplest  basic  events 
in  learning,  and  we  would  do  this  with  minimum  reference  to  the  pre- 
conceptions of  the  processes  involved  that  we  ourselves  invent  or  that  we 
have  inherited  in  the  form  of  'syntheses'  achieved  by  students  now  long 
dead.  Our  experimental  plan  and  essential  results  have  already  been 
described  and  need  not  be  repeated  here  (ist  Macy  Conference);  we  have 
been  observing  evoked  EEG  responses  in  simple  learning  situations.  Our 
modest  progress  to  date  may  be  summarized  under  several  general 
headings. 

I.  hi  normal  cats  and  monkeys  the  EEG  response  evoked  by  a  brief 
acoustic  or  visual  signal  of  constant  strength  is  not  constant  in  size  or 
duration.  This  variability  in  response  is  not  restricted  to  the  cortical 
terminus  of  the  specific  analyser  but  can  be  measured  in  widespread 
cortical  and  subcortical  regions  as  well.  Presumably  the  observed  vari- 
ability reflects  the  processes  underlying  the  'orienting  response'  intensively 
studied  in  many  laboratories,  and  is  related  to  what  others  call  'attention' 
(Galambos,  Sheatz  and  Vernier). 

3.  Reinforcement  of  these  auditory  or  visual  signals  (CS)  by  shock,  food 
or  mildly  noxious  stimuli  like  a  puff  of  air  in  the  fice  (US),  remarkably 
increases  the  probability  that  the  response  to  the  CS  will  be  large  in 
amplitude  and  prolonged  in  duration  at  all  sites  where  it  is  recordable. 
Fig.  I  illustrates  this  phenomenon  as  well  as  other  relevant  points. 

3.  If,  however,  the  CS  is  a  signal  that  an  operant  response  (e.g.  pressing 
a  lever)  will  avoid  shock  or  procure  food,  the  brain  activity  evoked  by  the 
CS  tends  to  become  reduced  during  acquisition  and  may  disappear  in  the 
fully  trained  animal  (Hearst  ct  ah).  The  evoked  activity  returns,  however, 
when  the  behavioural  response  is  prevented  (e.g.  bv  moving  the  lever  out 


ROBERT    GALAMBOS  237 

of  reach  of  the  animal).  It  is  evident,  therefore,  that  the  CS  can  evoke  a 
lar^e  or  a  small  response  from  the  brain  of  a  conditioned  annual  depending 
on  the  kind  of  trainnig  he  has  received.  This  fict  may  explain  the  varia- 
tions in  results  obtained  by  others  using  this  method  of  study  (Kogan). 

HABITUATED  REINFORCED  WITH  PUFF  OF  AIR 

TRIAL  12  13  5  7 

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EXTINCTION  REINFORCED 

TRIAL  ec  87  95      ONCE  95  I  2 

Fig.  I 
Effect  of  classical  conditioning  procedure  on  amplitude  and  duratum  tit  response  evoked  by 
click.  Rhesus  monkey,  chronic  bipolar  electrodes  implanted  in  four  brain  areas  as  indicated. 
The  fifth  line  in  each  record  signals  delivery  of  acoustic  click  whose  intensity  remained 
constant  throughout.  Record  to  be  read  from  left  to  right,  and  top  to  bottom.  In  Habituated 
Trials  (i,  2)  the  click  evoked  small  modest  responses  at  all  electrode  locations.  Effect  of 
reinforcing  click  with  puff  of  air  to  face  is  to  increase  amplitude  and  duration  of  click  response 
in  all  brain  loci.  After  discontinuation  of  reinforcement  (E.xtinction  Trial)  response  amplitvides 
and  durations  decrease  progressively  until  they  revert  (Trials  87,  95)  approximately  to  control 
values.  A  single  reinforcement  (96)  restores  response  amplitude  once  more  (i,  2). 

4.  There  arc  many  subcortical  areas  in  which  remarkably  sinnlar 
activity  is  aroused  by  both  visual  and  auditory  CSs  after  their  reinforce- 
ment. This  is  in  contrast  to  the  well-known  fact  that  in  certain  regions 
(e.g.  the  classical  visual  cortex)  only  one  of  the  stimuli  proves  effective. 
Brain  locations  where  a  common  event  is  produced  by  different  sense 
modalities  in  learning  situations  include  midbrain  reticular  and  limbic 


238  BRAIN    MECHANISMS    AND    LEARNING 

Structures  at  least,  and  the  exact  specification  of  where  this  occurs  would 
appear  to  be  valuable  information  to  collect  (Galanibos  and  Sheatz). 

5.  Anaesthetization  profoundly  modifies  the  brain  response  to  click  or 
flash.  Several  waves  disappear  from  the  cortical  record;  the  earliest  one 
persists  as  the  well-known  evoked  response  of  the  deeply  anaesthetized 
cortex.  Furthermore  the  number  of  brain  locations  where  responses 
appear  becomes  smaller  as  the  anaesthetic  constricts  activity  into  approxi- 
mately the  limits  of  the  classical  afferent  pathway. 

6.  Whereas  several  years  ago  we  felt  the  evoked  response  variations 
here  under  discussion  might  reflect  the  specific  changes  connected  with 
the  formation  of  the  'temporary  connection'  we  presently  view  them,  in 
agreement  with  many  others  (e.g.  Voronin  ct  a\.),  as  more  probably 
related  to  attention,  orientation  responses  and  the  like.  This  conclusion 
does  not  at  all  diminish  our  interest  in  them,  however,  for  the  brain 
processes  they  signify  unquestionably  underlie  the  one  we  originally  set 
out  to  study.  The  brain  is  somehow  primed  or  prepared  for  the  specific 
event  it  undergoes  when  learning  is  achieved,  and  an  exact  definition  of 
the  factors  responsible  for  this  is  a  necessary  first  step. 

CONCLUSION 

observation  and  experimental  analysis  are  said  to  be  of  value  only  in  so 
far  as  they  provoke  a  new  and  more  comprehensive  synthesis.  If  what  has 
gone  before  in  this  essay  can  be  called  an  analysis  it  is  surely  a  small  and 
imperfect  one  and  the  syntheses  to  be  derived  from  it  are  merely  specula- 
tive questions.  One  may  observe,  however,  that  physiologists  are  perhaps 
overly  impressed  by  the  learning  abilities  of  man;  deeply  involved  in  the 
search  for  an  explanation  for  his  unusual  capacities  they  seem  to  reject  the 
thought  that  human  learning  almost  surely  represents  merely  an  extension 
and  elaboration  of  a  general  capacity  possessed  by  most  living  animals. 
While  the  principles  in  operation  may  indeed  work  more  efficiently  or  to  a 
more  elaborate  degree  in  man  with  his  highly  developed  neocortex,  it 
seems  only  reasonable  to  assume  that  the  same  principles  operate  not  only 
to  produce  his  learned  reactions,  but  also  to  guarantee  performance  of  his 
unlearned  respc^nses  (e.g.  breathing)  and  to  make  possible  the  learning 
displayed  by  animals  with  simple  nervous  systems  as  well  (but  see  Pantin, 
p.  193  for  an  opposite  view).  It  could  be  argued,  in  brief,  that  no  important 
gap  separates  the  explanations  for  how  the  nervous  system  comes  to  be 
organized  during  embryological  development  in  the  first  place;  for  how  it 
operates  to  produce  the  innate  responses  characteristic  of  each  species  in 


ROBERT    GALAMBOS  239 

the  second  place;  and  ior  how  it  becomes  reorganized,  fnially,  as  a  resuk 
of  experiences  during  hfe.  If  this  idea  should  be  correct,  the  solution  of 
any  one  of  these  problems  would  mean  that  the  answer  for  the  others 
would  drop  like  a  ripe  plum,  so  to  speak,  into  our  outstretched  hands. 


GROUP   DISCUSSION 

Magoun.  Dr  Galambos's  dcnionstraticm  that  rcinforccniciu  leads  to  a  wide- 
spread generalization  of  afferent  signals  within  the  CNS,  together  with  an  incre- 
ment in  their  amplitude  and  configuration,  makes  the  third  such  report  to  appear 
recently.  Drs  Killam  and  John  found  that  the  central  distribution  and  amplitude  ot 
responses  to  a  series  of  llashes  were  increased  during  reinforcement  in  avoidance 
conditioning.  Drs  Worden  and  Marsh  found  the  same  thing  using  tones  as  signals 
and  a  food  reward  as  remiorcement.  This  alteration  of  the  conditioned  signal 
induced  by  reinforcement  may  provide  the  situation  which,  in  Dr  Fessard's 
opinion,  is  prc-rcquisite  for  the  formation  of  a  novel  connection:  namely,  the 
elaboration  of  a  stage  in  which  convergence  of  the  conditioned  and  unconditioned 
signals  can  occur.  At  the  Moscow  colloquium,  Dr  Gastaut  stressed  the  importance 
of  subcortical  brain  mechanisms  in  this  regard,  because  these  then  provided  the 
only  known  sites  at  which  the  conditioned  and  unconditioned  signals  might  con- 
verge upon  common  neurones.  With  the  demonstration  that  a  reinforcing  stimulus 
opens  widespread  regions  of  the  brain  to  an  incoming  signal,  we  need  not  search 
tor  tocal  sites  where  such  convergence  might  occur,  for  many  possibilities  then 
emerge.  The  role  ot  reintorcement,  in  generalizing  and  increasing  the  amplitude  ot 
the  responses  of  the  central  nervous  system  to  afferent  signals,  represents  an  out- 
standing achievement  of  recent  electrophysiological  investigation  of  the  processes 
ot  learning  in  the  brain. 

Galambos.  May  I  add  that  it  was  Arteniyev  and  Bezladnova  lo  years  ago  who 
dealt  first  with  the  problem  [Artemyev  and  Bezladnova  (1952).  Electrical  reaction 
ot  the  auditory  area  ot  the  cortex  of  the  cerebral  hemisphere  during  the  formation 
of  a  conditioned  defence  reflex.  Trudy  Inst.  Fiziol.  I,  22S-36.] 

Palestini.  I  would  like  to  know  whether  you  notice  any  difference  in  the  rate  of 
development  of  habituation  by  recording  in  different  sites  of  the  brain. 

Galambos.  I  cannot  give  a  precise  answer.  The  extraordinary  variation  in 
response  amplitude  encountered  during  the  experiments  has  thus  tar  prevented  the 
precise  measurements  that  would  be  required. 

Palestini.  In  our  laboratory  we  have  observed  some  difference  in  the  rate  of 
habituation,  between  the  specific  and  non-specific  sensory  pathways;  the  habitua- 
tion is  faster  for  the  non-specific  responses.  The  places  we  recorded  at  were  the 
reticular  formation,  the  mesencephalon,  the  centrum  medianum  and  the  non- 
specific responses  in  the  cortex.  We  also  found  that  both  habituation  and  condi- 
tioning are  better  shown  in  the  slow  late  potentials. 

Thorpe.  I  think  the  suggestion  that  an  investigation  of  the  organization  of  the 
'centres'  for  instinctive  behaviour  may  throw  a  light  on  the  process  ot  learning,  is  a 
very  important  one.  Often  when  you  are  dealing  with  animals  which  have  fairly 
elaborate  innate  behaviour,  learning  consists  chiefly  in  making  a  fine  adjustment  to 
these  innate  behaviour  patterns,  and  so  in  studying  instinctive  behaviour  one  often 


240  BRAIN   MECHANISMS    AND    LEARNING 

sees  that  the  animal  seems  set  to  learn  one  particular  thing  and  notliing  else.  The 
instinctive  mechanism  is  ready  to  take  it  just  so  tar  along  the  line  towards  perfection 
of  the  particular  performance  but  no  further  and  from  there  on  learning  takes  over, 
hi  such  a  situation  the  suggestion  that  the  fundamental  mechanisms  are  of  the  same 
kind  seems  valuable.  Also,  it  has  been  suggested  that  when  animals  are  not  in 
perfect  health  the  innate  behaviour  may  fail  to  come  out  automatically  in  its  full 
perfection  but  can  nevertheless  be  perfected  by  learning.  But  there  is  one  point 
where  I  think  the  differences  are  great:  in  innate  motor  patterns  the  action  is  often 
highly  elaborate  and  the  innate  adjustment  may  be  very  fine;  but  the  innate 
receptive  mechanism  by  which  responses  arc  released  is  seldom  or  never  capable  b}- 
itself  of  coping  with  complex  stimuli,  hi  other  words  releasers,  if  they  have  to  be 
recognized  innately,  without  any  learning  coming  into  the  process,  must  be  very 
simple.  So  in  complex  releasing  situations  learning  has  pertorce  to  take  a  corre- 
spondingly more  important  part,  since  the  innate  component  cannot  take  the 
animal  very  far.  hi  this  respect  of  complexity  there  does  seem  to  be  a  significant 
difference  between  the  mechanisms  for  organizing  motor  patterns  and  those 
controlling  perceptual  recognition. 

EccLES.  Dr  Galambos  refers  to  overlapping  neuronal  fields  for  various  functions 
of  the  medulla  and  suggests  to  us  that  some  new  stimulus  or  new  input  will 
galvanize  this  group  of  neurones  into  an  entirelv  new  response.  There  need  be  no 
mystery  about  this  if  you  consider  the  mode  of  operation  of  neuronal  networks. 
I  don't  think  we  have  considered  these  properties  sufficiently.  We  must  think  of  the 
nervous  system  as  composed  of  immense  assemblages  of  neurones  with  patterns  of 
connections  at  each  synaptic  relay.  If  an  impulse  is  going  to  be  propagated,  there 
must  be  convergence  —  and  therefore  there  must  be  a  lot  of  collusion  (if  you  like) 
in  neuronal  operations,  hi  any  knid  of  possible  connections  in  neuronal  networks  it 
can  be  demonstrated  thai  if  you  alter  the  input,  you  alter  the  output.  The  particular 
situation  that  Dr  Galambos  mentions  provides  an  example.  In  the  whole  of  this 
medullary  assemblage  of  neurones  there  are  all  kinds  of  pathways  and  the  particular 
input  you  get  by  pharyngeal  tickling  operates  in  one  particular  way  to  give  you  the 
vomiting  output.  We  have  to  think  of  neuronal  patterns  and  how  varying 
inputs  give  varying  outputs  and  how  modifications  can  be  produced  in  this  way  by 
habituation  and  learnnig. 

Galambos.  There  are  of  course  several  models  one  could  use  as  one  attempts  to 
visualize  the  principle  of  organization  at  work  in  neuronal  networks  and  nuclei. 
Dr  Eccles  prefers  the  input-output  model  in  which  the  essential  phenomena  in- 
volved are  exclusively  synaptic  transmissions  and  excitation  and  inhibition.  Surely 
there  is  no  law,  however,  against  looking  for  some  other  organizing  principle.  No 
less  an  authority  than  that  grand  old  man  of  American  comparative  anatomy,  C. 
Judson  Herrick,  has  said  something  is  going  on  in  the  neuropile  that  we  do  not 
understand. 

Olds.  From  Dr  Gaiambos's  slides,  it  seems  that  a  common  message  pervades  the 
system  at  a  certain  stage  of  learning  before  the  response  is  fully  developed.  We  used 
to  think  that  the  message  was  coded  by  the  place  to  which  it  was  projected,  or  b)- 
the  system  of  units  to  which  it  was  projected,  but  tlois  pervasiveness  suggests  that 
the  message  may  somehow  be  characterized  by  its  pattern.  This  brings  me  to  my 
question  —  is  there  any  characteristic  difference  observed  between  this  complex 
event,  depending  on  the  nature  of  the  input  signal  or  the  nature  of  the  reinforce- 


ROBERT    GALAMBOS  24 1 

mciit,  or  both.  Docs  a  diftcrcncc  in  this  complex  event  ever  arise  when  the  stiniukis 
is  changed,  say  from  chck  to  hghtr 

Galambos.  Again,  we  do  not  have  the  information  for  answering  this  question 
precisely.  The  evoked  response  seems  to  be  identical  in  many  brain  loci  with 
different  stimuli,  but  in  other  places  this  is  not  so.  One  of  our  current  problems  is 
to  obtain  just  the  data  required  to  answer  the  question  Dr  Olds  asks. 

HeknAndez-Peon.  I  would  like  to  ask  two  brief  questions  —  1  noticed  that 
during  anaesthesia  there  was  an  enhancement  of  one  of  the  waves  of  the  auditory 
cortical  potentials.  I  would  like  to  know  what  is  the  interpretation  ot  this  fact. 
The  other  question  is:  where  was  the  puff^  of  air  applied,  because  probably  its 
localization  is  of  some  importance  in  conditioning.  For  example,  it  it  is  applied  to 
the  eye,  the  response  is  probably  not  extinguished  or  habituated.  But  we  have 
observed  at  the  spinal  V  sensory  nucleus  that  the  potential  evoked  by  a  puff  oi  air 
is  decreased  with  repetition  of  the  stimulus  —  and  the  habituation  disappears  by 
giving  anaesthesia.  We  also  found  that  the  pinna  reflex  evoked  by  giving  repetitive 
puffs  of  air  disappears,  but  if  we  anaesthetize  the  cat  the  pinna  reflex  returns  and  is 
not  habituated  under  anaesthesia. 

Galambos.  I  had  not  considered  the  possibility  that  the  exact  region  to  which  the 
air  puff  reinforcement  was  delivered  might  make  much  difference.  We  have  simply 
blown  the  air  into  the  animal's  face.  As  to  your  question  ot  whether  the  evoked 
response  amplitude  increases  with  anaesthesia,  the  answer  is  a  somewhat  qualified 
yes.  In  the  awake  animal  two  electrical  events  are  identifiable  in  the  first  20  or  30 
msec,  of  the  cortical  response  to  a  click.  One  of  these  disappears  with  anaesthesia. 
Since  the  two  sum  algebraically,  removal  of  one  allows  the  other  —  the  well-known 
'evoked  response'  —  to  stand  alone,  and  it  often  seems  then  to  have  grown  in  size. 

Segundo.  So  far  work  on  electrographic  aspects  of  conditioning  has  analysed 
changes  that  occur  in  the  direct  response  to  the  indifferent  and  later  conditioned 
stimulus  (Anokhin,  1958;  Fessard  and  Ciastaut,  1954)-  It  seems  opportune  to 
mention  that,  as  a  consequence  ot  training,  the  conditioned  signal  also  became 
capable  of  modifying  the  response  to  the  absolute  stimulus  (in  somatic  sensory 
cortex  and  perhaps  mesencephalic  reticular  formation).  Namely,  the  potential 
evoked  by  a  painful  stimulus  is  larger  when  preceded  by  its  conditioned  signal  than 
when  not  preceded  by  it :  in  terms  of  human  experience,  it  is  larger  when  'expected' 
than  when  'unexpected'.  (Segundo  and  Sommer-Smith;  Galeano  and  Roig,  1959). 

Finally,  I  would  like  to  ask  the  interpretation  for  the  short  latency  of  visual 
cortical  responses  to  clicks.  And  it  shapes  of  cortical  and  sub-cortical  responses  are 
similar  to  shapes  encountered  in  primary  sensory  cortex? 

Galambos.  We  are  presently  closely  comparing  cortical  and  subcortical  records 
for  similarities  and  differences  in  their  morphology  and  duration.  Published  data 
confirm  our  own  impression  that  such  records  show  remarkable  similarities 
throughout  a  period  ot  0.5  to  i.o  seconds  following  the  conditioned  stimulus.  If 
this  should  turn  out  to  be  correct,  some  new  unexplained  phenomenon  existing  in 
large  parts  of  the  brain  ot  the  conditioned  animal  would  have  to  be  assumed. 
Such  a  phenomenon  would  certainly  be  worth  careful  stud)-. 


fUJ 


THE  SIGNIFICANCE  OF  THE  EARLIEST 

MANIFESTATIONS  OF  CONDITIONING 

IN  THE  MECHANISM  OF  LEARNING^ 

E.  Grastyan 

In  the  electrophysiological  investigation  of  the  temporary  connection 
there  are  at  least  as  many  incongruous  observations  between  behavioural 
and  electrical  manifestations  as  there  arc  consistent  ones.  The  significance 
of  these  inconsistencies,  however,  is  at  least  as  important  as  that  of  the 
consistencies,  since  they  disclose  the  limitations  of  our  classical  methods 
of  observation. 

In  the  majority  of  our  experiments  we  are  looking  for  electrical  corre- 
lates of  well-defined  types  of  behaviour.  Sometimes,  however,  our 
attention  is  first  attracted  by  a  definite  and  consequent  electrical  change 
which  has  no  conspicuous  behavioural  correlate,  or  has  a  correlate  which 
was  concealed,  or  one  which  we  had  not  hitherto  regarded  as  important. 
Sometimes  phenomena,  which  from  a  behavioural  aspect  seem  to  be 
identical,  prove  to  be  distinct  in  the  course  of  the  electrophysiological 
investigation.  In  other  cases  the  boundary  of  well-separated  behavioural 
manifestations  becomes  indistinct  from  the  aspect  of  the  electrical  events. 
I  am  convinced  that  behind  these  discrepancies  the  possibilities  of  further 
development  lie  and  that  they  deserve  special  attention.  Let  me  demon- 
strate the  problem  with  some  concrete  observations. 

According  to  the  classical  Pavlovian  conception,  the  orientation  retlex 
represents  a  typical  unconditioned  phenomenon.  This  view  is  nowadays 
generally  accepted.  According  to  this  assumption  the  orientation  reflex 
can  easily  be  elicited  by  every  new,  unknown  stimulus.  The  essence  of  the 
reaction  consists  of  characteristic  movements  by  means  of  which  the 
animal  turns  with  all  of  his  receptors  towards  the  situation  or  the  source  of 
the  stimulus  in  order  to  ensure  a  better  acquaintance  with  it.  The  orienta- 
tion reflex  was  also  called  a  'what  is  it  reflex'  by  Pavlov.  This,  I  think, 
expresses  the  essence  of  the  reaction  better  than  its  accepted  English 
equivalent,  the  orientation  reflex,  which  does  not  imply  necessarily  the 
idea  of  motion.  Below  I  will  use  the  orientation  reflex  in  this  Pavlovian 
sense. 

1  A  part  of  this  study  was  carried  out  under  a  Fellowship  from  the  Foundations'  Fund  tor 
Research  in  Psychiatry  at  the  Department  of  Anatomy,  University  of  California  at  Los 
Angeles. 

R  243 


244  BRAIN    MECHANISMS    AND    LEARNING 

The  observations  to  be  reviewed  were  made  on  cats  with  chronically 
implanted  electrodes  during  the  elaboration  of  conditioned  alimentary 
and  avoidance  responses.  By  means  of  a  careful  analysis  of  the  motion 
pictures  taken  synchronously  with  the  electrical  recordings,  it  was 
established  that  the  orientation  reflex  was  invariably  accompanied  by  a 
series  of  characteristic  slow  potentials  (4-7  c/s)  in  the  hippocampus  and  in 
some  points  of  the  reticular  formation.  Attention  to  this  reaction  as  a 
peculiar  kind  of  archicortical  arousal  was  directed  by  Green  and  Arduini 
(1954).  According  to  our  observations,  this  theta  activity  was  an  excellent 
indicator  of  the  orientation  reflex,  since  it  invariably  and  synchronously 
appeared  with  the  orientation,  irrespective  of  whether  it  manifested  itself 
spontaneously  or  was  elicited  by  a  conditioned  stimulus. 

So  far  these  observations  do  not  represent  any  contradiction  of  the 
classic  conception.  Later,  however,  a  careful  analysis  of  the  electrical 
recordings  disclosed  a  challenging  fact.  It  turned  out  that  unfamiliar 
stimuli,  even  at  their  first  application,  elicited  neither  the  hippocampal 
slow  potentials  nor  behavioural  orientation  in  the  great  majority  of  the 
cases.  The  unfamiliar  stimuli  elicited  in  these  cases  a  desynchronization  in 
the  hippocampus  quite  similar  to  that  in  the  neocortex.  The  characteristic 
slow  potentials  did  not  appear  until  after  several  presentations  of  the 
stimulus  to  be  conditioned,  and  were  also  accompanied  by  typical 
orienting  and  searching  movements. 

From  these  consistent  observations  we  were  compelled  to  conclude  that 
the  orientation  reflex  cannot  be  an  unconditioned  phenomenon  but  must 
be  an  extremely  rapidly  developing  conditioned  manifestation.  This 
surprising  conclusion  seems  to  be  supported  by  the  long  known  fact  that 
the  orientation  reflex  can  be  easily  extinguished,  like  conditioned  but 
unlike  unconditioned  reflexes. 

On  the  basis  of  these  considerations  we  have  to  conclude  that  for  the 
elicitation  of  the  orientation  reflex,  the  stimulus  has  to  be  famihar  in  a 
certain  measure.  I  should  like  to  emphasize  the  attribute  of  the  'certain 
measure'  since  the  significance  of  the  conditioned  stimulus  at  the  time  of 
appearance  of  the  orientation  reflex  is  still  uncertain  in  the  animal.  It  has 
some  motivational  effects,  but  it  does  not  evoke  the  proper  conditioned 
reflex  yet,  or  only  with  a  very  long  latency.  In  other  words  the  animal 
performs  orientation  movements  for  the  very  reason  that  he  'does  not 
know'  the  exact  meaning  of  the  stimulus.  (What  is  it  reflex.) 

In  perfect  agreement  with  this,  it  has  been  observed  that  at  the  stage  of 
stabilization  of  the  conditioned  reflex,  when  the  conditioned  movements 
become  automatic,  both  the  hippocampal  slow  waves  and  the  orientation 


E.    GRASTYAN  245 

reflex  disappear.  In  this  stage  the  significance  of  the  stnnuhis  becomes 
'certain'  and  as  a  consequence  the  'what  is  it  reflex'  loses  its  biological 
usefulness. 

It  is  very  easy,  however,  to  regain  the  orientation  reflex  after  this  stage 
also,  if  we  make  a  slight  change  in  the  learning  situation.  This  happens 
for  example,  if  we  introduce  a  differentiating  stimulus  or  during  extinction. 
As  a  consequence  of  the  application  of  the  unreintorced  stimulus,  the  effect 
of  the  positive  stimulus  transicndy  regresses,  i.e.  it  elicits  again  the  charac- 
teristic slow  waves  in  the  hippocampus  and  the  orientation  reflex. 

At  the  time  of  stabilization  of  differentiation,  the  slow  potentials  again 
disappear  and  desynchronization  will  be  elicited  by  both  kinds  of  stimuli; 
however,  in  some  cases  when  the  differentiation  proves  to  be  too  difficult, 
remnants  of  the  slow  potentials  can  be  observed  to  the  very  last. 

The  conception  that  the  orientation  reflex  corresponds  to  a  conditioned 
phenomenon  seems  to  be  contradicted  by  the  common  experience  that 
every  new  and  unfamiliar  stimulus  is  capable  of  eliciting  the  orientation 
reflex  if  it  is  strong  enough.  However,  I  believe  that  the  problem  of 
intensity  of  the  stimulus  requires  special  consideration.  It  seems  probable 
that  with  strong  stimuli  the  conditioned  factor  is  represented  by  the 
intensity  in  itself,  which  is  independent  of  the  quality  or  the  modality  of 
the  stimulus.  The  animal  in  natural  conditions  often  meets  strong  stimuli 
signalling  danger.  The  unknown  amount  of  natural  conditioned  reflexes, 
however,  makes  it  difficult  to  decide  in  every  case  whether  a  stimulus  is 
new  or  not.  By  means  of  the  tendency  towards  generalization,  probably 
considerable  numbers  of  stimuli  become  more  or  less  familiar  to  the 
animal  m  natural  conditions.  As  a  consequence,  it  is  sometimes  very 
difficult  to  find  a  completely  indifferent  stimulus  for  a  mature  animal. 

In  asserting  that  the  orientation  reflex  represents  a  conditioned  mani- 
festation, I  have  no  intention  of  implying  that  the  unfaimliar  stimulus  has 
no  effects  at  all  at  its  very  first  application.  Disregarding  the  well  known 
electrical  reactions,  marked  somatic  reactions  can  often  be  observed  too. 
These  reactions,  however,  are  not  orientation  movements,  or  at  least  are 
not  identical  with  those  observed  following  the  reinforcement  of  the 
stimulus. 

The  most  common  effect  elicited  by  a  new  stimulus  is  the  well-known 
startle  response,  or  a  transitory  form  between  the  startle  and  orientation, 
a  quick,  phasic  movement  of  the  head  towards  the  stimulus.  The  startle 
reaction  has  aroused  the  attention  of  several  researchers  in  the  past,  and  its 
significance  m  relation  to  the  temporary  connection  has  recendy  been 
reviewed  by  Gastaut  (1957).  Let  me  give  a  short  account  of  some  of  our 


246  BRAIN    MECHANISMS    AND    LEARNING 

recent  observations  concerning  this  problem  made  in  Li-)ng  Beach  in 
collaboration  with  Drs  Lesse  and  Eidelberg. 

The  first  question  arising  here,  too,  is  whether  the  startle  response  is  an 
unconditioned  or  a  conditioned  reaction,  and  also  what  is  the  relationship 
between  the  startle  response  and  the  orientation  reflex.  I  think  that  the 
solution  of  this  problem  is  beyond  the  scope  of  a  simple  terminologic 
question.  Thus,  if  it  becomes  apparent  that  the  organization  of  these  two 
reactions  is  not  an  inborn  property  of  the  nervous  system,  then  we  are 
facing  the  two  simplest  and  most  basic  forms  of  the  learning  process,  the 
understanding  of  which  must  be  an  indispensable  condition  for  the 
approach  to  more  complex  conditioned  patterns. 

Prosser  and  Hunter  in  1936  and  later  Landis  and  Hunt  (1939)  established 
that  the  startle  response  could  easily  be  conditioned.  According  to  our 
own  observations  in  a  well-isolated,  sound-proof  experimental  situation, 
a  single  reinforcement  of  a  click  stimulus  (which  in  itself  does  not  evoke 
the  startle  response)  results  in  a  long-lasting  and  stable  conditioned 
startle  response.  The  extremely  fast  development  of  the  conditioned  startle 
response  makes  it  highly  probable  that  a  great  majority  of  the  startle 
responses  elicited  by  moderate  stimuli  through  the  telereceptors  represent 
conditioned  phenomena.  The  question  arises,  however,  whether  they 
really  represent  true  conditioned  reflexes  or  only  sensitization  phenomena, 
i.e.  a  pseudoconditioning.  It  is  known  that  repetition  of  a  strong  stimulus 
eliciting  startle  response  in  itseli  might  increase  the  general  excitability 
for  every  kind  of  stimuli  without  any  pairing  of  them  (Grether,  1938). 
In  addition  it  is  an  everyday  experience  that  in  hyperexcited  states  every 
stimulus  may  elicit  startle  responses.  The  arguments  of  Larssen  (1956), 
however,  seem  to  contradict  this  supposition. 

He  has  shown  that  the  unconditioned  stimulus  could  not  bring  about  an 
increase  of  the  response  to  the  conditioned  stimulus  unless  the  two  stimuli 
were  paired  with  a  definite  interval.  Moreover,  the  conditioned  reactions 
could  be  inhibited  differentially.  On  the  basis  of  these  observations  he 
rejects  the  explanation  of  sensitization  for  his  own  experiments.  Our  own 
observations  also  throw  doubt  on  the  hypothesis  of  simple  sensitization; 
because  no  electrical  or  behavioural  signs  of  increased  excitation  could  be 
observed  before  the  critical  second  application  of  the  conditioned  stimulus. 
The  fact  that  many  stimuli,  similar  to  the  one  reinforced,  also  elicit  the 
startle  response  is  a  consequence  rather  of  generalization  and  so  does  not 
exclude  the  true  conditioned  nature  of  these  reactions. 

For  the  correct  estimation  of  the  general  excitatory  level  of  the  CNS  or, 
better,  the  excitatorv  level  of  the  unconditioned  mechanisms  and  drives, 


E.    GRASTYAN  247 

we  have  an  excellent  indicator  in  the  rapid  (40  c/s)  oscillations  of  the  baso- 
lateral  amygdaloid  complex  discovered  by  Lesse  (1957).  In  our  experi- 
ments the  presence  of  this  activity  did  not  seem  to  be  prerequisite  for  the 
elicitation  of  the  conditioned  startle  response. 

On  the  basis  of  these  considerations  we  have  to  conclude  that,  for  the 
establishment  of  the  most  simple  form  of  the  temporary  connection,  a 
single  reinforcement  of  the  conditioned  stimulus  may  be  sufficient. 

The  extremely  rapid  development  of  the  startle  response  is  surprising 
when  compared  with  the  development  ot  the  classic  conditioned  processes. 
This  difference  suggests  that  the  conditioned  reflex,  considered  as  simple 
is  in  reality  a  very  complex  chain  ot  reflexes.  Under  natural  conditions  an 
extremely  rapid  development  of  relatively  complex  conditioned  reflexes  is 
often  observed.  From  this  it  is  obvious  that  the  conditioned  stimulus,  used 
in  general  laboratory  practice,  takes  a  highly  artificial  place  among  the 
natural  signals  which  necessarily  accompany  the  unconditioned  stimulus 
and  which  cannot  be  removed  from  the  experimental  situation.  As  a 
consequence  our  artificially  attached  conditioned  stimulus  will  represent 
a  second,  third  or  many-fold  order  signal  of  the  unconditioned  factor. 

At  the  present  time  all  the  theories  of  learning  are  based  on  the  view 
that  repetition  is  an  indispensable  condition  for  learning.  The  compelling 
evidence  presented  by  these  rapid  forms  of  learning  obliges  us  to  revise 
our  concepts,  because  they  might  require  a  very  different  explanation 
from  those  suggested  so  far.  Let  me  quote  in  this  respect  the  extremely 
clearly  defined  concept  of  Lashlcy :  'The  basic  problem  of  learning  is  what 
we  call  "incident  memory",  learning  in  one  trial.  We  have  to  seek  the 
explanation  of  learning  and  memory  somewhere  else  than  repetition.  All 
the  neurological  theories  dealing  with  the  learning  process,  that  I  have 
seen,  have  assumed  an  effect  of  repetition  on  synaptic  nerve  endings,  but 
the  fact  is  that  most  learning  does  not  involve  repetition.'  Only  one  thing 
which  I  have  to  add  to  this  as  a  small  disagreement  is,  that  incidental  and 
instant  learning  does  not  exclude  necessarily  the  existence  of  repetitive 
synaptic  events. 

The  startle  response  and  the  orientation  reflex  represent  the  earliest 
manifestations  of  the  development  of  the  temporary  connection,  or  as  I 
tried  to  make  evident,  they  represent  already  true  conditioned  manifesta- 
tions, so  that  the  investigation  of  their  intimate  neural  mechanisms  would 
have  basic  importance.  Unfortunately  in  this  respect  our  possibilities  — 
except  for  some  basic  facts  —  are  still  limited  to  speculation  and  conjecture. 

The  differences  showing  themselves  between  the  somatic  accompani- 
ments of  the  startle  and  orientation  reflex  suggest  already  highly  different 


BRAIN    MECHANISMS    AND    LEARNING 


neural  mechanisms.  The  startle  response  is  characterized  essentially  by  a 
tendency  to  generalized  flexion,  and  whereas  the  orientation  reflex  is  not 
exactly  the  contrary  of  this,  its  more  complex  nature  indicates  a  basically 
different  biological  character.  The  essential  characteristic  of  the  startle 
response  is  protective,  it  has  a  tendency  to  exclude  influences  coming  from 
the  environment,  but  in  the  orientation  reflex  on  the  contrary,  the  readi- 
ness to  accept  the  influence  is  the  most  typical. 

From  these  absolutely  contrasting  features  it  is  evident  that  the  two 
phenomena  cannot  be  regarded  simply  as  quantitatively  different  repre- 
sentatives of  an  essentially  identical  mechanism.  Supporting  evidence  is 
offered  for  this  assumption  in  the  older  literature,  according  to  which 
the  intensity  of  the  startle  response  is  not  in  a  causal  relationship  with  the 
appearance  of  the  orientation  reflex.  (Secondary  manifestations  of  the 
startle  (Strauss,  1938.))  During  the  continuous  reinforcement  of  the  con- 
ditioned stimulus  the  startle  response  progressively  decreases,  or  disappears. 
It  could  not  be  excluded  that  it  is  even  this  inhibitory  process  which  makes 
possible  the  appearance  of  the  orientation  reflex. 

According  to  earlier  observations  (Forbes  and  Sherrington,  1914)  typical 
startle  responses  could  be  observed  on  decerebrated  animals.  This  observa- 
tion clearly  shows  that  the  basic  mechanism  of  the  startle  response  is 
located  somewhere  in  the  lower  brain  stem.  It  docs  not  mean,  however, 
that  in  an  intact  animal  higher  processes  do  not  play  a  role  in  the  integra- 
tion of  the  startle  response.  This  is  supported  by  the  observation  of 
Gastaut  and  Hunter  (1950)  that  startle  responses  ehcited  by  flicker  are 
modified  by  the  removal  of  the  occipital  cortex,  further  by  the  observa- 
tions of  Haas  ct  al.  (1953)  who  established  that  the  motor  cortex  plays  a 
similarly  important  role  in  the  integration  of  experimental  myoclonus. 

Considering  that  every  kind  of  stimuli  can  be  used  for  the  conditioning 
of  the  startle  response,  its  organization  must  occur  in  a  structure  which  has 
the  capacity  to  integrate  these  stimuli.  On  the  basis  of  this  requirement  the 
reticular  formation  offers  itself  as  a  suitable  region  in  the  brain  stem 
(Moruzzi  and  Magoun,  1949;  Starzl,  Taylor  and  Magoun,  195 1;  French, 
Amerongen  and  Magoun,  1952).  This  supposition  finds  strong  support  in 
the  earlier  observations  of  Muskens  (1926)  that  lesions  of  the  medial 
reticular  formation  alone  result  in  a  permanent  disappearance  of  the  startle 
response. 

The  origin  and  nature  of  the  inhibition  of  the  startle  response  represent 
a  more  difficult  problem  than  its  primary  integration.  Adey,  Segundo 
and  Livingston  (1957)  established  the  important  fact  that  descending 
hippocampo-cortical  impulses  exert  a  profound  inliibitory  influence  on 


E.    GRASTYAN  249 

ascending  reticular  conduction.  This  nihibition  seems  to  be  mediated 
chiefly  through  the  cntorhynal  cortex  and  stria  medullaris  system  (Adey, 
Merrillees  and  Sunderland,  1956;  Adey,  Sunderland  and  Dunlop,  1957; 
Adey,  1957).  Similar  inhibitory  influence  has  been  shown  by  our  labora- 
tory (Grastyan  ct  al.,  1956,  Lissak,  ct  al.  1957).  Unfortunately  no  direct 
observations  have  been  made  in  these  experiments  on  the  startle  response. 
As  we  shall  see  later  the  inhibitory  role  of  the  hippocampus  has  to  be 
considered  in  the  inhibition  of  the  orientation  reflex  too. 

A  further  inhibitory  mechanism  which  might  be  responsible  for  the 
inhibition  of  the  startle  response  is  offered  by  the  observations  of  Her- 
nandez-Peon (195s)  and  Hernandez-Peon,  Scherrer  and  Jouvet  (1956). 
This  inhibition  seems  to  control  the  effect  of  incoming  impulses  in  the 
first  sensory  relays.  At  present,  however,  we  are  still  uncertain  about  the 
exact  structural  origin  of  this  inhibition.  Some  evidence  has  been  furnished 
that  it  originates  in  the  reticular  formation. 

An  important  inhibitory  mechanism  oi  diffuse  neocortical  origin, 
controlling  reticular  influences  on  peripheral  reflex  function,  has  recently 
been  discovered  by  Hugelin  and  Bonvallct  (1957).  This  inhibitory  mechan- 
ism has  to  be  considered  first  as  responsible  for  the  brief,  phasic  character 
of  the  startle  response.  However,  its  possible  role  in  the  extinction  of  the 
startle  response  as  well  as  its  relation  to  the  archicortical  inhibitory  mech- 
anisms mentioned  above,  remains  a  matter  of  speculation  at  the  present 
time. 

A  definite  difference  between  the  mechanisms  of  the  startle  response  and 
the  orientati(Mi  reflex  is  reflected  by  the  accompanying  electrical  manifesta- 
tions of  the  two  responses.  These  differences  are  particularly  characteristic 
in  the  hippocampus.  As  I  already  mentioned,  the  appearance  of  the 
startle  response  is  accompanied  in  the  hippocampus  by  a  desynchroniza- 
tion.  At  the  appearance  ot  the  orientation  reflex  a  marked  change  occurs; 
the  characteristic  thcta  rhythm  replaces  the  former  desynchronization.  In 
the  course  of  regular  reiniorcement  of  the  conditioned  stimulus,  the 
latency  of  the  starting  of  these  theta  potentials  gradually  shortens,  and 
finally  the  stimulus  elicits  theni  instantaneously. 

The  hippocampal  evoked  potential  undergoes  a  similar  marked  change 
during  the  develc>pment  oi  the  orientation  reflex.  At  the  time  ot  the 
manifestation  of  the  startle  response,  the  changes  of  the  amplitude  of 
the  evoked  potential  seem  to  be  rather  inconsistent;  at  the  appearance  of  the 
slow  waves,  however,  in  the  great  majority  of  cases  a  significant  decrease 
in  amplitude  or  even  disappearance  of  the  potentials  can  be  observed. 

These  marked  electrical  changes  would  suggest  that  the  hippocampus 


250  BRAIN    MECHANISMS    AND    LEARNING 

played  an  active  role  in  the  integration  of  the  orientation  reflex.  Un- 
fortunately this  cannot  be  stated  with  certainty  because  the  functional 
interpretation  of  the  otherwise  significant  electrical  happenings  is  still 
extremely  uncertain.  The  only  thing  which  can  be  established  with 
certainty  is  that  something  important  happens  in  the  hippocampus  at  the 
time  of  appearance  of  the  orientation  reflex.  Let  us  consider  what  sugges- 
tions are  offered  by  the  stimulation  experiments. 

An  orientation  reflex  most  similar  to  the  natural  one  can  be  elicited  in 
the  freely  moving  animal  by  stimulation  of  the  hypothalamus  and  reticular 
formation  (Grastyan,  Lissak  and  Kckcsi,  1957).  The  same  stimulation  is 
one  of  the  most  effective  in  eliciting  the  theta  rhythm  from  the  hippocam- 
pus (Green  and  Arduini,  1945).  Stimulation  of  the  hippocampus,  on  the 
other  hand,  effectively  inhibits  the  orientation  reflex  and  conditioned 
reflexes  (Grastyan  ct  al,  1957).  This  stimulation  is  accompanied  in  the 
contralateral  hippocampus  by  a  clear-cut  desynchronization.  From  these 
observations  it  would  follow  that  during  the  appearance  of  the  rhythmic 
slow  waves  the  function  of  the  hippocampus  is  inhibited.  These  observa- 
tions, together  with  the  fact  that  the  orientation  reflex  disappears  at  the 
stabilization  of  the  conditioned  reflex  and  at  the  same  time  a  desyn- 
chronization (presumably  representing  a  more  active  state)  takes  place  in 
the  hippocampus,  would  suggest  that  the  hippocampus  inhibits  the 
orientation  reflex.  Since  the  inhibition  of  the  orientation  reflex  is  a 
necessary  condition  for  the  final  stabilization  of  the  conditioned  reflex, 
this  inhibitory  function  would  provide  the  hippocampus  with  a  role  in 
proportion  to  its  morphological  importance. 

This  supposition  is,  however,  valid  only  if  the  interpretation  of  the 
electrical  events  and  the  behavioural  effects  elicited  by  stimulation  of  the 
hippocampus  are  correct. 

An  inhibitory  function  oi  the  hippocampus  is  suggested  by  some  interes- 
ting observations  of  John  and  Killam.  These  authors  observed  that  during 
the  presentation  of  a  negative  conditioned  stimulus  (repetitive  flicker) 
definite  following  can  be  observed  with  a  predominance  in  the  hippo- 
campus ;  while  during  the  presentation  of  the  positive  stimulus  (which  is 
of  the  same  modality  as  the  negative  one,  differing  only  in  frequency)  no 
following  can  be  recorded  in  the  hippocampus. 

Our  own  observations  concerning  the  disappearance  or  decrease  of  the 
hippocampal  evoked  potentials  during  the  presence  of  the  slow  waves 
seem  to  offer  adciitional  supporting  evidence.  The  decrease  in  the  evoked 
potential  might  be  an  expression  of  the  inhibited  state  of  the  elements 
responsible  for  the  evoked  activity. 


E.    GRASTYAN  25I 

Unfortunately  we  have  very  little  and  incomplete  information  about 
the  importance  of  the  diffuse  thalamic  projection  system  in  the  elaboration 
of  the  startle  response  and  orientation  reflex.  Recently  Eidelberg  (1959) 
made  an  important  observation  that  a  lesion  of  the  centrum  medianuni 
irreversibly  eliminates  the  possibility  of  eliciting  the  hippocampal  rhyth- 
mic slow^  potentials.  According  to  this  observation  the  role  of  the  thalamus 
is  crucial  in  the  control  of  hippocampal  function.  Unfortunately,  no  direct 
observations  arc  available  concerning  the  effects  of  this  lesion  on  the 
startle  response  and  orientation  reflex. 

The  greatest  difficulty  is  found  at  the  present  time  in  understanding  the 
mechanism  responsible  for  the  transition  of  the  startle  response  to  the 
orientation  reflex  and  the  orientation  reflex  to  the  proper  conditioned 
reflex.  When  we  consider  that  the  most  dramatic  electrical  changes  during 
this  period  of  time  can  be  observed  in  the  hippocampus,  it  seems  vcrv 
probable  that  the  solution  to  these  questions  is  more  or  less  identical  with 
the  understanding  of  the  generation  of  the  hippocampal  slow  potentials. 

In  reviewing  the  above  facts  my  first  intention  was  to  demonstrate  the 
highly  complex  nature  of  the  manifestations  preceding  the  establishment 
of  the  most  simple  conditioned  reflex.  I  am  convinced  that  for  the 
approach  to  the  neural  mechanisms  of  conditioning,  an  inescapable 
requirement  would  appear  to  be  the  breakdown  of  the  learning  process 
into  its  most  elementary  components,  as  was  necessary  in  research  on  the 
spinal  cord.  That  is  the  only  way  in  which  we  may  secure  a  more  exact 
correlation  between  electrical  and  behavioural  phenomena. 

GROUP   DISCUSSION 

MoRRELL.  Dr  Fcssard  has  asked  nic  to  begin  the  discussion  ot  Dr  Grastyaia's 
report  and  to  present  some  ot  the  material  partially  reported  at  the  Moscow 
symposium  and  which  has  not  \et  appeared  in  print.  Some  of  this  material  agrees 
beautituUy  with  that  now  before  us  and  may  serve  to  underscore  the  lack  of 
behavioural  correlation  with  some  clcctrographic  criteria  of  conditioning  and 
perhaps  indicate  in  some  measure  why  this  is  so.  In  addition  I  think  we  can  illustrate 
some  features  ot  hippocampal  participation  in  the  conditioning  process. 

As  Dr  Grastyan  has  so  well  pointed  out,  it  has  been  dirticult  to  assign  specific 
excitatory  or  inhibitorv  connotations  (with  reference  to  cell  discharge)  to  the 
electrical  activity  recorded  with  large  electrodes  from  various  ganglionic  regions. 
This  is  perhaps  one  ot  the  more  important  reasons  for  the  great  ambiguity  in 
relating  the  previously  discovered  electrical  signs  o(  conditioning  to  any  aspect  of 
behavioural  learning.  Causallv  related  interactions  between  various  levels  of  the 
central  nervous  system  as  well  as  the  degree  of  participation  of  these  elements  in 
the  total  integrated  response  are  probablv  better  expressed  as  changes  in  a  rate  of 
unit  discharge  than  in  terms  of  the  slow  oscillations  reflecting  dendritic  polariza- 
tions. Because  the  latter  may  be  non-propagated,  they  are  perhaps  less  likely  to 


252  BRAIN    MECHANISMS    AND    LEARNING 

LA-R  Triol    I  Robbii  m3   4-28   58 


RA-R 


— L_ 


LVis  (Bp) 
RVis  (Bp) 


Triol  19 


^N/w^vYVW^^V 


'- — - — ■ — -~--Ay\/\jyyyif"//v'^/\/^  v — « — ^ 


Trial  42 


'^f^{,'{j^yWiJVM\lJ'/'^ 


-s>A'u\AAnvjWVV.^^/VV\'\,V% 

Fig.  I 

Sample  conditioning  trials  illustrating  responses  before 
conditioning  (Trial  i),  repetitive  response  (Trial  19), 
and  localized  desynchronization  of  Stage  III  (Trial  42). 
Desynchronization  is  barely  visible  because  of  the  low 
amplifier  gain  necessitated  by  simultaneous  tape  re- 
cording. The  repetitive  response  of  Stage  II,  however, 
is  clearly  evident.  Equally  evident  is  the  lack  of  re- 
petitive response  in  Stage  III.  The  signal  channel  (S) 
indicates  by  the  first  deflection  the  onset  of  the  con- 
ditional acoustic  signal.  A  photoelectrical  cell  records 
the  light  flashes  superimposed  on  the  signal  channel 
and  the  final  deflection  indicates  the  cessation  of  tone. 
The  onset  of  the  tone  precedes  the  light  by  2  seconds 
and  is  continuous  with  it  for  a  further  5  seconds,  both 
signals  going  off" together.  This  convention  is  followed 
in  the  succeeding  figure  as  well.  Calibration:  200 
microvolts  and  i  second.  Channel  designations  are 
as  follows:  left  auditory  to  reference,  right  auditory  to 
reference,  signal,  left  visual  (bipolar),  right  visual 
(bipolar),  left  visual  to  right  visual,  left  visual  to 
reference,  right  visual  to  reference.  The  electrodes 
were  implanted  over  the  respective  cortical  regions 
prior  to  this  examination.  The  animal  is  unanaesthctized 
but  restrained  in  a  comfortable  hammock.  (From 
Morrell,  Barlow,  and  Brazier.  Analysis  of  conditioned 
repetitive  response  by  means  of  the  average  response 
computor.  Biolo^icnl  Psych'uitry.  In  Press.) 


E.    GRASTYAN  253 

influence  other  neuronal  systems.  Our  use  of  niicroelectrodes  implanted  in 
cortical  and  subcortical  regions  was  designed  to  evaluate  relationships  in  unit 
discharge  characteristics  of  these  structures  during  the  course  of  a  developing 
conditioned  response. 

In  previous  studies  (Morrell  and  Jasper,  1955;  MorrcU,  1957)  we  have  described 
the  historical  development  of  electrocerebral  conditioning  to  combinations  of 
sound  and  intermittent  light  as  consisting  of  three  stages.  The  first  evidence  of 
conditioning  is  manitested  by  a  generalized  desynchronization  produced  by  the 
conditioned  stimulus  in  all  cortical  derivations.  Next  there  is  a  brief  transitory  stage 
when  the  conditioned  stimulus  evokes  a  repetitive  response  which  is  at  or  close  to 
the  frequency  of  the  imposed  stroboscopic  light  it  that  frequency  is  within  the 


Robbit  M3        5-1-58 


B 


'"^^'^--^-V 


T  Noise 

Fig.  2 

Recurrence  of  repetitive  response  in  Stage  III  after  adventitious  noise.  Note  that  the  noise 

itself  may  elicit  rhythmic  discharge  (B).  Cahbration:  200  microvolts  and  i  second. 

range  of  3-12  per  second.  The  third  stage  is  characterized  by  localized  desyn- 
chronization in  visual  derivations  elicited  h\  the  acoustic  conditioned  stimulus. 
Since  this  discussion  was  not  foreseen,  I  have  not  brought  adequate  illustrations 
of  all  of  these  stages  for  demonstration.  However,  some  features  may  be  illustrated 
by  examples  from  a  study  on  cortical  conditioning  carried  out  with  Dr  Barlow 
and  Dr  Brazier  of  the  Massachusetts  General  Hospital  and  the  Massachusetts 
Institute  of  Technology.  Fig.  i  provides  two  bits  of  pertinent  information.  If 
attention  is  directed  to  the  tracing  labelled  trial  19,  one  may  see  a  good  example 
of  the  repetitive  response  to  an  acoustic  stimulus.  This  is  the  pattern  characteristic 
of  Stage  II  of:  the  conditioning  procedure.  In  the  tracing  labelled  trial  42  all  trace 
of  the  conditioned  repetitive  response  has  disappeared,  to  be  replaced  by  the 


254  BRAIN    MECHANISMS    AND    LEARNING 

localized  dcsynchronization  characteristic  of  Stage  III.  The  latter  cannot  be  clearly 
seen  in  this  figure  because  the  gain  has  been  greatly  reduced  in  order  to  avoid 
blocking  of  the  amplifiers  in  a  tape  recorder  ted  through  the  EEG  machine  by  the 
high  voltage  transients. 

INITIAL  PRESENTATION 


Vis.  Cortex  %*«^*^  **^JPr  • 

ucs 


cs 


Vent.  Ant.  .    ,     . 

UCS 


cs 


Mes.  Ret. 


UCS 


cs 


Hippocampus 


CS 


Fig.  3 
Simultaneous  microelectrode  records  from  the  cortex  and  subcortical  regions  in  a  cat  during 
clectroccrebral  conditioning.  Onset  of  the  conditioned  stimulus  (tone  500  cycles  per  second) 
is  indicated  by  the  first  widening  of  the  signal  channel.  Onset  of  the  unconditioned  stimulus 
(intermittent  light  10  per  second)  is  indicated  by  the  second  widening  of  the  signal  channel. 
This  convention  applies  to  all  the  microelectrode  figures.  The  derivations  also  apply  to  the 
same  figures  and  they  are  all  tracings  from  the  same  animal. 

In  the  light  of  Dr  Grastyan's  comment  that  the  slow  rhythms  in  the  hippocampus 
may  be  caused  to  reappear  by  a  change  in  the  stimulus  situation  after  they  have 
disappeared,  I  might  add  that  we  have  observed  a  similar  phenomenon  with 
respect  to  the  slow  waves  wliich  constitute  the  Stage  II  response.  If,  during  Stage 


E.    GRASTYAN  255 

HI,  when  the  repetitive  response  had  completely  disappeared,  an  extraneous  noise 
is  introduced  into  the  experimental  room,  a  prompt  reappearance  of  the  condi- 
tioned repetitive  response  to  the  acoustic  signal  may  be  observed  on  the  very  next 
conditioning  trial  (Fig.  2).  Indeed  the  noise  itself  may  elicit  some  vestige  of  these 
slow  rhvthms  (Fig.  2b).  Our  repetitive  response  is  derived  from  cortical  rather  than 
hippocampal  regions,  but  it  may  have  a  significance  similar  to  that  envisaged  by 

HABITUATION 


Vis.  Ceirtex 


CS 


Vent.  Ant.         ^(^'^'^\^^^.^^^,^J^'f^^^ 


CS 


Mes.  Ret.         '^'•■•K^jiM^'^  nT-  ^-^-  ^-NvV-ArNAv-*^'^-f""^  "t^  ■ 


CS 


Hippocampus 


CS 


Fig.  4 
Pattern  of  response  after  habituation.  (See  text  for  further  explanation.) 

Dr  Grastyan.  The  relationship  of  these  stages  to  behavioural  learning  is  not  fully 
understood  although  there  is  some  evidence  that  the  Stage  II  repetitive  response  is 
not  adequate  for  behavioural  transfer  (Chow,  Dement  and  John,  1957)  while 
Stage  III  or  localized  desynchronization  ma}-  be  correlated  with  a  motor  response 
(Morrell  and  Jasper,  1956;  Gastaut  cr  al,  1957). 

The  initial  microelectrode  investigation  involved  a  survey  of  unit  discharge  in 
various  subcortical  nuclei  compared  with  stages  in  the  evolution  of  the  conditioned 


256  BRAIN    MECHANISMS    AND    LEARNING 

clcctroccrcbral  response.  The  stages  were  defined  b\-  changes  in  the  surface 
electrical  activity  according  to  the  scheme  just  outlined.  Simultaneous  recordings 
were  made  from  the  visual  cortex,  nucleus  ventralis  anterior  of  the  thalamus,  the 
periaqueductal  portion  of  the  mesencephalic  reticular  system,  and  the  hippocampus. 
The  signal  stimuli  were  bright  intermittent  light  (UCS)  and  low  intensity  pure 
tone  (CS)  delivered  in  the  same  pattern  as  illustrated  in  the  previous  figures,  except 

STAGE  I 


Vis.  Cortex  *^, 

UCS 


'mm>,Ji$^lt^^llfm0^ 


CS 


Vent.  Aiit.  .y-  fft^f'-\' 

UCS 


CS 


Mes.  Ret. 

UCS 


CS 


Hippocampus  „^^  ^,.,  „  ..«».,^«4»^^^J,*^, 

UC^ 

CS 


Fig.  5 
Pattern  of  response  during  Stage  I  of  the  conditioning  prticedure.  (See  te.xt  for  further 

explanation.) 

that  the  duration  was  shortened  so  that  the  entire  trial  could  be  included  on  a 
single  sweep  of  the  oscilloscope.  Thirty-tour  animals,  both  cats  and  rabbits,  were 
used.  All  observations  were  made  during  acute  experiments.  Ether  anaesthesia 
was  used  for  tracheotomy  and  craniotomy.  Animals  were  immobilized  under 
Flaxedil  and  placed  in  the  Horsley-Clarke  stereotaxic  instrument  after  injection 
of  procaine  into  points  ot  pressure  and  contact.  Tungsten  microelectrodes  of  the 


E.    GRASTYAN  257 

type  dcsitrncci  by  Hubcl  (1957)  with  a  tip  diameter  ot  1-5  [X  were  used.  For  sub- 
cortical recordings  these  electrodes  were  encased  in  a  glass  micro-pipette  in  order 
to  avoid  damage  to  the  needle  tip.  The  electrodes  were  connected  to  capacity- 
coupled  amplifiers  having  a  moderatcK'  long  time-constant  (0.04  seconds)  so  that 
some  slow"  components  could  be  visualized.  Attempts  were  made  to  use  DC 
recording  for  simultaneous  observation  ot  steady  potential  states  but  we  were 

STAGE  II 


Vis.  Corte.x  '  #^^^^4^*^*^^ 

ucs 


cs 


Vent.  Ant.        -^./yiA/y ■^,' 

UCS 


cs 


Mes.  Rot.         •    ^-^^-^.j,y.A  4^^-A,A^ - 

UCS 


cs 


Hippocampus      ^    t<>>Jw*4iiniiiii  ii»>iii<jwi»il>i#*ik^j^«i||ijk|ii<i<|  1  ii-l^**^^ 

^  UCS 


cs 


Fig.  6 
Pattern  of  response  during  Stage  II  of  the  conditioning  procedure.  (See  te.\t  for  further 

explanation.) 

usuallv  unsuccesstid  in  resolving  single  units  with  that  method.  Indeed,  even 
capacity-coupled  amplification  did  not  always  provide  discrete  resolution. 
Nevertheless,  the  recording  system  was  adequate  to  determine  the  presence  or 
absence  or  change  in  frequencv  ot  unit  discharge  at  the  sites  sampled  and,  in 
many  cases,  individual  units  were  clearly  identified.  Most  ot  you  are  aware  of  the 
tremendous  technical  diiliculties  one  faces  in  attempting  to  record  simultaneously 


258  BRAIN    MECHANISMS    AND    LEARNING 

from  several  inicroclcctrodcs  and  will  bear  with  us  in  these  early  faltering  steps. 
The  results  must  be  viewed  as  only  first  order  approximations  since  adequate 
statistical  analysis  awaits  the  accumulation  of  more  data  with  the  use  of  multiple 
microelectrodes  concurrently  sampling  the  same  cellular  population. 

As  soon  as  conditioning  trials  were  begun,  it  was  obvious  that  there  was  wide 


STAGE  III 


Vis.  Cortex 


'"******"^^''wfTP(WiflM||PI|Pf|^^ 


ucs 


cs 


Vent.  Ant.        -h.,^..  ....  ^U.., .  ..,,^,v'^^f^>^^V>w.  wt|f^f^^ 

UCS 

CS 


Mes.  Ret. 


Fig.  7 

Pattern  of  response  during  Stage  III  of  the  conditioning  procedure.  (See  text  for  further 

explanation.)  Cahbration:  250  msec. 

variation  in  the  pattern  of  unit  discharge  to  both  conditioned  and  unconditioned 
stimuli.  This  was  true  even  of  different  but  adjacent  units  in  the  same  ganglionic 
grouping  within  any  given  stage  of  the  conditioning  procedure.  For  this  reason 
the  results  to  be  demonstrated  can  be  considered  valid  only  in  a  rough  statistical 
sense.  For  example,  we  define  'increased  firing'  as  meaning  that  more  than  50  per 


E.    GRASTYAN 


259 


cent  of  the  units  recorded  in  a  given  area  at  a  given  stage  ot  conditioning  showed 
an  increase  in  discharge  frequency.  The  foUov^^ing  figures  are  taken  from  a  cat  in 
which  the  sequential  pattern  to  be  described  was  particularly  prominent. 

On  the  initial  presentation  of  the  signal  stimuli  before  conditioning  (Fig.  3)  the 
visual  cortex  is  observed  to  respond  only  to  the  unconditioned  stimulus,  i.e. 
intermittent  light.  Units  in  ventralis  anterior  did  not  respond  cither  to  the  condi- 
tioned or  to  the  unconditioned  stimulus,  whereas  units  in  the  mesencephalic 
reticular  formation  responded  with  increased  discharge  to  both  stimuli.  At  this 
stage  units  in  the  hippocampus  were  observed  to  respond  only  to  the  unconditioned 
stimulus.  Habituation  trials  were  then  carried  out  in  which  the  conditioned  stimulus 
was  presented  repeatedly  without  reinforcement.  Habituation  was  considered 
complete  when  no  change  in  unit  discharge  occurred  in  any  area  on  presentation 
of  the  conditioned  stimulus  (Fig.  4).  Paired  trials  were  then  reintroduced  until  the 


L  Mot   -L  Som   S«n5 


STAGE   III 
Mot    -L  Sotn  S«ftl 

Som  5«ns  -  L  Aud 


UWUM"M'l!jJ^- 


L   4ud    -  L  Vis 

^'.V.V>\\V.'',V.M'.V,V.'.V,'vV*'i-' — ■• 

<.VA^/w^'■^;5'■''','*'^'•  - 

R^d  -RSomS^os     '  '  „  V,    R   IVu« 

B  Som  Sens  -H  Moi  R  lud  -  R   Mol 


Fig.  8 


Examples  of  EEG  tracings  from  surface  cortical  electrodes  for  each  of  three  stages  of  electro- 
cerebral  conditioning.  Unanaesthetized  animal.  Derivations  are  from  implanted  electrodes  at 
the  sites  indicated.  First  upward  deflection  on  the  signal  channel  indicates  onset  of  soo  c/sec. 
tone.  A  photocell  records  the  stroboscopic  flashes  superimposed  upon  the  signal  line.  The  final 
downward  deflection  indicates  cessation  of  tone  and  light.  Calibration :  50  uV  and  i  second. 


first  signs  of  conditioning  were  observed,  hi  Stage  I  (Fig.  5)  which  was  character- 
ized by  generalized  desynchronization  in  the  cortical  surface  tracing,  units  in  the 
visual  cortex  responded  to  both  the  conditioned  and  unconditioned  stimulus.  Units 
in  the  ventralis  anterior  showed  no  change  in  response  to  the  conditioned  stimulus 
but  had  now  developed  distinct  increase  in  discharge  frequency  to  the  uncondi- 
tioned stimulus.  Units  in  the  mesencephalic  reticular  system  again  responded  to 
both  stimuli.  At  this  stage,  however,  it  was  noted  that  hippocampal  discharge 
occurred  in  response  to  the  conditioned  stimulus  as  well  as  the  unconditioned 
stimulus.  Stage  II  (Fig.  6),  characterized  by  the  appearance  of  a  repetitive  response 
in  surface  cortical  tracings,  was  correlated  with  suppression  of  discharge  in  the 
visual  cortex  when  the  conditioned  stimulus  was  presented  and  also  in  ventralis 
anterior  during  presentation  of  both  of  the  signal  stimuli.  Spontaneously  firing 
units  in  the  mesencephalic  reticular  formation  were  also  suppressed  by  both  stimuli, 
while  in  contrast,  those  of  the  hippocampal  formation  were  increased  in  discharge 
frequency  during  both  conditioned  and  unconditioned  signals.  The  development 
of  Stage  in  (Fig.  7)  was  defined  by  the  appearance  oi  desynchronization  limited  to 
S 


26o 


BRAIN    MECHANISMS    AND    LEARNING 


visual  cortex  derivations.  Unit  discharge  in  the  visual  cortex  was  observed  to 
increase  upon  the  presentation  of  both  conditioned  and  unconditioned  stimuli  and 
the  same  augmented  response  to  both  signals  was  noted  in  a  spontaneously  firing 
unit  of  nucleus  ventralis  anterior.  Units  in  both  the  mesencephalic  reticular 
formation  and  the  hippocampus  no  longer  responded  to  cither  stimulation  nor  did 
any  further  responses  develop  even  when  trials  were  continued  to  as  many  as  one 
hundred. 

Table  I 

PATTERN    OF    UNIT    DISCHARGE    DURING    DEVELOPMENT 
OF    CONDITIONED    ELECTRICAL    RESPONSE 


Respome  to: 

CS 

UCS 

0 

Visual  Cortex 

t 

Initial 

0 

Vent.  Ant. 

0 

presentation 

t 

Mes.  Retic. 

t 

0 

Hippocampus 

t 

Habituation* 

0 

Visual  Cortex 

0 

Vent.  Ant. 

0 

Mes.  Retic. 

0 

Hippocampus 

t 

Visual  Cortex 

t 

Stage  I 

0 

Vent.  Ant. 

-. 

(Trial  32) 

■■ 

Mes.  Retic. 

t 

Hippocampus 

• 

Visual  Cortex 

t 

Stage  II 

Vent.  Ant. 

t 

(Trial  39) 

,, 

Mes.  Retic. 

Hippocampus 

t 

t 

Visual  Corte.x 

t 

Stage  III 

Vent.  Ant. 

t 

(Trial  78) 

0 

Mes.  Retic. 

0 

0 

Hippocampus 

0 

*  Relay  nuclei  in  Auditory  System  not  monitored. 
I    >  50  per  cent  increased  firing, 
i    >  50  per  cent  decreased  firing. 
o  No  change. 

Table  I  presents  a  summary  of  these  data.  The  findings  suggest  that  some  sequen- 
tial pattern  of  involvement  does  indeed  exist.  However,  the  interplay  of  these  gang- 
lionic systems,  if  changes  in  one  can  be  assumed  to  be  related  to  changes  in  any 
other,  does  not  provide  evidence  of  any  one-to-one  relationship  such  that  excita- 
tion of  one  area  can  be  assumed  always  to  inhibit  or  activate  another  area.  For 
example,  the  proposal  of  Lissak  and  Grastyan  (1957)  that  the  hippocampus  exerts 
an  inhibitory  influence  on  the  ascending  reticular  activatiiiir  svstem  is  borne  out 


E.    GRASTYAN  261 

only  in  a  record  ot  Stage  II.  In  Stage  1  both  mesencephalic  reticidar  formation  and 
the  hippocampus  show  increased  discharge.  Thus  the  relation  between  hippo- 
campal  and  reticular  discharge  could  not  be  described  as  reciprocally  inhibitory 
but  rather  changed  with  change  in  stage  of  conditioning.  On  the  other  hand,  the 
evidence  does  support  the  contention  of  Gastaut  (1958)  and  Yoshii  (1957)  that 
participation  of  elements  in  the  thalamic  reticular  system  is  essential  for  the  fmal 
development  of  a  conditioned  response  and  that  some  form  of  thalamo-cortical 
linking  forms  the  substrate  of  a  iully  developed  learned  response.  As  Dr  Grastyan 
has  already  noted,  our  results  as  well  as  his  own,  tend  to  support  the  impression  of 
John  and  Killam  (1959)  with  respect  to  the  particular  role  of  the  hippocampus  in 
the  early  stages  of  conditioning. 

In  different  ways  it  would  appear  that  both  hippocampus  and  mesencephalic 
reticular  formation  are  concerned  in  the  initial  steps  which  determine  what  events 
will  or  will  not  become  crystallized  as  engram.  In  no  case  where  this  entire  sequence 
has  been  observed  did  the  thalamo-cortical  linkage  appear  without  prior  activity 
in  hippocampal  and  mesencephalic  systems.  Of  particular  interest  was  the  fact  that 
definite  inhibitory  sequences  were  always  evident  (in  the  form  of  suppression  of 
resting  unit  discharge)  in  the  course  of  acquisition  of  the  simple  positive  temporary 
connection.  The  fact  that  these  inhibitory  unit  events  were  highly  correlated  with 
the  development  of  the  so-called  frequency-specific  repetitive  response  in  the 
gross  surface  electrical  tracing  may  help  explain  the  lack  of  correlation  between 
this  particular  electrical  manifestation  and  behavioural  transfer. 

It  may  well  be  that  these  conditioned  changes  in  discharge  patterns  of  single 
nerve  cells  are  a  different  order  of  phenomenon  from  that  understood  as  be- 
havioural learning.  Yet  it  would  seem  that  ultimately  alterations  in  behaviour  of 
the  total  organism  must  be  related  in  some  way  to  changes  in  behaviour  of  nerve 
cells.  It  is  in  this  sense  and  in  this  context  that  we  believe  that  we  can  demonstrate 
learning  (defined  as  a  change  in  discharge  frequency  consistently  related  to  an 
experimentally  imposed  signal  pattern)  in  single  cells  of  the  central  nervous  system. 

JouvET.  Dr  Grastyan,  I  agree  with  you  that  extinction  of  the  orientating  reflex 
may  come  from  some  upper  level.  I  have  also  been  studying  extinction  of  orienta- 
tion reflex  in  chronic  decorticate  cats  and  in  chronic  mesencephalic  cats.  I  could 
never  habituate  the  startled  response  in  decerebrated  animals.  Sometimes  after  as 
many  as  800  stimuli  I  still  obtained  startled  responses.  Concerning  decorticate  cats 
but  with  paleocortex  remaining,  I  could  not  get  a  true  extinction  of  orientation 
reflex  and  in  other  cats  after  removing  the  frontal  lobes  I  found  that  this  also  would 
cause  a  disturbance  in  the  extinction  of  the  orientation  reflex.  I  expect  to  show  that 
this  inhibitory  influence  may  come  mainly  from  the  neo-cortex  and  from  the 
frontal  lobes.  I  think  this  is  in  agreement  with  Dr  Konorski.  But  of  course  there 
must  be  some  relationship  between  the  hippocampus  structure  and  the  diffuse 
thalamic  nuclcii.  I  feel  that  the  cortex  is  absolutely  necessary,  at  least  some  part  of 
it,  for  this  inhibition  ot  the  orientation  reflex. 

Hebb.  One  of  the  things  that  arouse  orientation  is  the  'strange'  object.  But  it  is 
not  one  that  has  never  been  presented  before.  It  acquires  its  capacity  to  arouse. 
This  is  seen  clearly  in  Riesen's  chimpanzees  reared  in  darkness.  The  visual  event  in 
the  form  of  a  light  flash,  would  produce  a  startle  response;  but  otherwise  the  visual 
event,  which  by  definition  was  strange,  had  no  capacity  at  all  to  produce  an  orienta- 
tion reflex.  The  tenor  of  Dr  Grastyan's  paper  is  that  we  need  pay  attention  to  the 


262  BRAIN   MECHANISMS    AND    LEARNING 

histor\-  ot  the  stimulus  when  we  apply  it  to  the  animal  and  I  think  this  should  be 
extended  also  to  his  comment  about  immediate  learning,  rapid  one-trial  learning, 
in  the  higher  species.  It  is  a  different  matter  in  the  lower  species  —  in  the  higher 
species  it  is  not  done  with  unfamiliar  material.  You  are  dealing  with  something 
that  has  a  long  history,  as  tar  as  the  elements  of  the  response  are  concerned.  One 
weakness  of  manv  investigations  of  learning  is  their  disregard  of  the  past  naturalistic 
history  of  the  animal.  The  study  of  learning  without  regard  to  the  past  history  of 
the  animal  is  totally  unrealistic. 

Palestini.  I  want  to  add  some  observations  regarding  the  pretrigeminal  pre- 
paration, that  is  to  say,  a  cat  with  a  midpontine  transsection.  These  cats  remain 
permanently  awake.  There  is  a  desynchronized  activity  of  the  cortex  and  they 
present  ocular  vertical  movements  of  the  eyes.  We  believe  that  these  movements 
are  purposeful,  because  when  a  mouse  is  presented  to  the  cat,  the  cat  follows  it  with 
its  eyes.  These  movements  are  maintained  during  the  whole  period  of  stimulation 
by  the  passing  object.  This  contrasts  with  the  normal  intact  cats.  We  think  that  in 
the  lower  pons  and  medulla  there  exist  inhibitory  structures,  which  exert  an 
ascending  inhibition  towards  higher  levels.  We  believe  that  lower  structures  also 
must  be  taken  into  account  in  explaining  all  the  inhibitory  phenomena. 

Gerard.  I  wanted  to  talk  on  the  same  subject  as  Dr  Hebb.  Dare  one  draw  the 
conclusion  that,  because  a  single  event  has  led  to  a  permanent  trace,  this  excludes 
the  need  of  some  continued  activity  to  produce  morphological,  chemical  and 
other  changes  in  the  neurone  pattern?  A  single  impulse  may  continue  to  cause 
activity,  by  reverberation  or  other  mechanisms,  for  very  long  times.  This  has  been 
demonstrated  by  sending  brief:  stimuli  to  several  centres,  which  then  continue 
discharging  tor  months.  Further,  there  is  a  continued  dynamic  state,  with  responses, 
memories,  etc.,  which  is  still  quite  different  from  the  permanent  structured  en- 
gramme  which  is  established  and  endures  long  after  the  dynamic  memory  has 
gone.  The  fact  that  one  can  get  a  permanent  change  after  one  stimulus  does  not 
exclude  the  reverberation  type  of  mechanism  in  establishing  fixation. 

Chow.  We  have  prepared  cats  with  lesions  in  the  n.  centrum  medianum  bilater- 
ally and  these  cats  have  been  presented  with  learning  problems  before  lesion.  After 
lesion  they  can  still  remember  these  problems. 

Segundo.  It  appears  to  me  that  Dr  Grastyan  made  a  distinction  between  'orienta- 
tion' and  'startle'  responses.  Does  he  believe  the  difference  to  be  qualitative  or 
simply  quantitative  in  the  sense  that  they  constitute  different  intensities  of  response 
to  novel,  or  significant  stimuli. 

Hernandez-Peon.  Have  you  done  any  lesion  experiments  on  the  hippocampus 
and  observed  the  effect  on  the  extinction  of  orientation  reflex? 

Grastyan.  I  think  that  Dr  Morrell's  observations  are  partly  in  agreement  with 
my  own  —  namely  the  second  stage  in  which  the  big  increase  ot  unit  discharge  is 
observed  in  the  hippocampus  and  disappearance  of  unit  discharge  in  the  reticular 
formation.  There  seems  to  be  a  discrepancy  concerning  the  first  stage  when  both 
structures  show  an  increase  in  firing.  Unfortunately  we  don't  know  the  relation- 
ship of  this  firing  to  the  gross  electrical  recording  and  the  behaviour  manifestations. 
Perhaps  this  is  a  transitory  stage  in  which  both  structures  were  activated.  In  the 
third  phase  —  and  this  would  be  an  answer  to  Dr  Hernandez-Peon  as  well,  the  unit 
activity  in  the  hippocampus  disappeared  completely  —  which  might  correspond 
to  the  picture  we  got  during  the  final  phase  of  extinction,  when  the  stimulus 


E.    GRASTYAN  263 

ceased  to  elicit  changes.  I  agree  with  Dr  Jouvct  that  after  decortication  ot  the 
animal  the  extinction  of  the  orientation  reflex  becomes  very  ditiicult.  We  made 
exactly  the  same  observation  after  extirpation  ot  both  hippocampi.  The  animal 
can  still  learn,  but  yon  cannot  extinguish  its  orientation  reflex  —  it  remains  always 
the  orientation  reflex  which  mediates  the  final  act. 

BuSER.  I  wonder  if  Dr  Grastyan  could  give  us  some  more  details  about  l^r 
Eidelbcrg's  experiments  on  coagulation  of  centre  median.  What  was  the  behaviour 
of  those  animals?  My  question  is  in  connection  with  the  observation  made  on  one 
animal  with  very  large  bilateral  destruction  of  the  medial  thalamus  (including 
centre  median):  this  animal  would  show  strong  orientation  as  well  as  startle 
reactions. 

Grastyan.  Dr  Eidelberg's  experiments  were  carried  out  on  the  rabbit.  After 
bilateral  lesion  of  the  centre  median  —  the  slow  potentials  irreversibly  disappeared 
euiirely  from  the  hippocampus.  In  some  cases  after  unilateral  lesion  it  disappeared 
on  the  same  side. 

BusER.  What  about  behaviour; 

Grastyan.  He  did  not  make  any  observations  on  behaviour. 

RosvoLD.  It  is  comforting  to  hear  of  these  electrical  eliects  because  they  help  to 
explain  the  findings  that  human  memory  is  affected  by  hippocampal  damage,  and 
that  the  monkey  with  hippocampal  damage  has  dirticultv  in  solving  problems 
involving  memory. 


BEHAVIOURAL  AND  EEG  EFFECTS  OF  TONES 
'REINFORCED'  BY  CESSATION   OF   PAINFUL   STIMULF 

J.  P.  Segundo,  C.  Galeano,  J.  A.  Sommer-Smith  and  J.  A.  Roig 


Major  contributions  to  the  neurophysiology  of  learning  have  issued  from 
the  study  of  so-called  'signal  responses'  established  by  way  of  systematic 
association  of  two  stimuli  (one  indifferent,  one  effective),  a  combination 
leading  frequently  to  a  change  in  responses  provoked  by  the  former 
(Anokhin,  1957;  Pavlov,  1941).  In  most  work,  initiation  of  the  indifferent 
(later  conditioned)  stimulus  IS  was  followed,  after  a  brief  interval,  by 
initiation  of  the  absolute  excitation  AS  (Fig.  lA).  It  has  been  suggested 
and/or  established  that  other  combinations  also  are  useful:  for  instance, 
tone  cessation  —  pain  initiation  (Fig.  iB),  tone  initiation  —  cessation  of 
eating,  etc.  (Galeano,  Roig,  Segundo  and  Sommer-Smith,  1959;  Konorski, 
1948;  Rowland,  1957;  Segundo,  Roig  and  Sonnner-Smith,  1959; 
Zbrozyna,  1958;  Zeleny  cited  by  Pavlov,  1951).  In  the  present  series,  a 
brief  indifferent  tone  was  systematically  followed  by  cessation  of  a  pro- 
longed painful  stimulus  SS  (Fig.  iC) :  this  routine  was  capable  of  inducing 
a  learning  process  and  animals  came  to  respond  bchaviourally  (in  a 
manner  similar  to  the  effect  of  pain  substraction)  and  electroencepha- 
lographically  (with  reduction  of  sensory  cortical  potentials)  to  tones 
treated  in  this  fashion. 


material  and  methods 

Experiments  were  performed  upon  seven  cats  carrying  electrodes 
unplantcd  chronically  in:  (i)  subcutaneous  tissue  of  foreleg  (for  stimula- 
tion) ;  (ii)  extradural  space  overlying  both  somatic  sensory  and,  some- 
times, one  acoustic  and/or  visual  cortical  receiving  areas  (for  recording) 
(these  leads  shall  be  referred  to  as  'cortical') ;  (iii)  subcortical  structures  as 
nucleus  medialis  dorsalis  of  thalamus  (NMDT),  mesencephalic  reticular 

1  This  work,  published  in  abstract  fashion  in  the  XXI  Physiological  Congress  Volume 
(Sommer-Smith,  Galeano,  Roig  and  Segundo,  1959),  was  supported  in  part  by  grants  from 
Rockefeller  Foundation  (58122)  and  U.S.A.F.  Office  for  Scientific  Research  (AF49-638-585). 

265 


266  BRAIN    MECHANISMS    AND    LEARNING 

formation  (MRF)  and  or  mesencephalic  central  grey  matter  (MCG)  (for 
recording  and/or  stimulation). 

Details  of  electrode  construction  and  implantation  will  be  described 
elsewhere  (Roig,  Segundo,  Sommer-Smith  and  Galcano,  to  be  published). 
Main  technical  points  were:  (i)  placement  of  recording  'cortical'  and  of 
stimulating  subcutaneous  electrodes  was  controlled  elcctrographically 
until  a  complete  response  (including  early  positive  spike  and  later  waves) 
occurred  in  the  former  to  single  shock  excitation  of  the  latter;  (2)  elec- 
trodes were  implanted  in  subcutaneous  foreleg  tissues  and  carried  per- 

TEMPORAL       RELATIONSHIP 

BETWEEN      STIMULI 

IS  ^.  IS 

A)  _=  C)  =—= 


AS  SS 


IS  „,       CT 

B)  _=   «  o  .  ^=^  D)  


E) 


AS  SB 

T. 


SS  SS 

Fig.  1 

TEMPORAL  RELATIONSHIP  BETWEEN  ABSOLUTE  AND  INDIFFERENT  STIMULI  (modified  from  Konor- 

ski,  1948).  (A)  Initiation  of  indifferent  stimulus  IS  followed  by  initiation  of  absolute  stimulus 
AS.  (B)  Cessation  of  indifferent  stimulus  followed  by  initiation  of  absolute  stimulus.  (C) 
Initiation  of  mdiftcrent  stimulus  followed  by  interruption  of  feeding  or  of  subcutaneous 
stimulus  SS.  (D)  Interruption  of  SS  preceded  by  application  of  tone  T;  initiation  of  SS 
preceded  by  application  of  a  different  frequency  (conditioned)  tone  CT  (see  te.xt).  (E)  Alterna- 
tion of  subcutaneous  stimulus  SS  and  of  tone  T  (see  text).  AS,  absolute  stimulus;  IS,  indifferent 
stimulus;  SS,  subcutaneous  stimulus;  T,  tone. 

mancntly  by  animals,  thus  permitting  repeated  excitation  of  same  area  in 
consistent  fashion  (this  assumption  was  borne  out  by  study  of  evoked 
responses,  characteristics  of  which  did  not  vary  over  weeks  or  months). 
Therefore,  throughout  the  entire  procedure  recordings  were  derived  from 
the  primary  cortical  representation  of  one  same  excited  region. 

Sessions  were  carried  out  daily  in  a  relatively  sound-proof  room  in 
which  animals  did  not  see  the  investigator  but  were  observed  by  him. 
EEG  was  recorded  with  a  Grass  HID  machine;  amplified  signals  were  also 
led  from  after  the  first  stage  of  the  power  amplifier  (outlets  fs  and  J6) 


J.    p.    SEGUNDO,    C.    GALEANO,  J.    A.    SOMMER-SMITH   AND  J.    A.    ROIG   267 

through  a  0.02  (jfd.  condenser  (to  reduce  movement  artefacts)  and  then  in 
parallel  to  both  beams  of  a  Dumont  322-A  cathode  ray  oscilloscope. 
Triggering  by  stimulators  enabled  display  (and  photography)  of  cortical 
evoked  potentials:  in  upper  beam,  control  potentials  during  silence 
immediately  preceding  tone  initiation;  in  lower  beam,  responses  during 
tone  immediately  following  tone  initiation.  Grass  S  4  models  (with  SIU 
4A  isolation  units)  served  as  stimulators.  Tones  were  generated  by  a 
Hewlitt  Packard  200A  audio-oscillator  connected  with  a  loudspeaker. 

Training  proceeded  in  two  stages. 

Stage  I.  A  tone  T  and  a  subcutaneous  stimulus  SS  were  applied  ni- 
dependently  and  exhibited  no  constant  temporal  relationship.  T  was  kept 
constant  for  each  preparation  (frequency,  200-2000  c.p.s.;  duration,  4-10 
seconds).  SS  lasted  from  30  seconds  to  30  minutes  and  consisted  in  rectan- 
gular pulses  (applied  singly  or  in  pairs  separated  by  10-100  msec.)  with  the 
following  characteristics:  voltage,  1.5-15  volts;  pulse  duration,  o.i  msec; 
frequency,  2.5-8  c.p.s.  Voltages  were  adjusted  so  as  to  obtain  visible 
manifestations  described  below;  choices  between  single  or  paired  shocks 
and  between  different  frequencies  were  decided  in  each  animal  depending 
on  what  parameters  elicited  larger  late,  slow  and  labile  cortical  pheno- 
mena (see  below). 

The  tu-st  presentation  of  T  occurred  either  alone  (three  cats)  or  during 
SS  (four  cats) :  behavioural  and  EEG  effects  were  noted.  Thereafter,  T  was 
applied  independently  of  SS  and  repeatedly  until  no  response  occurred: 
when  habituation  had  thus  ensued,  it  was  again  tested  against  a  back- 
ground SS. 

Stage  II.  The  basic  feature  of  the  training  schedule  was  that  prolonged 
SS  were  interrupted  systematically  2-5  seconds  after  initiation  of  T 
(Fig.  iC):  hence,  T  initiation  consistently  preceded  SS  cessation.  Sessions 
lasted  up  to  90  minutes  and  involved  up  to  twenty-five  such  combina- 
tions. 

Acquired  responses  to  T  were  eventually  established  (see  below). 
Since  they  involved  simultaneous  behavioural  and  EEG  effects,  the  pos- 
sibility arose  that  the  latter  were  a  result  of  the  former:  T  clectrographic 
effects  were  tested  in  trained  animals  immobilized  by  intravenous  Flaxedil 
(artificial  respiration;  rectal  temperature  over  36    C). 

'Learned'  effects  produced  by  T  application  (during  SS)  were  compared 
with  effects  of  agents  known  to  affect  cortical  sensory  responses,  as: 
(i)  voltage  reduction  (or  cessation)  of  SS  (seven  cats);  (ii)  MRF  stimulation 
(Grass  S  4  model  and  SIU  4A:  voltage  0.25-2  volts;  pulse  duration, 
0.1  msec;  frequency,  200  c.p.s.;  total  duration,  1-2  seconds)  (two  cats); 


268  BRAIN    MECHANISMS    AND    LEARNING 

(iii)  same  T  when  novel  (on  first  presentation)  (four  cats) ;  (iv)  intense 
crashing  soiuid  (three  cats) ;  (v)  different  frequency  tone  (CT)  that  signalled 
SS  initiation  (tone  conditioned  in  the  usual  sense)  (Fig.  iD)  (two  cats). 

Specificity  of  learned  effects  was  tested  by  comparing  them  with  con- 
sequences encountered  in  slightly  dissimilar  circumstances  as:  (i)  effect 
of  different  frequency  tone  upon  response  to  same  SS  (four  cats);  (ii) 
effect  of  same  T  upon  response  to  SS  applied  to  different  limb  (three  cats) ; 
(iii)  effect  of  same  T  upon  response  to  different  modality  stimulus  (repeti- 
tive flash)  (two  cats). 

In  three  preparations,  T  and  SS  were  alternated  so  that  T  initiation 
preceded  SS  cessation  by  5  seconds  and  T  cessation  was  followed,  5 
seconds  later,  by  SS  initiation  (Fig.  i  E) :  behavioural  and  EEG  effects  of  T 
initiation  were  identical  to  those  encountered  in  remaining  animals  of  this 
group  (in  which  tone  cessation  did  not  signal  shock  application.^ 

RESULTS : 
(l)  EFFECT    OF    SUBCUTANEOUS    STIMULI    (ss) 

{A)  SS  application.  When  prolonged  SS  were  applied,  extreme  voltage 
values  proved  inadequate:  relatively  low  ones  evoked  little  or  no  be- 
havioural manifestations;  relatively  high  ones  produced  notorious  and 
even  violent  signs  of  discomfort  (cats  moved  and  mewed  continuously, 
tried  to  escape  and  attacked  cables  or  cage;  jerks  of  limb,  body  and  head 
were  prominent).  Hence  'intermediate'  values  (1.5-15  volts)  were  used: 
under  these  conditions,  SS  effects  though  variable,  composed  a  list  that 
was  limited  and  included  for  the  group  an  initial  startle  followed  by  head 
depression  or  rotation,  ear  retraction,  eye  closure  or  blinking,  plaintive 
mewing,  shoulder  hunching,  general  position  shift  and  obvious  'concern' 
with  the  excited  forelimb  that  currently  exhibited  flexion  jerks  syn- 
chronous w'th  shocks  and  was  regarded  and/or  licked.  Responses  usually 
consisted  in  an  aggregation  of  various  individual  movements,  each  cat 
exhibiting  a  short  number  of  characteristic  combinations  that  could  differ 
from  one  animal  to  another.  Two  cats  in  the  group  responded  in  a  stereo- 
typed and  consistent  fashion  to  SS  initiation  by  adopting  a  'tense'  attitude 
(head  depressed,  ears  retracted,  eyes  closed,  body  bent  forward)  that, 
except  for  minor  shifts,  was  maintained  for  the  duration  of  SS  (Fig.  2). 

Comments  on  the  electrographic  consequences  of  SS  will  be  restricted 
to  general  EEG  effects  and  to  potentials  evoked  by  SS  in  contralateral 

^  Observations  pertaining  to  eiTects  of  tone  cessation  in  these  (and  other)  cats  will  be 
discussed  elsewhere  (Galeano,  Roig,  Segiindo  and  Soninicr-Smith,  1959). 


J.   p.   SEGUNDO,   C.   GALEANO,  J.   A.   SOMMER-SMITH  AND  J.   A.   ROIG  269 

BEHAVIOURAL  AND  EEC  EFFECTS 
I.     CESSATION     OF    SS 


CSC 


<,V«..w»M»,»»iV»rtvMt^ 


//.    T    DURING     APP.     OF    SS 


».,wv,^v*v*'jWim!«#k-^ 


v.'V ;,  '^f^^^y^\^^^'if  ' 


Fig.  2 
behavioural  and  eeg  effects.  (l)  cessation  of  subcutaneous  stimulus.  left, 
control;  centre,  SS  effect;  right,  SS  interruption  effect.  (II)  tone  application 
DURING  subcutaneous  STIMULUS.  Left,  control;  centre,  SS  effect;  right,  influence  of 
T  on  SS  effect.  Note  similarity  of  consequences  of  SS  subtraction  (without  previous 
T)  (top  line)  and  of  T  application  (during  SS)  (bottom  line).  In  this  and  in  other 
figures  using  EEG  records,  application  of  SS  and  of  T  are  indicated  by  broken  and 
by  continuous  bars,  respectively  and  calibrations  represent  50  nv.  and  i  second  AFP., 
application ;  BEHA  V.,  behavioural ;  CSC,  contralateral  sensory  cortex. 


270  BRAIN    MECHANISMS    AND    LEARNING 

sensory  cortex.  A  detailed  report  covering  cortical  evoked  potentials  in 
free,  inianaesthetized  cats  is  ni  preparation  (Roig,  Segundo,  Soninier- 
Smith  and  Galeano,  to  be  published):  it  will  indicate  that,  in  'chronic' 
cats  cortical  responses  to  single  subcutaneous  shocks  consisted  (when 
recorded  as  described  above)  in  a  succession  of  positive  (P)  and  negative 


POTENTIAL  EVOKED  BY  SUBCUTANEOUS  SHOCK 
ON  CSC 


Fig.  3 
potential  evoked  by  single  subcutaneous 
shock  on  contralateral  sensory  cortex: 
(unless  specified  otherwise,  records  from  all  figures 
arc  from  sensory  corte.x  contralateral  to  peripheral 
shocks).  As  recorded  with  equipment  described 
in  text,  potentials  consisted  in  a  succession  of 
positive  (downward  deflections  P)  and  negative 
(upward  deflections  N)  peaks  named,  according 
to  polarity  and  chronological  order  of  pre- 
sentation. Pi,  Ni,  P2,  N2,  P3  and  N3.  Arrow 
indicates  application  of  subcutaneous  shock.  Cali- 
brations: 20  uv.,  50  c.p.s.  (as  in  all  figures  using 
cathode  ray  oscilloscope),  CSC,  contralateral 
sensory  corte.x;  SUBCUT.,  subcutaneous. 


(N)  peaks,  tentatively  named  as  follows  (Fig.  3):  Pi  (initial  positive  spike) 
was  comparable  to  that  encountered  regularly  but  designated  variously 
and  ascribed  to  presynaptic  activation  in  specific  terminals  (Figs.  3,  6,  8, 
9,  II,  12).  Ni  was  similar  to  first  part  of  subsequent  negative  wave 
(Figs.  3,  6,  8,  9,  10,  II,  12).  P2,  N2  and  P3  constituted  a  variable  sequence 
exhibiting  similarity  with  'augmenting'  complexes;  when  N2  was  absent. 


J.   p.   SEGUNDO,   C.    GALEANC),  J.   A.   SOMMER-SMITH  AND   ].   A.   ROIG  27I 

P2  was  practically  continuous  with  P3  (Figs.  6,  1 1 ) ;  as  N2  developed,  separa- 
tion between  P2  and  P3  became  evident  (Figs.  6,  8,  10,  i  r,  12);  when  N2 
was  large,  P3  preserved  its  individuality  but  P2  became  a  minor  indenta- 
tion between  Ni  and  N2  (Figs.  6,  8,  10).  All  delayed  negative  oscillations 
were  included  as  N3  (since  latencies  and  shapes  were  variable,  this  group 

EEG  EFFECT  OF  T  ALONE 

Tl 

Tn  " 


'\'  'ii,',iu.fj 


T-CESSSS  180 
a. 


'^iA^({i^\k4^4^j^^ii^lj^^ 


S£C     00  tit*'i»¥t'ff^f^^•/^^^i^'\fM^^^H^h^ 


2  ^  VW^Vf,^1'*^>^'V**.^^1W%^^ 

Fig.  4 
EEG  EFFECTS  OF  TONE  APPLIED  ALONE  (without  background  SS).  Ti  (first  application  of  T) : 
'desynchronization'.  Tn  (after  numerous  applications) :  T  was  no  longer  ctfcctive  (habituation). 
T-CESS  SS  180  (after  180  associations  with  cessation  of  SS) :  {a)  if  applied  against  a  background 
'relaxed'  rhythm,  T  produced  'desynchronization' ;  (/))  even  when  applied  against  an  'activated' 
background,  T  was  followed  (time  24  seconds)  by  reinforcement  of  slow  rhythms  and  spindles 
lasting  for  about  20  seconds  (up  to  time  34  seconds).  CESS.,  cessation. 


272 


BRAIN    MECHANISMS    AND    LEARNING 


could  be  heterogeneous)  (Figs.  6,  8,  lo,  1 1)  (Adrian,  1941;  Bartley  and 
Heinbecker,  1938;  Bremer  and  Bonnet,  1950;  Brookhart  and  Zanchctti, 
1950;  Buser  and  Albe  Fessard,  1957;  Dempsey  and  Morison,  1943; 
Dcmpsey,  Morison  and  Morison,  1941 ;  Eccles,  195 1 ;  Forbes  and  Morison, 
1939;  Li,  Cullen  and  Jasper,  1956;  etc.). 

In  each  ainmal,  responses  exhibited  marked  "spontaneous'  variations 
that,  as  noticed  by  earher  investigators,  predominantly  involved  the 
slower,  later  phenomena  (waves  N2,  P3,  N3  and,  to  a  lesser  extent,  Ni) 
(Adrian,  1941;  Dcmpsey  and  Morison,  1941;  1943;  Eccles,  1951;  Forbes 


EFFECT  OF  T  ON  POT.  EV.  BY  SS  ON  CSC 


Tl 


lV«¥/^*lUl*M^I 


Tn 


jW^fF'W^^'^ 


r- 

CESS.  SS 
200 


,i^4^t*r^^ 


Fig.  5 
effect  of  tone  on  potentials  evoked  by  ss  on  cxjntralateral  sensory  cortex.  tl  (first 
application):  T  produced  a  drop  in  amplitude  and  duration  of  slow  waves  induced  by  each 
peripheral  shock.  Tn  (habituation):  T  produced  little  effects  if  any.  T-CESS.  200  (after  being 
followed  200  times  by  cessation  of  SS) :  T  produced  notorious  'masking"  effects.  EV.,  evoked. 
FOT.,  potentials. 


and  Morison,  1939).  These  more  variable  waves  were  also  the  most  suscep- 
tible to  T  effects  (see  below).  It  is  necessary  to  point  out  that  modifications 
induced  in  evoked  potentials  by  effective  agents  (including  tones)  occurred 
always  within  the  range  of  possible  'spontaneous'  oscillations.  Relative 
heights  and  duration  of  individual  waves  differed  also  from  one  prepara- 
tion to  another. 

(B)  SS  iiitaruptioii.  When  SS  was  cut  off,  cats  reacted  in  a  variable 
manner;  the  list  of  movements  appearing  at  this  instant  was  limited,  how- 
ever, and  included  head  elevation  or  rotation,  ear  movements,  eye 
opening  or  blinking,  body  straightening  (or  general  shift)  and  interruption 


J.    p.   SEGUNDO,   C.   GALEANO,  J.   A.   SOMMER-SMITH  AND  J.   A.   ROIG   273 

ot  certain  previous  activities  as  mewing,  paw  jerks  and  licking,  etc.  As 
was  the  case  with  SS  application,  response  movements  evoked  by  SS 
interruption  were  usually  combined  by  each  animal  into  a  short  number 
of  typical  patterns.  The  two  cats  that  responded  consistently  to  SS 
initiation  by  adopting  a  'tense'  attitude,  reacted  to  SS  interruption  by 
reverting  to  the  normal  'relaxed'  attitucie  in  an  also  stereotyped  fashion 
(raisnig  head,  elevating  ears,  opening  eyes,  straightening  body)  (Fig.  2). 

When  SS  ceased,  evoked  potentials  naturally  disappeared  leaving  low- 
voltage,  fast  activity. 

(II)  EFFECTS  OF  TONE  (T).  When  the  tirst  T  was  applied  alone  an  investiga- 
tion reflex  wdth  EEG  'desynchronization'  occurred  (Fig.  4  — Ti).  When 
presented  against  a  background  SS,  the  preparation  usually  did  not  responci 
behaviourally;  late  waves  of  evoked  potentials  tended  to  be  reduced  in 
amplitude  and  duration  (Fig.  6  —  novel  T).  Behavioural  and  EEG  effects 
diminished  and  disappeared  in  the  course  c^f  Stage  I;  finally,  tones  produced 
little  or  no  effect,  either  when  applied  alone  or  when  presented  against  a 
background  SS  (Fig.  4  —  Tn;  5  —  Tn). 

Thereafter  (Stage  II),  T  initiation  w^as  consistently  tollowcd  by  cessation 
of  SS  (Fig.  I  —  C).  During  this  period,  animals  came  to  react  rapidly 
(before  interruption  of  SS)  to  T:  percentage  of  positive  responses  in- 
creased gradually  and,  in  3-10  sessions,  reached  and  later  remained  at  (or 
close  to)  100  per  cent  (Fig.  7).  From  a  behavioural  standpoint,  the  same 
general  comments  mentioned  in  reference  to  SS  application  and  interrup- 
tion were  applicable  to  T.  (i)  Responses  to  T  were  variable  but  the  list  was 
limited  to:  hcati  elevation  or  rotation,  ear  movements,  eye  opening  or 
blinking,  body  straightening  (or  general  shift)  and  interruption  of  previous 
activities  (mewing,  licking).^  This  list  was  identical  to  that  of  SS  interrup- 
tion, (ii)  Each  cat  associated  individual  movements  into  a  short  number  of 
responses  that  characterized  that  preparation  (but  could  vary  from  one 
animal  to  another).  These  compound  responses  to  T  coincided  with  those 
provoked  by  SS  interruption,  (iii)  In  the  two  cats  that  reacted  in  a  uniform 
manner  to  SS  application  or  substraction,  T  (when  presented  during  SS) 
also  gave  a  stereotyped  pattern  that  consisted  in  head  elevation  or 
rotation,  ear  elevation,  eye  opening  or  bhnking,  body  straightening 
(Figs.  2;  7  — Icwer  graph).  This  pattern  was  identical  to  that  produced 
by  SS  interruption  (Fig.  2). 

Tone  initiation  became  capable  also  of  modifying  potentials  (EP)  evoked 
by   SS   on   contralateral   sensory  cortex.   Effects   consisted    in  reduction 

^  As  far  as  exclusively  (and  obviously  insutficieiu)  visual  observation  is  concerned,  limb 
jerks  were  not  modified  by  T. 


274 


BRAIN    MECHANISMS    AND    LEARNING 


EFFECTS  ON  POT.  EV.  BY  SS  ON  CSC 


REDUCTION 
SS       VOLTAGE 


W*V*&^V'^^'*^ 


NOVEL    TONE 


CRASH 


1 


COND       T 


sil         , 


Fig.  6 
comparison  of  modifications  produced  in  evoked  poten- 
TIALS BY  DIFFERENT  EEG  'aROUSAl'  INDUCING  INFLUENCES  (I). 

'Masking'  effects  of  T  were  comparable  in  each  instance  to 
those  of  SS  voltage  reduction  (from  8  to  5  volts,  top  line), 
first  application  o"f  tone  (NOVEL  TONE  NT,  second  line) 
and  application  of  intense  sound  (CRASH  CR,  third  line); 
a  conditioned  tone  (COND.  T.  CT,  fourth  line)  was  less 
effective. 


J.   p.   SEGUNDO,   C.   GALEANO,  J.   A.   SOMMER-SMITH  AND  J.   A.   ROIG  275 

of  amplitude  and  duration  (or  even  complete  suppression)  of  cortical 
response  waves  (Figs.  2,  5,  6,  8).  Susceptibility  was  different  for  each 
peak.  Pi  was  resistant  to  the  acquired  influence  of  T  (Fig.  6  —  left  column 
—  second  Hue).  Ni  was  insensitive  in  certain  preparations  (Figs.  8;  9  — 


BEH      EFFECT      OF       TONE 

%    COND    RESP 


Fig.  7 
LEARNING  CURVE.  On  abscissae,  number  of  training  sessions;  on  ordinatcs,  per- 
centage of  tones  giving  behavioural  responses.  Curve  with  narrow  line  and 
open  circles,  percentage  of  all  responses;  curve  with  broad  line  and  black  circles, 
percentageof 'typical',  stereotyped  response  (see  text).  Top  graph:  cat  exhibit- 
ing frequent  but  variable  reactions  to  T  (head  raising  or  turning  to  right  or 
left,  blinking,  etc.).  Bottom  graph:  cat  exhibiting  a  frequent  'typical'  stereo- 
typed response.  BEH.,  behavioural:  RESP.,  response. 


left  column;  lo;  11)  but  responsive  in  others  (Figs.  6  —  Ictt  column  — 
third  line;  9  —  II).  The  P2-  N2-  P3  complex  was  modified  by  T  initiation: 
effects  upon  P3  were  notorious  (Figs.  6  —  left  column;  8;  9;  10  —  I;  11 ; 
12);  N2  frequently  responded  well  (Figs.  6  —  left  column  —  fourth  line; 
8  — IV;  10  — I),  but,  occasionally,  was  not  affected  by  or  even  became 

T 


276 


BRAIN    MECHANISMS    AND    LEARNING 


more  clear-cut  after  T  (Fig.  6  —  left  column  —  first  line;  8  — I-II-III; 
9  —  I;  II  —  I-II);  P2  variations  appeared  to  be  a  consequence  of  modifica- 
tions in  Ni  and  N2  (Figs.  6  —  left  column  —  hrst  and  fourth  lines;  8  —  III, 


EFFECT  OF  T  ON  POT    EV.  BY  SS  ON  CSC 
I  SINGLE  3-1/  //  PAIRS  10  msec  3-v 


s/7. 


///  PAIRS  100  msec  3 


IV  PAIRS  100  msec  2.5  -^ 


Fig.  8 
effect  of  tone  upon  potentials  evoked  by  subcutaneous  stimuli.  advan- 
TAGES OF  PAIRED  SHOCKS.  I,  Single  shocks  at  3  c.p.s. :  slow,  labile  phenomena 
are  obvious  and  respond  to  T.  II,  pairs  (10  msec,  interval)  at  3  c.p.s.;  Ill,  pairs 
(100  msec.)  at  3  c.p.s.;  IV,  pairs  (100  msec.)  at  2.5  c.p.s.;  application  of  second 
shock  facilitated  development  of  late,  slow  waves  affected  preferentially  by 
T  application;  contrastingly,  responses  to  first  shocks  are  either  small  or 
suffered  little  modification. 


IV;    II  —  I).    When   present   in   control   responses,    N3    was   markedly 

reduced  or  abolished  by  T  (Figs.  6  —  left  column;  8;  13— I;  10  — I;  11). 

Paired    shocks    (at    i-ioo    msec,    intervals)    or    different    stimulation 

frequencies  (2.5-8  c.p.s.)  were  used  to  enhance  slow  phenomena  and  thus 


J.   p.   SEGUNDO,    C.    GALEANO,    |.   A.   SOMMER-SMITH  AND  J.   A.    ROIG  277 

provide  a  more  susceptible  background,  upon  which  T  effects  if  any 
would  become  more  notorious  (Figs.  6  —  left  column  —  hrst,  fourth  line; 
8  —  II,  III,  IV;  9;  10  —  I).  Figs.  6  —  first  line,  8  —  III  and  9  —  I  illustrate 
specially  well  the  advantages  of  double  stimuli  showing  instances  in  which 
T  markedly  modified  potentials  evoked  by  second  shock. 

Efficacy  of  T  was  critically  related  with  two  issues,  (i)  Voltage  of  SS 
background  stimulation:  responses  (behavioural  and  EEG)  to  values 
producing  reduced  or  intermediate  conduct  effects  were  susceptible; 
lability  ciccreased  and  disappeared  if  stronger  stimuli  were  used,  (ii)  Control 
responses  (evoked  by  SS  prior  to  T) :  if  T  was  presented  against  background 
EP  exhibiting  important  slow  components,  electrographic  T  effects 
were  clear-cut;  as  control  potentials  became  smaller,  EEG  effects  became 
less  obvious  in  a  parallel  fashion  (behavioural  effects  occurred  no  matter 
the  type  of  background  potentials). 

When  SS  was  not  discontinued  after  T,  cats  eventually  (10-30  seconds) 
readoptcd  behavioural  and  electrographic  patterns  exhibited  prior  to 
sound  application.  If  applied  during  SS,  intense  intercurrent  stimuli 
(e.g.  loud  crash)  provoked  effects  described  below:  if  T  were  presented  a 
few  seconds  later,  animals  usually  did  not  respond  to  it  ('external  inhibi- 
tion'). 

Under  Flaxedil,  T  provoked  modifications  of  EP  similar  to  those  seen, 
in  the  same  trained  preparation,  when  freely  mobile  (Fig.  9) :  hence, 
electrographic  alterations  were  not  a  consequence  of  concomitant 
performance.  Pupillary  dilatation  occurred  in  flaxedilized  animals  upon 
application  of  T.^ 

Electrographically  T  effects  resembled  results  of  reducing  SS  voltage. 
In  Fig.  6  —  upper  line,  T  (left  column)  a  passage  from  8  volts  excitation  to 
5  volts  (right  column)  reduced  waves  N2  and  N3  (after  second  shock)  and 
P3  (after  both  shocks)  (Pi  was  larger  with  8  volts  during  T  than  with  5 
volts).  Observed  with  ink-writer,  T  application  induced  a  shift  similar  to 
that  occurring  in  SS  interruption  (specially  when  spike  Pi  was  not 
prominent)  (Fig.  2).  With  oscilloscope  (showing  potentials  more  clearly), 
resemblance  was  not  complete  unless  voltages  used  were  threshold  for 
EP:  in  these  circumstances,  responses  were  effaced  by  T  and  st^  obscured 
by  'spontaneous'  rhythms  that  patterns  became  comparable  to  those 
obtained  without  peripheral  excitation. 

Changes  in  configuration  of  cortical  evoked  potentials  are  known  to  be 

'  Apart  from  this  one,  other  learned  EEG  responses  were  found  to  subsist  in  preparations 
immobihzed  with  Flaxedil  (Galeano,  Roig,  Segundo  and  Somnier-Sniith,  1959;  Segundo, 
Sommer-Smith,  Galeano  and  Roig,  1959). 


278 


BRAIN    MECHANISMS    AND    LEARNING 


associated  with  EEG  'arousal'  (Gauthier,  Parma  and  Zanchctti,  1956): 
therefore,  T  eil^ect  was  compared  with  changes  resulting  from  application 
of  certain  EEG  'activating'  agents,  (i)  MRF  stimulation  (contralateral  to 
SS)  reduced  amplitude  and  duration  of  N3,  P3.  N2,  and,  to  a  lesser  extent, 


T  EFFECT 


I.     FREE  MOV. 


II.     FLAXEDIL 


«//. 


*t^^^ 


t       t 


/.     FREE       MOV. 


CSC     ^^f^^(,/A''"^"""' 


,\  VWV*"*^  /\a/ 


//,     FLAXEDIL 


Fu..  'J 

PERSISTENCE  OF  TONE  EFFECTS  IN  FLAXEDILIZED  PKEPAKATION.  I,  T  cftccts  ill  freely 

moving,   unanaesthetized    cat;    II,    same   cat   under   Flaxedil:   electrographic 
effects  were  comparable. 

Ni ;  intensity  of  effects  could  be  graded  by  variations  in  central  excitation 
voltages:  as  far  as  morphological  mutations  are  concerned,  MRF  excita- 
tion and  T  effects  were  indeed  comparable  (Fig.  10).  (li)  Tones  that  after 
training  provoked  results  described  above  had  induced  similar  (diough 
usually  less  noticeable)  effects  when  novel  (on  fu'st  application)  (Figs.  5  — 


J.    p.    SEGUNDO,    C.    GALEANO,  j.    A.    SOMMER-SMITH    AND  J.    A.    ROIG   279 

Ti ;  6  —  second  line),  (iii)  Effects  ot  loud  crashing  noises  resembled  diosc 
of  T  (Fig.  6  —  diird  line),  (iv)  In  two  cats  training  involved  use  of  different 
frequency  tones,  one  (conditioned  tone  CT)  indicating  SS  initiation  and 

EFFECTS  ON  POT.  EV.   BY  SS  ON  CSC 
I.      T 


sil 


II.      MRF       SUM 


15V  . I  -  200 


CONT 


STIM 


t        ^t 


/   V 


fSjfV^^ 


05   V 


Fig.  10 
comparison  of  modifications  produced  in  evoked  potentials: 

I,  tone;  II,  MESENCEPHALIC  RETICULAR  FORMATION  STIMULATION  (pulse 

duration,  o.i  msec;  frequency,  200  c.p.s.).  Modifications  induced  on 
evoked  potentials  by  T  or  by  0.75-1.5  volts  were  comparable;  stimu- 
lation with  o.s  was  ineffectual.  CC^NT.,  control. 


the  Other  (T)  signalling  SS  cessation  (Fig.  i  D) :  the  latter  T  acquired  an 
intense  capacity  to  affect  behaviour  and  evoked  potentials  (w^hcn  applied 
during  SS).  The  former  became  conditioned  in  the  current  sense  produc- 
ing behavioural  and  EEG  effects  (startle,  leg  retraction,  'activation',  etc.) 


280  BRAIN    MECHANISMS    AND    LEARNING 

DISCRIMINATION 

I.  DIFF    T   ON    SS 
A       GENERALIZATION  B       DIFFERENTIATION 

ieoo-\,  (-CESS   SS)       ieo-\,  leoo^  (-cess  ssi         leo 

ri 


i^Py^^.  tA^^A'      ,flf^!^p^ 


II     T    ON      SS       TO      DIFF        LEG 
SSLF  SSRF 

RSC  LSC 


$11 


III      T       ON      DIFF      UODALITY 
SSLF  n 

RSC  RVC 


^^*«!«^ 


/       OlFF       T       ON       SS 

0       ClUCO'LIIiTIOH 


^-    —    —    -^    ~    "*    •"    ~    ^  ""    ""  160  ■ 


e     oifFificsniTiON 


Ul.|;^Y''''lf''v'^\^»'«i'*"""*'  * tfi»»y>^"r*-  '"■ 


J.'*vW»;,i''|ili.\w^;^2.vW4-''-'^^^ 


//      T       ON      SS       TC       DIFF       LEG 


/</      T       ON      DIFF       MODALITY 

Fig.  II 
SPECIFICITY  OF  TONE  EFFECTS.  I.  Specificity  for  T  frequency  (DIFF.  T  ON  SS).  a  (or  A) 
GENERALIZATION  stage:  both  'reinforced'  (i6oo  c.p.s.  -CESS  SS)  and  non-' reinforced' 
(i6o  c.p.s.)  tones  affected  responses,  b  (or  B)  DIFFERENTIATION  stage:  only  i6oo  c.p.s. 
tones  were  effective.  II.  Specificity  for  localization  (T  ON  SS  TO  DIFF.  LEG).  No  differentia- 
tion was  established :  T  affected  both  types  of  response,  those  on  right  sensory  cortex  (RSC) 
after  left  foreleg  stimuli  (SSLF)  (currently  cut  off  after  T)  and  those  on  left  sensory  cortex 
(LSC)  after  right  foreleg  stimuli  (SSRF)  (currently  not  cut  off  after  T).  III.  Specificity  for 
modality  (T  ON  DIFF.  MODALITY).  Differentiation  was  estabhshed:  T  affected  responses 
on  right  sensory  cortex  after  left  foreleg  stimuli  occurring  on  right  visual  cortex  (RVC)  after 
repetitive  flashes  (FL.)  (currently  not  cut  off  after  T).  DIFF.,  different;  FL.,  flashes;  LSC,  left 
somatic  sensory  cortex;  RSC,  right  sensory  cortex;  RVC,  right  visual  cortex;  SSLF,  sub- 
cutaneous stimulus  to  left  foreleg;  SSRF.  subcutaneous  stimulus  to  right  foreleg. 


J.   p.   SEGUNDO,   C.   GALEANO,  J.   A.    SOMMER-SMITH  AND   ).   A.   ROIG  28 1 

but,  in  spite  of  having  clear-cut  'dcsynchronizing'  abilities  (when  applied 
alone)  was  incapable  (when  applied  during  SS)  of  affecting  evoked 
potentials  in  a  manner  comparable  to  that  of  T  (Fig.  6  —  fourth  line). 
Resemblance  of  effects  of  T  on  the  one  hand  and  of  EEG  'arousal'  — 
inducmg  influences  on  the  other,  did  not  go  beyond  the  electrographic 
sphere.  Separation  could  be  established  in  the  behavioural  held:  MRF 
excitation  was  inoperant  (sub-threshold) ;  novel  T  and  intense  sounds  were 
either  ineffective  or  produced  'surprise'  effects  (investigation  reflex, 
startle) :  conditioned  tones  (CT)  produced  slight  or  no  changes  when 
applied  during  SS. 

'OPPOSITE'  EFFECTS  OF  DIFFERENTIATED  TONES 
I    leOO'x.f-CESS  SS)  II    leO^(DIFF) 


sil 


Fig.  12 
'opposite'  effects  of  differentiated  tones,  a  tone  of  1600  c.p.s.  (but  not  one  of  160  c.p.s.) 
was  reinforced  by  cessation  of  SS.  Eventually,  differentiation  ensued  (see  te.xt  and  Fig.  11). 
Reinforced  tones  (1600  —  CESS.  SS)  masked  large  control  evoked  potentials;  non-reinforced 
tones  (160  DIFF.)  augmented  small  control  potentials. 

Specificity  of  effects  described  above  was  explored  from  different  points 
of  view. 

I.  Frequency  specificity.  When  a  cat  had  been  trained  to  respond  to  a  tone 
of  a  given  frequency  (e.g.  1.600  c.p.s.)  habitually  'reinforced'  by  cessation 
of  SS,  the  first  applications  of  a  different  frec]ucncy  (e.g.  160  c.p.s.) 
provoked  a  smiilar  effect  (generalization)  (Fig.  11  —  I,  and  A).  After  a 
number  of  sessions  in  which  one  tone  (1600  c.p.s.)  but  not  the  other 
(160  c.p.s.)  was  reinforced  by  substraction  of  SS,  three  cats  out  of  four, 
reached  a  point  in  which  effects  were  produced  consistently  by  1600 
c.p.s.  and  exceptionally  by  160  c.p.s.  (differentiation)  (Fig.  11  —  I-b,  B). 
In  this  situation,  it  occurred  frequently  that  small  cortical  responses  (not 
modified  by  the  'positive'  tone)  were  augmented  by  application  of  the 
'negative'  tone  (Fig.  12). 


282  BRAIN    MECHANISMS    AND    LEARNING 

2.  LoaiJi^iitioii  specif  city.  After  establishment  of  learned  responses  to  T 
by  the  usual  practice  of  associating  T  with  cessation  of  SS  (to  left  foreleg), 
routine  was  changed  in  three  cats.  Thereafter,  SS  were  applied  separately 
to  right  and  left  forelegs:  presentation  of  T  during  SS  to  left  foreleg  was 
followed  (as  before)  by  substraction  of  shocks;  presentation  of  T  during 
SS  to  right  foreleg  was  not  followed  by  change  in  shocks.  Cats  reacted  to 
this  procedure  as  follows:  (i)  in  two  preparations,  efficacy  of  T  during  left 
SS  was  not  modified  and,  m  addition,  application  of  T  during  SS  to  right 
foreleg  led,  from  the  beginning,  to  identical  behavioural  and  EEG  effects 
(that,  since  SS  continued,  were  transitory)  (generalization)  (Fig.  ii  —II); 
(ii)  in  the  remaining  animal  and  after  a  brief  initial  phase  of  generalization, 
responses  to  T  (during  excitation  of  either  leg)  became  unpredictable. 
Therefore,  'differcntation'  could  not  be  established  in  the  sense  of  restrict- 
ing T  influence  to  effects  of  SS  applied  to  one  single  foreleg. 

(3)  Modality  specificity.  A  repetitive  flash  (Fl.)  was  used  as  non-somatic 
excitation.  Flicker  did  not  cause  behavioural  responses  (except  for  initial 
orienting  reflexes) :  hence,  considerations  refer  exclusively  to  the  electro- 
graphic  sphere.  In  a  first  effort  {a)  SS  and  Fl.  were  applied  separately,  T 
being  followed  by  cessation  of  SS  but  not  of  Fl.:  no  differentiation 
occurred  (T  continued  to  mask  somatic  and  visual  potentials).  In  a  second 
effort  [b]  Fl.  was  presented  continuously  during  the  entire  session;  SS  was 
applied  intermittently  and  interrupted  following  T  in  the  usual  way. 
With  this  technic]ue  successful  'differentiation'  took  place:  T  application 
modified  potentials  evoked  in  somatic  sensory  cortex  by  SS  but  did  not 
usually  alter  responses  elicited  at  the  same  time  in  visual  area  by  flashes 
(Fig.  II- III). 1 

Concomitantly  with  observation  of  behaviour  and  with  sampling  of 
activity  from  sensory  cortex  (contralateral  to  SS),  EEG  records  were  taken 
from  different  regions  of  the  central  nervous  system  comprising  (in  the 
entire  series)  sensory  cortex  (homo-lateral  to  SS)  HSC,  acoustic  cortex, 
visual  cortex,  NMDT,  MRF  and  MCG.  If  activity  in  these  areas  exhibited 
relatively  large  voltage,  slow  waves  and/or  spindles  during  silence, 
application  of  T  (producing  typical  effects  in  contralateral  sensory  cortex 
(CSC)  could  be  followed  by  shift  to  low  voltage,  fast  patterns  (EEG 
'arousal').  This  was  particularly  consistent  in  HSC  (three  cats)  and  NMDT 
(one  cat):  EP  masking  was  never  encountered  without  'desynchroniza- 
tion'  appearing  in  HSC  or  NMDT.  This  was  not  always  the  case  with 

1  Effort  (/))  succeeded  in  producing  'modality'  specificity  whereas  effort  (a)  did  not.  Failure 
to  establish  localization  specificity  (see  above)  may  have  been  due  to  application  of  a  routine 
similar  to  that  of  (i?)  to  a  problem  that  might  have  been  solved  by  a  routine  similar  to  that 
of(b). 


J.    p.    SEGUNDO,    C.    GALEANO,  J.    A.    SOMMER-SMITH   AND    |.    A.    ROICi   iH} 

Other  Structures  (acoustic  cortex,  visual  cortex,  MRF  and  MCG):  in 
frequent  instances,  typical  effects  occurred  on  CSC  and  little  or  no  altera- 
tion took  place  in  the  other  regions. 

Tones  reinforced  by  cessation  of  SS  and  capable  of  provoking  EEG  and 
behavioural  effects  described  above  when  applied  against  a  background 
SS  were  usually  also  effective  when  presented  alone.  Though  behaviour- 
ally  responses  were  poor  (minor  shifts,  investigation  movements),  tones 
consistently  produced  EEG  'arousal'  generalized  or  localized  to  CSC 
(Fig.  4  —  TCESS  1 80,  a).  Another  characteristic  EEG  effect  was  a  relatively 
delayed  (initiation  10-30  seconds  after  T)  and  prolonged  (10-30  seconds) 
discharge  of  large  voltage  and  slow  (4-14  c.p.s.)  waves  and  spindles  that 
followed  hiitial  'desynchronization':  this  effect  was  noticeable  even  it  T 
was  presented  against  a  background  'desynchronized'  tracing  (Fig.  4  —  T- 
CESS  SS  180  b). 

When  habituated,  T  initiation  had  no  obvious  consequences;  after 
training  (and  against  relatively  slow  background  EEG)  it  eliciteti  an 
evoked  potential,  specially  noticeable  on  CSC,  MRF  and  MCG. 

In  two  animals,  T  was  applied  (with  no  previous  SS)  during  natural 
sleep  (behavioural  and  EEG).  Responses  were  cither  absent  or  conhned  to 
slight  and  transient  EEG  'desynchronization'.  Hence  tones  associated  with 
shock  cessation  lacked  arousing  potentialities  of  sounds  reinforced  by 
other  absolute  stimuli  (e.g.  SS  initiation,  brain  stem  excitation)  (Rowland 
Segundo,  Roig  and  Sommer-Snnth,  iQsy). 

DISCUSSION 

Chronological  relationship  is  critical  when  'neutral'  and  'biologically 
significant'  stimuli  are  paired  with  the  purpose  of  establishing  a  learned 
response.  Efficacy  of  certain  temporal  sequences  (tone  initiation  —  feeding 
or  pain  initiation;  tone  cessation  —  pain  initiation)  has  been  widely  con- 
firmed (Pavlov,  1941;  Rowland,  1954;  Segundo,  Roig,  Sommer-Smith, 
1959;  Zeleny  cited  by  Pavlov,  1941,  etc.).  Contrastingly,  usefulness  of 
other  alliances  (e.g.  feeding  —  tone  initiation,  backward  conditioning, 
etc.)  has  been  less  convincing  (Zbrozyna,  1958).  Conceivably,  application 
of  yet  other  possible  patterns  (e.g.  tone  initiation  —  cessation  of  absolute 
stimulus)  might  also  develop  novel  (learned)  responses  to  previously 
indifferent  stimuli  (Konorski,  1948).  Experimental  observations  have 
supported  this  assumption:  if  each  time  a  sound  was  applied  food  was 
withdrawn  forcibly  from  an  eating  dog,  animals  eventually  stopped  eating 
on  presentation  of  the  auditory  stimulus  in  spite  of  continued  availability  of 
aliment  (Zbrozyna,   1958);  in  backward  conditioning  (rats)  indifferent 


284  BRAIN    MECHANISMS    AND    LEARNING 

Stimuli  could  signal  cessation  of  unconditioned  excitation  (Barlow,  1956); 
in  the  present  experiments,  a  cat  came  to  react  to  a  formerly  ineffectual 
tone  after  the  latter  was  followed,  in  a  regular  fashion  by  substraction  of 
prolonged  painful  stimuli.  Accordingly,  'signal  reactions'  may  indeed  be 
created  as  suggested  by  Konorski  when  absolute  'stimuli'  are  provided  by 
interruption  of  biologically  significant  excitations  —  feeding,  pain  (Konor- 
ski, 1948);^  this  is  not  altogether  surprising  since  suppression  of  pain 
(feeding)  constitutes  a  biologically  important  reward  (punishment), 
probably  associated  with  central  nervous  readjustments  as  great  as  those 
accompanying  their  application. 

Behavioural  effects  of  SS  cessation  (when  not  preceded  by  T)  and  of  T 
initiation  (during  application  of  SS)  were  variable.  Nevertheless,  affniity 
between  consequences  of  both  phenomena  could  be  established,  both  as  a 
group  and  individually.  In  the  tirst  place,  variability  though  wide  was  not 
unlimited  and  lists  of  single  movements  and  of  combined  responses 
provoked  by  SS  substraction  and  by  T  presentation  were  coincident.  In 
the  second  place,  observation  of  cats  answering  to  SS  cessation  with  one 
predominant  behaviour  pattern  indicated  that  this  same  performance 
constituted  their  most  frequent  response  to  T.  Therefore,  when  T  was 
apphed  cats  behaved  in  an  anticipatory  fashion  as  if  SS  had  been  inter- 
rupted (even  though  excitation  were  sustained). 

Tones  used  in  this  training  routine  also  acquired  the  ability  to  modify 
potentials  evoked  in  sensory  cortex  by  SS  excitation;  effects  consisting 
essentially  in  masking  or  cancelling  of  peaks  N3,  P3,  N2  and,  commonly, 
P2  and  Ni;  analysis  of  electrographic  changes  may  serve  to  clarify 
problems  posed  by  this  type  of  learning.  Similar  blocking  influences 
act  upon  ccutical  sensory  evoked  potentials  as  a  result  of:  (1)  physio- 
logical stimuli  (e.g.  blowing  air  into  nostrils);  (ii)  central  nervous  stimuli 
(e.g.  of  MRF);  (iii)  anti-cholmesterase  administration  (Bremer  and 
Stoupel,  1959;  Desmedt  and  La  Grutta,  1957;  Gauthier,  Parma  and 
Zanchetti,  1958;  etc.).  Agents  (1),  (ii)  and  (iii)  exhibit  the  second  common 
feature,  of  provoking  EEG  'dcsynchronization'.  It  is  possible  that  T 
applied  during  SS  also  exerted  an  EEG  'desynchronizing'  influence.  This 
contingency  was  supported  by  the  following  observations:  {a)  such  an 
effect  was  observed  frequently  as  a  generalized  or  localized  (to  somatic 
sensory  cortices)  phenomenon  when  T  was  presented  alone;-  (/')  on  T 

'  One  cannot  discard  the  possibility  that  new  hnks  could  be  established  if  indifferent  tones 
were  associated  with  cessation  of  relatively  'non-significant'  stimuli  (e.g.  repetitive  flash). 

-  When  T  was  applied  during  SS,  'dcsynchronization'  on  sensory  cortex  was,  strictly 
speaking,  difficult  to  appreciate.  Subsequent  tracings  added  little  because  cessation  of  SS 
itself  (preceded  or  not  by  T)  was  followed  always  by  low-voltage,  fast  activity. 


J.   p.   SEGUNDO,   C.   GALEANO,  J.   A.   SOMMER-SMITH  AND    ).   A.    ROIG  285 

application  and  simultaneously  with  the  potential  drop  in  CSC,  other 
areas  frequently  showed  EEC  'arousal'. 

Therefore,  T  probably  operated  by  way  of  a  process  inducing  EEG 
'activation'  and  acting  predominantly  upon  the  somatic  sensory  cortices. 
All  EEG  'activating'  influences  of  this  type  are  not  necessarily  identical, 
however,  and  may  perhaps  be  separated  on  the  basis  of  other  criteria  as 
intensity  and  distribution  of  EEG  'arousal',  types  of  concomitant  modifica- 
tions in  cortical  evoked  potentials  and  behaviour,  etc.  In  these  experiments, 
effects  of  tones  reinforced  by  cessation  of  painful  stimuli  were  compared 
with  consequences  of  other  EEG  'arousing'  agents,  applied  in  similar 
circumstances  and,  if  various  criteria  were  taken  into  account,  global 
responses  were  indeed  different.  Firstly,  dissimilar  behaviour  resulted  from 
causes  affecting  evoked  potentials  in  a  similar  manner:  novel  tones  pro- 
duced minor  investigation  reflexes;  intense  sounds,  startle  patterns;  tones 
conditioned  to  SS  initiation  were  inoperant  during  SS;  MRF  excitation 
was  sub-threshold  for  visible  effects;  T  produced  'anticipatory'  effects 
described  above.  Secondly,  ability  to  produce  EEG  'arousal'  and  capacity 
to  affect  EP  were  not  exhibited  in  a  quantitatively  parallel  fashion  by 
various  agents:  evoked  potentials  responded  little  or  irregularly  to  novel 
tones,  'conditioned'  tones  or  intense  sounds  that  determined  clear-cut 
'activation';  they  reacted  markedly  to  T  or  to  MRF  excitation.^  Finally, 
inffuences  compared  here  differed  in  regional  selectivity,  either  provoking 
generalized  (MRF  excitation ;  novel  tone ;  intense  sound ;  conditioned  tone) 
or  localized  (conditioned  tone)  effects.  T  itself  w^as  not  consistent  in  this 
respect:  an  important  fact,  however,  was  that  masking  of  potentials  (in 
contralateral  sensory  cortex)  definitely  could  be  associated  with  restricted 
EEG  'arousal'  (present  in  CSC,  HSC  and  NMDT;  absent  in  acoustic  and 
visual  cortices,  MRF  and  MCG).  Further  signs  of  topographical  specificity 
issued  from  comparison  of  somatic  sensory  and  visual  effects  of  T: 
modification  of  subcutaneously  induced  responses  (somatic  sensory 
cortex)  could  take  place  without  concomitant  alteration  of  photically 
evoked  potentials  (visual  cortex). 

In  short,  and  to  summarize,  the  electrographic  ability  acquired  by  T 
(through  association  with  substraction  of  SS)  consisted  in  a  capacity  to 
mask  somatic  sensory  cortical  evoked  potentials  in  an  intense  and  fre- 
quently restricted  fashion;  such  blocking  seemed  associated  with  a  simul- 
taneous and  similarly  distributed  EEG  'activating'  influence.  Localized 

1  Blocking  of  cortical  potentials  during  EEG  'arousal'  has  been  known  for  some  years; 
augmentatory  effects  have  been  reported  recently  (Bremer  and  Stoupel,  1959;  Dumont  and 
Dell,  1958;  Gauthier,  Parma  and  Zanchctti,  195O;  Segundo,  Sommer-Smith,  Galeano  and 
Roig,  1959)- 


286  BRAIN    MECHANISMS    AND    LEARNING 

'activating'  influences  have  been  shown  to  operate  in  rostral  cortical 
areas  upon  repetitive  excitation  of  vcntralis  posterior,  centre  median 
(rostral  pole)  or  ineso-ventral  intralaminar  nuclei  of  thalamus  in  acute 
experiments  (Jasper,  Naquet  and  King,  1955;  Starzl,  Taylor  and  Magoun, 
195 1).  It  is  reasonable  to  advance  the  working  hypothesis  that  the  same 
nuclei  participated  ni  similar  responses  acquired  by  chronic  preparations. 
A  mechanism  similar  (in  terms  of  general  structures  and  influences 
involved)  to  that  surmised  above  was  presumed  to  intervene  in  the 
establishment  of  current  conditioned  reactions  (Gastaut,  1959).  No 
information  is  available  as  to  the  manner  whereby  T  eventually  became 
capable  of  selectively  energizing  these  structures  and  specifically  triggering 
these  patterns. 

Most  features  (method,  similarity  of  absolute  and  learned  effects, 
inhibitions,  EEG  manifestations,  etc.)  of  typical  conditioning  were  present 
in  the  learning  process  described  here:  if  one  considers  that  substraction  of 
pain  (and  not  pain  itself)  acted  as  absolute  stmiulus,  this  learned  reaction 
may  be  incorporated  to  the  conditioned  reflexes  group  (Konorski,  1946; 
Zbrozyna,  1958).  Terms  'excitatory'  and  'inhibitory'  are  vague  unless 
referred  to  precise  effects:  in  this  respect,  T  influence  was  not  homo- 
geneous, appearing  either  inhibitory  (in  the  sense  that  it  revoked  posture 
and  movements  induced  by  SS)  and  excitatory  (in  the  sense  that  it 
provoked  'desynchronization'). 

SS  produced  behavioural  maniicstations  of  pain  and  elicited  potentials 
on  contralateral  sensory  cortex;  on  application  of  T,  performance  and 
electrographic  signs  were  altered.  Before  entering  into  the  final  considera- 
tions, the  unavoidable  questionability  of  the  following  points  should  be 
stressed,  (i)  The  afflictive  consequences  of  similar  excitation  in  man  plus 
behavioural  manifestations  exhibited  by  cats  when  receiving  SS  favoured 
the  assumption  that  stimuli  were  basically  painful  subjectively;  though 
heavily  significant,  this  evidence  was  not  totally  decisive,  (ii)  Participation 
of  cerebral  cortex  in  pain  perception  is  accepted  currently  in  experimental 
and  clinical  literature  and  it  is  therefore  possible  that  at  least  part  of  the 
evoked  potentials  was  due  to  activation  of  pam-conducting  afferent 
fibres  (Anguelergues  and  Hccaen,  1958;  Melzack  and  Haugen,  1957); 
this  must  be  demonstrated  conclusively,  however,  (iii)  Tones  reduced 
evoked  potentials  and  dns  could  in  fact  mean  that  their  application  blocked 
afferent  volleys  on  their  way  to  or  at  the  cortex;  the  possibility  subsists, 
however,  that  cortical  waves  were  obliterated  by  way  of  some  other  type 
of  influence  (that,  for  instance,  modified  the  temporal  pattern  of  and  the 
relationship  between  individual  discharges),  (iv)  Finally  and  even  if  SS 


J.    p.   SEGUNDO,   C.   GALEANO,  J.   A.   SOMMER-SMITH   AND  j.   A.    ROIG   287 

were  painful  and  cortical  responses  were  dependent  (in  part  or  in  roto) 
on  pain-producing  centripetal  volleys,  it  should  be  kept  in  mind  that  any 
ofFort  to  establish  the  behavioural  (and,  we  may  add,  subjective)  correlates 
to  cerebral  action  potentials  is  '  ...  bound  to  be  tentative'  (Morison, 
Dempsey  and  Morison,  1941).  Therefore,  experiments  described  in  this 
presentation  cannot  be  construed  as  evidence  that,  after  trainnig,  T 
application  blocked  afferent  volleys  initiated  by  SS  and,  consequently, 
cats  experienced  less  pain  and  relaxed;  discussion  of  this  possibility  would 
be  entirely  conjectural. 

In  spite  of  the  previous  cautious  remarks,  two  main  conclusions  may 
justifiably  be  drawn  from  these  experiments.  In  the  first  place,  that  within 
certain  limits,  conduct  and  electrographic  changes  induced  by  sub- 
cutaneous, presumably  painful  stimuli  are  subject  to  variations,  'spon- 
taneous' or  provoked.  In  the  second  place,  that  learned  issues  established 
through  adequate  training  are  significant  m  the  determination  of  induced 
oscillations.  Similar  deductions  may  issue  from  experiments  in  which 
painful  excitation  became  the  conditioned  signal  for  feeding  and,  con- 
comitantly, discomfort-suggesting  manifestations  were  lessened  (Pavlov, 
1941). 

Suggestion  and  hypnosis  have  been  used  for  centuries  by  physicians 
and  the  laity  to  alleviate  pain  and  its  consequences:  it  is  perhaps  within 
this  labile  range  confirmed  experimentally  and  by  way  of  mechanisms 
related  to  those  mobilized  in  chronicallv  implanted  cats,  that  pain  effects 
are  vulnerable  to  such  pocn^ly  understood  but  frequently  effective  measures. 


SUMMARY 

Experiments  were  performed  on  cats  with  chronically  implanted 
electrodes  in  which  application  and  substraction  of  prolonged  subcutan- 
eous stimuli  (SS)  induced  variable  but  characteristic  electrographic  (in 
somatic  sensory  cortex)  and  behavioural  patterns.  During  training  stage  I, 
a  tone  (T)  was  presented  repeatedly  until  rendered  inoperant  (habituation). 
During  stage  II,  SS  was  consistently  interrupted  2-5  seconds  after  T  initia- 
tion. 

A  learning  process  was  established  by  this  'reinforcement'  of  indifferent 
T  with  interruption  of  pain  and  cats  eventually  came  to  react  to  T  m  a 
consistent  fashion.  Behavioural  responses  to  T  initiation  (during  SS) 
resembleci  those  to  SS  substraction  (without  previous  T)  and  consisted  in 
head,  eye  and  or  limb  movements,  frequently  carrying  from  a  'tense'  to  a 
'relaxed,  natural'  position. 


288  BRAIN    MECHANISMS    AND    LEARNING 

Electrographically  (and  even  under  Flaxcdil)  T  masked  potentials 
evoked  by  SS  on  contralateral  sensory  cortex;  amplitude  and  duration  of 
individual  waves  were  reduced  markedly  (initial  spike  was  resistant). 
T  effects  were  compared  clectrographically  as  to  quality,  intensity  and 
distribution  with  results  induced  by  application  of  other  agents  known  to 
reduce  cortical  evoked  potentials  (e.g.  SS  voltage  reduction;  EEG 
'activating'  influence  as  brain  stem  stimulation  or  presentation  of  novel, 
intense  or  conditioned  sounds).  T  effects  exhibited  specificity:  non- 
reinforced  tones  of  different  frequency  become  ineffectual;  T  influence 
could  be  restricted  to  the  somatic  sensory  areas. 

T  application  was  followed  by  EEG  'activation',  generalizeci  or  localized 
(to  sensory  cortices  and  to  nucleus  mcdialis  dorsalis  of  thalamus);  delayed 
and  transitory  reinforcement  of  slow  rhythms  also  occurred. 

Experiments  indicated  that  changes  (behavioural,  EEG)  induced  by 
painful  stimuli  are  subject  to  variations  'spontaneous'  anci  provoked;  they 
indicated,  moreover,  that  learned  issues  established  through  adequate 
training  are  significant. 


GROUP   DISCUSSION 

Gerard.  In  less  careful  terms  than  you  used,  how  long  can  you  fool  the  cat  into 
thinking  that  it  does  not  hurt; 

Segundo.  For  a  period  of  10-30  seconds;  after  that  and  it  shocks  were  continued, 
cats  reassumed  the  characteristic  attitude  and  potentials  returned  to  their  initial 
amplitude. 

Gerard.  Is  the  sound  effect  extinguished; 

Segundo.  Tone  effects  will  be  extinguished  it  sounds  are  repeated  without  their 
usual  'reinforcement'  by  shock  interruption. 

Myers.  I  found  it  very  exciting  to  hear,  Dr  Seo;undo,  that  the  animals  in  vour 
experiment  did  not  differentiate  between  opposing  extremities  in  responding  to 
the  conditioning  stimuli.  Such  a  result  closely  resembles  the  findings  of  Anrep  and 
others  working  with  tactile  conditioning  in  the  dog.  Specifically,  they  found  that 
after  a  positive  conditioned  salivary  response  had  long  been  established  to  tactile 
stimulation  of  a  given  skin  area  on  one  leg,  first  stimulation  of  the  homologous 
locus  of  the  opposite  leg  also  gave  profuse  salivary  flow,  whereas  stimulation  of 
nearby  loci  on  either  side  gave  litde  if  any  salivary  response.  Furthermore,  it  was 
not  found  possible  to  establish  separate  conflicting  reflexes  to  tactile  stimulation  of 
the  separate  homologous  skin  loci.  Rather,  as  the  response  to  tactile  stimulation  of 
one  locus  changed  character,  that  of  its  homologous  locus  tended  always  also  to 
change  'spontaneously'  in  the  same  direction,  the  change  in  the  homologous  locus 
occurring  without  direct  conditioning  through  its  own  receptor  field.  Thus  was 
demonstrated  a  remarkable  mirroring  or  symmetry  of  development  of  tactile 
'gnosis'  over  both  sides  of  the  body  surface  subsequent  to  one-sided  conditioning. 
Bvkov  subsequently  found  that  section  o{  the  corpus  callosum  disrupted  this 


J.    p.    SEGUNDO,    C.    GALEANO,  J.    A.    SOMMER-SMITH   AND  J.    A.    ROIG   2<S9 

symmetrical  development  ot  tactile  conditioned  reHexcs,  and  turther,  that  in  corpus 
callosLim  sectioned  dogs  one  could  tor  the  first  time  establish  conflicting  condi- 
tioned responses  to  tactile  stimulation  of  the  separate  homologous  skin  loci.  I 
wonder  if  vou  have  consiciered  carrying  out  your  series  of  experiments,  Dr 
Scgundo,  in  corpus  callosum  sectioned  animals  to  see  if  your  results  with  regard 
to  generalization  between  the  extremities  might  not  be  different  in  such  animals. 

Segundo.  I  ■was  not  aware  ot  Anrcp's  or  Bykov's  results  and  they  interest  me 
very  much.  Before  proceeding  further,  however,  we  would  like  to  perform  other 
experiments  to  be  sure  of  the  impossibility  of 'ditierentiating  between  paws'. 

Naquet.  Have  you  placed  some  electrodes  in  the  afferent  pathway: 

Segundo.  With  ink  writer  we  explored  potentials  evoked  by  shocks  in  sensorv- 
motor  cortex,  visual  cortex,  acoustic  cortex,  nucleus  medialis  dorsalis  ot  thalamus, 
centre  median  ot  thalamus,  mesencephahc  reticular  formation  and  central  grev; 
with  oscilloscope  in  primary  cortical  receiving  area  exclusiveK'. 

Naquet.  If  I  remember  your  slides  you  do  not  find  any  reduction  ot  the  first 
part  of  the  evoked  potential  during  desynchronization,  only  the  last  two  were  cut. 
Is  that  right; 

Segundo.  Yes,  when  applied  during  subcutaneous  shocks,  tones  blocked  or 
reduced  sensory  potentials  evoked  by  same  in  somatic  cortex:  late  waves  were 
susceptible,  but  the  early  spike  was  resistant.  Waves  evoked  elsewhere  (e.g.  on 
visual  cortex  b}-  flashes)  were  sometimes  left  unaffected.  Tones  trec]uently  produced 
localized  EEG  "desvnchronization'  but  capacity  to  produce  this  effect  was  not 
parallel  with  ability  to  'block'  sensory  cortical  evoked  potentials. 

JouvET.  In  your  last  slides,  during  subcutaneous  stimulation,  it  looked  as  if  you 
get  slow  waves  on  the  cortical  area,  or  at  least  the  EEG  is  not  desynchronized.  Did 
you  get  any  slow  waves  in  the  reticular  formation  during  subcutaneous  stimulation ; 

Segundo.  During  shock  application  we  occasionallv  observed  cortical  and  sub- 
cortical spindles. 

JouvET.  Because  I  wondered  it  this  late  component  has  not  got  something  to  do 
with  supra-liminal  inhibition  in  Pavlovian  terms. 

Asratyan.  It  I  am  not  mistaken  about  the  conditions  ot  vour  experimentation 
you  have  elaborated  a  backward  conditioning. 

Segundo.  The  tone  preceded  the  cessation  of  a  prolonged  subcutaneous  stimulus. 

Asratyan.  But  the  electrical  stimulation  precedes  the  tone  by  many  minutes. 
And  in  these  cases  tone  became  a  conditioned  stimulus  and  produced  the  same 
effect  as  electrical  stimulation.  It  seems  to  me  that  this  is  an  expression  of  Reverse 
connection  from  tone  to  electrical  stimulation.  Have  you  some  signs  that  you  have 
also  some  direct  conditioned  connection  ?  That  is  that  the  application  of  the  elec- 
trical stimulus  alone,  after  such  a  combination,  is  able  to  produce  some  change 
characteristic  ot  the  application  of  tone  alone. 

Segundo.  We  believe  shock  'interruption'  and  not  shock  'application'  acted  as 
absolute  stimulus.  Substraction  of  environmental  agents  may  produce  positive 
effects  within  the  central  nervous  system  as,  for  instance,  in  the  case  of  auditory 
units  that  react  to  tone  interruption  (Galambos,  1952).  On  the  other  hand,  it  is 
true  that  shocks  preceded  tones  and  therefore  possible  that  the}-  could  acquire 
some  behavioural  or  electrographic  feature  corresponding  to  the  latter.  In  the 
behavioural  sphere,  we  started  off  with  tones  to  which  cats  had  been  habituated 
and  therefore  were  inoperant;  it  would  thus  be  difficult  to  define  an  absolute  tone 


290  BRAIN    MECHANISMS    AND    LEARNING 

effect.  In  the  EEG  sphere,  I  am  atraid  we  did  not  search  for  possible  effects  of 
somatic  stimuU  in  auditory  regions. 

Magoun.  IDid  your  conditioned  reduction  oi  potentials  occur  in  the  thalamus  as 
in  the  cortex? 

Segundo.  Thalamic  potentials  were  not  studied. 

Gerard.  I  would  have  assumed  that  you  have  evidence  against  any  serious 
decrease  in  the  input  from  the  fiict  that  your  early  waves  often  did  not  change  at  all. 
Is  that  unsound? 

Segundo.  The  classical  mterpretation  of  somatic  sensory  evoked  potentials 
considers  that  the  early  wave  of  the  cortical  response  is  due  to  afferent  volleys  and 
late  waves  to  intracortical  processes.  I  find  it  difficult  to  admit,  however,  that  no 
afferent  activity  at  all  reaches  the  cortex  during  those  delayed  oscillations. 

Magoun.  My  interest  in  subcortical  potentials  is  related  to  the  question  of: 
whether  activity  evoked  in  the  sensory  cortex  is  to  be  correlated  with  pain  percep- 
tion. Might  some  feature  of  the  evoked  cortical  potential  later  than  the  early  spike 
or  some  activity  which  never  reached  the  cortex  at  all,  be  of  importance  here?  The 
reduction  or  block  of  pain  perception  might  not  be  correlated  with  what  you  are 
recording  in  the  sensory  cortex.  Conceivably  you  might  fmd  potentials  subcorti- 
cally  that  would  be  more  directly  related  to  the  perception  of  pain.  Could  you  give 
us  your  impression  of  what  potentials  are  evoked  in  the  CNS  by  a  peripheral  pain 
stimulus? 

Segundo.  Various  potentials  were  evoked  bv  subcutaneous  stimuli  in  our 
'chronic'  cats :  though  we  did  not  explore  extensively,  it  was  obvious  that,  in  these 
animals  as  in  certain  'acute'  preparations,  subcutaneous  stimuli  evoked  at  least 
'cortical  primary',  'cortical  associative'  and  'reticular'  responses.  A  number  o{ 
dubious  issues  is  involved,  however,  in  the  question  of  which  electrograpliic 
phenomenon  was  correlated  with  perception  of  pain:  correlation  of  pain  probably 
experienced  by  our  cats  on  the  one  hand,  with  potentials  evoked  in  different  areas 
or  individual  waves  on  the  other  is  extremely  hazardous  (see  Discussion  in 
text). 

Lundberg.  I  would  like  to  ask  to  what  extent  you  think  it  is  likely  that  some  of 
the  evoked  potentials  are  due  not  to  stimulation  of  pain  fibres  but  to  stimulation  of 
touch  fibres.  If  so,  these  evoked  potentials  may  not  have  any  relation  to  the 
nociceptive  behaviour  of  the  animal. 

Segundo.  As  mentioned  above,  we  cannot  correlate  individual  waves  pertaining 
to  cortical  evoked  potential  with  cat  behaviour  or  pain  sensations.  Other  types  of 
peripheral  fibres  were  probably  activated  as  well  and  we  do  not  know  to  what 
extent  each  type  participated  in  determination  of  each  wave. 

BusER.  I  would  like  to  ask  whether  in  Dr  Segundo's  opinion,  the  cat  felt  pain 
during  the  period  it  submitted  to  sound;  in  trying  to  correlate  the  amplitude  of  an 
evoked  potential  to  the  'conscious  perception'  of  the  corresponding  stimulus,  we 
are  used  to  the  fact  that  a  higher  level  of  wakefulness  may  correspond  to  a  smaller 
amplitude  of  the  cortical  response  (at  least  with  peripheral  stimuli) ;  in  the  case  of  Dr 
Segundo's  experiments,  could  it  not  be  the  opposite? 

Gerard.  I  think  you  are  talking  about  the  differences  between  sensing  something 
and  attending  to  the  sensation.  We  know  morphine  does  not  raise  the  threshold  to 
pain  stimulation,  it  just  makes  the  person  not  worry  about  it  so  much;  and  frontal 
lobe  operations  do  the  same  thing.  I  was  wondering,  along  the  same  lines,  whether 


J.   p.   SEGUNDO,    C.   GALEANO,  J.   A.   SOMMER-SMITH  AND  J.   A.   ROIG  29I 

perhaps  your  two  separate  waves  represent  the  arrival  ot  the  initial  peripheral 
stimulus  and  the  secondary  attending  to  it. 

Segundo.  I  think  there  are  two  main  points  in  Dr  Buser's  comment.  As  regards 
the  first,  we  cannot  know  for  certain  what  the  cat  felt.  As  to  the  second,  it  is 
indeed  true  that  EEG  'arousal'  is  associated  usually  with  decreased  cortical  poten- 
tials. I  would  like  to  mention,  however,  recent  experiments  by  Bremer  and 
Stoupel  and  Dumont  and  Dell,  in  which  stimulation  of:  mesencephalic  reticular 
formation  produced  EEG  'arousal'  and  simultaneously  'facilitation'  ot  responses  in 
primary  receiving  cortices  (Bremer  and  Stoupel,  1959;  Dumont  and  Dell,  1959). 
Hence  'desynchronization'  is  not  associated  necessarily  with  reduction  of  sensory 
cortical  potentials. 

Olds.  I  think  it  relevant  to  the  problem  of  whether  pain  is  reduced  is  the  question 
of  whether  you  ever  get  adaptation  to  this  subcutaneous  stimulus  by  itself  How 
long  is  the  series  of  shocks  before  the  tone  is  introduced?  And  I  would  like  also  to 
ask :  Is  there  ever  any  change  in  responding  during  the  course,  either  recruitment 
or  readaptation? 

Segundo.  We  stimulated  between  seconds  and  hours  and  an  average  of  3-4 
minutes  was  used  currently.  There  were  marked  spontaneous  variations  of  evoked 
potentials:  for  instance,  and  since  you  mentioned  'recruitment',  in  certain  cats 
8  per  second  stimulation  produced  an  effect  that  was  entirely  comparable  to 
'augmentation'. 

Hernandez-Peon.  I  would  like  to  remind  Dr  Segundo  ot  the  experiments  of 
Bremer  and  Stoupel.  Electrical  stimulation  oi  the  mesencephalic  reticular  forma- 
tion produces  striking  facilitations  of  the  cortical  potentials  evoked  by  electric 
shocks  applied  to  the  optic  nerve.  But  when  they  used  a  flash  ot  light  instead 
(which  I  think  is  more  physiological  than  an  electric  shock  applied  to  the  optic 
nerve)  they  observed  a  striking  redtiction  of  the  evoked  potential.  With  reference 
to  Dr  Magoun's  question  about  subcortical  changes  in  the  somatic  afterent  path- 
ways, specially  where  pain  is  concerned,  I  can  say  that  we  have  recorded  evoked 
potentials  both  at  the  spinal  sensory  nucleus  in  the  bulb  and  in  the  lateral  column  of 
the  spinal  cord  in  conscious  cats.  Experiments  have  shown  at  both  levels  that  the 
potentials  evoked  by  nociceptive  stimuli  are  reduced  when  the  cat  focuses  its 
attention  upon  some  other  stimulus  of  greater  significance.  Of  course,  this  reduc- 
tion is  more  difficult  to  obtain  on  the  potentials  evoked  by  nociceptive  stimuli 
than  on  the  potentials  evoked  by  tactile  stimuli. 

Segundo.  A  priori,  one  would  tend  to  think  that  also  for  sensory  control,  the 
nervous  system  has  two  types  of  mechanisms,  one  facilitatory  and  another  in- 
hibitory: in  terms  of  unit  responses  this  is  true.  When  evoked  potentials  have  been 
controlled,  facilitation  has  not  been  frequent  but  we  must  remain  receptive  to  the 
idea  that  under  certain  conditions,  sensory  evoked  potentials  may  be  facilitated. 


NEUROHUMORAL  FACTORS   IN  THE  CONTROL  OF 
ANIMAL  BEHAVIOUR 

K.  LissAK  AND  E.  Endroczi 

The  homeostasis  of  the  organism  is  regulated  by  two  factors,  neural  and 
endocrine,  which,  by  complex  niteraction,  have  influenced  each  other 
throughout  the  course  of  evolution. 

Higher  nervous  activity  and  conditioned  reflexes  are  also  manifesta- 
tions of  the  adaptability  of  the  organism.  Without  wishing  to  disregard 
the  basic  role  played  by  neocortical  structures  in  the  development  of  higher 
nervous  processes,  we  regard  it  as  necessary  to  analyse  the  role  of  sub- 
cortical systems  ui  the  organization  of  conditioned  reflex  connections  and 
basic  emotional  behaviour. 

After  the  discovery  of  the  role  of  the  difi^iise  activating  system  in  the 
maintenance  of  the  waking  state  of  the  cortex,  a  whole  series  of  communi- 
cations has  appeared  in  recent  years.  All  show  that  the  neural  network, 
described  by  Cajal  sixty  years  ago,  and  termed  reticular  formation  today, 
can  be  influenced  not  only  by  neural  but  also  humorally.  Therefore, 
when  the  mechanisms  of  the  brain  stem  are  considered,  the  neural  organi- 
zation of  the  mesencephalon  and  diencephalon  must  be  regarded  as  an 
integrating  system  at  a  complex  neurohumoral  level. 

During  the  past  decade  one  of  the  subjects  investigated  in  our  Institute 
has  been  the  interrelationship  between  complex  neuroendocrine  processes 
and  behaviour.  The  problem  which,  first  of  all,  concerns  the  neuro- 
endocrine control  of  the  conditioned  reflex  and  basic  emotional  behaviour 
in  higher  animals,  is  enormously  complicated  by  the  fact  that  interference 
with  neural  organization  also  affects  endocrine  regulation,  the  changes 
of  which  react  on  the  nervous  system  and  influence  behaviour. 

In  our  earlier  investigations  (Endroczi,  Lissak  and  Telegdy,  1958)  it  was 
observed  that  during  lactation  the  domesticated  mother  rat  would  attack 
and  kfll  a  frog  put  in  her  cage.  This  maternal  aggressivity  can  be  observed 
only  during  the  period  of  lactation.  The  administration  of  oestrone 
for  a  few  days  (300-400  lU/ioo  g.b.w.)  will  abolish  it  completely  without 
interfering  with  the  care  of  the  offspring.  The  interesting  point  in  this 
experiment  was  that  in  the  prevention  of  this  folliculine  action  hydro- 
cortisone was  more  effective  than  progesterone.  At  the  same  time  it  was 
also   observed   that  hydrocortisone  not  only  abolished  the  inhibitory 

293 


294  BRAIN    MECHANISMS    AND    LEARNING 

influence  of  oestronc  but  also  elicited  it  in  animals  in  which  it  had  not 
been  present  previously.  The  phenomenon  is  based  on  the  antagonistic 
action  of  two  endocrine  factors  influencing  the  central  nervous  system. 
The  point  of  attack  has  not  been  quite  clarified  as  yet,  although  we  have 
findings  which  suggest  that  certain  subcortical  systems  play  an  important 
role  in  this  mechanism.  Thus  electrolytic  lesions  of  amygdale  or  of  the 
area  pyriformis  and  destruction  of  the  septal  region,  will  also  abolish 
maternal  aggrcssivity  in  the  lactating  rat.  Another  noteworthy  observa- 
tion of  ours  is  that  after  removal  of  the  amygdale  and  the  hippocampal 
formation,  the  mouse-catching  reaction  of  the  cat  is  abolished  for  a 
longer  period,  although  the  animal  feeds  well  and  the  somato-motor 
activities  are  satisfactory  (Endroczi  and  Martin  and  Bata,  1958).  These 
investigations  show  that  the  above-mentioned  archicortical  structures  not 
onlv  play  a  role  in  the  organization  of  emotional  behaviour  but  can  also  be 
influenced  by  endocrine  factors. 

CpdB 
Xll      XIII         XIV  XV  k      XVII 


I 


0    3      6     9      12     15    18    2f    24    27   30    33    36   39    42   A5   48 

\       I 1 1 i       I       1 1       \    ■       '       ■       ■       ■ \ '       ■ 

Fig.  I 

Papcrchroinatogram  showing  the  difference  of  corticoid  composition  in  the  blood  of  the 
adrenal  vein  in  wild  and  domesticated  rats. 

XII  (Reichstein,  S) :  the  main  component  in  the  wild  rat. 

XIII  and  XIV :  trace-components  in  wild  and  domesticated  rats. 

Cpd  B  (Corticosterone) :  the  main  components  in  the  domesticated  rat. 
XVII:  occasionally  in  the  domesticated  rat. 

As  is  generally  known,  the  hypophysial-adrenocortical  system  is 
important  in  keeping  the  endocrine  system  in  a  state  of  balance,  to 
changes  in  which  —  as  has  been  pointed  out  in  previous  detailed  studies  — 
the  adrenal  cortex  will  respond  specifically  by  a  change  in  the  composition 
of  its  secretion.  Not  many  investigators  pay  attention  to  the  variations  in 
the  composition  of  the  adrenocortical  secretory  products,  which,  accord- 
ing to  our  findings,  are  not  only  important  m  the  control  of  vegetative 
and  metabolic  processes  but  also  affect  complex  behavioural  processes. 
Analysis  of  adrenocortical  function  is  complicated  by  the  fact  that  not 
only  are  there  wide  differences  between  species  but  that  even  within  the 
same  species,  wide  individual  qualitative  and  quantitative  variations  may 


K.    LISSAK   AND    E.    ENDROCZI 


295 


be  observed.  How  wide  die  variadons  in  the  same  species  may  be  is 
illustrated  by  the  difference  between  the  corticoid  contents  of  the  adrenal 
venous  blood  in  domesticateci  and  wild  rats  respectively. 

The  corticoid  spectrum  of  the  blood  in  the  adrenal  vein  is  interesting 
not  only  in  its  quantitative  aspect  but  also  because,  under  certain  condi- 
tions, the  synthesis  of  such  compounds  may  occur  as  will  have  an  altered 
effect  on  central  nervous  organization.  Considering  all  these  aspects  we 


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Fig.  2 
Relationship  between  the  inhibitory  period  ot"  ahnientary  conditioned  reflex  caused 
by  electric  shock  on  the  hind-leg  and  the  corticoid  content  in  the  blood  ot  the 
adrenal  vein.  Black  columns:  duration  of  inhibitory  period  in  dogs.  Blank  columns: 
proportion  of  hydrocortisone  and  corticosteronc. 


should  like  to  deal  with  certain  data  concerning  the  endocrine  background 
of  temporary  connections  or  that  of  neuroses  resulting  from  a  break  in 
those  connections. 

An  alimentary  conditioned  reflex  was  established  in  dogs  in  the 
following  manner:  on  the  sound  of  the  positive  bell  the  animal  pushed  a 
swing-door  to  reach  the  food.  Another  bell  sound  served  as  negative 
acoustic  stimulus.  After  sixteen  daily  trials  at  three-minute  intervals,  the 


296  BRAIN    MECHANISMS    AND    LEARNING 

conditioned  rcHcx,  free  from  intersignal  reactions,  was  established  after  300 
associations.  This  was  followed  by  the  establishment  of  the  neurosis. 
Simultaneously  with  the  positive  bell  sound,  on  three  subsequent  occasions, 
a  strong  painful  electric  shock  was  administered  to  a  hind-leg  of  the 
animal  and  it  was  observed  how  many  days  after  the  break  the  normal 
conditioned  reflex  would  reappear.  When  the  conditioned  reflex  had  been 
fully  re-established,  the  corticoid  composition  of  the  blood  in  the  adrenal 
vein  was  examined. 

Although  the  break  of  the  conditioned  reflex  was  brought  about  under 
identical  conditions,  the  figure  shows  considerable  variations  in  the 
duration  of  the  inhibitory  period.  A  long  inhibitory  period  showed  a  close 
relationship  to  the  adrenal  secretion,  or  rather  to  the  ratio  of  hydrocorti- 
sone and  corticosterone.  In  the  case  of  short  periods  of  inhibition  the 
hydrocortisone-corticosterone  ratio  was  low,  in  prolonged  inhibition, 
however,  a  high  ratio  was  observed. 

The  question  of  whether  or  not  adrenocortical  secretion  and  duration  of 
inhibition  can  be  brought  into  a  direct  causal  relationship  was  answered  by 
our  next  experiment.  In  those  animals  which,  prior  to  the  break  in  the 
temporary  connection  had  been  treated  with  hydrocortisone  for  a  week, 
not  only  was  the  inhibitory  period  several  times  longer  than  that  observed 
in  the  animals  many  months  before  this  treatment,  but  it  was  also  accom- 
panied by  marked  neurotic  signs  which  were  not  observed  in  the  un- 
treated animals. 

Those  experiments  would  seem  to  indicate  that  the  neurotic  status 
caused  by  the  break  in  the  conditioned  reflex  is  influenced  by  the  ratio  of 
the  two  main  components  secreted  by  the  adrenal  cortex,  i.e.  hydrocorti- 
sone and  corticosterone.  The  qualitative  difference  in  the  effect  of  thes-e 
two  compounds  on  the  nervous  system  has  already  been  pointed  out  by 
Woodbury  and  his  co-workers  (1949-54).  According  to  their  observations 
hydrocortisone  lowers  considerably,  while  corticosterone  does  not 
influence,  the  convulsant  threshold  of  the  central  nervous  system;  more- 
over, corticosterone  counteracts  the  effect  of  hydrocortisone  in  this  respect. 
The  ratio  of  the  two  compounds  varies  with  the  individual,  and  this, 
according  to  our  investigations,  is  of  importance  in  the  development  of 
the  neurotic  state.  Our  experiments  on  the  rat  resulted  in  the  same  find- 
ings, on  the  basis  of  which  the  strain  examined  by  us  could  be  divided  into 
four  groups  with  different  inhibitory  periods.  In  each  group  the  adreno- 
cortical activity  was  found  uniform  and,  what  is  more,  could  also  be  well 
distinguished  quantitatively  (Endroczi,  Lissak,  Telegdy,  1957). 

On  the  basis  of  those  experiments  the  effect  of  the  adrenocortical 


K.    LISSAK    AND    E.    ENDROCZI 


297 


hormones  with  high  pohirity  was  interpreted  to  increase  the  intensity  of 
the  inhibitory  processes.  After  the  administration  of  ACTH,  Mirsky, 
Miller  and  Stein  (1953),  observed  facilitation  of  the  avoiding  conditioned 
reflex,  which  would  seem  to  indicate  that  hypophysial-adrenocortical 
activity  supports  the  neural  adaptation  of  the  defensive  mechanism.  In 
later  experiments,  however,  it  was  observed  that  ACTH  and  the  corti- 
coids  not  only  influence  exteroceptive  inhibitory  and  neurotic  pheno- 


1 


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Lady 


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5  days 


Fig.  3 
Fig.  3  shows  that  in  certain  cases  the  administration  of  ACTH  increases  inner  inhibition 
considerably.  Development  of  inner  inhibition  on  dogs.  The  ordinate  corresponds  to  the 
trials  for  each  day.  Blank  columns:  without  treatment  with  ACTH;  Black  columns:  after 
administration  ACTH  for  4  days  (2,  lU/kg.  Zn-Cortrophine,  Organon). 


mena  but  also  increase  the  inner  inhibition  which  develops  after  a  positive 
stimulus  administered  without  reinforcement  every  day  until  the  condi- 
tioned reaction  disappeared.  On  the  following  days  this  extinction  was 
repeated  until  the  conditioned  stimulus  elicited  no  response.  In  view  of  the 
fact  that  the  times  of  extinction  observed  after  an  interval  of  several 
months  were  practically  identical  in  the  same  animals,  it  was  possible  to 
check  the  effect  of  the  treatment  with  adrenocortical  hormones.  The 


298 


BRAIN    MECHANISMS    AND    LEARNING 


figure  shows  that  in  certain  cases  the  admniistration  of  ACTH  increases 
the  inner  inhibition  considerably  (Lissak,  Medgyesi,  Tcnyi,  Zorcnyi, 
195S). 

Several  examples  illustrate  that  the  conditioned  reflex  method  enables 
us  to  study  the  effect  of  humoral  factors  on  behaviour  under  objective 
conditions.  Naturally,  within  those  limits  it  is  not  possible  to  analyse  the 
immediate  effect  of  endocrine  factors  on  the  central  nervous  system.  In 
our  experiments  we  started  from  the  assumption  that  the  brain  stem  and 
the   subcortical    mechanisms  —  which   play   a   fundamental   role   in   the 


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5    10    15   20,  25  X  35  W   hScm 


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T 


CpdF    CpJB 


Fig.  4 
Effect  of  brain  stem  stimulation  upon  the  corti- 
coid  level  and  composition  of  the  blood  in  the 
adrenal  vein  of  cats.  The  figure  shows  marked 
elevation  of  hydrocortisone  and  corticosterone 
secretion  as  a  result  of  15  minutes'  stimulation. 


mouldmg  of  emotional  behaviour  —  are  concerned  m  the  integration  of 
conditioned  reflex  connections  and  also  in  the  organization  of  endocrine 
mechanisms.  There  are  several  data  to  indicate  that  humoral  factors  also 
influence  these  structures.  Experiments  with  chronically  implanted 
electrodes  and  electrocoagulation  carried  out  with  a  stereotaxic  instrument 
on  dogs,  cats,  rabbits  and  rats  revealed  a  complex  circuit  of  neural 
processes,  which  play  an  important  role  in  the  regulation  of  endocrine 
mechanisms. 

Without  going  into  the  details  of  the  large  number  of  observations  I 
wish  to  deal  only  with  the  main  points  of  our  results.  It  has  been  observed 


K.    LISSAK    AND    E.    ENDROCZI 


299 


in  experiments  with  depth  electrodes  that  stimulation  of  mesencephalic 
reticular  formation,  posterior  hypothalamus  including  the  mamillary 
bodies  and  the  intralaminar  nuclei  of  the  thalamus  activates  the  pituitary- 
adrenocortical  system.  This  can  be  checked  directly  by  estimating  the 
corticoid  content  of  the  blood  in  the  adrenal  vein. 


li       S     12     i6    20    Ih    2S    iZ    36     W    'i'<Cm 


^        0  0 


n: 


Cpdf-    CpdaCpji     fioH- 

'  '  nroaestet^one 


pro(jt 


Fig. 


Effect  of  stimulation  ot  ainygdale  and  pyritorni  cortex  on  dogs.  The 
figure  shows  appearance  of  17-hydroxy-progesteronc  following 
repeated  stimulation  (15  minutes  daily  for  5-6  days)  of  medial  part 
of  amygdale-pyriform  cortex.  Stimulation  of  lateral  areas  elicited 
only  marked  ele^'ation  of  resting  corticoid  secretion  without  the 
appearance  of  new  secretory  product  or  sexual  hyperactivity. 


Step-like  changes  in  the  behaviour  of  animals  were  observed  tiuring  the 
stimulation  of  the  above-mentioned  structures  as  a  consequence  of  rising 
intensity  of  stimuli.  Marked  orientation  cliciteci  by  threshold  stimuli  was 
followed  by  emotional  reactions  (fear,  avoiciing-reaction),  and  further 
elevation  of  stimulus  mtensity  induced  extreme  furious  behaviour 
(O,  5-5,  O  V,  60-90  H,  3  msec).  After  cessation  of  stimulation  the  original 
behaviour  returned  without  delay. 


300 


BRAIN    MECHANISMS    AND    LEARNING 


In  addition  to  these  short  direct  activating  pathways  influcncins;  the 
pituitary-adrenocortical  axis,  there  is  a  long  circuit,  which,  with  regard  to 
its  controlhng  effect,  is  of  a  modifying  and  inhibitory  nature.  Repeated 
stimulation  of  the  medial  nuclei  of  amygdale  and  pynform  cortex  resulted 
in  a  change  of  composition  of  adrenal  secretory  products,  whose  endo- 
crine manifestations  were  coupled  with  marked  sexual  hyperactivity  in 
the  post-stimulatory  period  (lordosis,  copulative  activity  in  females  and 
copulative  activity,  priapism  in  male  cats  and  dogs). 


m 


^ 


.-S^ 


^ 


O 

•o 
■SO 


m 
w 

50 

w 

50 
20 


i 


I 


^      S    iZ    16    20   2h   28   62    56    W    ^hcm 


S 


^   \)     \)        VI 


CpdF 


B     A        11'  OH  proaesterone 


Fig.  6 

Shows  the  appearance  of  i  i-hydroxyprogesterone  in  the  blood  of  the  adrenal  vein  after 
stimulation  of  medial  part  of  amygdale  and  pyriform  cortex  ot  cats. 


In  female  ovaricctomized  cats  we  were  not  able  to  elicit  the  above- 
mentioned  endocrine  and  behavioural  changes  which  permit  an  insight 
into  the  complex  mechanism  induced  by  stimulation  of  area  pyriformis. 

In  contrast  to  the  stimulation  of  archistriatum  (amygdale)  which  can 
modify  adrenocortical  activity  and  somatic  behaviour  through  the  pitui- 
tary-gonadal  system,  we  found  an  inhibitory  influence  of  hippocampal 
stimulation   on   the   stress   mechanism   and   in   some   extent  on  somatic 


K.    LISSAK    AND    E.    ENDROCZI 


301 

behavie:)ur.  Stimulation  of  the  hippocampus  in  various  laboratory  animals 
diminished  the  resting  corticoid  level  in  the  blood  of  the  adrenal  vein 
and  prevented  the  adrenocortical  hyperactivity  elicited  by  humoral  or 
neurotropic  stimuli  (Endroczi  and  Lissak,  1959). 

Except  for  a  slight  initial  orientation-reaction  no  changes  were  observed 
during  hippocampal  stimulation.  This  is  in  agreement  with  die  findings  of 
other  authors  (Pentield  and  Jasper,  1953;  Akert  and  Andy,  1953). 


■^20 

^5 


t 


'i  ^   K'    f6  20  z'i  li  jz  36  'ji  "vr 


'^     » 


CpdF 


CpcJb 


Fig.  7 
rhc  mrtucncc  iif  hippocampal  stinuilation  (through 
1 5  minutes)  on  the  corticoid  content  of  blood  in  the 
adrenal  vein  of  cats.  Marked  lowering  of  corticoid 
level  v^'as  observed. 


It  may  be  asked  in  what  pathways  these  neuroendocrine  processes  and 
behavioural  changes  are  regulated  by  the  archicortex  and  archistriatum. 
Without  going  into  the  details  of  relevant  literary  data  we  suppose  that 
the  chief  ascending  afferent  pathways  of  archicortex  and  archistriatum 
pass  through  the  septum  and  c^riginate  from  the  tegmental  nuclei.  Electro- 
coagulation destruction  of  the  subcallosal  area  in  the  septum  resulted  in  a 
spectrum  of  corticoids  similar  to  that  found  after  repeated  stmiulation  of 
the  medial  part  of  the  pyriform-amygdale  complex.  Other  lesions  of  the 
septum  touched  only  the  subcallosal  grey  matter  and  elicited  an  opposing 
effect.  In  these  animals  a  diminished  content  of  corticoids  in  the  blood  of 
the  adrenal  vein  was  found  2-3  weeks  after  the  operation.  With  regard  to 
the  varied  localization  of  these  lesions,  we  suppose  it  must  be  due  to  the 
chronic  irritation  of  afferent  connections  related  to  the  hippocampus. 
Complete  destruction  of  these  afferent  pathways  can  abolish  the  hippo- 
campal inhibitory  influence  on  the  stress  mechanism  and  the  control  of 


302 


BRAIN    MECHANISMS    AND    LEARNING 


archistriatuni  influencing  the  pituitary-adrenocortical  system  then  comes 
into  prominence.  It  is  an  interesting  fact  that  the  animals  clectrocoagulatcd 
in  the  subcallosal  area  did  not  show  sexual  hyperactivity.  The  pituitary- 
adrenc^cortical  activity,  however,  was  in  accordance  with  that  of  animals 
stimulated  in  the  amygdale-pyriform  complex.  The  lesion  of  these  path- 
ways resulted  in  a  separation  of  behavioural  and  endocrine  processes 
integrated  by  the  telencephalon. 


bo  ■ 


So 


Uo 


\o 


l?-3H 


Control 
6 


SZ-bS 


i 


// 


m-5? 


Histamine 

5 

Fig.  8 


AHer  5t"»mu\ot\o(\ 

5 


Prevention    of  histamine   induced   adrenocortical  hypcrfunction, 
induced   by  hippocampal  stimulation. 


Summing  up  the  above-mentioned  results,  we  may  say  that  common 
subcortical  mechanisms  take  part  in  neuroendocrine  control  and  in 
elaborating  emotional  or  sexual  behaviour.  Naturally,  for  these  complex 
integrating  mechanisms  we  must  take  into  account  the  feed-back  action  of 
the  humoral  system  as  we  have  demonstrated  by  the  stimulation  of  area 
pyriformis  (Endroczi,  Lissak,  Bohus  and  Kovacs,  1959;  Lissak,  Endroczi, 
Bohus  and  Kovacs,  1958;  Endroczi,  1959). 

It    may    be   asked    in    what   way    those   neuroendocrine   controlling 


K.    LISSAK    AND    E.    ENDROCZl 


mechanisms  are  concerned  with  behavioural  processes  or  the  development 
of  higher  nervous  activity.  There  is  no  doubt  that  ni  the  subcortical 
organization  of  the  conditioned  reflex  we  must  assume  the  participation 
of  the  same  structures  previously  considered  in  connection  with  neuro- 
endocrine control.  The  action  of  the  endocrine  factors  on  the  central 
nervous  system  cannot  be  regarded  as  the  result  of  changes  in  the  general 


CpdFBA  ii-OH         CpdF 

proaedtrone 


bh  H-OH 

prooesierone 


Fig.  9 
Influence  of  septal  lesions  on  the  adrenocortical  secretion  of  cats.  Part  I  shows  a  marked 
elevation  of  resting  corticoid  level  and  appearance  of  gestagens  in  the  blood  of  the  adrenal 
vein.  Part  2  shows  the  diminished  corticoid  level  as  a  result  of  local  irritation  of  septal  pathways. 


metabolic  processes  of  the  nervous  tissue.  Obviously,  this  is  a  more  specific 
phenomenon.  So,  according  to  our  observation  on  the  dog,  2-3  minutes 
after  an  epileptic  attack  induced  by  the  stimulation  of  the  temporal  lobe, 
the  animal  w'ill  respond  to  an  alimentary  conditioned  stimulus  in  a  normal 
manner,  although  at  the  same  time  a  large  number  of  post-convulsive 
metabolic  changes  are  still  taking  place.  On  the  basis  of  earlier  experi- 
ments, according  to  which  the  development  of  a  neurotic  state  is  enhanced 


304 


BRAIN    MECHANISMS    AND    LEARNING 


by  adrenocortical  hormones,  it  cannot  be  denied  that  the  endocrine  action 
is  brought  about  by  the  inhibition  of  a  specific  temporary  connection, 
which  does  not  affect  the  whole  series  of  conditioned  reflex  connections 
concerned  in  the  shaping  of  behaviour.  Effects  of  a  similar  character  may 
be  mentioned  in  connection  with  the  action  of  sexual  steroids,  however,  at 
a  different  level. 

We  should  now  like  to  pass  on  to  some  observations  which  show  the 
influence  of  the  environment  on  the  development  of  conditioned  reflex 


Fig.  10 
Structural  relationships  between  forniatio  reticularis,  hypothalamus,  septum, 
archicortcx  and  pyriform  area.  Thick  solid  line  shows  the  direct  activating 
mechanism,  thin  lines  correspond  to  the  modifying  pathways  and  dotted  lines 
show  the  inhibitory  pathways. 


connections.  In  recent  years  we  have  been  studying  in  conditioned  reflex 
experiments  the  effect  of  the  stimulation  of  the  reticular  formation  of  the 
tegmentum  on  alimentary  conditioned  reflex  activity  elaborated  pre- 
viously in  the  normal  and  the  neurotic  states.  Experiments  on  dogs  showed 
that  stimulation  of  the  reticular  formation,  more  precisely  of  the  grey 
matter  round  the  aqueduct  of  Sylvius,  induced  a  conditioned  reflex,  even 
though  no  positive  sound  stimulus  was  applied.  This  phenomenon 
resembles  a  finding  by  Grastyan  and  his  co-workers  (1956,  1959)  at  our 


K.    LISSAK    AND    E.    ENDROCZI  3O5 

Institute  in  experiments  on  cats  after  diencephalic  stimulation.  Further- 
more, it  was  interesting  to  sec  what  changes  in  behaviour  were  elicited  in 
the  dogs  by  stimulation  outside  the  conditioned  reflex  chamber.  The 
experiments  resulted  in  the  surprising  observation  that  in  the  new  situa- 
tion either  a  simple  orientation  reflex  or  a  dominant  conditioned  reflex 


Fig.  II 
Schematic  illustration  of  cross-section  of  dog's  brain 
at  the  mesencephalic  level.  Numbers  show  the  points 
of  stimulation  eliciting  positive  conditioned  reactions. 
(BIC:    brachium   of  inferior   colliculus;  CC:  corpus 
callosum;  H:  hippocampus;  LGP:  lateral  geniculate 
body,  pars  post.;  MG:  Medial  geniculate  body;  OT 
optic  tract;  P:  posterior  nucleus  and  pyramid;  PC 
post,  commissure;  PL:  pulvinar;  PRE:  prctectum;  RN 
red  nucleus;  SN:  substantia  nigra.) 

corresponding  to  the  new  environment  appeared.  Thus,  the  animal  lay 
down  or  sat  down  or  gave  its  paw  to  the  observer,  which  corresponded  to 
a  conditioned  reflex  learned  before.  An  interesting  result  was  obtained  in 
the  course  of  these  observations  by  Lissak  and  Endroczi  (1959)  when 
stimulation  was  carried  out  in  the  neurotic  state.  In  animals  in  which 


306  BRAIN    MECHANISMS    AND    LEARNING 

Stimulation  of  the  reticular  formation  elicited  the  conditioned  reflex,  a 
neurotic  state  was  produced  by  the  administration  of  a  painful  stimulus 
simultaneously  with  the  positive  sound  stimulus.  In  this  state  all  signs  of 
neurosis  (barking,  defaecation,  urination,  escape  reaction  and  fear)  were 
elicited  by  the  sound  stimulus.  When  in  this  state  stimulation  was  begun 
the  animal  calmed  down  and,  as  a  result  of  stimulation,  the  conditioned 
reaction  appeared.  However,  a  few  minutes  after  the  cessation  of  stimula- 
tion the  signs  of  neurosis  were  found  to  be  dominant  again.  It  should  be 
mentioned  that  the  conditioned  reflex  elicited  by  stimulation  of  the 
reticular  formation  appeared  only  if  the  parameters  of  stimulation  ex- 
ceeded a  certain  limit.  If  the  intensity  of  the  stimulus  was  increased 
emotional  reactions  (fear,  escape  reaction),  appeared  instead  of  the 
orientation  or  conditioned  reflexes. 

From  the  above-described  experiments  two  conclusions  may  be  drawn: 

1.  The  conditioned  reflex  elicited  by  stimulation  of  the  diffuse  activa- 
ting system  depends  on  the  environment  which  influences  the  animal 
through  the  specific  projection  system; 

2.  The  neurotic  state  is  due  to  a  break  in  the  temporary  connection 
between  the  specific  and  diffuse  projection  systems. 

From  the  foregoing  it  is  obvious  that,  even  in  the  elementary  manifesta- 
tions of  behaviour,  a  whole  series  of  neural  and  humoral  processes  are 
involved.  Present-day  data  do  not  indicate  what  neural  structures  are 
responsible  for  the  behavioural  changes  caused  by  a  certain  endocrine 
factor.  However,  they  call  attention  to  the  fact  that  in  the  development  of 
normal  as  well  as  neurotic  states,  humoral  factors  play  an  important  role. 
The  individual  differences  in  the  endocrine  system  will  probably  explain 
why  the  establishment  and  stability  of  temporary  connections  elaborated 
under  similar  condition  as  well  as  neurotic  phenomena  show  those  great 
individual  variations. 


GROUP   DISCUSSION 

MoRRELL.  I  wonder  if  Dr  Lissak  has  considered  the  role  of  diurnal  variations  in 
hormonal  output  in  evaluating  both  electrical  and  behavioural  signs  of  condition- 
ing. One  might  expect  that  hormonal  influences  on  behaviour  and  on  conditioning 
would  vary  with  the  time  of  day  at  which  the  experiments  were  carried  out.  This 
might  be  another  variable  to  be  added  to  those  determining  individual  differences 
with  which  much  of  Dr  Lissak's  previous  work  has  been  concerned. 

The  data  on  hypophysial  adrenocortical  influences  are  most  interesting  and 
bring  to  mind  some  unpublished  observations  from  our  laboratory  which  indicate 


K.    LISSAK    AND    E.    ENDROCZI  307 

that  ACTH,  hydrocortisone  and  progesterone  have  a  marked  normahzing  effect 
on  the  EEG  oi  animals  with  chronic  experimental  epilepsy. 

LissAK.  In  our  laboratory  wc  are  domg  chronic  experiments  registering  the 
electrical  activity  and  introducing  microcannules  for  recording  the  effects  of 
different  hormones  or  humoral  factors  parallel  with  the  electrical  activity. 

CoviAN.  We  have  been  working  for  some  years  in  hemidecorticate  rats  in 
which  changes  in  the  weight  ot  the  following  glands  were  observed:  adrenals, 
thyroids,  thymus,  hypophysis,  ovaries  and  seminal  vesicles  —  Regarding  adrenals 
there  was  a  sexual  difference.  Did  you  find  any  sexual  difference  by  stimulating  the 
hippocampus? 

LisSAK.  No.  We  have  not  found  any  sexual  difference.  There  was  a  complete 
inhibition  ot  the  adreno-cortical  activity  in  both  sexes. 

Galambos.  Over  what  time  duration  have  you  studied  the  adrenal  vein  level  of 
hormones?  Drs  Mason  and  Nauta  at  the  Walter  Reed  Laboratories  have  been 
stimulating  paleocortical  structures  in  monkey  and  studying  adrenal  hormone 
levels  in  much  the  same  way  you  have  described.  They  fmd  that  stimulation  in 
some  structures  leads  to  profound  suppression  of  17-hydroxycorticosteroid  output 
for  a  period  of  days.  Similarly  if  one  stimulates  a  particular  paleocortical  structure 
he  may  find  the  expected  response  from  stimulation  of  another  structure  to  be 
different  for  many  hours  or  days.  Some  ot  these  events  thus  have  an  astonishingly 
long  time  scale.  Over  what  time  scale  were  your  measurements  made  ?  Could  it  be 
that  if  you  had  delayed  making  your  measurements  for,  say,  2  days  you  might  have 
found  even  larger  responses  than  you  have  observed? 

LissAK.  One  of  the  chief  difficulties  of  our  present  method  of  experimentation, 
is  that  we  need  to  anaesthetize  the  animal,  because  we  take  the  blood  directly  from 
the  adrenal  vein.  Our  experiments  were  done  with  stimulation  times  of  between 
5  to  40 1.  We  have  not  done  experiments  with  such  long  stimulation.  I  hope  that  we 
can  invert  our  method  with  the  modified  London-cannule,  and  then  we  will  look 
for  the  result  of  longer  stimulation  on  unanaesthetized  animals. 

Porter.  The  initial  studies  indicating  hippocampal  inhibition  of  adrenocortical 
function  were  done  using  the  eosinophil  count  as  an  index  of  the  release  of  corti- 
coids.  In  these  experiments,  there  was  no  apparent  effect  of  electrical  stimulation  of 
the  hippocampus  upon  the  level  of  circulating  eosinophils  in  the  blood.  However, 
known  stress-evoking  stimuli  applied  during  such  hippocampal  stimulation  failed 
to  induce  their  usual  eosinophilic  response.  Subsequently  Dr  Mason  showed  that 
there  is  a  marked  fall  in  the  level  of  circulating  17-hydroxycorticosterone  following 
hippocampal  stimulation  which  may  persist  for  a  day  or  two.  This  may  be  preceded 
by  a  slight  rise  in  the  level  of  corticoids,  but  it  is  small  compared  with  the  response 
obtained  by  hypothalamic  or  amygdala  stimulation. 

I  should  like  to  sav  how  much  I  enjoyed  hearing  Dr  Lissak's  discussion  ot  these 
rather  complex  neural-endocrine  interrelationships.  Considerable  attention  has  been 
paid  in  the  last  few  years  to  the  control  which  the  brain  exerts  over  the  endocrine 
system  but  much  less  has  been  directed  towards  the  effects  of  circulating  hormones 
upon  the  function  of  the  central  nervous  system.  Dr  Feldman  working  in  Dr 
Magoun's  laboratory  has  shown  that  the  adrenocortical  hormones  have  a  rather 
consistent  effect  upon  the  non-specific  systems  of  the  bram.  Usmg  evoked  potential 
techniques  he  has  found  that  the  response  in  the  reticular  formation  to  sciatic  nerve 
stimulation    is    greatly    augmented    after   the    administration    of  adrenocortical 

X 


30S  BRAIN    MECHANISMS    AND    LEARNING 

hormones,  whereas  that  in  the  classical  sensory  pathway  was  cssentialK'  unchanged. 
It  seems  likely  then  that  the  adrenal  cortical  hormones  influence  behaviour  to  a 
large  extent  through  their  eifects  upon  the  non-specific  brain  stem  structures. 

Olds.  Dr  Lissak's  work  and  ours  have  run  parallel  but  different  courses.  He 
observes  effects  of  stimulation  on  hormones;  we  observe  the  effects  of  hormones  on 
stimulation ;  he  has  observed  the  effects  of  stimulation  on  preformed  conditioned 
responses;  we  have  observed  the  effect  of  stimulation  reinforcement  to  form 
conditioned  responses.  But  the  same  areas  are  always  involved,  indicating,  I  believe, 
reciprocal  relations.  For  example  in  the  hypothalamic  amygdaloid  system  self- 
stimulation  rate  or,  that  is,  the  reinforcement  of  electrical  stimulation  is  stopped  by 
castration  and  renewed  by  replacement  therapy,  with  electrodes  in  some  places. 
With  electrodes  in  quite  different  places  of  the  same  system,  self  stimulation  is 
stopped  by  satiation  and  replaced  by  hunger.  I  believe  that  the  places  where  he 
provokes  sexual  behaviour  arc  the  places  where  castration  stops  self  stimulation. 
Similarly  in  the  other  studies  of  the  posterior  hypothalamus,  the  places  where  his 
stimulation  evoked  the  preformed  alimentar)-  reactions  our  stimulus  seems  to  us  a 
positive  reinforcement,  related  to  food. 

LissAK.  Do  you  hnd  a  sexual  difference,  with  anngdala  stimulation  between  the 
male  and  female  ratsf  I  think  that  the  main  point  is  to  find  the  structure  in  C.N.S. 
where  the  sexual  difference  can  be  made. 

AsRATYAN.  Though  little  is  known  at  present  may  I  refer  to  the  question  of 
structural  and  functional  relationships  between  the  reticular  formation  and  auto- 
matic centres,  especially  the  hypothalamic  structures  in  the  mid-brain.  It  seems  to 
me  that  Dr  Lissak's  results  show  that  a  certain  role  is  played  bv  higher  sympathetic 
structures  in  this  region.  The  basis  for  such  an  assumption  is  that  sympathetic 
structures  innervate  all  endocrine  glands  'and  in  addition  exert  a  powerful  imme- 
diate influence  on  the  functions  of  different  svstems  of  the  organism,  particularly  on 
the  activity  of  the  N.S.  as  was  piroved  by  Orbeli  and  his  collaborators.  I  think  that 
these  data  may  be  partially  explained  as  follows:  the  structures  stimulated  in  Dr 
Lissak's  experiments  also  activate  sympathetic  structures  of  hypothalamus  and 
therefore  the  changes  in  the  aciivitv  of  the  brain  cortex  may  be  partialK-  conditioned 
by  this  factor. 

LissAK.  In  the  tradition  of  Cannon  our  first  line  of  investigations  was  directed  to 
the  sympatho-adrenal  activity.  The  neuro-humoral  factors  in  the  control  of 
animal  behaviour  and  the  manifestations  of  higher  nervous  activity  in  the  adapta- 
tion of  the  organism  constitute  a  very  complicated  mechanism  in  which  sym- 
pathetic activity  also  plays  a  role. 


CONSIDERATIONS   ON   THE  HISTOLOGICAL  BASES  OF 
NEUROPHYSIOLOGY^ 

C.    ESTABLE 

It  might  have  been  appropriate  to  begin  this  study  with  a  critical 
evaluation  of  the  three  general  conceptions  of  the  structure  of  the  nervous 
system  held  by  different  authors:  (i)  that  of  radical  neuronism,  (2)  that  of 
absolute  reticularism,  (3)  that  of  neuronism  modified  by  the  assumption  of 
anastomosis  between  tlie  interstitial  cells,  this  being  accepted  by  the 
founder  of  the  neuronal  doctrine. 

The  remarkable  summary  made  by  Cajal  in  his  last  monograph, 
'Neuronismo  o  reticularismo'  (Cajal,  1933)  and  published  in  German  under 
the  title  of  Die  Ni'iiroiislclirc,  in  1935,  did  not  convince  such  supporters  of 
the  reticular  theory  as  Boeke,  Brauer,  Stoer  Jr.  and  others  (Boecke,  1949; 
Bauer,  1953;  Stoer,  1957). 

Even  Bielschowsky,  who  regards  Cajal  with  reverence  and  calls  him 
Dcr  i^rossc  Altiiicistcr,  fnids  that  the  basis  of  the  neuronal  doctrine  and  the 
criticism  of  the  reticular  theory  made  by  the  great  ncurohistologist  are 
unconvincing  (Bielchowsky,  1955).  Gagel  calls  the  said  doctrine  arrogant 
(stolzes  Gabiiudc)  but  recognizes  that,  despite  all  the  objections  to  neuron- 
ism, Cajal's  law  of  axifugal  conduction  remains  unshaken  and  intact. 

In  a  report  submitted  to  the  International  Neurological  Congress  in 
Brussels  (Estable,  1957),  we  compared  and  studied  the  three  conceptions 
and  concluded  that  the  doctrine  best  adapted  to  the  facts  revealed  by  the 
electron  microscope  and  by  experimental  neurohistology  is  that  of 
neuronism,  but  without  the  restriction  of  interstitial  cells,  for  it  is  shown 
that  those  perceived  in  anastomosis  with  the  aid  of  and  within  the  field  of 
the  optical  microscope  are  connective  neuronoid  cells  and  not  actual 
neurones. 

It  is  unnecessary  to  reconsider  here  problems  we  regard  as  already 
solved.  It  is  our  thesis  that  the  neuronal  cioctrine  is  correct,  as  /('//ij  as  it 
remains  open  to  the  possibilities  of  iiitenieiiroiial  iiifiueiices  that  (^o  beyond  the 
laws  of  iusulated  conduction  and  dynamic  pohvization. 

Microscopic  and  submicroscopic  observations  prove  that  the  nervous 
tissue  is  devoid  of  intercellular  spaces  through  which  a  fluid  internal 

'  Supported  in  part  by  grants  t'roin  the  Rocketcllcr  Foundation  (58122)  and  tlic  U.S.A.F. 
Office  of  Scientific  Research  (Contract  AF4y  (638)  (585)). 

309 


310 


BRAIN    MECHANISMS    AND    LEARNING 


medium  might  move  about.  As  neurones  lack  any  direct  contact  with 
capillaries,  except  for  the  ones  which  they  innervate,  their  nutrition  is 
ensured  by  aiK^iooUocytcs.  Furthermore,  there  are  neither  anastomosis  nor 


***/-..^     -  V 


gl  inv  -* 


gl.  capsule. ji   .'*^ 


Fig.  I 


Insulation  contact  between  neurone  and  glial  cell.  Electron-micrograph  of  a  nerve  cell  belong- 
ing to  a  ganglion  o{  Xyleiis  fiiscipeiniis  (Brunner)  Gistel  (orthoptcra)  gl.  inv.  shows  tlnger-like 
processes  of  glia  cells  penetrating  the  perikaryon  of  a  neurone  and  thus  establishing  a  close 
'insulating'  contact  with  the  neurone.  No  fusion  or  perforation  of  the  cell  membrane  exists. 
G.  =  Golgi  components;  m  =  mitochondria;  gl.  =  glial  capsule. 

loose  ciui<  in  the  nervous  textures.  All  interactions  occur  by  contact 
between  membranes,  with  or  without  invaginations,  the  membranes 
being  either  of  the  same  or  of  different  natin-c.  The  tu-st  requirement,  in  an 


C.    ESTABLE 


311 


orderly  and  systematic  review  of  the  neurohistological  bases  of  neuro- 
physiology, is  to  discriminate  between  the  various  types  of  contacts  of  a 
neurone.  The  second  requirement  must  be  the  functional  elucidation  of 
such  contacts. 


Fig.  2 
Dendro-dendritic  contact.  Photo-micrograph  of  cerebellum  of  cat 
showing  a  typical  dendro-dendritic  synapse  (Dd.  syn.)   between 
grains.  Gr.  =  grains.  (Golgi-Cajal  method). 


Each  neurone  has  two  kinds  oi  contacts:  (A)  insulation  and  nutrition 
(neuroglial)  contacts;  (B)  transmission  contacts  probably  having  either 
(i)  one-way  influence  (dynamic  polarization),  or  (2)  mutual  influence 
(reversibility),  including  trophic  effects  in  it,  independent  of  the  glio- 
ueuronal  ones. 

When  the  contact  is  neuroglial  ov  neuroschwannian,  whether  with 


312 


BRAIN    MECHANISMS    AND    LEARNING 


Fig.  3 
Dendro-somatic  contact.  Photo-micrograph  of  acoustic  ventral  ganghoii  of  adult 
cat  showing  a  dendro-somatic  synapse  (D.s.  Syn.).  One  dendrite  of  the  neurone  N. 
(v.a.g.)  is  seen  ramifying  around  the  body  of  the  other  neurone.  (Cajal's  silver 
method.) 


C.    ESTABLE  313 

or  without  myelin  sheaths,  it  is  an  insulation  contact  (Fig.  i):  it  is  not 
known  whether  it  is  possible  for  a  neurone  to  act  upon  another  neurone, 
through  the  slightest  and  thinnest  glial  sheaths.  According  to  Dc  Castro's 
theory,  the  synapse  might  comprise  three  elements,  the  aftector,  the 
effector  and  the  glial  layer  (De  Castro,  1947,  195 1);  our  observations, 
reported  in  1952  and  1953  (one  of  them  in  collaboration  with  Reissig  and 
de  Robertis)  do  not  confirm  the  existence  of  the  glial  layer  taken  for 
granted  by  De  Castro  (Estable,  Reissig  and  De  Robertis,  1954). 


V.ssyn. 


*  3»- 


Fig.  4 
Deiidro-somatic   contact.   Photo-micrograph  of  two   cells  of  the 
reticular  formation  of  the  human  pons.  D.s.  syn.  shows  a  dcndro- 
somatic  synapse  which,  because  of  closeness  of  contacts,  appears  as 
an  anastomosis  between  neurones.  (Cajal's  silver  method.) 

Functional  contacts  occur  either  between  neurones  or  between  neurones 
and  differentiated  cells  such  as  receptor  cells  (neuro-receptive  contact), 
secretory  cells  or  contractile  units  (neurone-effector  contact).  Since  nerves 
and  particularly  axons  have  been  studied  with  more  attention  and  accuracy 
than  dendrites  and  the  perikaryon  —  except  as  to  the  trophic  function  of 
the  latter  —  it  is  easy  to  realize  why  a  certain  axonism  overshadows  the 
doctrinary  aspects  of  the  general  physiology  of  the  nervous  system.  For 
the  same  reason,  this  axonism  has  been  biased  by  the  concept  that  the  axon 


314 


BRAIN    MECHANISMS    AND    LEARNING 


is  the  exclusive  outlet  for  neuronal  influence  and  acts  only  by  way  of  its 
terminal  portion,  this  being  a  generalization  of  what  occurs  at  the  level  of 
better  studied  synapses,  in  the  cord  and  neuromuscular  junctions.  Numer- 
ous electrophysiological  facts  and  the  discovery  of  specific  chemical 
mediators  released  at  the  axon  endings  supported  the  thesis  that  neurones 


Fig.  5 
Dendro-dendritic  and  dendro-soniatic  contacts.  Photomicrographs  of  albino  rabbit 
retina  demonstrating  dendro-dendritic  and  dendro-somatic  synapses  between 
horizontal  neurones.  D.s.d.  syn.  shows  a  dendrite  establishing  relationship  with  body 
and  prolongations  of  neurone  D;  D.s.  syn.  is  a  synapse  between  the  dendrite  D.  and 
the  soma  of  neurone  P.  (Cajal's  silver  method.) 


do  act  by  these  terminations.  The  statement  that  a  neurone  acts  upon 
another  through  its  axonic  extremities  cannot  be  gainsaid,  but  one  should 
be  careful  not  to  infer  that  no  other  possible  manner  of  interneuronal 
induction  can  exist. 

Numerous  investigations  in  recent  years  have  shown  the  existence  in 
the  C.N.S.  of  Vertebrates  and  Invertebrates  of  the  following  contacts 


C.    ESTABLE 


315 


which  are  as  intimate  as  the  classical  ones  (axosomatic  and  axo-dendritic- 
synapse) ;  contacts  between  one  dendrite  and  another  dendrite  {dciidro- 


irMdr9i0«r'^   .^^l^fap.  .^|fJE:c 


t^-. 


(C 


D.dsyn 


Dd  syn. 


Fig.  6 
Deiidro-dcndntic  contact.  Electron-micrograph  of  the  albino  rabbit  retina 
where  the  dendro-dendritic  contacts  between  horizontal  neurones  are  shown. 
D.d.  syn.  ■'  15.600. 

dendritic  synapses)  (Figs.  2,  5,  6),  between  dendrites  and  perikaryon 
[deudro-soniatic  synapses)  (Fig.  3),  between  dendrites,  soma  and  dendrites 
{deiidro-soniato-dcndritic  synapses)  (Figs.  5,  <S),  between  adjacent  neuronal 


3i6 


BRAIN    MECHANISMS    AND    LEARNING 


.•»jUi/D 


D.ssyn. 


,-^^ 


7k 


■f* 


Fig.  7 
Dendro-somatic  contact,  (a)  Schematic  drawing  reproduced  from  Fig.  23.4  of  Cajal's  Texiura 
del  sisteiiia  iieri'ioso  del  hoinhre  y  los  vertehrados.  In  this  figure  Cajal  drew  the  ending  of  the 
retinipetal  fibre  on  an  aniacrine  cell  and  included  a  dendro-dendritic  connection  between 
amacrines  and  ganglionic  cells,  {h)  This  photomicrograph  serves  to  demonstrate  the  relation- 
ship between  amacrine  cells  and  ganglionic  neurones  of  retina,  as  well  as  the  ending  on  the 
amacrine  of  one  type  of  retinipetal  fibres.  The  retinipetal  fibre  ends  on  the  perikaryon  of  the 
amacrine  and  the  dendrite  D  of  this  cell  surrounds  the  ganglionic  cell  body  G.  The  retinipetal 
amacrine  synapse  is  of  the  currently  accepted  a.xo-somatic  type;  the  amacrine-ganglionic 
synapse  of  the  dendro-somatic  type.  (Cajal's  silver  method.) 


C.    ESTABLE 


317 


bodies  (soniato-soiiiatic  synapses)  (Fig.  12)  and  between  axons  [cixo-axoiiic 
synapses).  The  latter  kind  includes  three  different  types:  {a)  parallel 
contacts;  (/>)  cross  contacts;  (c)  axon  endings  on  a  non-terminal  part  of 
another  axonic  fibre.  In  the  ganglia  of  Invertebrates,  only  axodendritic, 
axo-axonic  and  dendro-dendritic  synapses  exist. 


Fig.  8 
IDcnclro-dendritic  and  dendro-soniatic  contacts.  Micrograph  of  the  human  dorsal  spinal 
cord  (3  months  old  embryo);  section  perpendicular  to  the  plane  of  symmetry.  See  dis- 
position of  dendrites  in  the  interneuronal  fascicles  in  which  many  dendro-somatic  and 
dendro-dendritic  contacts  take  place.  (Cajal's  silver  method.) 


Close  dendro-dendritic,  dendro-somatic,  dendro-somato-dendritic  and 
somato-somatic  contacts  having  been  brought  to  light  in  all  nervous 
regions  explored  and,  if  at  variance  with  the  principle  of  polarization  of 
the  nervous  influx,  might  well  explain  many  until  now  unexplained 
physiological  processes  of  the  nervous  system.  Consequently,  we  hnd  it 


3t8 


BRAIN    MECHANISMS    AND    LEARNING 


necessary  to  complement  the  notion  of  synapse  with  a  wider  knowledge  of 
interneuronal  relations.  A  more  adequate  basic  notion  of  synapse  should 
not  exclude  any  kind  o{ close  contact  between  two  Diemhraiies,  of  which  at  h'ast 
one  is  of  a  nervons  nature.  If  this  dctmition  is  accepted,  different  types  of 
synapses  can  be  described:  their  distinction  into  synaptic  and  non-synaptic 
contacts  would  be  a  matter  of  words  rather  than  of  facts. 

If  we  remember  that  the  physiological  concept  of  synapse  was  worked 
out  with  a  partial  knowledge  of  the  functional  contacts  between  neurones, 


Fig.  9 
Axo-dcndritic  cross  contact  in  cerebellum  (I).  Photomicrograph  ot  the  cerebellum  of  cat. 
A.d.  syn.  shows  a  typical  cross  contact  between  a  parallel  fibre  (horizontal  in  figure)  and  a 
dendrite  of  a  Purkinjc  cell  (vertical  in  figure)  (see  also  Figs.  lo  and  ii).  (Golgi  chromo-argent 
c  methods.  Cajal's  variance.) 


we  shall  be  more  willing  to  admit,  within  the  general  theory  of  synaptic 
function,  the  existence  of  interneuronal  influences  which  form  a  comple- 
ment to,  and  do  not  contradict,  the  law  of  dynamic  polarization,  and  we 
shall  be  even  more  willing  to  admit  that  the  law  of  insulated  conduction 
is  complemented  by  a  conduction  which  is  neither  insulated  nor  massive. 
What  the  fundamental  functional  differences  between  neuronal  sub- 
structures are  is  not  known.  Neither  structures  nor  substructures,  similar 
in  all  neurones,  can  account  for  notable  physiological  differences.  The 
synaptic  spectruni  (afferent  and  efferent  connections  of  one  neurone)  allows 


C.    ESTABLE 


3^9 


US  to  obtain  a  better  understanding  of  the  functional  specificity  of  neu- 
rones. This  concept  is  clear  so  far  as  the  afferent  and  ei^^erent  pathways  and 
their  respective  centres  are  concerned. 

What  are  the  functional  differences  and  similarities  existing  among  the 
manifold  contacts  between  membranes,  one  of  which  at  least,  is  nervous? 
Is  it  merely  ct^nventional  to  consider  all  c»f  them  synaptic,  or  some  of 


Fig.  10 
A.xo-dendritic  cross  contact  in  cerebellum  (II).  This  figure  shows  a 
tight  fascicule  of  parallel  fibres,  each  of  which  holds  an  intimate 
cross  contact  (A.d.  syn.)  with  a  (D.)  dendrite  (as  shown  in  Fig.  9). 
The  large  amount  of  these  axons  (p.f.b.)  in  the  plexiform  layer  is 
clearly  evident  (see  also  Figs.  9  and  11). 


them  synaptic  but  not  the  others?  Is  there  a  factual  or  conceptual  issue  at 
stake  or  is  it  simply  a  matter  of  words  ? 

No  structural  characteristic  (except  contiguity  and  discontinuity)  is 
typical  of  synapses: 

[a)  The  existence  of  mitochondria  having  been  rediscovered  in  the 
axonal  terminal  pars  of  certain  synapses  (in  1897  Held  haci  pointed  them 
out  in  the  cerebellar  glomeruli  under  the  name  of  neurosomes),   the 


320 


BRAIN    MECHANISMS    AND    LEARNING 


1  % 


yJ^^ 


^4 


Fig.  II 


A.\t)-dcndritic  cross  contacts  in  ccrebcUuiu  (III).  Low  magnification  electron- 
micrograph  of  rat  cerebellum  (molecular  layer)  showing  the  relationship  of  a 
Purkinjc  dendrite  —  p  d  —  with  crossing  fibres  f  These  are  more  or  less  of  equal 
diameter  and  are  supposed  to  be  parallel  fibres.  Palay  interprets  them  as  derivating 
from  Fananas'  cells  (Palay,  1958).  The  clear  spaces  may  correspond  to  glial  fibres 
—  s.  At  Mc  a  micro-club  or  dendrite  thorn  can  be  depicted  —  M  —  Mitochondria, 
d.f.  dendrite  filaments  <  22.000.  (See  also  Figs,  y  and  10.) 


C.    ESTABLE 


321 


investigations  of  Bartelmcz,  Bartclmcz  and  Hocrr  Bodian  (1937-40)  led  to 
the  definition  oi  a  synapse  as  a  contact  between  membranes  with 
mitochondria  subjacent  in  the  prc-synaptic  region  (Bartehiiez,  191 5; 
Bartehnez  and  Hoerr,  1933;  Bodian,  1937;  Bodian,  1942;  Held,  1H97). 


N 


N 


^ 


Y-". 


^1...«A 


Fu,.  12 
Somato-scimatic    contacts.    Low    inai;nification  clectroninicrograph  of  the  rat   ccrcbcllmu 
granular  layer  showing  the  intimate  soniato-soniatic  relationship  between  grains.  N.  Nuclei, 
ni  —  mitochondria   ■   16.000. 


This  definition,  based  on  structure  only,  is  not  satisfactory,  as  it  excludes 
incontrovertible  synaptic  types. 

(/))  The  microvesicles  having  been  discovered  by  Sjoestrand  —  and  by  him 
called  'granules'  —  in  the  synapse  of  cones  and  rods  with  the  dendrites  of 


32: 


BRAIN    MECHANISMS    AND    LEARNING 


bipolars,  a  scries  ot  investigations  was  initiated  (De  Robertis  and  Bennett, 
1955;  Palade,  1954;  Palay,  1954;  Palay,  1956;  Palay,  1958;  Robertson, 
1956;  Sjocstrand,  1954).  with  the  purpose  ot  determining  whether  the 
only  and  general  characteristic  ot  the  synapse  was  the  presence  of  the 


Fig.  13 
Dendro-soin.uic  and  dendro-dcndntic  contacts.  N,  and  N..  neurones  of  tlie 
human  common  oculo-motor  nucleus  showing  dcndro-soinatic  synapses  Ds.  syn. 
and  dendro-dendritic  synapses  Dd  syn. ;  ax,  axon  which  goes  to  form  the 
common  oculo-motor  nerve.  These  are  no  intercalar  neurones  or  recurrent 
axonic  collaterals;  the  connections  between  the  neurones  ot  this  nucleus  are  only 
dendro-somatic,  dendro-dendritic  and  dcndro-somato-dendritic. 


above-mentioned  microvcsiclcs.  Some  neurophysiologists,  such  as  Del 
Castillo  and  Katz,  and  more  recently  Ecclcs,  have  attempted  to  correlate 
the  so-called  synaptic  microvcsiclcs  with  certain  physiological  observations 
(Del  Castillo  and  Katz,  1955;  Del  Castillo  and  Katz,  1956;  Fxcles,  1957): 


C.    ESTABLE 


323 


in  effect  Del  Castillo  and  Katz  refer  to  the  possibility  of  accounting  for  the 
miniature  end-plate  potentials  which  they  discovered  by  regarding  them 
as   due   to   discharges   of  acetylcholine   supposedly   pre-existent   in   the 


^l»' 


Fig.  14 
Parasyiuipscs  (I)  —  Parasynapsis  fibres  —  s.  parasyn  —  in  the  cervical  Cdrd 
of  an  adult  man.  Tight  bundle  of  closely  placed  a.xons. 


microvcsiclcs.    However,   there  is  no  evidence  that  acetylcholine  ions 
gather  as  microvcsiclcs,  and  even  less  evidence  that  the  microvesicles, 
which  exist  in  certain  synaptic  types,  are  'quanta'  of  the  chemical  mediator. 
Y 


324  BRAIN    MECHANISMS    AND    LEARNING 

The  term  'synaptic  microvesiclcs'  docs  not  imply  more  than  calhng  the 
mitochondria  of  the  motor  plates  and  the  synapses  that  contain  them 
synaptic  mitochondria.  It  must  be  borne  in  nnnd  that  these  substructures 
do  not  exist  at  all  synaptic  levels  and  that,  furthermore,  there  are 
synapses  without  special  groupings  of  mitochondria  or  microvesicles. 

It  is  our  opinion  that  a  synapse  is  characterized  by  disavitiuiiity  and  by 
coiitioiiity\  the  contact  between  membranes  is  very  close,  but  lacks  fusion. 


.1 


pa^qsyn.  's^ 


/ 


Fig.  15 
Parasynapses  (II)  —  Neurone  of  the  cervical   spinal  cord  of  adult  man 
showing  the  terminal  fibres  of  the  perisomatic  axonic  plexus  contacting 
with  each  other. 


the  space  between  them  being  measured  in  Angstroms.  Nevertheless,  the 
contact  of  membranes  alone  is  not  a  sufficient  criterion  of  a  synapse;  the 
nature  of  those  membranes  must  also  be  considered  because  one  of  them  at 
least  must  be  nervous;  excluding  neuroglial  contacts  which  are  probably 
insulation  contacts  only  and  therefore  not  synaptic. 

Therefore,  we  propose  the  following  concept:  ..4  synapse  is  an  anatoiiii- 
cally  close  and  finictionally  operant  contact  between  nienibranes,  one  of  them,  at 
least,  beinii  of  a  nen'oiis  nature. 

Many  questions  remain  unanswered:  What  is  the  functional  difference 


C.    ESTABLE 


325 


between  the  synapses  [a)  with  microvesiclcs  and  mitochondria  only  in 
the  pre-synaptic  pars;  (h)  with  microvesiclcs  and  only  mitochondria  in 
the  post-synaptic  pars;  [c)  with   nncrovesiclcs  only  m   the  pre-synaptic 


Fig.  16 
Parasynapscs  (III)  —  Axo-somatic  synapses  —  A.S.  syn.  —  of  a  motor 
neurone  of  the  cervical  spinal  cord.   Adult  man.   This  shows  tiic 
terminations  of  fibres  depicted  in  Figs.  14  and  15. 


pars;  (d)  with  microvesiclcs  and  mitochondria  only  in  the  pre-synaptic 
pars;  {e)  with  only  microvesiclcs  in  the  post-synaptic  pars;  (f)  without 
mitochondria  or  microvesiclcs,  either  in  the  pre-synaptic  or  in  the  post- 
synaptic pars? 


326  BRAIN    MECHANISMS    AND    LEARNING 

In  the  ganglionic  nervous  system  of  Invertebrates,  the  rule  is  that  the 
perikaryon  iiei'cr  takes  part  in  the  synapses,  as  it  is  located  in  the  periphery 
of  the  ganglion,  so  tightly  enclosed  in  a  glial  capsule  (Fig.  i)  that  it  even 
shows  deep  membranous  glial  invaginations  in  the  neurone.  In  addition, 
neither  dendrites  nor  axons  reach  the  cellular  body;  all  these  extensions, 
together  with  the  glial  ramifications  towards  the  centre  of  the  ganglion, 
constitute  a  dense,  delicate  and  heterogeneous  plexus  improperly  named 
'neuropilc'.  In  the  nervous  centre  of  Invertebrates  there  are  only  three 
synaptic  types  to  be  seen:  [a)  axo-dendritic ;  (/))  axo-axonic  and  (c)  dendro- 
dendritic  synapses.  In  contrast,  in  the  nervous  system  of  vertebrates  the 
perikaryon  takes  part  in  the  synapse,  with  the  only  exception  of  the 
neurones  of  the  sensitive  ganglia  along  the  neuraxis  and  the  mesencephalic 
nucleus  of  the  trigeminal  nerve  which,  by  the  morphology  of  its  neurones, 
is  equivalent  to  a  spinal  ganglion. 

In  the  nervous  system  of  Vertebrates,  intimate  contacts  occur  in  the  three 
morphological  regions  of  a  neurone;  perikaryon,  dendrites  and  axon. 
These  contacts  are  iioiiiolo(^oiis  or  lu'tcrolo(^oiis  according  to  whether  the 
membranes  are  in  contact  with  the  same  or  different  morphological 
elements.  The  homologous  contacts  are  [a)  dendro-dendritic,  [b)  axo- 
axonic, (f)  somato-somatic.  The  heterologous  contacts  are  [a]  axo-den- 
dritic, (/))  axo-somatic,  (c)  dcndro-somatic,  [d)  dcndro-somato-dendritic, 
those  of  neurones  with  sensory  or'  receptor  cells  and  of  neurones  with 
effectors,  namely  secretory  cells  (crinocytcs),  contractile  fibres  (myo-fibres), 
etc.  The  contact,  either  homologous  or  heterologous  may  be  terminal, 
de  passable  ('de  trayecto')  or  mixed. 

In  addition  to  the  types  of  synapses  described  above  we  call  para- 
synapses  the  axo-axonic,  pre-terminal  contacts  between  axons  having 
different  origins  but  converging  upon  a  common  post-synaptic  element 
(Figs.  14,  15,  16).  Parasynapses  are  as  frequent  as  synapses;  they  enable  a 
slender  pre-terminal  fibre  to  influence  not  only  its  own  terminal  synapse, 
but  also  the  synapse  of  all  the  pre-terminal  fibres  with  which  it  has  a 
parasynaptic  contact.  Parasynapses  may  guarantee  synaptic  security. 

In  the  next  part  of  our  study  we  wish  to  emphasize  the  importance  of 
dendro-dendritic,  somato-somatic,  dendro-somatic,  dendro-somato- 
dendritic  and  axo-dendritic  cross  synapses.  The  frequency  of  dendro- 
dendritic  contacts  in  the  cerebellar  glomeruli,  in  the  horizontal  neurones  of 
the  retina,  in  the  sympathetic  ganglia,  in  the  medulla,  in  the  pons  and  in 
general  in  all  the  nervous  centres  explored  is  such  that  there  is  no  place  for 
the  interpretation  that  these  contacts  are  aberrant,  exceptional  or  even 
physiologically  meaningless. 


C.    ESTABLE  327 

Dendro-dendritic  and  dcndro-somatic  synapses  can  be  described  under 
many  types:  (i)  with  special  modelling  of  the  expansions  ni  contact 
(glomeruli,  Fig.  2;  chalices,  Fig.  3);  (2)  with  dendrites  not  configuring  a 
special  articular  contact  splicing  or  connection  device  (Figs.  5,  6);  (3)  with 
an  equivalent  interchange  of  dendrites  between  the  neurones  united  by  the 
synapse  (Fig.  4) ;  (4)  with  an  unequal  participation  ot  dendritic  endings  in 
the  dendro-dcndrito-somatic  reciprocal  synapses  (Fig.  13);  (5)  with  the 
dendritic  participation  of  one  neurone  and  the  perikaryon  and  the  dendrite 
of  another  neurone,  that  is,  dendro-somato-dendritic  synapse  in  one  way 
and  dendro-dendritic  in  the  opposite  way;  (6)  with  the  dendritic  participa- 
tion of  a  neurone  and  the  perikaryon  of  another  or  other  neurones  (dcn- 
dro-somatic synapse) ;  (7)  of  parallel  dendritic  contacts ;  (8)  of  cross-dendritic 
contacts;  (9)  complex  synapses,  dcndro  and  axo-dcndritic  at  the  same 
time. 

Functionally  there  are  two  kinds  of  direct  interneuronal  relations:  (a)  one 
way,  in  which  pre-  and  post-synaptic  pars  of  different  nature  constitute 
polarized  and  irreversible  synapses;  (b)  reciprocal,  in  which  pre-  and  post- 
synaptic pars  of  similar  nature  constitute  reversible  synapses.  The  former 
are  exclusively  axo-somatic  and  axo-dendritic;  in  such  cases,  the  neurone 
whose  axon  models  the  pre-synaptic  pars  controls  the  other.  Prevalence  of 
reciprocity  may  be  suggested  for  the  dendro-dendritic  and  dendro-somatic 
synapses  and  the  somato-somatic  and  the  axo-axonic  contacts.  Such  useful 
reciprocity  might  be  for  isofunctional  neurones  of  a  same  centre,  which 
lack  recurrent  collaterals,  to  correlate  themselves  directly  by  means  of 
dendro-dendritic,  dendro-somatic  and  somato-somatic  contacts  (Figs.  2, 
12).  Thus  the  small  neurones  improperly  called  cerebellar  grains,  are 
reciprocally  connected  only  by  means  of  particularly  modelled  dendro- 
dendritic  branches  and  close  somatic  contacts,  but  never  interconnected 
through  axonic  collaterals.  On  the  contrary,  Purkinje  neurones  are 
reciprocally  comiected  by  means  of  double  polarized  pathways  (axo- 
somatic  and  axo-dendritic  synapses  at  the  end  of  recurrent  collaterals) 
never  by  means  of  dendritic  interchange.  The  rule  we  have  formulated 
does  not  exclude  the  co-existence,  in  certain  centres,  of  the  two  kinds  of 
neuronal  connections  of  reciprocal  action. 

Cajal  did  not  commit  himself  when  considering  the  existence  of  dendro- 
dendritic  synapses:  dealing  with  the  neuronal  connections  of  the  sym- 
pathetic ganglia  (Cajal,  1 891)  he  wisely  and  cautiously  wrote:  'It  is  difficult 
to  reject  the  possibility  of  the  passage  of  a  nervous  impulse,  either  between 
non-medullated  contiguous  nerve  fibres  or  between  juxtapositional 
protoplasmic  branches.  To  exclude  this  possibility  would  mean  giving  the 


328  BRAIN    MFX'HANISMS    AND    LEARNING 

theory  of  dynamic  polarization  too  absolute  a  character'  (Cajal,  1897). 
However,  it  happened  that  the  synapses  established  by  Cajal  belonged  to 
the  polarization  type;  this  explains  why,  a  short  time  after,  he  stated  the 
neuronal  doctrine  and  formulated  the  law  of  dynamic  polarization.  Thus 
the  Spanish  author  admitted  the  possibility  of  dendritic  contacts  and 
intennfluences,  but  later  hesitated  and  disregarded  tliem.  However,  he 
never  denied  their  existence  expressly  or  categorically  (Cajal,  1891, 
Cajal,  1897;  Cajal,  1897).  Cajal's  conviction  was  that,  if  dendro-dendritic 
connections  existed  at  all,  they  were  rare.  He  came  to  think  that  only 
occasionally  did  real  dendritic  interchanges  exist.  He  therefore  denied 
them  an  outstanding  physiological  signiticance  as  he  believed  them  to  be 
exceptional.  In  the  second  volume  of  his  Histolooic  chi  Systciiii'  Ncrveiix, 
when  dealing  with  the  sympathetic  ganglia,  there  is  a  passage  which,  once 
more,  shows  his  uncertainty  (Cajal,  191 1). 

Our  present  aim  is  to  emphasize  the  existence  oi  neuronal  interrelations 
through  dendritic  contacts,  and  their  probable  functional  significance. 
Our  observations,  first  upon  the  cerebellar  dendritic  glomeruli  and  retina 
and  then  upon  many  other  centres,  have  shown  the  presence  of  (i)  a 
certain  closeness,  not  contact,  of  dendrites  of  two  or  more  neurones  which 
held  contacts  with  axonal  expansions  (axo-dendritic  synapses) ;  (2)  direct 
dendritic  contact  in  closely  grouped  microglomeruli,  formed  exclusively 
by  dendrites  belonging  to  different' neurones;  (3)  axo-dendro-dendritic 
glomeruli  in  which  there  exists  a  double  type  ot  close  contacts;  {a)  axo- 
dendritic and  (/))  dendro-dendritic. 

The  cerebellar  glomeruli  are  characterized  by  the  diversity  of  their 
synapses:  (i)  according  to  the  origin  of  the  mossy  fibres;  (2)  according  to 
their  composition,  (<;)  axo-dendritic,  with  the  exclusive  participation  of  the 
mossy  fibres,  (/>)  with  the  exclusive  participation  oi  the  slender  collaterals 
of  Golgi  type  II  neurones,  {c)  with  the  double  participation  of  rose-shaped 
endings  of  the  mossy  fibres  and  of  the  collaterals  oi  the  above-mentioned 
Golgi  II  neurones,  plus  glial  fibres  with  a  special  terminal  device,  (d)  with 
only  the  presence  of  dendrites  of  the  grains;  (3)  according  to  quantitative 
variations  besides  qualitative  ones;  there  are  glomeruli  of  very  different 
sizes,  as  well  as  glomeruli  gathering  in  more  or  less  numerous  groups  in 
which  all  the  aforesaid  synapses  can  be  discovered,  and  also  close  somato- 
somatic contacts  between  grains  (Fig.  12). 

All  cerebellar  grains  possess  complex  synaptic  spectra:  dendro-dendritic 
and  somato-somatic  in  their  connections  with  other  grains ;  axo-dendritic 
in  their  connections  with  vestibular,  spinal,  bulbar,  protuberantial  and 
Golgi  II  neurones;  axo-somatic  in  connection  with  this  last  neurone;  in 


C.    ESTABLE  329 

addition,  the  important  cross  synapses,  with  all  the  neurones  whose 
dendrites  are  spread  within  the  plexiforni  layer. 

In  an  article,  published  in  1923,  we  called  iiiossy-cclliilar  conicoarcbcUar 
system,  a  complex  of  neurones  directly  and  functionally  linked,  on  the 
one  hand,  by  means  of  axo-dendritic  cross  synapses,  on  the  other  hand, 
through  synapses  of  the  mossy  fibres  with  the  dendrites  of  the  grains 
(glomeruli).  The  afferent  synaptic  spectrum  of  each  Purkinje  neurones  is 
integrated  by  a  small  number  of  axo-somatic,  axo-dendritic  and  axo- 
axonic synapses  of  pre-synaptic  terminal  pars,  while  the  cross  axo-dendritic 
synapses  are  astoiiisliinoly  ntiinerons,  existing  in  the  proportion  of  about  one 
million  to  each  Purkinje  neurone  (Estable,  1923). 

In  the  spreading  and  beautiful  dendritic  arborescence,  the  slender 
axons  of  the  grains,  in  parallel  fibres,  establish  as  many  intimate  contacts 
with  Purkinje  neurones  as  verticils  are  formed  by  the  microcluhs  or  thorns 
bristling  on  their  surface  (Figs.  9,  to). 

It  may  be  deemed  fantastic  to  talk  about  one  million  cross  synapses  for 
each  Purkinje  neurone.  There  are,  however,  many  techniques  that  confirm 
this  figure.  Furthermore,  the  axon  of  each  single  grain  contacts  all  the 
Purkinje  neurones  in  a  cerebellar  convolution,  succeeding  one  another  in 
the  same  direction. 

Three  more  significant  facts  prove  the  importance  of  the  axo-dendritic 
cross  synapses:  (i)  they  are  not  missing  in  any  centre  examined;  (2)  the 
said  synaptic  type  is  the  only  one  in  the  afferent  spectrum  of  Golgi  short 
axon  cerebellar  neurones;  (3)  the  cross  synapses  are  remarkably  prevalent 
over  all  the  other  synaptic  types  in  the  brain  cortex.  A  single  axon, 
among  billions  in  the  plexiforni  layer  of  the  brain  cortex,  relates  itself  by 
means  of  cross  synapses,  with  the  neurones  that,  from  the  different 
layers,  send  their  dendrites  up  to  the  pial  surface. 

In  a  re-examination  of  the  neuro-histological  bases  of  neuro-physio- 
logy,  it  is  particularly  important  to  study  the  retina. 

Most  heterogeneous  ramifications  occur  in  the  outer-plexiform  layer: 
[a)  thin  filaments  branch  oR  the  feet  of  the  cones  and  rods  and  in  them  no 
dendritic  penetration  has  been  noticed,  as  happens  in  the  widest  part  of 
the  feet;  (b)  dendrites  of  variable  thickness,  of  two  origins,  from  bipolar 
neurones  and  from  horizontal  neurones  (there  is  no  evidence  that  all  the 
dendritic  ramifications  of  the  bipolar  invagmate  in  the  pedal  widening  of 
cones  and  rods);  (c)  axonic  ramifications  of  the  horizontal  neurones  and 
perhaps  of  the  stellate  neurones  of  the  inner  granular  layer,  besides  certain 
ascending  axons  similar  to  the  retinopetal  fibres  of  the  inner  plexiforni 


330  BRAIN    MECHANISMS    AND    LEARNING 

layer;  [d)  very  slender  transversal  filaments  rising  from  Miiller's  fibrocells. 
It  is  in  this  extremely  dense  plexus  of  heterogeneous  nature  that  Dr  Villegas 
(in  her  unpublished  observations)  has  discovered  the  existence,  in  fish,  of  a 
sort  of  neuropilc  similar  to  that  appearing  in  other  centres  (Villegas, 
personal  communication) ;  we  have  also  observed  it  in  the  retina  of 
mammals. 

Dendro-dendritic,  dendro-somatic  and  dendro-somato-dendritic  syn- 
apses are  most  abundant  in  the  retina  and  appear  clearly  in  the  horizontal 
neurones  and  in  the  amacrine  cells,  for  instance.  The  synaptic  spectrum 
of  the  horizontal  neurones  shows  a  prevalence  of  the  dendro-dendritic, 
dendro-somatic  and  dendro-somato-dendritic  synapses  (Figs.  5,  6). 
However,  not  all  horizontal  neurones  have  the  same  synaptic  spectrum. 

The  influence  ot  some  areas  or  foci  over  other  areas  or  foci  of  the  same 
retina  has  remained  unexplained.  However,  we  may  take  into  account  that 
there  exist  transversal  contacts  ((7)  of  the  filiform  pedal  expansions  of  cones 
and  rods;  (/))  of  the  dendritic  tufts  of  bipolars;  of  the  dendrites  of  gan- 
glionic neurones,  whose  axons  very  rarely  give  oft  collaterals. 

Despite  these  connections,  the  intrinsic  retinal  associations  are  mainly 
due  to  dendritic  connections  of  two  kinds  of  neurones,  the  horizontal  and 
the  amacrine  cells  (Fig.  ja). 

Cajal  discovered  the  retinopetal  fibres  which  form  synapses  with  the 
body  of  the  amacrine  cells  (Fig.  7/)). 'Two  more  categories  of  retinopetal 
fibres  arc  to  be  considered;  those  establishing  direct  synapses  with  the 
dendrites  of  ganglionic  cells;  others,  more  dispersed,  with  their  collaterals 
spreading  out,  covering  the  field  of  the  dendrites  of  these  neurones  and  the 
amacrine  cells  (this  last  category  was  confirmed  by  Poliak  (Poliak,  1941)). 

According  to  Cajal,  the  centrifugal  optic  fibres  are  undivicied  in  all  their 
intra-retinal  course,  and  end  in  a  little  bunch  of  short  collaterals  on  the 
soma  of  an  amacrine  cell.  The  abot'c-iiiciitioiicd  retinopetal  fibres  would  lack 
functional  nieanino  (a)  //  the  conduction  in  the  dendrites  of  the  amacrine  cells  were 
not  'antidromic',  (b)  //  the  dendro-dendritic  contacts  were  not  functional,  or  if  the 
excitatory  state  did  not  propagate  through  it  —  in  other  words,  if  it  did  not  con- 
stitute a  real  synapse. 

We  have  already  mentioned  three  kinds  of  retinopetal  fibres.  There  are 
fibres  too,  which,  following  the  same  course,  end  in  the  capillaries  of  the 
retina  which  may  be  taken  for  visual  fibres  if  their  vascular  ending  is  not 
noticeci. 

As  concerns  the  neuro-muscular  junctions,  let  us  mention  a  type  of 
synapse  in  which  the  ending  of  the  axon  or  its  collaterals  go  into  the 


C.    ESTABLE  33  I 

niyofibres,  as  far  as  the  nucleus.  We  have  given  it  the  name  of  dxokaryo- 
Iciiiiiial  synapse. 

By  calhng  it  axokaryolenimal  we  do  not  imply  that  the  sarcolemma  is 
not  interposed  between  the  axolemma  and  the  karyolcmma,  but  refer 
simply  to  the  direction  of  the  growth  cone  towards  the  nuclei  of  the 
motor  plate  and  the  apposition  of  the  synaptic  membranes  to  the  nuclear 
membrane. 

The  question  of  the  trophic  function  of  the  synapse  may  also  be  men- 
tioned. When  synapses  are  already  modelled,  the  neuronal  trophism 
depends  so  much  on  them,  that  the  neurones  may  atrophy  and  die  if  the 
former  are  suppressed.  When  speaking  of  the  polarization  of  the  nervous 
impulse,  no  account  is  given,  besides  the  new  synaptic  types  we  have 
described,  of  the  trophic  function  of  the  synapse,  whose  direction  is  the 
same  as  the  direction  ot  the  propagation  of  the  excitatory  state  —  oscillo- 
graphically  registrable  —  or  the  reverse.  By  means  of  the  trophic  function 
of  the  synapse  we  might  account  for  the  existence,  within  it,  of  mito- 
chondria and  perhaps  microvesicles,  and,  as  far  as  the  neuromuscular 
synapse  is  concerned,  for  the  abundance  of  nuclei  in  the  sole. 

To  sum  up  our  thesis: 

It  is  unanimously  recognized  that  in  the  normal  activity  of  the  neurones, 
the  excitatory  or  inhibitory  state  starts  from  dendrites  or  somata,  the 
excitation  coming  from  a  sensorial  cell  or  another  neurone.  It  is  also 
known  that  the  dendrite  is  receptor  and  conductor,  while  the  axon  is  triins- 
initter  and  effector,  whether  it  ends  on  anotlier  neurone,  on  a  myofibre  or 
in  a  crniocyte. 

The  rigidity  of  our  conceptions  concerning  inter-neuronal  relationship 
contrasts  with  the  functional  plasticity  of  the  nervous  system,  particularly 
well  illustrated  in  the  study  of  learning.  The  new  contacts  we  have 
described  extend  this  way  of  thinking.  Dendrites,  perikaryon  and  axon 
may  normally  fulfd  the  three  mentioned  functions;  that  of  reception, 
conduction  and  efiection.  The  axon  woulci  be  receptor  and  conductor  in 
the  cone  of  origin  (axon  hillock)  receptor,  conductor  and  effector  in  the 
parasynapses;  and  effector  in  the  axo-dendritic  and  axo-somatic  synapses. 
The  dendrites  would  be  receptor,  conductor  and  effector  in  the  dendro- 
dendritic  synapses  (perhaps  in  the  dendro-somatic  synapses  also),  and  only 
receptor  and  conciuctor  in  the  axo-dendritic  and  axo-somatic  synapses. 
The  soma  or  perikaryon  would  be  receptor,  conductor  and  effector  in  the 
soniato-somatic  synapses  (perhaps  in  the  dendro-somatic  synapses 
also). 


332  BRAIN    MECHANISMS    AND    LEARNING 

SUMMARY 

The  purpose  of  this  chapter  is  to  insist  upon  the  frequent  presence,  in 
many  species  and  centres,  of  interneuronal  contacts  that  (i)  are  as  close  as 
classically  accepted  synapses  and  (ii)  exhibit  the  same  variable  submicro- 
scopic  structure.  These  contacts  are  dciidro-dcudritic,  dendro-somatk,  soinato- 
sonmtic  and  axo-axoiiic.  No  valid  morphological  reason  enables  us  to  deny 
that  these  contacts  are  operant  and,  at  the  same  time,  to  accept  that 
regular  axo-somatic  or  axo-dendritic  contacts  arc  functional.  Two 
formulae  sum  up  all  the  facts: 

I.  Pre-  and  post-synaptic  pars  of  a  diftcrent  nature  arc  tunctitMially 
polarization  synapses; 

II.  Pre-  and  post-synaptic  pars  of  a  similar  nature  arc  reversibility 
synapses,  which  means  functional  alternance  between  the  receptor  and  the 
effector  pars. 

No  submicroscopic  entity  (chondrioma,  microvesicules,  etc.)  is  typical 
of  a  functional  contact.  Only  discontinuity  and  contiguity  are  always 
present. 

GROUP   DISCUSSION 

EccLES.  I  am  very  interested.  Professor  Establc,  in  all  that  wealth  oi  histological 
material  that  you  have  just  shown  us;  it  gives  rise  to  a  great  many  problems  of  a 
functional  kind.  There  are  certain  physiological  reactions  which  we  have  not  yet 
fully  understood  and  I  think  that  some  of  these  new  kinds  oi  synaptic  contacts  will 
be  important  in  trying  to  develop  explanations.  I  refer  particularly  to  the  dorsal 
root  potential,  where  depolarization  of  the  presynaptic  fibres  is  conducted  elec- 
tronically out  along  the  dorsal  roots  which  may  also  carry  the  Toennies  reflex 
discharge.  The  nervous  system  does  not  always  work  in  the  forward  running 
direction,  it  can  work  backwards  too  and  these  synaptic  contacts  which  )ou  have 
mentioned  give  us  possibilities  of  making  explanations  of  such  phenomena.  But 
the  point  I  v^ant  to  make  in  a  general  way  is  that  the  clectron-microscopists  are 
showing  us  what  a  highly  specific  and  very  intimate  structural  relationship  there  is 
across  the  synaptic  junction;  yet  I  still  feel  that  the  essential  criterion  of  a  synapse  is: 
does  it  work  functionally?  I  believe  that  even  a  contact  with  200  A  separation  over 
a  large  area  is  insufficient  to  give  any  functional  meaning  or  pertormance.  There 
must  be  a  process  of  specific  chemical  secretion  on  the  one  hand  and  specific 
chemical  receptivity  on  the  other,  linking  across  that  junction  to  give  a  functional 
performance  to  a  s\-napse.  I  wonder  whether  we  should  define  a  synapse  as  a 
structure  with  a  close  histological  relationship ;  or  whether  we  should  try  to  restrict 
the  word  to  close  relationships  that  do  work  functionally  as  far  as  the  generation  or 
inhibition  of  impulses  is  concerned. 

EsTABLE.  Morphologically  one  must  accept  contiguity  plus  discontinuity  as  the 
basic  criteria.   Thereafter,  wc   must  be  carcKi!   in   discarding  as  non-functional 


C.    ESTABLE  333 

contacts  that  are  anatomically  similar  to  those  known  to  be  functional.  As  men- 
tioned in  the  text,  we  have  indirect  evidence  that  in  some  instances  they  do  operate 
(e.g.  in  cerebellar  cortex  or  retina,  in  invertebrate  ganglia). 

EccLES.  I  readily  agree  that  at  the  crossing  of  two  fibres  there  can  be  a  iunctional 
contact  providing  there  is  chemical  secretion  from  one  and  chemical  receptivity  on 
the  other. 

EsTABLE.  The  electronmicroscope  has  not  shown  in  cross-synapsis  microvesicules 
or  mitochondria.  That  does  not  necessarily  mean  that  a  chemical  mediator  is 
absent  but,  at  the  same  time,  it  certainly  does  not  suggest  its  presence :  but,  can  we 
be  too  dogmatic  as  to  the  necessity  of  a  chemical  mediator  for  contacts  to  be 
operant? 

Gerard.  One  of  the  main  points  in  your  summary  was  the  relation  oi  reciprocal 
or  irreciprocal  conduction  to  symmetrical  or  asymmetrical  contacts.  This  is,  of 
course,  fully  consistent  with  many  physiological  and  model  experiments  and  it  may 
interest  the  group  to  recall  first  the  experiments  Lillie  did  with  his  iron  wire  model. 
He  covered  most  of  the  wire  with  a  glass  tube,  leaving  two  ends  sticking  out  for 
different  lengths.  He  excited  the  model  by  scratching  one  of  these.  The  large  one 
would  cause  the  small  one  to  respond,  by  currents  through  the  wire  and  the 
medium;  but  the  small  one  would  not  excite  the  large  one.  This  is  asymmetry  in 
structure  and  in  action.  With  equal  sizes,  this  was  always  symmetrical  activation. 

A  more  direct  biological  experiment  was  done  by  compressing  the  parallel 
fibres  at  the  middle  of  the  sartorius  muscle  with  a  block  of  wood.  If  the  muscle  was 
squeezed  symmetrically  conduction  block  occurred  from  either  end  to  the  other; 
but  if  it  was  squeezed  asymmetrically  it  was  possible  to  get  conduction  in  one 
direction  but  not  in  the  other.  Of  course,  this  fits  with  the  emergence  of  activity 
from  the  cell  body  into  the  axon  and  not  always  in  the  reverse  direction,  and  main- 
other  experiments  m  the  central  nervous  system  at  least  seem  to  fit  well  with  the 
kind  of  valve  phenomena  that  have  been  demonstrated  peripherally,  such  as  the 
bouncing  back  of  impulses  from  a  cut  cord.  So  that  all  in  these  cases  Dr  Estable's 
thesis  is  supported;  and  it  seems  to  me  it  would  be  hard  to  justify  any  dogmatic 
statement  that  irreciprocal  transmission  can  occur  only  when  specific  neurohumours 
are  present;  they  could  hardly  be  present  in  most  of  these  instances. 

EcCLES.  I  don't  wish  to  be  on  record  as  dogmatically  asserting  that  electrical 
transmission  does  not  occur  in  the  vertebrate  nervous  system,  but  I  will  go  on 
record  as  saying  that  no  experiments  so  far  have  shown  that  it  does  occur  in  an 
undamaged  C.N.S.  Possibly  the  dorsal  root  potential  and  the  Toennies  reflex  of 
Vertebrates  are  due  to  electrical  synaptic  transmission.  Elsewhere,  when  we  have 
studied  cells  intracellularly  and  investigated  them  in  detail,  we  would  surely  have 
recognized  electrical  transmission  of  the  type  described  by  Furshpan  and  Potter 
with  some  crustacean  s\-napses.  There  is  no  evidence  whatsoever  that  such  electrical 
transmission  does  occur  in  the  cells  that  have  been  investigated  in  this  way. 

Fessard.  I  wish  Dr  Estable  would  clear  up  a  point  that  has  considerably  troubled 
me.  I  mean  his  statement  that  the  same  neurone  could  send  an  axon  branch  to  the 
radial  fibres  and  another  to  the  circular  fibres  of  the  iris ;  that  is  to  say,  it  could 
elicit  mydriasis  and  myosis  at  the  same  time.  This  sounds  rather  strange  to  me. 

Estable.  Yes. 

Fessard.  Have  you  good  proof  for  that?  It  is  certainly  very  disturbing. 

Estable.  One  can  see  in  the  iris  of  the  penguin,  whose  iris  is  striated,  axons 


334  BRAIN    MECHANISMS    AND    LEARNING 

which  gives  a  collateral  branch  to  the  sphincter  fibre  and  a  collateral  branch  to 
radiatory  fibres.  I  will  provide  you  with  the  reprint  of  the  paper  I  published  on  this 
subject. 

EccLES.  I  am  very  interested  in  the  physiological  significance  of  these  histo- 
logical findings.  If  the  same  nerve  fibres  do  innervate  these  two  different  muscles  of 
the  iris  they  might  still  do  it  by  the  same  chemical  transmitter  which  could  work  in 
opposite  ways  on  two  muscles.  It  depends  on  the  operation  of  the  respective 
receptive  sites  on  the  muscles.  For  example  we  know  that  acetyl-choline  can  work 
on  cardiac  muscle  inhibiting  it  and  on  skeletal  muscle  exciting  it.  We  certainly 
need  a  functional  and  pharmacological  investigation  of  neurones  concerned  in 
transmission  to  these  iris  muscles. 


THE  EFFECTS   OF  USE  AND  DISUSE  ON 
SYNAPTIC  FUNCTION 

J.    C.    ECCLES 

It  must  be  an  ultimate  objective  of  both  psychology  and  neurology  to 
account  for  all  the  phenomena  of  learning  and  conditioning  by  the  known 
properties  of  the  patterned  arrangements  of  nerve  cells  that  occur  in  the 
central  nervous  system.  We  are  still  far  from  this  goal ;  but  I  hope  to  show 
that  the  functional  connections  between  nerve  cells  exhibit  properties 
which  correspond  to  the  'plasticity'  that  has  long  been  the  basis  of  one 
explanation  of  learning  and  conditioning,  which  may  be  called  the  trace 
theory  of  memory  (cf.  Gomulicki,  1953). 

It  is  important  at  the  outset  to  state  that  it  will  be  assumed  throughout 
that  the  synaptic  connections  between  nerve  cells  are  the  only  functional 
connections  of  any  significance.  These  synapses  are  of  two  types,  excita- 
tory and  inhibitory,  the  former  type  tending  to  make  nerve  cells  discharge 
impulses,  the  other  to  suppress  this  discharge.  There  is  now  convincing 
evidence  that  in  vertebrate  synapses  each  type  operates  through  specific 
chemical  transmitter  substances  that  in  turn  change  the  ionic  permeability 
of  the  postsynaptic  membrane  and  so  bring  about  the  excitatory  or 
inhibitory  action  on  the  postsynaptic  cell  (Fatt,  1954;  Eccles,  1957). 

The  alternative  postulate  is  that,  at  least  in  part,  interaction  between 
neurones  is  caused  by  the  flow  of  electric  currents  generated  by  active 
neurones.  There  is  at  present  no  experimental  evidence  that  such  inter- 
action has  any  functional  significance  for  the  nervous  system  of  verte- 
brates. With  the  ordinary  random  relationships  of  neuronal  discharges  the 
flow  of  electric  currents  between  neurones  is  far  too  small  to  have  any 
significant  effect,  and  this  is  even  the  case  for  experiments  using  the  un- 
physiological  procedure  of  large  synchronous  volleys.  For  example  Wall 
(1958)  found  that  the  large  electrical  fields  generated  by  the  antidromic 
activation  of  the  motoneurones  in  the  ventral  horn  caused  no  detectable 
change  in  the  excitability  of  the  afferent  fibres  synapsing  on  those  moto- 
neurones. However,  under  abnormal  conditions  of  synchronization  of 
large  assemblages  of  nerve  cells,  the  propagation  of  electrical  waves 
suggests  that  there  is  direct  electrical  interaction  between  nerve  cells 
(cf.  Libet  and  Gerard,  194 1)  and  Jasper  has  produced  further  evidence 

335 


336  BRAIN    MECHANISMS    AND    LEARNING 

that  changes  in  excitabihty  of  neurones  may  be  produced  by  the  electrical 
fields  generated  by  activity  of  adjacent  neurones. 

But  even  such  conditions  of  electrical  field  interaction  would  merely 
have  the  effect  of  distorting  the  finely  patterned  influences  that  arise 
through  synaptic  action.  There  seems  to  be  no  alternative  to  the  highly 
selective  synaptic  actions  when  attempting  to  account  for  the  enormous 
wealth  of  information  that  is  preserved  during  transmission  through  the 
central  nervous  system.  It  may  be  stated  as  a  general  rule,  that  the  number 
of  nerve  fibres  in  any  pathway  is  related  to  the  wealth  of  information 
that  has  to  be  transmitted  along  that  pathway.  It  seems  inconceivable,  for 
example,  that  all  the  fine  grain  of  information  transmitted  by  the  optic 
nerve  and  tract  could  be  dissipated  in  the  mere  generation  of  electric 
fields  in  the  occipital  cortex.  In  contrast  it  should  be  mentioned  that  some 
synapses  in  Crustacea  do  operate  by  electrical  transmission  (Furshpan  and 
Potter,  1959).  But  such  a  mechanism  depends  on  special  permeability  and 
rectification  properties  of  the  apposed  synaptic  membranes,  and  is  thus 
just  as  unique  and  localized  in  its  action  as  is  chemical  synaptic  trans- 
mission. Moreover  such  an  electrical  synaptic  mechanism  would  have 
been  detected  if  it  were  opera.tive  at  any  of  the  vertebrate  central  synapses 
that  have  been  systematically  investigated. 

Two  explanations,  not  mutually  exclusive,  have  been  proposed  for  the 
neurological  basis  of  learning  and  'conditioning  (Hebb,  1949;  Eccles, 
1953;  Young,  1951;  Thorpe,  1956).  According  to  one,  learning  is  a 
dynamic  process,  due  to  continuously  circulating  patterns  of  impulses  in 
closed  neural  chains  (Rashevsky,  1938 ;  Young,  1938 ;  Hilgard  and  Marquis, 
1940;  Householder  and  Landahl,  1945).  As  a  consequence,  the  reaction  of 
the  nervous  system  to  any  particular  sensory  input  is  changed  in  a  unique 
way  so  long  as  this  circulation  of  impulses  continues.  Conceivably,  this 
explanation  could  apply  at  brief  intervals  —  seconds  or  minutes  —  after 
some  initial  conditioning  stimulus.  It  certainly  cannot  account  for 
memories  or  conditioned  behaviours  that  survive  either  a  virtual  suppres- 
sion of  all  activity  in  the  cerebral  cortex  —  e.g.  deep  anaesthesia,  concus- 
sion, coma,  extreme  cold,  or  even  deep  sleep  —  or  the  converse,  convulsive 
seizures  of  the  whole  cortex.  The  alternative  explanation  is  that  activation 
of  synapses  increases  their  efficacy  by  some  enduring  change  in  their  fine 
structure  (Tanzi,  1893;  Cajal,  191 1;  Hebb,  1949;  Toennies,  1949;  Eccles, 
1953  ;  jLiiig,  1953  ;  Mclntyre,  1953  ;  Thorpe,  1956).  We  may  assume  that  a 
given  sensory  input  results  in  a  uniquely  patterned  activation  of  central 
neurones,  and,  according  to  this  explanation,  a  subsequent  re-presentation 
of  this  input  would  tend  to  be  channelled  along  the   same   pathways 


J.    C.   ECCLES  337 

because  ot  the  increased  efficacy  of  the  synaptic  actions  exerted  by  all  those 
neurones  activated  initially.  There  would  thus  be  a  further  reinforcement 
of  the  synapses  responsible  for  the  unique  pattern  of  activation  and 
response,  with  consequently  a  more  effective  channelling;  and  so  on, 
cumulatively,  tor  each  successive  application  of  that  sensory  input. 
Necessarily,  the  postulated  changes  in  synaptic  efficacy  must  be  of  very 
long  duration  —  days  or  weeks.  There  is  no  way  in  which  relatively  brief 
durations  of  synaptic  change  for  each  synapse  of  a  serial  arrangement  can 
sum  to  give  a  more  prolonged  change. 

In  designing  experiments  to  test  for  this  postulated  effect  of  use  in 
causing  a  prolonged  increase  in  synaptic  efficacy,  it  was  initially  much 
simpler  to  test  for  the  opposite  effect  —  namely  regression  of  synaptic 
function  with  disuse.  The  very  recent  investigations  on  excess  use  will  be 
considered  subsequently.  Furthermore,  the  postulated  effects  of  use  in 
increasing  synaptic  efficacy  and  of  disuse  in  depressing  it  can  be  investi- 
gated most  rigorously  with  monosynaptic  pathways,  i.e.  where  there  is 
only  one  synapse  interpolated  between  the  known  input  and  the  observed 
output. 

The  extreme  complexity  of  neuronal  connections  in  the  higher  levels  of 
the  central  nervous  system  has,  hitherto,  prevented  critical  testing  of  the 
various  hypotheses  proposed  for  the  neural  mechanism  of  learning.  As  a 
consequence  there  has  been  an  unrestricted  growth  of  speculation,  as  may 
be  seen  by  reference  to  Gomulicki's  comprehensive  review  (1953).  It  is  an 
initial  postulate  of  the  present  investigation  that  synpases  at  spinal  level 
share  in  some  measure  the  synaptic  property  that  is  responsible  for  the 
phenomena  of  learning  at  higher  levels  of  the  nervous  system. 

The  experiments  have  been  restricted  to  the  monosynaptic  activation  of 
motoneuroncs  by  impulses  in  the  large  afferent  fibres  from  the  annulo- 
spiral  endings  of  muscle  spindles.  The  advantage  of  this  system  is  that  the 
input  is  under  precise  control  and  the  output  can  be  measured  as  the  size  of 
the  reflex  spike  response.  This  size  is  directly  related  to  the  number  of 
motoneurones  discharging,  and  hence  to  the  efficacy  of  their  mono- 
synaptic activation.  As  a  routine  procedure  before  all  the  monosynaptic 
testing  described  below,  the  spinal  cord  was  transected  in  the  upper 
lumbar  or  lower  thoracic  region  so  as  to  eliminate  the  possibility  of  reflex 
inequality  caused  by  a  tonic  asymmetric  discharge  of  suprasegmental 
origin.  In  addition  to  the  investigation  of  the  responses  evoked  by  single 
afferent  volleys,  there  has  regularly  been  an  investigation  into  the  potentia- 
tion of  these  responses  that  follows  a  high  frequency  tetanus  of  the  afferent 
pathway  usually  at  about  400  sec,  the  so-called  post-tetanic  potentiation. 


33^  BRAIN    MECHANISMS    AND    LEARNING 

Post-tetanic  potentiation  will  be  specially  considered  later,  when  discussing 
the  kind  of  enduring  changes  that  can  occur  in  synapses. 

EFFECTS    OF    DISUSE    ON    SYNAPTIC    FUNCTION 

Prolongcci  and  total  disuse  of  monosynaptic  reflex  arcs  has  been  secured 
by  severing  the  dorsal  roots  just  distal  to  their  ganglia,  thus  retaining 
functional  continuity  between  parent  cell  bodies  and  the  central  projec- 
tions within  the  spinal  cord  of  their  silenced  fibres  (Ecclcs  and  Mclntyre, 
1953).  Several  weeks  after  this  operation,  the  reflex  responses  evoked  by 
stimulation  of  these  disused  dorsal  roots  have  been  compared  with  the 
control  responses  on  the  other  side.  Volleys  in  the  disused  dorsal  roots 
were  always  much  less  effective  in  evoking  monosynaptic  reflexes  into 
either  flexor  or  extensor  muscles.  Post-tetanic  potentiation  was,  however, 
effective  in  restoring  much  of  the  lost  function,  but  it  was  still  far  below 
the  potentiated  control  response  (Fig.  i  A,  B). 

The  question  at  once  arises :  to  what  extent  can  reflex  deficiency  on  the 
operated  side  be  attributed  to  changes  in  the  presynaptic  pathways  other 
than  those  due  to  mere  absence  of  the  normal  impulse  barrage?  Histo- 
logical examination  revealed  two  possible  causes,  but  there  was  good 
evidence  that  only  part  of  the  discrepancy  could  be  so  explained.  For 
example,  there  was  in  some  experiments  destruction  of  some  dorsal  root 
fibres  either  at  the  initial  operation,'  or  subsequently  by  scarring.  Again, 
there  was  some  shrinkage  of  the  dorsal  root  fibres  (about  10  per  cent), 
which  is  probably  attributable  to  diminished  turgor  consequent  on  the 
regenerative  outgrowth  from  the  ganglion  cells  into  the  peripheral  stump 
(Gutmann  and  Sanders,  1943;  Sanders  and  Whitteridge,  1946;  Szenta- 
gothai  and  Rajkovits,  1955).  It  is  not  possible  conclusively  to  refute  the 
suggestion  that  the  synaptic  knobs  shrink  more  than  the  main  axonal 
shafts  from  which  they  spring,  the  large  depression  of  their  reflex  excita- 
tory power  being  thus  explained. 

However,  subsequent  to  a  prolonged  repetitive  stimulation  these 
disused  synapses  exhibited  a  behaviour  which  was  not  simply  explicable 
by  depressed  function  and  which  indicated  that  the  disused  synapses  had 
acquired  special  properties.  In  particular  the  post-tetanic  potentiation  of 
monosynaptic  reflexes  evoked  from  the  disused  roots  ran  an  abnormal 
time  course:  maximum  potentiation  of  the  reflex  occurrec^  later  than  in  the 
normal  control;  the  decline  from  this  maximum  occurred  several  times 
more  slowly;  and,  most  significantly,  the  reflexes  did  not  return  to  the 
initial  size,  as  with  normal  post-tetanic  potentiation,  but  exhibited  a 
residual  potentiation  that  persisted  for  hours  (Eccles  and  Mclntyre,  1953). 


J.    C.    ECCLES 


339 


N 


0    9 


0  13 


0  21 


0  29 


0  45 


1  10 


1'4  5 


Mice. 


A.  Monosynaptic  reflex  discharges  evoked  by  stimulating  the  appropriate  dorsal 
roots  and  recorded  in  gastrocnemius  nerves  40  days  after  extraganglionic 
operative  section  otthe  dorsal  roots  stimulated  in  the  O  records.  The  topmost 
record  (C)  of  O  and  N  series  is  the  reflex  response  before  any  tetanic  con- 
ditioning. The  remaining  series  show  potentiated  responses  after  a  conditioning 
tetanus  of  6000  volleys  at  400  a  second.  The  figures  above  each  response  show 
the  time,  in  minutes  and  seconds,  at  which  it  was  elicited  after  cessation  of 
the  conditioning  tetanus,  .^nlpliflcation  same  for  O  (operated)  and  N  (normal) 
responses. 

B.  The  crosses  plot  the  N  observations  of  Fig.  lA  and  the  open  circles  the 
O  observations  partly  shown  in  Fig.  lA.  The  vertical  line  marks  the  end  of 
the  conditioning  tetanus,  points  plotted  to  left  being  preliminary  controls  (c  of 
Fig.  I  A).  Horizontal  broken  lines  give  respective  mean  control  heights  of  reflex 
spikes.  The  filled  circles  are  also  O  responses  some  2  hours  later  than  the  open 
circles.  Note  that  initial  control  level  is  same  as  level  of  residual  potentiation 
surviving  at  end  of  first  potentiation  (open  circles  to  right).  Abscissae,  time 
after  end  of  conditioning  tetanus  (Eccles  and  Mclntyrc  (1953)  with  permission 
of  thejDi/rH(7/  of  Physiology). 


340 


BRAIN    MECHANISMS    AND    LEARNING 


Further  conditiouiiig  tctani  led  to  additional,  but  smaller,  residual  poten- 
tiations, showing  that  a  cumulative  process  was  involved  (Fig.  2).  The 
gradual  changes  which  unavoidably  occur  in  the  reflex  excitability  of  a 
preparation  (attributable  for  example  to  changes  in  anaesthesia  and  in 


20      6|30/ 


Jl^ 


4.0 


.ilg 


M 


■f. 


>i50 


Fu;.  2 
Plotting  of  post-tetanic  potentiation  and  residual  potential  as  in  Fig.  iB,  but  on  a  much  reduced 
time-scale,  note  time-scale  in  hours  and  minutes  on  abscissae.  Ordinates  give  sizes  of  mono- 
synaptic reflex  spike  in  millivolts.  L-  and  Sj  dorsal  roots  severed  extraganglionically  38  days 
previously.  The  open  circles  about  5.50  p.m.  give  reflex  spikes  in  biceps-semitendinosus  nerve 
in  response  to  single  volleys  in  the  combined  L-  and  Sj  dorsal  roots,  and  the  filled  circle  the 
mean  control  spike  in  gastrocnemius  nerve,  these  same  conventions  being  used  throughout. 
The  first  tetanic  conditioning  (7500  volleys  at  500  per  second)  is  shown  by  vertical  line  at 
5.55  p.m.,  and  the  five  other  tetanic  conditionings  (of  similar  severity)  are  likewise  indicated. 
The  post-tetanic  potentiation  curves  are  shown  for  gastrocnemius  and  biceps-semitendinosus 
after  first  and  second  conditioning  respectively  in  each  of  the  test  series.  As  indicated  by 
abscissae  the  vertical  shaded  columns  mark  lapses  of  2  hours,  20  minutes  and  55  minutes 
respectively,  and  during  the  second  an  injection  of  nembutal  was  given  (Eccles  and  Mclntyrc, 
1953,  with  permission  o{  x\\z  Journal  of  Physiology). 


circulation)  prevented  any  precise  determination  ot  the  time  constant  of 
decay  of  residual  potentiation,  but  probably  half  decay  takes  at  least 
3  hours,  which  would  make  it  about  i6o  times  slower  than  the  decay  rate 
for  the  normal  post-tetanic  potentiation  after  a  similar  conditioning 
tetanus. 

In  addition  to  this  investigation  on  the  effect  of  dorsal  root  section  on  the 


J.    C.    ECCLES  341 

monosynaptic  activation  of  niotoncuroncs,  the  monosynaptic  action 
exerted  by  the  same  afferent  fibres  on  the  cells  of  Clarke's  column  has  also 
been  investigated  (Mclntyre,  1953).  There,  too,  synaptic  depression  was 
observed,  but  it  was  less  readily  demonstrated,  since  that  synaptic  relay 
has  such  a  high  safety  factor. 

It  has  been  concluded  from  these  investigations  on  monosynaptic 
action  that  disuse  had  reduced  synaptic  efficacy  and  also  rendered  synapses 
more  susceptible  to  the  adjuvant  effects  of  activity.  In  particular  the  very 
prolonged  potentiation  of  disused  synapses  provided  a  response  that 
appeared  to  be  particularly  relevant  to  the  problem  of  the  synaptic 
mechanism  of  learning  (Eccles  and  Mclntyre,  1953  ;  Eccles,  1953  ;  Mclntyre 

T953)- 

Comparable  results  have  been  obtained  using  intracellular  recording 
of  the  excitatory  postsynaptic  potentials  induced  monosynaptically  in 
motoneurones  (Eccles,  Krnjcvic  and  Miledi,  1959).  Total  synaptic  disuse 
was  effected  by  severing  the  nerve  to  one  muscle  of  a  synergic  group,  the 
other  one  or  more  nerves  serving  to  give  control  synaptic  activation. 
This  procedure  also  introduced  the  complications  of  chromatolysis  of  the 
dorsal  root  ganglion  cells  and  shrinkage  of  the  afferent  fibres,  though  these 
effects  would  be  much  less  than  when  the  afferent  fibres  were  severed  just 
distal  to  the  dorsal  root  ganglion  cells.  There  was  as  well  chromatolysis  of 
those  motoneurones  with  severed  axons.  However,  there  was  the  advan- 
tage of  allowing  a  comparison  to  be  made  between  the  mtracellularly 
recorded  potentials  (the  excitatory  postsynaptic  potentials)  evoked  mono- 
synaptically ill  the  same  motoneurone  by  normal  afferent  pathways  and 
those  changed  by  operation.  No  additional  complication  was  introduced 
by  the  chromatolysis  of  motoneurones,  for  the  responses  of  chromatolysed 
motoneurones  to  monosynaptic  stimulation  via  normal  and  severed 
afferent  pathways  exhibited  the  same  ditiercnces  as  were  found  with 
normal  motoneurones.  It  was  found  that,  relative  to  the  control  afferent 
path,  the  monosynaptic  excitatory  action  of  the  disused  path  to  the  same 
motoneurone  was  reduced  to  about  half  after  2-4  weeks  of  the  total 
inactivity.  Furthermore,  it  was  increased  relatively  much  more  by  post- 
tetanic  potentiation,  so  that  the  normal  size  was  largely  regained  during 
the  maximum  potentiation  that  occurred  a  few  seconds  after  an  intense 
conditioning  activation  (Fig.  3).  Thereafter,  the  synaptic  potential 
progressively  declined,  but  often  a  small  residual  potentiation  occurred  for 
as  long  as  20  minutes,  while,  after  application  of  a  similar  conditioning 
stimulation  to  a  control  nerve,  the  post-tetanic  potentiation  usually  passed 
over  into  a  prolonged  phase  of  depression  (Fig.  4). 


342 


BRAIN    MECHANISMS    AND    LEARNING 


Besides  thus  confirming  the  earlier  work  in  which  synpatic  function 
was  tested  by  monosynaptic  reflexes,  this  investigation  of  synaptic 
potentials  allowed  quantitative  estimates  to  be  made  of  the  depression  of 
synaptic  function  and  established  that  this  depression  was  restricted  to  the 
inactivated  synapses  on  a  motoneurone.  It  also  revealed  the  time  course 


Fig.  3 
Intracellular  EFSPs  evoked  in  a  flexor  halliicis  longus  motoneurone  by  maxi- 
mum Group  la  volleys  in  flexor  hallucis  longus  nerve  (A),  and  in  flexor  digi- 
torum  longus  nerve  (B)  which  had  been  severed  1 5  days  previously.  Top  records 
in  A  and  B  were  taken  before  the  conditioning  tetanus  400  c/s  for  10  seconds, 
and  the  subsequent  records  at  the  indicated  intervals  after  the  tetanus.  Same 
time  scale  throughout,  but  different  voltage  scales  for  the  two  series  as  indicated. 
(Eccles,  Krnjevic  and  Miledi,  1959,  with  permission  ofthe  Jotmuil  ofPliysioloi^y). 


of  the  onset  of  depressed  function;  it  was  negligible  at  6  days,  but  by  10 
days  after  the  nerve  section  the  depression  was  already  about  half 
developed  and  by  1 3  days  it  was  fully  developed. 

As  we  have  seen,  the  operative  procedures  for  inducing  disuse  by 
sectioning  the  afferent  fibres  have  the  disadvantage  that  a  small  shrinkage 
of  the  dorsal  root  fibres  occurs  (Eccles  and  Mclntyre,  1953;  Szentagothai 
and  Rajkovits,  1955).  Conceivably,  this  shrinkage  may  extend  right  to  the 


J.    C.    ECCLES 


343 


synaptic  terminals  and  account  for  at  least  part  of  the  depressed  synaptic 
efficacy.  It  is  important,  therefore,  to  attempt  by  other  procedures  to 
produce  a  profound  diminution  of  the  discharge  of  impulses  from  the 
annulospiral  endings  of  the  muscle  spnidles  belonging  to  the  muscles 
under  test.  Several  experimental  procedures,  either  alone  or  in  suitable 
combination,  have  been  tried  (Wester man,  unpublished).  For  example, 
tenotomy  or  splinting  the  limbs  in  plaster  should  considerably  reduce  the 
activation  of  the  stretch  receptors  of  a  muscle,  although  it  must  be 
realized  that  annulospiral  endings  arc  extremely  sensitive  to  mechanical 
stimuli  and  certainly  could  not  be  silenced  by  these  procedures  (Matthews, 


Min 


Fig.  4 


Min 


Plots  of  the  time  courses  of  post-tetanic  potentiations  of  EPSPs  produced  by  a  conditioning 
tetanus  of  lo  seconds  at  400  c/s,  as  indicated  by  the  hatched  coknnns.  Specimen  records  are 
shown  in  Fig.  3.  In  Fig.  4  A  the  heights  of  the  EPSPs  are  plotted  relative  to  the  control  height, 
open  circles  being  for  the  operatively  severed  pathway  (FDL)  and  filled  circles  for  the  control 
pathway  (FHL).  Fig.  4B  as  for  Fig.  4A,  but  for  maxinuim  slopes  of  the  rising  phases  of  the 
EPSPs.  Note  that  in  Fig.  4A  the  time  scale  is  greatly  shortened  after  3  minutes  (reproduced 
from  Eccles,  Krnjevic  and  Miledi  (1959),  with  permission  01  the  Jonnuil  of  Physiology). 


1933;  Hunt  and  Kuffler,  195 1;  Kobayashi,  Oshima  and  Tasaki,  1952; 
Granit,  1955).  In  attempting  further  to  reduce  their  discharge,  the  appro- 
priate ventral  roots  have  been  severed  so  as  to  suppress  the  activation  of 
muscle  spindles  by  impulses  in  the  gamma  efferent  fibres  (Leksell,  1945; 
Kuffler,  Hunt  and  Quilliam,  195  i ;  Hunt,  1951 ;  Granit,  I955)-  I11  all  these 
experiments,  controls  were  provided  by  the  symmetrical  reflex  paths  of 
the  other  limb,  where  a  suitable  dummy  operation  had  been  performed; 
and,  in  addition,  the  degree  of  post-tetanic  potentiation  gave  a  sensitive 
measure  of  relatively  small  changes  in  synaptic  efficacy.  Finally  tests  for 
the  symmetry  of  monosynaptic  reflexes  were  made  with  afferent  paths 
which  were  unrelated  to  those  being  investigated,  e.g.  the  knee  flexor 
pathways  when  the  operative  procedures  were  restricted  to  muscles 
acting  on  the  ankle  and  digits. 


344  BRAIN    MECHANISMS    AND    LEARNING 

No  significant  change  has  been  observed  in  the  reflexes  from  such 
relatively  disused  pathways,  there  being  sometimes  a  small  depression 
relative  to  the  control,  but  more  often  an  increase,  as  has  been  mdepcnd- 
ently  reported  by  Beranck  and  Hnik  (1959);  furthermore,  no  significant 
changes  were  observed  in  the  post-tetanically  potentiated  reflexes.  A 
possible  interpretation  of  these  negative  results  is  that  the  various  pro- 
cedures were  ineffective  in  silencing  the  discharges  from  annulospiral 
endings,  there  being  sufficient  residual  activity  to  prevent  the  depression 
of  function  that  occurs  with  the  complete  disuse  of  severed  pathways. 
Alternatively,  it  could  be  maintained  that  disuse  does  not  cause  depression 
of  synaptic  function.  The  depression  observed  in  the  synaptic  action  of 
severed  pathways  (Eccles  and  Mclntyre,  1953;  Eccles  ct  al.,  1959)  would 
then  be  attributed  entirely  to  the  shrinkage  of  the  primary  afferent  fibres 
as  a  consequence  of  the  chromatolytic  changes  of  the  dorsal  root  ganglion 
cells.  This  dilemma  can  be  resolved  only  if  complete  inactivity  of  mono- 
synaptic synapses  can  be  secured  without  severing  the  primary  afferent 
fibres.  An  attempt  to  do  this  by  a  prolonged  cold  block  of  peripheral 
nerve  has  so  far  failed  on  account  of  technical  difficulties.  This  indecisive 
situation  for  the  disuse  experiments  makes  the  investigations  of  excess  use 
of  crucial  significance.  However,  it  must  be  remembered  that,  on  post- 
tetanic  potentiation,  the  synapses  belonging  to  severed  afferent  pathways 
exhibited  a  slower  recovery  and  a  residual  potentiation,  which  has  sug- 
gested that  the  depression  arose  specifically  from  disuse,  rather  than  from 
a  mere  shrinkage  due  to  chromatolysis  (cf  Eccles  and  Mclntyre,  1953; 
Eccles  et  al.,  1959). 

EFFECTS    OF   EXCESSIVE    USE    ON    SYNAPTIC    FUNCTION 

If,  as  seems  likely,  prolonged  disuse  has  a  deleterious  effect  on  the 
potency  of  synapses,  it  follows  that  normal  use  has  a  sustaining  function ; 
and  it  is  further  likely  that  excess  use  leads  to  an  enduring  enhancement  of 
synaptic  function  above  the  normal  level,  which  provides  of  course  the 
synaptic  basis  for  the  suggested  explanation  of  learning.  There  is,  however, 
in  the  literature  very  httle  experimental  data  on  the  effect  of  excess  use. 
The  most  significant  findings  were  the  increased  monosynaptic  reflexes, 
relative  to  the  control  side,  in  the  segment  immediately  rostral  to  those 
with  severed  dorsal  roots  (Eccles  and  Mclntyre,  1953)-  This  asymmetry 
may  reasonably  be  attributed  to  the  development  of  some  compensatory 
reaction  to  the  operative  disability,  particularly  in  extensor  muscles  that 
had  been  partlv  deafferented.  The  simplest  explanation  of  this  compensa- 


J.    C.    ECCLES 


345 


tion  is  that  the  partial  dcaftercntation  had  thrown  more  mechanical  stress 
on  the  remaining  stretch-receptors  of  the  weight-supporting  extensors, 
with  the  consequence  that  there  was  nicreased  activity  of  their  synapses, 


JJJJJUJL      BICEPS- SEMI  TENDINOSUS 
>■-«  (CONTROL) 


T  ^"^         A 


•L'^\J—LLL  LATERAL    GASTROCNEMIUS 

""""  (EXCESS    USEi 


lJ\^ 


T  smV  A 


.\_\_\_\_\_  DEEP   PERONEAL   NERVE 

iniMC  (CONTROL) 


L6 


T 


T  Jmv  A 


normol    side    '  -.       cut  side 


L7 


X, 


u 


~rrrrr        flexor  digitorum  longus 
-"•«  (EXCESS    USE) 


NORMAL  SIDE 


CUT   SIDE 


L7 


JV_  IJU 


Fig.  5 
Monosynaptic  reflexes  recorded  in  the  Lg,  L,  or  Si  ventral  roots  in  response  to  maximum 
group  la  afferent  volleys  from  the  four  muscles  as  specified.  On  the  left  side  of  the  figure,  the 
biceps-semitendinosus  and  deep  peroneal  volleys  served  to  control  the  symmetry  of  the 
preparation,  there  being  approximate  equality  of  the  reflexes  into  comparable  ventral  roots 
on  the  two  sides.  Each  of  the  reflexes  is  shown  before  (A)  and  during  maximum  post-tetanic 
potentiation  (T).  On  the  right  side  of  the  figure  the  monosynaptic  reflexes  from  the  two  other 
muscles  arc  similarly  assembled,  but  each  of  these  muscles  on  the  cut  side  had  been  subjected 
to  excess  use  as  described  in  the  text.  Note  that,  in  response  to  a  lateral  gastrocnemius  afferent 
volley,  both  A  and  T  reflexes  are  larger  into  the  Sj  and  L^  ventral  roots  on  the  cut  side.  This  is 
also  seen  for  the  flexor  digitorum  longus  reflex  into  L-  (reproduced  by  permission  ot  R.  M. 
Eccles  and  Westerman  (1959)  and  of  the  Editors  of  Nature). 


the  excess  use  giving  an  enhanced  function.  Of  less  significance  in  relation 
to  learning  is  the  finding  that  functionally  over-loaded  muscles  have 
hypertrophied  nerve  fibres  (Edds,  1950). 


346  BRAIN    MECHANISMS    AND    LEARNING 

In  investigating  further  the  effect  of  increased  use,  it  was  important  to 
design  experiments  in  which  central  synapses  were  subjected  to  an  exces- 
sive discharge  from  annulospiral  endings  and  in  which  adequate  controls 
were  available.  For  example,  tenotomy  or  nerve  section  for  all  but  one 
muscle  of  a  synergic  group  was  employed  in  order  to  place  excessive  stress 
on  the  remaining  muscle,  and  as  a  consequence  it  was  presumed  that  there 
was  excess  discharge  from  its  stretch  receptors.  An  appropriate  dummy 
operation  was  performed  on  the  other  side.  By  having  the  animals  walk 
in  a  treadmill  for  20  to  30  minutes  every  day,  it  was  ensured  that  there 
were  ample  opportunities  for  this  muscle  to  be  subjected  to  the  excessive 
stress.  After  some  weeks  the  monosynaptic  reflex  evoked  by  an  afferent 
volley  in  this  muscle  nerve  was  always  larger  (Fig.  5),  the  main  increase 
being  50  per  cent  or  more  in  the  fourteen  animals  so  far  investigated,  than 
for  the  corresponding  afferent  volley  on  the  other  side  (Eccles  and  Wester- 
man,  1959).  Control  observations  were  made  for  reflexes  from  nerves  to 
synergic  groups  of  muscles  with  undisturbed  innervation  on  both  sides 
(Fig.  5).  Since  there  was  no  significant  asymmetry  for  such  mono- 
synaptic reflexes,  it  can  be  concluded  that  tlie  excess  use  had  resulted  in 
enhanced  function.  A  slightly  smaller  relative  increase  was  also  observed 
during  post-tetanic  potentiation  of  the  reflexes  evoked  by  afferent  volleys 
from  the  stressed  muscle  and  its  symmetrical  control.  Thus  we  have  here 
the  most  convincing  demonstration  yet  provided  that  excess  synaptic  use 
over  several  weeks  results  in  enhanced  synaptic  function.  Experiments  are 
in  progress  to  test  for  the  effects  of  excess  synaptic  use  on  other  synaptic 
systems,  e.g.  for  the  activation  of  Renshaw  cells  from  the  ventral  spino- 
cerebellar tract  by  impulses  from  Golgi  tendon  organs. 

DISCUSSION 

It  will  be  appreciated  that  these  investigations  are  restricted  to  simple 
synaptic  systems  in  the  spinal  cord.  If,  as  now  seems  likely,  excess  activa- 
tion gives  a  prolonged  increase  in  synaptic  efficacy,  experimental  investiga- 
tion could  be  extended  to  the  more  complex  polysynaptic  reflex  pathways 
and,  finally,  to  pathways  in  the  higher  levels  of  the  nervous  system.  Since 
investigations  of  learning  and  of  conditioned  reflexes  have  been  carried 
out  almost  exclusively  with  these  higher  levels  of  the  central  nervous 
system,  it  has  generally  been  thought  that  synapses  at  these  levels  had 
properties  of 'plasticity'  that  were  not  shared  by  synapses  in  the  spinal  cord. 
Experimental  evidence  is  now  against  any  such  qualitative  distinction 
between  the  synapses  of  higher  and  lower  levels  of  the  central  nervous 


J.    C.   ECCLES  347 

system.  However,  there  may  be  quantitative  differences,  the  synapses  at 
higher  levels  being  more  sensitive,  relatively  few  impulses  producing 
large  and  prolonged  plastic  changes. 

On  account  of  the  very  long  time  scale  of  the  synaptic  changes  pro- 
duced by  use  and  disuse  it  would  be  extremely  difficult  to  discover  their 
nature  by  direct  investigation.  However,  in  many  respects  post-tetanic 
potentiation  resembles  the  effect  of  excess  usage,  and  it  can  be  readily 
investigated. 

With  post-tetanic  potentiation  of  neuromuscular  transmission  a  highly 
significant  finding  is  that  the  potentiation  is  paralleled  by  an  increased 
frequency  of  the  quantal  emission  of  transmitter  substance  from  the 
presynaptic  endings  (Brooks,  1956;  Liley,  1956;  Hubbard,  1959),  as 
signalled  by  an  increased  frequency  of  the  miniature  endplate  potentials 
(cf.  Katz,  1958).  Electron  microscopy  has  revealed  a  dense  assemblage  of 
the  so-called  synaptic  vesicles  in  the  presynaptic  terminal,  and  it  is  highly 
probable  that  the  quantal  emission  ot  transmitter  substance  is  due  to  the 
bursting  of  these  vesicles  into  the  synaptic  cleft.  Hence,  an  attractive 
explanation  is  available  for  post-tetanic  potentiation:  the  repetitive 
presynaptic  stimulation  causes  the  mobilization  of  these  synaptic  vesicles 
close  to  the  synaptic  surfice  {cf.  Palay,  1956),  so  that  not  only  is  their 
rate  of  spontaneous  emission  increased,  bui"  there  is  also  an  increase  in  the 
number  emitted  by  a  presynaptic  impulse  (cf  Eccles,  1957). 

However,  there  is  also  good  experimental  support  for  an  alternative 
explanation  of  post-tetanic  potentiation:  the  repetitive  presynaptic 
stimulation  is  followed  by  an  increased  membrane  potential  of  the  presy- 
naptic terminals,  with  the  consequence  that  the  presynaptic  impulse  is 
increased  in  size  and  so  synaptic  transmission  is  potentiated  (Lloyd,  1949; 
Eccles  and  Krnjevic,  1959  a,  b). 

Presumably  both  of  these  postulated  processes  are  concerned  in  post- 
tetanic  potentiation,  but  it  seems  most  improbable  that  an  increased 
membrane  potential  of  presynaptic  fibres  could  account  for  the  very  pro- 
longed increase  that  excess  use  causes  in  synaptic  efficacy,  or  even  for  the 
several  hours  of  the  residual  potentiation  displayed  by  disused  synapses. 
On  the  other  hand  it  seems  a  likely  possibility  that  changes  in  the  popula- 
tion or  disposition  of  synaptic  vesicles  could  account  at  least  in  part  for 
very  prolonged  changes  in  synaptic  efficacy. 

Besides  these  physiological  investigations  into  the  effects  ot  excess  use, 
it  is  important  to  see  whether  electron  microscopy  reveals  any  structrual 
changes  in  the  presynaptic  terminals.  Already  it  has  been  reported  that, 
after  several  days  of  disuse  brought  about  by  complete  darkness,  there  is 


348  15RAIN    MECHANISMS    AND    LEARNING 

diminution  in  the  size  of  the  synaptic  vesicles  at  the  synapses  made  by  both 
rods  and  cones  with  the  bipolar  cells  in  the  rabbit's  retina  (De  Robcrtis  and 
Franchi,  1956).  A  further  observation  was  that,  after  i  day  of  darkness,  the 
synaptic  vesicles  tended  to  accumulate  close  to  the  presynaptic  membrane 
(De  Robcrtis  and  Franchi,  1956).  It  would  be  of  interest  to  sec  whether, 
correspondingly,  there  is  a  phase  of  increased  synaptic  efficacy  after 
comparable  periods  of  disuse  brought  about  by  nerve  section  or  by  the 
other  procedures  outlined  above. 

The  ultimate  aim  of  these  investigations  on  plasticity  would  be  to 
correlate  the  observed  structural  and  functional  changes  and  to  under- 
stand the  way  these  changes  are  brought  about  by  excess  use  and  by  disuse. 
Inevitably,  such  a  programme  involves  questions  relating  to  the  control 
of  the  manufacture  of  transmitter  substance  and  to  its  availability  for 
release  by  the  activated  synapses.  It  would  seem  more  probable  that  use 
gives  increased  function  by  enhancing  the  manufacture  and  availability  of 
transmitter  substance,  although  enlargement  of  synaptic  knobs  and  even 
the  sprouting  of  new  knobs  are  alternative  devices  for  securing  an  increased 
synaptic  action  (Konorski,  1948,  1949;  Hebb,  1949;  Young,  1951;  Eccles, 
1953).  Evidently,  further  investigation  by  electron  microscopy  is  of  the 
greatest  significance  in  providing  evidence  discriminating  between  these 
alternatives. 

Perhaps  the  most  unsatisfactory  feature  of  the  attempt  to  explain  the 
phenomena  of  learning  and  conditioning  by  the  demonstrated  changes 
in  synaptic  efficacy  is  that  long  periods  of  excess  use  or  disuse  are  required 
in  order  to  produce  a  detectable  synaptic  change.  In  contrast,  conditioned 
reflexes  are  established  by  relatively  few  presentations,  and  unique  events 
may  be  remembered  for  a  life  time.  A  probable  explanation  is  that  pro- 
longed revcrberatory  activity  occurs  in  the  neuronal  network,  so  that  a 
single  event  may  activate  each  synaptic  link  in  a  spatio-temporal  pattern 
thousands  of  times  within  a  few  seconds.  Hebb  (1949)  makes  a  related 
postulate  when  he  supposes  that  'a  revcrberatory  trace  might  co-operate 
with  the  structural  change,  and  carry  the  memory  until  the  growth  change 
is  made'.  A  similar  suggestion  has  been  made  by  Gerard  (1949).  Further- 
more we  may  suppose  that  the  plastic  changes  in  synapses  are  susceptible 
to  reinforcement  by  the  replaying  of  the  specific  spatio-temporal  patterns 
each  time  that  the  memory  is  recalled.  It  is  also  possible  that  synaptic 
plasticity  may  be  much  more  highly  developed  in  the  cerebral  cortex. 


J.    C.    ECCLES  349 


GROUP   DISCUSSION 


Hebb.  Was  I  correct  in  understanding  that  the  excessively  used  synapses  were 
the  ones  that  showed  the  most  post-tetanic  potentiation?  Isn't  this  just  the  opposite 
of  what  one  would  expect?  They  arc  the  ones  which  have  been  exposed  the  most 
to  the  PTP,  in  their  use,  and  we  would  now  expect  them  to  react  the  least. 

EccLES.  The  figures  I  showed  you  did  indicate  something  like  that.  But  you  must 
remember  that  these  are  reflexes  in  ventral  roots  and  therefore  quite  unreliable  as 
samples  of  relative  synaptic  potency.  I  would  not  place  any  reliance  on  these 
results  with  reflexes  as  measures  of  PTPs.  Comparisons  of  relative  sizes  of  PTPs 
should  be  made  by  excitatory  post-synaptic  potentials. 

KoNORSKi.  The  view  put  forward  bv  Dr  Eccles  is  that  while  excessive  use  ot  given 
synaptic  connections  increases  their  efliciency,  the  disuse  produces  opposite  effects, 
namely  regression  of  synaptic  function.  This  would  be  the  simplest  physiological 
model  of  memorizing  and  forgetting.  I  held  the  same  view  several  years  ago  (cf. 
Konorski,  Conditioned  Reflexes  and  Nenron  Organization,  Cambridge,  1948),  in 
spite  of  the  fact  that  a  great  body  of  evidence  seemed  to  contradict  it.  Indeed,  we 
know  very  well  that  firmly  established  conditioned  reflexes,  as  well  as  our  own 
memory  traces  remain  intact  even  after  many  years  of  'disuse'.  But  I  couldn't 
conceive  any  other  mechanism  of  the  phenomenon  of  forgetting  than  the  atrophy 
ot  long  disused  synaptic  connections. 

The  realization  of  the  great  role  played  by  dynamic  memory  traces  in  establish- 
ing conditioned  connections  allows  me  now  to  overcome  this  difficulty  and  to 
interpret  the  phenomenon  of  forgetting  from  quite  a  different  point  of  view.  As  I 
pointed  out  in  my  paper  the  chief  feature  of  recent  memory  traces,  as  contrasted 
with  old  memor)-  traces,  is  that  the)'  are  based  on  some  dynamic  mechanism 
consisting  probably  in  the  transient  activation  of  reverberating  chains  of  neurones. 
The  ultimate  fate  ot  these  traces  depends  on  the  effects  they  produce :  either  they 
give  rise  to  appropriate  morphological  connections  and  are  then  transformed  into 
stable  memory  traces,  or  in  certain  conditions,  as  shown  in  my  paper,  they  have  no 
chance  to  do  so  and  are  then  totally  obliterated.  In  such  a  case  we  have  to  do  with 
the  phenomenon  of  forgetting. 

According  to  these  considerations  one  is  inclined  to  suppose  that  synaptic  con- 
nections once  formed,  whether  in  ontogenesis  or  as  a  result  of  special  training,  do 
not  atrophy  by  disuse,  and  that  forgetting  would  probably  concern  only  dynamic, 
but  not  stable,  memory  traces. 

The  recent  results  obtained  by  Dr  Eccles  seem  to  confirm  my  assumption. 
Excessive  use  of  the  given  spinal  pathways  led  in  his  experiments  to  the  increase  of 
efficacy  of  the  synaptic  connections  involved,  a  fact  analogous  to  the  formation  of 
stable  memory  traces.  But  the  disuse  o{  the  given  pathways  did  not  lead  to  the 
deterioration  of  the  reflex  because  of  the  stability  of  synaptic  connections. 

Eccles.  Now,  of  course,  you  cannot  know  what  is  going  on  in  the  dog's  brain  ! 
He  may  not  have  been  subjected  to  the  experimental  training  procedures  for  long 
periods,  but  he  may  be  'reliving'  them  in  some  experiential  way.  I  realize  that  the 
higher  level  synapses  are  probably  quantitatively  different  from  the  lower  ones,  but 
we  can  show  qualitatively  that  the  lower  ones  have  the  kind  of  properties  you 
would  postulate  as  the  basis  of  memor\-  in  the  higher  ones.  I  would  not  like  to 
comment  on  these  disuse  experiments  until  we  have  done  a  further  series  of 


350  BRAIN    MECHANISMS    AND    LEARNING 

experiments.  We  nuist  block  the  afferent  pathways  without  cutting  them, 
which  is  probably  a  matter  of  improving  our  technique  of  cold  blockage. 

Gerard.  This  is  the  same  kind  of  answer  I  gave  to  Dr  Grastyan's  point,  that  one 
single  stimulus  could  leave  a  trace.  Secondly  there  are  many  experiments  to  show 
that  memories  mostly  (not  always)  do  not  remain  unchanged  over  time;  pictures 
are  recalled  with  directional  distortions. 

EsTABLE.  I  would  like  to  make  some  comments:  in  the  first  place,  the  problems 
of  learning  are  usually  approached  taking  for  granted  that  the  neurone  is  static, 
that  it  is  not  modified  during  life.  Neurones  are  like  trees  that  modify  their  finer 
branches,  for  example,  the  neurones  in  the  skin,  which  change  the  direction  of 
their  terminal  branch  Vv^hen  the  cell  they  were  ennervating  dies  and  has  peeled  off. 
I  wonder  whether  something  like  this  might  not  occur  in  the  C.N.S.  and  provide 
an  explanation  for  the  changes  in  its  performance.  In  the  second  place,  small 
changes  in  synapses  may  give  large  functional  changes  —  for  example  in  certain 
diseases  and  after  some  drugs  —  and  in  the  embryo,  where  the  synapses  are  identical 
to  those  of  the  adult  but  do  not  yet  operate. 

EccLES.  I  do  agree  that  there  are  all  sorts  of  growth  processes  going  on  in  synapses. 
Anyone  who  has  seen  the  cine-photography  of  Pomerat  in  tissue  culture  will  agree 
that  the  outgrowing  nerve  terminal  is  vividly  alive.  It  is  growing,  retracting  and 
moving  all  the  time. 

Olds.  Dr  Eccles  has  shown  us  a  good  example  of  a  long  run  adaptive  change 
through  use,  and  with  such  few  examples  of  this  type,  it  cannot  be  ignored. 
However,  I  wish  to  sound  a  word  of  warning  to  my  fellow  psychologists.  What 
Dr  Eccles  has  suggested  is  that  by  sending  an  impulse  down  an  axon  we  cause  more 
transmitters  to  be  available  in  the  terminal,  and  note  that  this  is  true  whether  or  not 
the  impulse  'crosses'  the  synapse.  This  data  is  often  used  by  theorists  to  show  how 
the  successful  synapse  gains  power  at  the  expense  of  the  unsuccessful  synapse  — 
and  my  impression  is  that  both  these  synapses  arc  equalh'  reinforced  and  that 
makes  this  mechanism  unusable  for  theories  like  those  of  Hebb,  Konorski  and 
Gerard. 

Eccles.  I  think  Dr  Olds  had  misunderstood  the  problem.  I  am  not  interested  in 
whether  a  particular  synapse  generated  an  impulse  or  not.  All  I  am  interested  in 
showing  is  that  every  time  you  activate  synapses  the)'  become  more  efficacious. 
Every  time  a  signal  comes  in  from  some  receptor  it  fires  more  cells  and  thus 
operates  along  channels  that  become  progressively  more  powerful  with  more 
impulses  in  parallel,  more  convergence  on  the  next  stage  and  so  on  ...  Thus  there 
is  a  progressively  more  effective  channelling.  Now  this  would  only  occur  if  the 
'unsuccessful'  synapses  shared  in  the  potentiation. 

AsRATYAN.  I  want  to  congratulate  Dr  Eccles  on  his  valuable  new  data  which  is  a 
great  contribution  to  neurophysiology.  I  want  to  draw  attention  to  the  extreme 
importance  of  new  data  provided  by  Dr  Eccles  concerning  the  stable  results  of 
excessive  use  and  disuse  of  synaptic  apparatus  on  their  structural  and  functional 
properties.  Recently  we  have  obtained  in  our  laboratory  some  facts  which  are  in 
full  accordance  with  this  data,  although  it  was  not  obtained  under  such  precise 
conditions.  We  worked  with  dogs  whose  spinal  cord  has  been  transected  at  the 
level  of  the  lower  thoracic  segments.  If  the  animals  are  strictly  limited  in  their 
mobility  it  leads  to  an  evident  muscular  atrophy  of  these  limbs  and  to  a  lessening  of 
their  reflex  activity.  If,  however,  these  limbs  are  systematically  treated  by  special 


J.    C.    ECCLES  351 

trainino;,  or  massage  or  mechanical  and  electrical  stimulation,  etc.,  this  results  in  a 
good  trophic  state  of  the  limbs  and  a  very  rich  and  lively  reflex  activity  of  the 
caudal  part  of  the  transected  spinal  cord.  The  precise  data  obtained  by  Dr  Eccles 
has  importance,  not  only  in  general  neurophysiology,  or  in  the  problem  of 
recovery  of  functions  in  injured  organisms,  but  also  in  the  problem  of  learning.  It 
seems  to  me  that  although  morphological  and  functional  changes  of  synaptic 
apparatus  as  a  result  of  their  excessive  use  is  a  common  property  ot  all  the  nervous 
structures,  nevertheless,  these  changes  lead  to  an  elaboration  ot  conditioned  reHex 
only  in  the  neural  structures  ot  the  higher  parts  of  the  nervous  system,  at  least,  m 
high  developed  organisms.  I  cannot  agree  with  Shurrager  and  other  authors  that 
the  spinal  cord  is  also  able  to  elaborate  conditioned  reflexes.  In  any  case,  Dr  Eccles's 
data  shows  that  achievements  in  general  neurology  are  and  will  ever  remain  a 
source  of  investigations  of  brain  processes  and  especially  conditioned  reflex 
research. 

Eccles.  Thank  you  Dr  Asratyan.  We  have  very  similar  experiments  going  on 
in  Canberra.  Dr  Kozak  from  Dr  Konorski's  laboratory  is  investigating  the  changed 
reflex  pattern  that  occurs  in  spinalized  kittens.  There  is  here  evidence  that  you  have 
new  patterns  developing  in  the  C.N.S.  under  changed  conditions. 

Fessard.  Wotild  you  consider  that  an  inhibition  at  the  synapse  would  produce 
the  same  effect  as  a  long  disuse  ? 

Eccles.  If  the  cell  does  not  fire  impulses,  the  synapses  that  it  makes  with  other 
cells  would  be  disused. 

Fessard.  Disuse  obtained  by  inhibition  would  be  produced  in  a  more  natural 
way  than  by  section  of  the  nerve.  Would  it  be  possible  technically  to  make  such  an 
experiment? 

Eccles.  I  have  thought  about  such  a  possibility  but  I  do  not  know  how  to  do  it 
experimentally. 

Segundo.  Dr  Eccles,  when  vou  compared  the  'used'  side  with  the  "non-used' 
side,  tetanic  potentiation  was  greater  in  the  latter  (as  measured  in  reterence  to  a 
100  per  cent  value  of  the  initial  monosynaptic  response  amplitude).  How  did  you 
select  stimulus  intensity  in  order  to  make  effects  on  both  sides  comparable 

Eccles.  With  all  experiments  there  was  maximum  stimulation  of  group  I  fibres 
and  in  addition  the  series  were  repeated  in  alternate  sequences  many  times. 

Hebb.  I  would  like  to  make  a  comment  on  a  different  track.  There  is  some 
evidence  which  needs  to  be  considered  when  you  discuss  learning  over  a  long- 
range  period.  Chimpanzees  put  into  darkness  after  being  raised  in  light  to  the  age 
of  6  months  suffer  complete  forgetting  of  visual  responses  when  brought  out 
again.  The  clinical  ophthalmologist  tells  us  that  if  a  child  becomes  blind  before  the 
age  of  2  years  he  will  be  indistinguishable  from  the  congenitally  blind  at  maturity. 
If  he  becomes  blind  at  the  age  of  4  years  he  will  never  be  like  the  congenitally 
blind,  he  is  like  the  person  who  has  had  vision  until  maturit)'.  In  other  words  there 
can  be  well  established  visual  learning  but  it  will  not  last  if  it  is  not  maintained  for 
4  or  5  years.  Once  thoroughly  established,  it  will  last  for  good. 

Anokhin.  In  our  laboratory  we  are  now  doing  experiments  which  have  a  direct 
correlation  with  yours.  We  have  changed  muscles  from  extensor  or  flexor  position. 
For  3  or  5  weeks  these  cats  presented  abnormal  movements  —  but  after  i 
year  they  moved  in  the  normal  fashion.  The  electromyographical  analysis  shows 
that  the  muscles  performed  their  new  function.  But  after  spinahzation  these  muscles 


352  BRAIN    MECHANISMS    AND    LEARNING 

reverted  to  their  old  function.  Do  you  think  this  process  occurs  only  at  spinal  levels 
or  is  capable  of  being  produced  by  the  whole  nervous  system? 

EccLES.  I  am  very  interested  in  the  experiments  of  Dr  Anokhin.  We  have  done, 
too,  transplantation  of  muscles  but  have  tested  only  the  monosynaptic  pathways  in 
the  spinal  animal.  We  find  that  the  original  pathways  have  been  retained,  and 
there  has  been  little  or  no  resculpturing  of  the  spinal  connections.  Mclntyre  has 
done  similar  experiments.  There  is  general  agreement  that  at  the  spinal  level  there 
is  little  or  no  change  of  connections  after  muscle  transplantation. 


LA    FACILITATION    DE    POST-ACTIVATION    COMME 

FACTEUR  DE   PLASTICITE   DANS   L'ETABLISSEMENT 

DES   LIAISONS  TEMPORAIRES 

A.  Fessard  et  Th.  Szabo 


Quelle  que  soit  la  complexite  d'organisation  des  structures  iiervcuses  et 
dcs  operations  qui  sent  iiupliquees  dans  tout  comportenient  d'appren- 
tissage,  il  est  certain  que  la  question  se  pose  a  tout  esprit  analytique  de  la 
nature  des  processus  elcmentaires  impliques  dans  ce  coniportement.  Que 
se  passe-t-il  dans  les  neurones  d'un  cerveau  qui  modifie  de  fa^on  durable 
ses  potentialites  reactionnellcs  sous  I'influence  d'actions  exterieures 
appropriees,  dont  la  plus  simple  est  la  repetition  monotone  d'un  stimulus, 
dont  une  autre  est  I'association,  plusieurs  fois  presentee,  d'un  stimulus  avec 
un  autre,  comnie  dans  la  technique  du  conditionnement  pavlovien:  Que 
se  passe-t-il  enfin  au  niveau  moleculaire,  puisque,  en  tni  de  compte,  cette 
modification  durable  de  I'excitabilite  neuronique  doit  avoir  un  support 
dans  les  ultra-structures  actives  de  la  cellule  nerveuse? 

Sans  doute,  ces  questions  etant  supposees  rc'solues,  il  ne  s'ensuivrait  pas 
que  nous  serions  capables  d'expliquer  entierement  I'apparition  d'un 
phenonicne  d'  'habituation',  ou  la  formation  de  nouvelles  liaisons  fonc- 
tiomielles,  car  les  caracteristiqucs  de  V origan isatioii  des  apparcils  de  la  vie 
de  relation  mis  en  jeu  —  centre  nerveux,  recepteurs  et  effecteurs  —  jouent 
evidemment  un  role  cssentiel  dans  la  realisation  des  manifestations 
globales  du  comportenient  d'apprentissage,  comme  de  tout  comporte- 
nient. Il  n'eii  restc  pas  moiiis  vrai  que  les  composantes  priniaires  de  ces 
manifestations  doivent  etre  rechcrchees  au  niveau  du  neurone  d'abc^rd  et, 
dans  la  mesure  ou  les  techniques  le  permettent,  au  niveau  moleculaire, 
pour  tenter  fmalement  d'etablir  les  bases  physico-chimiques  de  la  con- 
servation des  traces  d'activite. 

Ces  reflexions  ne  soiit  pas  nouvelles,  mais  tandis  qu'elles  soiit  restees 
loiigtcmps  purement  speculatives,  elles  peuvent  aujourd'hui  par  suite  du 
progres  considerable  des  microtechniques,  trouver  des  prolongements 
efficaccs  dans  des  approches  experimciitales  diverses:  recherche  a  I'aide  de 
la  microscopic  clectronique  de  changements  dans  les  ultra-structures  dus  a 
I'activite  repetee,  application  des  techniques  cytochimiques  modernes  a  la 

353 


354  BRAIN    MECHANISMS    AND    LEARNING 

misc  en  evidence  des  moditications  moleculaires  d'origiiie  metabolique, 
exploration  de  I'etat  electriquc  cellulaire  a  I'aidc  de  microelectrodes  ultra- 
fines.  A  vrai  dire,  ces  techniques  raftmees  ont  encore  peu  servi  a  I'etude  des 
traces  cellulaires  durables  d'activite.  Mais  ces  techniques  cxistant,  et  se 
perfectionnant  sans  cesse,  on  pent  prcvoir  que  des  donnees  nouvelles  nc 
tarderont  pas  a  etayer  certaines  hypotheses  anciennes,  a  en  f;iire  ecarter 
d'autres,  et  peut-etre  a  suggerer  des  niecanisnies  encore  insoup(;onncs. 

Parnii  les  hypotheses  Ics  plus  anciennes,  celle  qui  fait  appel  a  la  croissance 
de  nouvelles  terniinaisons  et  a  la  formation  de  synapses  encore  iiicxistautcs 
n'a  conserve  que  peu  de  hdeles,  faute  de  preuves;  niais  certains  faits 
pcrmettent  aujourd'hui  de  penser  qu'elle  regagne  des  chances,  et  qu'il 
serait  imprudent  de  la  rejeter  completement.  Elle  rendrait  compte,  evidem- 
nient,  des  traces  bien  tixees,  ou  me  moires  a  long  terme.  Plus  recemnient 
suggeree,  I'hypothese  d'une  perseveration  dynaniique  des  traces  d'activite 
par  I'mtermediaire  de  circulations  d'influx  dans  des  boucles  fermees 
('circuits  reverberants')  souleve  tant  d'objections  justihees  (voir  notre 
article  du  Symposium  'Sensory  Communications',  Boston,  1959)  que 
nous  ne  considerons  ce  mccanisme  que  conime  au  plus  capable  d'entre- 
tenir  passagerement  une  certaine  dynamogenie,  sans  pouvoir  preserver  la 
structure  de  I'information  qui  I'a  declenchc. 

A  I'echelle  clcmentaire,  il  ne  reste  de  vraiment  plausible  parmi  les  idees 
anciennes,  que  celle  d'une  'permeab'ilite'  plus  grande  vis-a-vis  de  I'influx 
nerveux  pour  des  synapses  dcja  cxistaiitcs  et  qui  ont  longuement  travaille; 
c'est-a-dire,  en  langage  moderne,  d'un  accroissement  durable  de  leurs 
potentialitc's  transmettrices,  qu'il  s'agisse  d'excitation  ou  d'inhibition. 

Si  nous  posons  en  principe  qu'en  I'ctat  actuel  de  nos  connaissances,  tres 
pauvre  comme  nous  I'avons  rappele,  il  est  sage  de  ne  negliger  aucun  fait 
qui  ressemble  a  la  formation  d'une  trace,  si  peu  durable  soit-elle,  nous 
sommcs  en  droit  de  nous  etonner  que  Ton  n'ait  pas  encore  exploite  le 
phenomcne,  aujourd'hui  reconuu  general,  de  la  'potentiation  post- 
tetaniquc'  que  nous  appellerons  ici  potciiriatioii  tctaniqiic  proloii(^cc  pour  lui 
conserver  la  mcme  abreviation  qu'en  anglais,  FTP  [post-tctaiiic  potent iarioii). 
Nous  allons  essayer  de  voir  dans  quelles  conditions  cette  FTP  pourrait  etre 
une  des  causes,  peut-etre  la  principalc,  de  la  conservation  a  court  tcniic 
de  traces  d'activite  et  I'un  des  factcurs  de  I'amorce  d'associations  inter- 
centrales  a  plus  long  terme,  de  'liaisons  temporaires'  au  sens  dynamique  de 
la  thcorie  des  reflexes  conditionnes. 

Nous  ne  ferons  pas  un  expose  preliminaire  sur  la  FTP,  le  phcnomene 
ctant  suppose  bien  connu.  On  se  reportera  au  bcsoin  a  la  Revue  generale 


A.    FESSARD    ET    TH.    SZABO  355 

dej.  R.  Hughes  (1958).  Que  cc  phcnomcue  ne  cesse  de  susciter  I'interet  dcs 
neurt")physiologistcs  est  prouvc  ici  nieme,  dans  ce  symposium  (voir  I'article 
dc  J.  C.  Ecclcs)  et  par  Ics  mcmoircs  rc'cents  de  Eccles  et  Krnjevic  (1959, 
a  ct  /))  et  de  Curtis  et  Eccles  (i960).  Il  est  bien  ctabli  que  son  siege  est  dans 
Ics  terminaisons  presynaptiques  qui  appartiennent  aux  fibres  tetanisces  et 
a  cclles-la  seulemcnt,  qu'il  se  signale  par  une  hyper  polarisation  et  par 
I'accroisscment  d'amplitude  qui  en  resulte  pour  Ic  potentici  d'action  ct  son 
post-potentiel  de  dcpolarisation;  mais  sa  cause  cxactc  rcstc  matiere  a 
conjecture.  Pour  notre  theme,  le  fait  majeur  est  qu'il  s'agit-la  d'un  processus 
de  facilitation  residuelle  qui  s'ctend  sur  plusieurs  dizaines  de  secondes,  ou 
nieme  plusieurs  minutes,  ce  qui  reprcscnte  un  ordre  de  grandeur  temporelle 
convenant  bien  pour  tout  un  ensemble  de  phenomenes  explicitcs  par  les 
techniques  de  conditionnement  d'une  part  et  correspondant  d'autre  part 
sur  Ic  plan  psychologique,  a  ce  qu'on  appelle  des  retentions  mnemoniques 
a  court  terme.  Une  autre  caractcristique  favorable  a  notre  conception  est 
que  ce  processus,  decouvert  d'abord  en  etudiant  les  transmissions  mono- 
synaptiques  ganglionnaires  ct  spinales,  s'est  revele  trcs  general,  puisqu'on 
I'a  retrouve  au  niveau  des  relais  visuels,  auditifs  et  olfactifs.  Cctte  gcneralite 
a  suscite  la  reflexion  suivantc  de  Granit  (1956):  '  ...  un  phcnomcne 
fonctionnel  aussi  commun,  puissant  et  frappant  que  la  facilitation  residuelle 
post-tctanique  doit  joucr  un  role  majeur  dans  la  physiologic  du  systeme 
nerveux  central'.  Et  pourtant,  on  n'a  guerc  cherche  jusqu'ici  a  attribucr  un 
role  fonctionnel  precis  a  cc  phenomcnc.  Nous  n'avons  trouvc  que  Kupalov 
(1956),  pour  qui  I'accroisscment  des  reflexes  absolus  (dans  certaines  condi- 
tions) doit  ctre  base  'sur  cc  mecanismc  d'intcnsification  des  rcponscs 
reflexes  qui  a  ete  ctudic  sous  Ic  nom  dc  potentiation  post-tctanique  ...  ' 
Nous  pcnsons  qu'il  est  possible  d'allcr  plus  loin  et  d'envisagcr  pour  la 
PTP  un  role  dans  retablisscmcnt  des  liaisons  temporaires.  Mais,  avant 
d'cntrcprcndre  notre  demonstration,  nous  devons  refuter  certaines  objec- 
tions, celles  que  sans  doute  bcaucoup  dc  neurophysiologistcs  ont  dans 
I'csprit,  et  qui  expliquent  la  note  dccouragcante  de  Strom  (195  0  declarant: 
'La  potentiation  post-tctanique  scmblc  avoir  peu  d'lniportancc,  si  mcme 
clle  en  a  une,  pour  les  formes  physiologiqucs  cie  la  transmission  rcflcxc  . 
Quclles  sont  done  ces  objections:  Ellcs  sont  de  cieux  sortes: 

La  premiere  est  que  la  PTP  ne  se  manifeste  ncttemcnt,  en  general,  dans 
les  expc'riences  classiqucs,  que  pour  des  tctanisations  d'assez  longue  duree 
(plusieurs  secondes  ou  dizaines  dc  secondes)  a  frequence  relativcmcnt 
clevee  (plusieurs  centaincs  par  seconde)  c'cst-a-dirc  dans  dcs  conditions 
cxperimentales  asscz  rarcment  rcncontrces  dans  la  rc'alitc  iiaturclle. 

La  seconde  met  I'accent  sur  le  fait  que  cctte  facUitation  ne  profite  qu'a 

AA 


356  BRAIN    MECHANISMS    AND    LEARNING 

I'affcrcncc  tctaniscc,  ct  nullcmcnt  aux  voisincs  qui  convergent  sur  des 
neurones  communs:  ce  caractcre  'privc'  du  processus  intimc  de  la  PTP 
n'intcrdit-il  pas  de  le  considcrcr  conime  un  agent  possible  d'un  transfcrt  de 
facilitation  d'unc  voie  activec  efticace  a  unc  voie  d'abord  inefticacer 

Ces  objections  sont  legitimes  si  Ton  s'en  tient  aux  observations  classiques, 
generalement  tirees  de  I'ctude  des  proprietcs  du  reflexe  nionosynaptiquc 
spinal  chez  I'animal  anesthcsie.  Le  test  de  la  PTP  est  alors  la  capacitc  de 
reponse  du  motoneurone,  mesurcc  soit  statistiqucment  par  I'accroissement 
d'aniplitudc  d'un  potenticl  d'action  multi-hbres,  soit  unitaircnient,  par 
raugmentation  de  la  probabilite  de  dcchargc  du  motoneurone  etudie. 
C'est  deja  I'indication  qu'un  rclais  synaptique  simple  qui  a  beaucoup 
fonctiomic  sc  trouve  de  ce  fait  facilite  pendant  un  certain  temps,  nettcment 
plus  long  que  les  durccs  auxquelles  I'electrophysiologiste  du  neurone  est 
generalement  habitue.  Mais  la  liaison  de  ce  fait  avec  les  phenomcnes 
macroscopiques  de  I'apprentissage  n'cst  pas  claire.  On  ne  voit  pas  bicn  a 
premiere  vue  comment  il  pcut  etre  la  cause  d'associations  interccntrales; 
et  il  est  sommc  toute  a  I'opposc  de  ce  qu'on  observe  le  plus  souvent  en 
considerant  la  reaction  d'un  organisme  a  des  stimulations  rcpetees:  declin 
des  reponscs,  ou  'habituation',  phenomenc  que  Ton  sait  dependre  de 
processus  d'inhibition.  Fmalement,  il  apparait  que  vu  a  I'echelle  du 
neurone,  tout  phenomene  d'apprentissagc  doit  sc  rcsoudre  en  interactions 
associativcs  d'une  certaine  'duree  de'vie',  comportant  done  au  minimum 
deux  termes,  meme  lorsqu'il  s'agit  de  I'apprentissage  negatif  que  rcpresente 
unc  habituation  a  un  stimulus  uniforme  (ou  'accoutumance',  pour 
employer  un  tcrme  que  la  langue  fraiKjaise  acccpterait  plus  volontiers); 
car  dans  ce  cas  il  y  a  interaction  entre  une  categoric  d'aftcrcnces  excita- 
trices  avec  celles  que  declenchc  progressivement  une  contre-reaction 
negative.  Les  neurones  interesses  doivent  done  etre  dans  tons  les  cas  des 
neurones  a  afferences  multiples  et  hctcrogenes,  c'est-a-dire  appartcnir  a  des 
architectonics  du  type  polyneuroniquc  et  rcticulaire.  L'experimentation 
classique,  electrophysiologiquc  et  operatoirc,  sur  animaux  soumis  a  des 
conditionnements,  a  confirme  a  cet  cgard  les  propositions  de  la  logique: 
pour  s'associer,  les  messages  hctcrogenes  doivent  d'abord  se  rencontrcr,  et 
ils  ne  peuvent  le  faire  que  dans  les  structures  non-specifiques  de  I'organisa- 
tion  cerc'bralc.  D'ou  I'lmportancc  de  mieux  en  mieux  reconnue,  pour 
I'etablissement  de  nouvcllcs  liaisons  fonctionnelles,  du  role  des  noyaux 
intcgratcurs  du  mesencephale  et  du  diencephale,  et,  bicn  entcndu,  des 
aires  'associativcs'  du  cortex  cerebral.  (Cf  Fessard  et  Gastaut,  1958,  Syin- 
positiDi  lie  Strashonr{^,  1956). 

Le  probleme  devient  done,  pour  nous,  de  comprcndre  comment  la 


A.    FESSARD    ET   TH.    SZABO  357 

PTP  pourrait  modifier,  pendant  le  temps  dc  sa  persistance,  les  proprietes 
transmissives  ct  intcgratrices  de  ces  structures  polysynaptiques.  A  premiere 
vue,  encore  une  fois,  la  perspective  n'est  pas  cncourageante.  Processus  de 
localisation  pre-synaptique,  dont  I'influence  n'a  etc  constatce  qu'a  propos 
de  transmissions  monosynaptiqucs  (voir  ccpcndant  V.J.  Wilson,  1955)  la 
PTP  seniblc  representer  un  phenomcne  de  trace  de  caractere  strictement 
prive,  noil  capable  de  diffusion  latcralc  ou  catenaire,  done  pen  faite  pour 
imprimcr  une  marque,  memc  tcmporaire,  dans  une  structure  centrale  de 
type  rc'ticulaire. 

Il  y  a  cependant  une  clef  qui  ouvrc  a  cc  processus  I'acces  a  une  conquete 
efficace  des  rt'seaux  polyneuroniques,  c'est  celle  qui  fait  jouer  la  propriete 
de  beaucoup  de  neurones  des  parties  supericures  du  ncvraxe  de  se  trouver, 
chez  I'animal  non-ancsthesie,  en  etat  d'activitc  permancnte.  Ce  fait,  que 
I'exploration  systcmatique  par  microelectrodes  des  structures  corticales  et 
sous-corticales  a  bien  mis  en  evidence  chez  I'animal  eveille,  n'a  pourtantpas 
etc,  en  gc'ncral,  considere  a  sa  juste  importance.  Il  est  vrai  que  les  etudes 
de  microphysiologie,  chez  I'animal  eveille,  out  etc  jusqu'ici  relativement 
peu  nombreuscs;  et  d'autre  part,  I'autorythmicite  neuronique,  si  facile  a 
declencher  artificicUement  par  des  lesions,  est  souvent  suspectee  dc  n'etre 
qu'un  artehxct  provoquc  par  le  traumatismc  qu'engendre  la  microelec- 
trode.  Si  cela  est  parfois  vrai,  on  ne  peut  plus  douter  aujourd'hui  que  ces 
dcchargcs  rcpctitives  aiitoi^ciiiqiics,  conimc  nous  les  appellerons  de  preference 
au  termc  ambigu  d'activitc  'spontanee',  soieiit  un  des  phcnomenes  elemen- 
taires  fondamentaux  de  I'activitc  nerveuse  centrale  normale. 

Qu'apportent  done  de  particulier  pour  notre  problcme  ces  decharges 
repctitives  autogeniques  r 

Tout  d'aborci,  on  saisit  immcdiatement  qu'elles  entretieiment  dans 
toutes  les  extremites  d'axone  appartenant  aux  neurones  qui  les  engendrcnt 
un  certain  etat  d'activation  terminale,  fonction  de  la  frequence  moyeixne 
des  decharges  cellulifuges,  et  marque  par  un  niveau  tie  polarisation 
mcmbranaire  superieur  a  cc  qu'il  serait  en  I'abscnce  de  toute  autoactivite. 
De  ce  niveau  depend  I'cfficacite  des  transmissions,  commc  les  recherches 
sur  la  PTP  nous  font  appris.  En  eftet,  il  est  evident  que  leurs  resultats  sont 
applicables,  non  seulement  a  ce  qui  se  passe  aprcs,  mais  aussi  pendant  la 
tetanisation.  L'autoactivite  d'un  neurone  realise  en  sommc  de  fac^on 
naturellc  une  tetanisation  quasi  continue  des  terminaisons  plus  ou  moins 
profuses  qui  ramifient  son  axone  et  elle  y  crce  un  dcgre  plus  ou  moins 
eleve  d'efficacitc  transmettrice  que  nous  nommerons  simplement  'poten- 
tiation tetanique'  ou  PT.  Lorsque,  par  le  fait  des  variations  de  frequence 
qui  sont  la  modalite  ordinaire  de  travail  dc  ces  neurones  la  polarisation  et 


358 


BRAIN   MECHANISMS    AND    LEARNING 


I'cfticacite  transinottricc  des  tcrmiiiaisous  se  modificnt,  ccttc  modification 
no  disparait  pas  imnicdiatcmcnt  avcc  sa  cause.  Si  par  cxemple  ccllc-ci  est 
un  bref  accroisscnicnt  dc  la  frequence  du  pace-maker  neuronique,  soit 
AF,  il  en  rcsultera  un  accroissemcnt  APT  qui  sera  lui-mcme  prolonge, 
car  il  mettra  plusieurs  sccondes,  ou  meme  plusieurs  minutes  a  se  dissiper. 


PT2  \,  ^  /I—   ^P^2 


Fig.  I 
Schema  figurant  une  partie  d'une  chaine  de  neurones 
autoactifs,  de  frequences  Fj,  Fj  ...,  transniettant  les 
effets  d'une  breve  acceleration  initiale  de  frequence 
AFi  par  I'intermediaire  des  accroissements  APTj, 
APTj,  de  la  potentiation  tetanique  et  de  I'auginen- 
tation  correspondante  des  potentiels  synaptiques, 
APSE.,,  APSE3  ...  On  a  symbolise  la  region  du  pace- 
maker par  une  forme  sinucuse  et  la  modification  pre- 
synaptiquc  correlative  dc  la  potentiation  par  un  con- 
tour soulignant  les  boutons.  Noter  rallongement  dc 
AF2  par  rapport  a  AFi- 


Introduisons  cette  operation  dans  une  structure  catenaire  d'abord,  puis 
dans  une  structure  en  rcseau,  ct  voyons  ce  qui  pent  arriver. 

Dans  une  chaine  de  neurones  autoactifs,  il  convicnt  de  se  preoccuper, 
pour  chaque  clement,  de  la  cause  de  son  ,\¥  et  de  I'eftet  de  son  APT. 
Aidons-nous  d'un  schema  simple  reduit  a  deux  neurones  N^  et  Ng  (Fig.  i) 
et  donnons-nous  pour  commenccr  AF^,  en  laissant  de  cote  la  question  de 
sa  cause  que  nous  supposcrons  quelconque.   AFj  va  done  produire  aux 


A.    FESSARD    ET   TH.    SZABO 


359 


extreniites  axonales  un  APTj,  qui  survivra  un  certain  temps  a  sa  cause.  Si 
le  neurone  N^  n'etait  pas  autocatif,  cette  potentiation  serait  a  la  lettre 
unc  potentiation  post-tetanique,  attendant  pour  etre  revelce  les  choc- 
tests  appliques  par  I'experimentateur.  Ici,  c'est  le  nerf  lui-meme  qui  fournit 
les  dccharges  repetitives:  elles  jouent  le  role  des  chocs-tests.  Ceux-ci 
actualisent  periodiquement  la  potentiation,  produisant  en  No  pour  chaque 
'spike'  afferent  un  potentiel  synaptique  d'excitation  (PSEo)  plus  ample 
qu'avant  la  stimulation  (Fig.  2)  (Fessard  ct  Tauc,  1958;  Curtis  et  Eccles, 
i960).  Si  No  n'etait  pas  autoactif,  rien  d'autrc  ne  se  passcrait  tant  que  PSE.^ 


mV 

15- 


30/sl  10/ 

6   (h     &) 


-A 


A  P  LY  S I A 
eps  p 


■<  5    7 


20 


30 


40 


50 
sec 


Fig.  2 
Variations  d'amplitude  du  potentiel  synaptique  d'excitation  d'un  neurone  ganglionnaire 
d'Aplysie,  soumis  a  une  excitation  orthodromique  repetee,  d'abord  a  basse  frequence  (i/sec), 
puis,  de  I  a  2,  a  30/sec,  et  de  2  a  3,  a  lo/sec.  A  partir  de  3,  on  revient  au  regime  de  i/sec.  A 
chaque  regime  correspond  une  amplitude  d'cquilibre.  A,  B  ou  C,  vers  laquelle  on  tend  apres 
chaque  transition  (D'aprcs  Fessard  et  Tauc  non  publie). 


n'aurait  pas  fourni  un  taux  de  depolarisation  capable  de  faire  attcindre  au 
neurone  son  niveau  critique  de  dccharge;  mais  si  Ton  a  encore  affaire  a  un 
neurone  autoactif,  le  moindre  accroissement  de  PSE.2  n'aura  pas  etc 
produit  en  vain,  et  le  pace-maker  de  N.,  accclerera  son  rythme  en  con- 
sequence. Il  le  maintiendra  plus  clevc  que  sa  valeur  primitive  tant  que  la 
potentiation  supplcmentaire  APT^  crcce  par  ^F^  n'aura  pas  etc  dissipce. 
Si  le  mcme  processus  se  reproduit  plusieurs  fois,  au  niveau  des  synapses  et 
des  pace-makers  d'une  succession  de  neurones  N3,  N4,  etc. . . . ,  la  trace  active 
laissee   par  une   breve   surexcitation   initiale    /\¥i   pourra  atteindre,  en 


36o 


BRAIN    MECHANISMS    AND    LEARNING 


principc,  unc  durec  bien  superieurc  au  temps  de  dissipation  d'uue  simple 
PTP.  En  fait,  le  mccanisme  d'enscmble  doit  ctrc  bien  plus  complcxe,  a  cause 
de  Tintervention  certaine  de  processus  d'inhibition.  On  sait  que  Ics  processus 
synaptiques  de  I'inhibition  directe  sont  cgalemcnt  soumis  aux  normes  de  la 
PTP  (Lloyd,  1949).  Seulcment,  la  cinetiquc  de  I'niduction  en  chaine 
des  phcnomcncs  de  desactivation  par  inhibition  n'cst  probablement 
pas  la  menie  que  celle  des  phenomcnes  d'activation  et  de  leur  persevera- 
tion. C'est  la  un  point  a  etudier,  expcrimcntalemcnt  et  thcoriquemcnt. 

Pcu  aprcs  la  presentation  dc  ccs  idees  au  Symposium  dc  Montevideo,  dc  nouvcllcs 
observations  microphysiologiques  ont  cte  faites  sur  Ic  ganglion  visceral  dc  I'Aplysic 
par  Fcssard  ct  Tauc  (i960).  Il  a  scmblc  intcrcssant  dc  Ics  rapporter  succinctcmcnt 


MiMMMMMMiM'!^ 


ittmMmmMtMimmiiMMMMMMMmtmMiMMtmM 


Fig.  3 
Dccharges  dc  neurones  autoactifs  du  ganglion  d'Aplysic.  En  A,  traces  pris  siniultancnicnt  dans 
deux  cellules  du  nieme  ganglion.  Action  durable  d'un  bref  tetanos  de  la  voie  orthodromique 
sur  la  frequence  des  dccharges.  En  B,  autre  exeniplc.  En  C,  Ic  tetanos  a  ete  applique  directement 
a  la  cellule  dc  B  (niicroclcctrode  anodiquc  interne). 


ici.  On  stimulc  unc  voic  aftcrcntc  par  un  train  dc  chocs  d'unc  durcc  limitcc,  ct  on 
observe  I'cffct  produit  sur  la  rythmicitc  autogcniquc  d'une  cellule  autoactivc 
pourvuc  d'unc  niicroclcctrode  interne.  On  constate  souvcnt  (mais  non  toujours) 
que  I'acccleration  dc  frequence  ^F  pcrsistc  aprcs  la  cessation  du  stimulus  (Fig.  3) 
parfois  pendant  plusicurs  dizaines  dc  sccondcs  (unc  courtc  pause  precede  souvcnt  Ic 
depart  du  regime  accelcre).  Unc  stimulation  directe  de  la  cellule  pendant  un  temps 
analogue  nc  produit  que  facceleration  concomitantc  ct  la  pause  consecutive,  sans 
aucune  persistance  d'acccleration  (Fig.  2  C). 

La  persistance  de  A?  observee  aprcs  la  stimulation  par  voic  synaptique  peut 
s'expliquer  commc  une  consequence  d'un  processus  de  PTP,  a  condition  que  la 
stimulation  ait  en  memc  temps  active  Ics  pace-makers  dc  neurones  autoactifs 


A.    PESSARD    ET    TH.    SZABO 


361 


coimectcs  a  cclui  que  nous  intcrrogcons,  qu'il  s'agissc  dc  neurones  mtercalaires,  ou 
bien  de  neurones  de  meme  categorie  pourvus  de  collateralcs  intercurrentcs  (schenias 
de  la  Fig.  4).  Nous  sommcs  alors  ramenes  au  cas  precedent,  I'clement  interroge 
apparaissant  connnc  une  unite  du  deuxicme  ordre  lorsqu'on  I'atteint  par  ce 
detour.  Le  bombardemcnt  qu'il  subit  de  la  part  des  neurones  autoactits  actualise  sur 
les  surfaces  post-s^■naptiques  correspondantes  la  potentiation  £\PT  de  ces  neurones 
et  accclere  le  rvthnie  de  son  pace-maker  pendant  le  temps  de  la  persistance. 


Fig.  4 
Deux    types   coinimiiis   de   connexions   grace   auxquelles,    si   Ics 
neurones  sont  autoactifs,   tout  brcf  train   d'influx  incident  doit 
avoir  un  effet  prolongc  sur  la  frequence  du  neurone  principal. 


Cependant,  nous  avons  souvent  echoue  a  mettre  en  c:vidence  un  tel  bombarde- 
mcnt (cc  qui  ne  prouve  pas  son  inexistence).  Peut-etrc  existe-t-il,  du  cote  post- 
synaptique  cette  tois,  un  autre  processus  de  conservation  de  traces,  co-opcrant  avec 
cclui  que  maniteste  la  PTP.  Dans  une  structure  catenaire,  il  contribuerait  a  allonger 
considerablement  la  durce  de  perseveration  des  variations  de  Irequence. 

Dc  cc  qui  precede,  nous  avons  tire  la  notion  que  Ic  phc'nomcnc  dc  trace 
rcprt'scntc  par  une  facilitation  latentc  localise'e  prc'-synaptiqucnient,  la 
PTP,  pcut  s'actualiser,  sc  prolongcr  et  se  re'pandrc  dans  Ics  structures 
polyneuronic]ues,  a  condition  que  leurs  e'lenients  soient  des  iicuroncs  auto- 
actifs. A  cet  cgard.  on  pent  dire  que  dans  chacuii  dc  ces  neurones  I'infornia- 
tion  contenue  dans  une  tranche  d'activite  repe'titivc  niodulec  de'pend 
davantage  du  passe  que  du  present.  La  mission  'intc'rieurc'  des  trains 
d'influx  engendres  par  le  pace-maker  d'un  neurone  est  d'informer  ses 
ternnnaisons  d'axone,  gene'ralement  divergentes  et  profuses,  sur  les  traces 
d'activite'  antc'rieure  qui  subsistent  dans  les  ternnnaisons  du  neurone  qui  le 
precede,  operation  qui  exige  I'autoactivite  dc  cc  dernier.  Pareillemcnt,  ces 
ntflux  auront  a  leur  tour  une  mission  'cxterieure',  celle  d'actualiser  pour 
les  neurones  de  I'ordre  suivant  les  "souvenirs'  d'hyper-  (ou  d'hypo-) 
activitc  que  les  terminaisons  d'axone  auront  retenus. 


362  BRAIN    MECHANISMS    AND    LEARNING 

Rcmarquoiis  aussitot  que  I'abscncc  d'autoactivitc  dans  un  des  elements 
d'unc  chaine  lineaire  de  neurones  interrompt  fatalement  ce  processus  de 
conqucte  des  structures  polyneuroniques  par  des  messages  informatifs 
marques  par  un  passe  recent.  Or,  I'exploration  microphysiologique  des 
territoires  associatifs  chez  I'animal  cvcille  revele  qu'une  assez  grande  pro- 
portion de  neurones  sont  non  seulemcnt  inactifs  mais  inactivables  par  un 
stimulus  simple.  Il  est  tentant  d'cmettre  I'hypothcse  qu'un  des  premiers 
effets  de  I'apprentissage  pourrait  etrc  de  reveillcr  les  'pace-makers'  d'un 
certain  nombre  de  neurones  silencieux  et  de  permettre  ainsi  a  des  vestiges 
presynaptiques  d'un  passe  recent  de  se  faire  connaitre  a  une  plus  grande 
masse  de  tissu  nerveux.  Inversemcnt,  les  processus  d'oubli  commence- 
raient  par  le  simple  evanouissement  des  traces  clcmentaires  au  niveau  des 
terminaisons  nerveuses,  et  auraient  pour  consequence  immediate  un 
'desamor(;-age'  de  I'autoactivitc  d'un  certain  nombre  de  neurones,  d'ou 
restriction  progressive  du  champ  des  neurones  impliques  dans  les  activites 
residuelles.  On  doit  admettre  en  outre  que  les  processus  d'habituation, 
d'extinction  et  de  difFerenciation  comportent  de  telles  operations  de 
desamor^age,  avec  le  concours  actif  de  comiexions  inhibitrices. 

Les  processus  de  conservation  des  traces  d'activite  ne  sont  qu'un  des 
aspects  de  I'apprentissage,  plus  precisement  une  dc  scs  conditions  neces- 
saires.  Envisageons  maintenant  I'opcration  elementaire  capitale,  qui  est 
cvidemment  la  formation  de  nouvellcs  liaisons  stimulus-reponse.  Si,  lais- 
sant  de  cote  ici  les  questions  relatives  a  la  participation  des  grandes  struc- 
tures nerveuses  centrales  aux  mecanismes  de  conditionnement  nous  nous 
limitons  a  considcrer  ce  qui  pent  se  derouler  au  niveau  des  reseaux  neuro- 
niques,  nous  avons  a  nous  demandcr  si  I'introduction  de  I'opcration  ele- 
mentaire AF—^APT,  defmie  plus  haut,  dans  une  structure  de  neurones 
autoactifs  disposes  en  reseau,  pent  nous  fournir  des  elements  pour  placer  a 
ce  niveau  un  mecanisme  d'association. 

Aidons-nous  pour  cela  d'un  schema  aussi  simple  que  possible  (Fig.  5), 
tigurant  la  maille  elementaire  d'un  reseau  polyneuronique,  et  limitant  a 
deux  seulement  Ic  nombre  des  aftcrences  rec^ues  par  le  neurone  central 
{a  et  b)  et  a  deux  aussi  le  nombre  de  ses  rameaux  divergents  (notes  ah). 
Cela  suffit  pour  les  deductions  essentielles.  La  question  est  alors  de  savoir  si 
la  facilitation  de  post-activation  laissee  par  une  activitc  de  a  pourra  profiter 
a  un  message  ulterieur  arrivant  par  /).  Pour  simplifier  encore,  supposons 
que  a  ct  b  transportent  uniquement  des  messages  d'activation  phasique, 
sans  assurer  aucun  bombardement  tonique  (d'autres  afferences,  non 
representees,  peuvent  jouer  ce  role).  Les  neurones  en  presence  seront  notes, 
selon   leur   ordre,    N^    et    N^,    (ler   ordre),  N^^  (2cme  ordre),  N^^,^^  et 


A.    FESSARD    ET   TH.    SZABO 


363 


I^\BD  (s^iiT^c  ordrc).  N^^^  ct  Ics  deux  neurones  du  3cmc  ordre  sont  sup- 
poses autorythmiques.  Soit  maintcnant  un  train  d'influx  arrivant  par  N^.  Si 
la  synapse  est  excitatrice,  il  en  resultera  un  accroissement  dc  frequence 
AF  pour  les  influx  cmis  par  le  pace-maker  de  N^g,  accroissement  qui 
pourra  ou  non  durcr  plus  longtemps  que  sa  cause.  En  outre,  par  suite  d'une 
certainc  potentiation  en  a,  unc  nouvellc  arrivce  d'influx  A  sera  plus 
etficacc  pendant  Ic  temps  de  dissipation  dc  la  PTP;  mais  une  action  venant 
de  B  sur  la  frequence  en  N^^  n'cn  sera  pas  renforcec;  et  mcme  sera  parfois 


ABC 


ABD 


Fig.  5 
Schema  figurant  Li  niaillc  clcnicntairc  d'un  roscau  polyneurimique.  Regions  de  pace- 
makers (segment  initial  d'axone)  symbolisees  par  une  sinuosite.  Potentiation  syinbolisee 
par  un  contour  soulignant  les  boutons  synaptiqucs.  Voir  texte. 


amoindrie  (par  exemple  si  A?  a  fait  atteindre  au  pace-maker  son  regime 
de  plafond).  Par  contrc,  les  traces  de  I'hyperactivite  de  N^„  (processus 
APT)  laissees  dans  toutes  les  tcrminaisons  d'axone  de  ce  neurone  (en  a  b) 
pourront  aprcs  coup  ct  pendant  un  certain  temps  ctre  utilisees  par  les 
influx  originaires  dc  N,,  au  moment  ou  le  transmetteur  de  Texcitation, 
renforcc  par  la  APT,  s'appretera  a  agir  sur  les  neurones  du  3eme  ordre. 
Tout  neurone  autoactif  commun  a  plusieurs  afterenccs  pent  joucr  ce  role, 
ct  pcrmettre  ainsi  a  un  certain  groupe  d'aftcrences  de  beneticicr  des  traces 
d'activite  laissees  par  la  mise  en  jeu  prealablc  d'un  autre  groupe.  De  tcls 
transferts  de  facilitation  sont  done  parfaitement  concevables  au  sein  des 


364  BRAIN    MECHANISMS    AND    LEARNING 

Structures  polyucuroniqucs  ayant  unc  architectonic  reticulairc  ct  dcs 
elements  autoactifs  en  nonibre  suftisant. 

Il  est  facile  d'iniagincr  les  difterents  cas  qui  peuvcnt  se  presenter  au 
niveau  ci'une  niaille  clc'nientaire,  moins  aise  dc  prcvoir  cc  qui  pent  se 
passer  lorsque  des  complications  interviennent :  reseau  a  nombreuses 
mailles,  chaines  rc:currentes,  c'lements  inhibiteurs,  etc.  ...  Pour  nous  limiter 
aux  idees  les  plus  simples,  notoiis  que  la  tetanisation  en  A  doit  avoir  pour 
eftet  d'augmenter  I'efticience  des  influx  cnvoyes  par  B,  cctte  efficience 
etant  mcsuree  par  la  proportion  de  neurones  du  troisieme  ordre,  ou 
d'ordre  supc'rieur,  qui  sont  recrutes  additionnellement  (s'ils  etaient  muets) 
ou  hypcractives  (s'ils  etaient  dcja  autoactifs).  Un  cas-limite  est  celui  ou 
rafferencc  B  n'aurait  d'abord  aucune  action  decclable  a  la  sortie  du  reseau, 
et  en  acquerrait  une  apres  la  tetanisation  de  A.  Ce  sont-la  des  eftcts  facilita- 
teurs  capables  de  se  manifester  sur  le  plan  de  I'electrophysiologie  macro- 
scopique  (potentiels  evoques)  ou  sur  celui  du  comportcment,  comme 
intensificateurs  des  rcponses.  On  en  connait  de  nombreux  excmples.  On 
coiK^oit  qu'il  puisse  en  rcsultcr  aussi  un  'frayage'  de  voies  jusquc-la  inex- 
ploitees,  et  que  ce  mecanisme  elenientaire  puisse  ctre  en  quelque  sorte 
I'amorce  d'un  processus  de  conditionnement  au  sens  de  Pavlov. 

Nous  n'expliquons  pas  cependant,  avcc  ce  qui  precede,  la  nc'cessite 
presque  absolue  ou  Von  se  trouve  pour  obtenir  un  conditionnement,  de 
commencer  a  appliquer  le  stnnulus  c'onditionnel  un  pen  avant  le  stimulus 
inconditionnel.  Il  est  probable  que  cette  regie  correspond  a  unc  necessitc 
representee  a  des  niveaux  fonctionncls  superieurs  en  complexite  a  ceux  011 
nous  nous  pla^ons  ici.  Il  est  logique  que  le  stnnulus  destine  a  prendre  la 
signification  d'un  autre,  a  devenir  capable  en  quelque  sorte  dc  I'annoncer, 
precede  cet  autre  dans  le  temps  lorsqu'ils  sont  presentes  par  paires;  mais  les 
rescaux  nerveux  que  nous  considerons  ici  ne  peuvcnt  pas  ctre  rendus 
responsables  de  ces  processus  d'anticipation. 

Quoi  qu'il  en  soit,  dans  les  sequences  de  paires  de  stimuli  associes,  BA- 
BA-BA-etc.  ...  ,  telles  qu'on  les  applique  dans  la  technique  d'etablissement 
d'un  reflcxe  conditionne,  il  faut  bien  admcttre  que  chaquc  paire  trouve 
pour  iniprimer  son  action  un  terrain  plus  favorable  que  la  precedente, 
done  que  le  A  d'une  paire  (ou,  niieux,  un  ensemble  BA  quelconquc) 
laisse  une  trace  dont  profite  le  B  de  la  suivante  pour  produire  un  eftet 
chaque  fois  plus  intense,  jusqu'a  declenchcr  la  reponse  que  le  stimulus 
conditionnel  etait  initialement  impuissant  a  provoquer.  Nous  avons 
tendance  a  croire  que  si  la  potentiation  post-tetanique  est  pour  quelque 
chose  dans  I'etablissemcnt  dc  nouvelles  liaisons  dynamiqucs,  c'est  en 
fournissant  la  base  de  cette  persistance  evidente  de  traces  d'activite  de  BA 


FESSARD    ET    TH.    SZABO 


365 


an  BA  suivant,  et  en  oftrant  a  ccs  traces,  qui  peuvent  etre  au  debut  tres 
discretes,  la  possibilitc'  de  s'accuinuler. 

[usqu'ici,  nous  avons  raisonne  par  deduction,  en  partant  de  taits  dont  la 
realite  est  bien  ctablie,  mais  dont  I'enchainement,  tel  que  nous  nous  le 
rcprc'sentons,  teste  a  soumettrc  a  I'c'preuve  de  I'experience.  Nous  avons 
reserve  pour  la  tni  de  cet  expose  la  presentation  des  quelques  evidences 
experinientales  deja  obtenues  par  nous  et  qui  deniontrent  la  possibilite  du 


rm 


•^     ll" 


Fu;.  6 
Enrcgistrcnients  des  roponscs  glob.ilcs  d'Lin  lobe  electrique  de  Torpillc  (centre  iicrveux  qui 
coniin.mde  les  organes  electriques)  lorsqu'on  stinuile  Tune  ou  I'autre  de  deux  voies  affercntcs, 
a  ou  b. 

A  gauche,  les  trois  colonnes  de  traces  se  suivcut.  lis  sont  pris  chaque  secoiide  sauf  pendant  la 
tetanisation  de  a  (a  12/sec).  Noter  la  potentiation  post-tetanique. 

A  droitc,  c'est  I'afFerence  b  qui  est  tetanisee.  Lc  benefice  de  la  potentiation  est  transfere  de  b 
a  a.  Noter  qu'initialcment  la  stimulation  de  a  n'activait  pas  les  neurones  du  lobe  (niais  provo- 
quait  certaincment  la  decharge  du  neurone  interniediaire). 

transfert  de  facilitation  dont  nous  venous  de  parler.  Ce  sont  des  experiences 
d'electrophysiologie  niacroscopique,  qui  devront  etre  prolongces  par  unc 
etude  plus  fine,  a  I'echclle  du  neurc^ne.  Nous  les  avons  deja  brievement 
relatccs  dans  des  publications  anterieures  (Fessard  et  Szabo,  1959;  Fcssard, 
1960(7). 

Nous  nous  sommes  d'abord  adresses  au  dispositif  bulbaire  de  commande 
des  organes  electriques  de  la  Torpille.  Ce  dispositif  (schema,  Fig.  6)  a 


366  BRAIN    MECHANISMS    AND    LEARNING 

I'avantagc  dc  presenter  un  arrangement  neuronique  particulicrcnient 
simple  et  de  structure  bien  connue  (Fessard  et  Szabo,  1953;  Szabo,  1954). 
Il  est  le  support  d'un  reflexe  disynaptique,  avec  un  noyau  d'interneurones, 
rccepteurs  d'afterences  convergentcs.  Enregistrant  seulement  la  rcponsc 
eff'crcntc  avec  une  macroelectrode  posce  sur  un  des  lobes  electriques,  nous 
avons  pu  montrer  que  ce  dispositif  permet  de  transferer  le  benefice  de  la 
PTP  d'un  ensemble  d'aftcrences  b  a  un  autre  a  (Fig.  6).  C'est  un  cas  ou  les 
deux  affcrences  peuvent  isolcment,  Tunc  comme  I'autre,  provoquer  la 
decharge  rythmique  du  noyau  intcrmcdiaire  reconnu  comme  pace- 
maker de  la  decharge  des  organes  electriques  (Fessard  et  Szabo, 
1954).  Il  nest  done  pas  necessaire  ici  que  les  cellules  de  ce  noyau  soient  le 
siege  d'lme  autoactivitc  permanente,  proprictc  qu'en  fait  elles  n'ont  pas. 

Nous  avons  cgalement  obtenu  des  transferts  de  potentiation  dans  le 
cerveau  du  Chat  en  prenant  comme  test  la  reponse  des  cellules  pyramidales 
de  I'Hippocampe  a  la  stimulation  d'affercnces  fornicales  homolatcrales.  La 
stimulation  tctanisante  etait  appliquce  a  difterentes  voies  connues  pour 
converger  sur  les  memes  cellules,  mais  seulement  aprcs  mi  ou  plusieurs 
relais.  La  figure  7  est  un  exemple  typique,  dans  lequel  la  potentiation  etait 
obtenue  par  tctanisation  du  groupe  amygdalicn  median.  On  remarquera 
que  I'accroissement  du  potentiel  evoquc  porte  sur  la  seconde  onde, 
c'est-a-dirc  sur  la  reponse  qui  correspond  a  une  liaison  certainement  poly- 
synaptique.  On  voit  aussi,  sur  les  en-registrements-tests,  quelqucs  indices 
d'une  activitc  'spontance'  (points  blancs)  qui  n'cxistait  pas  avant  la 
tetanisation.  Dans  rcchantillon  du  milieu,  3eme  colonne,  I'onde  spon- 
tanee,  survenant  par  hasard  juste  avant  une  stimulation-test,  a  bloquc  la 
grande  reponse,  mais  non  la  petite. 

Il  est  certain  que  seule  une  analyse  microphysiologique  des  proprietes 
des  structures  polysynaptiques  de  type  catcnaire  ou  rcticulaire  permettrait 
de  fonder  la  validite  de  nos  hypotheses.  Cette  analyse  reste  a  faire  en  ce 
qui  concerne  les  mecanismes  de  I'apprentissage.  Dans  une  certainc  mesure 
cepcndant,  on  pent  considcrer  que  les  donnees  de  microphysiologie 
ccrebrale  obtenues  sur  des  animaux  soumis  a  un  conditionnement  par 
Ricci,  Doane  et  Jasper  (1957)  et  par  Morrell  (i960)  appuient  partiellement 
nos  idees,  puisqu'elles  ont  montre  qu'a  I'cchelle  unitaire  les  progrcs  de 
I'apprentissage  se  marquent  par  des  changements  dans  les  rythmes  auto- 
geniques  de  la  decharge  des  neurones  etudies. 

Nous  avons  essaye  d'aller  plus  loin  thcoriquement  en  spcculant  sur  les 
causes  possibles  de  ces  changements.  Nous  avons  utilise  pour  ccla  des 
donnees  maintenant  classiques:  existence  dans  les  structures  cerebrales 
d'architectonies  polyneuroniques  en  chaincs  et  en  rcseaux,  importance 


A.    FESSARD    ET    TH.    SZABO 


1^1 


longtcmps  insoup^onucc  dcs  champs  dc  neurones  multivalents,  vers 
lesquels  convergent  des  aftcrences  heteroscnsorielles,  generalite  de  la 
rythmicitc  autogc'niquc  des  neurones  centraux  chez  I'animal  non- 
ancsthesic,    et   enfm    existence    d'une    propriete    generale    de    plasticite^ 


Fig.  7 
Enrcgibtrcinent  d'unc  acti vite  cvoquce  au  niveau  dcs  cellules 
pyrainidales  de  THippocanipe  du  Chat,  par  stimulation  du 
fornix  homolateral  (chocs-tests  a  i  par  sec).  Aprcs  un 
tetanos  de  4  sec  a  20/sec  applique  au  groupe  amygdalien 
median,  il  y  a  transfert  de  facilitati^m.  Lcs  points  indiquent 
des  activites  autotrenes. 


representee  par  cette  remanencc  des  effets  de  I'activite  nerveuse  au  niveau 
dcs  synapses  que  Ton  nomme  'potentiation  post-tctanique'.  Ccs  faits  ont 
entrc  eux  d'etroitcs  relations.  Il  nous  est  apparu  qu'cn  lcs  considcrant  dans 
leur  ensemble,  sous  Tangle  du  systeme  dynamique  qu'ils  formcnt,  ils 


368  BRAIN    MECHANISMS    AND    LEARNING 

pouvaicnt  nous  apporter  dcs  bases  d'cxplicatiou  pour  uii  certain  nombrc 
cic  phcnonicncs  dc  comportemcnt  sc  rattachant  aux  themes  de  I'appren- 
tissage. 


RESUME 


1.  Scion  I'idcc  courante,  le  processus  fondaniental  qui  sous-tend  tout 
coniportenient  d'apprentissage  au  niveau  du  neurone  semble  ctre  la 
persistancc  aux  synapses  d'effets  facilitateurs  ou  inhibiteurs  resultant  de 
la  presentation  repetce  du  nienie  stimulus  ou  celle  du  meme  enscnable 
de  stimuli  assocics. 

2.  Le  seul  residu  facilitateur  (ou  nihibiteur)  de  post-activation  qui  ait 
ete  jusqu'ici  dccouvert  et  soit  maintenant  reconnu  comme  processus  pre- 
synaptique  general  est  celui  qu'on  nommc  'potentiation  post-te'tanique'. 
C'est  en  fait  plutot  une  'potentiation  tctanique  prolongee'  (PTP). 

3.  Les  etudes  classiques  sur  la  PTP  la  reprcsentent  comme  un  processus 
strictement  localise  dans  les  terminaisons  prc-synaptiques  des  fibres  qui 
ont  ete  impliquees  dans  une  hyperactivation  assez  intense  (stimulation  a 
frequence  elcvee).  Si  le  benefice  de  la  PTP  ne  pent  etre  transfcre  d'une 
sorte  d'afterences  a  une  autre,  s'il  rcste  monosynaptique  alors  que  les 
processus  d'apprentissage  nccessitent  en  tait  la  participation  de  structures 
polyneuroniques,  comment  pouvons-nous  ici  faire  jouer  un  role  a  ce 
phenomener 

4.  La  clef  semble  ctre  dans  le  fait  maintenant  bien  ctabli  que  la  plupart 
des  neurones,  dans  le  cerveau  d'un  animal  en  etat  de  veille,  foumissent 
contmuellcment  des  dccharges  repetitives  autogeniques.  Celles-ci  mam- 
tiennent  dans  les  terminaisons  d'axone  un  certain  niveau  d'etiicacite 
transmettrice  que  nous  avons  propose  d'appeler  'potentiation  tctanique 
(PT).  Tout  accroissement  transitoire  de  frequence  AF  entrainera  un 
accroisscment  APT  qui  survivra  a  sa  cause  pendant  des  secondes  ou  des 
minutes.  Par  suite,  les  potentiels  post-synaptiqucs  de  tous  les  neurones 
recevant  dcs  afferences  de  ceux  dans  lesquels  un  A?  s'est  produit  scront 
augmentes  en  amplitude,  aussi  longtemps  que  I'increment  de  potentiation 
persistera.  Get  effet  a  son  tour  accroitra  la  frequence  de  dccharge  des 
neurones  impliques,  ct,  parmi  ceux  auparavant  mucts,  en  induira  quelques- 
uns  a  commencer  a  se  decharger. 

5.  Il  est  facile  de  comprendre  comment  la  meme  suite  d'cvenements 
operant  plusieurs  fois  le  long  d'une  structure  polyneuronique  en  chaine 
pent  aboutir  a  un  tres  important  allongement  cie  la  trace  tinale  laissee 
par  une  hyperactivite  de  durce  breve  a  I'entree.  Des  A?  ncgatifs  dus  a 


A.    FESSARD    ET   TH.    SZABO  369 

line  chute  d'activite  ou  a  I'intcrvention  de  processus  inhibiteurs  pcuvent 
pareillcment  donner  naissance  a  des  traces  durables  d'inactivation. 

6.  Dcs  caractcristiques  dc  rescaux  existent  dans  toutes  les  structures 
polyneuroniques  du  ccrvcau.  Beaucoup  de  neurones  y  sont  dc  cc  fait 
connectes  a  des  voies  aftercntes  hetcrogcnes  et  pen  vent  ainsi  etre  actives  par 
des  signaux  de  difFerentes  qualites  scnsorielles.  Un  neurone  multivalent  de 
ccttc  categoric  pent  cvideniment  transferer  a  n'iniporte  lequel  de  ses 
groupcs  d'afferences  le  benefice  d'un  /PT  residuel  cause  par  I'hyper- 
activite  transitoire  d'un  autre  groupe.  Si  le  neurone  coniniun  est  autoactit 
ct  que  les  influx  afferents  n'en  provoquent  pas  la  dccharge,  le  transfert 
est  neanmoins  possible  par  rintermcdiaire  du  changcmcnt  resultant  AF 
dc  la  frequence  dc  son  pace-maker. 

Dcs  influx  afferents  d'une  categoric  ne  produisant  pas  d'cftct  decelable 
a  la  sortie  d'un  rcseau  sont  ainsi  supposes  pouvoir  acquerir  dc  I'cfticacite 
s'ils  arrivent  pendant  I'intcrvallc  dc  dissipation  des  traces  d'activite 
laissees  par  une  activation  plus  forte  amcnee  par  unc  autre  sorte  d'influx 
afferents. 

7.  Des  sequences  de  paircs  dc  stimuli  associes,  comnic  on  en  applique 
dans  les  precedes  dc  conditionncment  classiques,  opcrent  probablemcnt  de 
le  fa^on  dccrite  ci-dcssus  lorsqu'elles  ctablissent  progressivement  de 
nouveaux  liens  fonctionnels  au  sein  du  Systcme  nervcux  central. 

8.  Quelqucs  preuves  experimentalcs  ctayant  la  validite  des  hypotheses 
prcccdentes  ont  etc  obtenucs.  Les  cellules  ganglionnaires  autorythmiques 
de  I'Aplysie  ont  etc  utilisces  pour  montrcr  les  changements  durables  de 
frequence  du  pace-maker  qui  survivent  aux  effets  immediats  d'un  bret 
tctanos  applique  a  un  tractus  afferent.  Un  test  satisiaisant  du  mccanisme 
de  transfert  de  tacilitation,  tel  que  nous  le  suggerons  dans  notrc  theorie, 
a  etc  applique  au  systcme  disynaptique  de  neurones  qui  controlc  les 
decharges  des  organes  clectriques  chez  la  Torpillc.  Nous  avons  prouve 
aussi  que  les  cellules  pyramidales  de  I'Hippocampc  pcuvent  reveler  des 
transferts  de  potentiation,  quand  on  les  active  a  travers  des  voies  diffc- 
rentcs  qui  convergent  sur  les  structures  polysynaptiques  intermcdiaires 
qui  y  conduiscnt. 

9.  En  concluant,  on  a  d'abord  insistc  sur  la  necessite  dc  completer  notrc 
evidence  experimentale  avec  des  explorations  microphysiologiques  de 
structures  de  type  rcticulaire;  et  I'attcntion  a  etc  attiree  vers  le  fait  que 
notrc  conception  a  etc  cntiercmcnt  tirce  de  donnces  classiques,  qui  ont 
ici  etc  considerees  conjointcmcnt  au  lieu  dc  I'etrc  scparement:  rythmicite 
cellulaire  autogeniquc,  potentiation  post-tctaniquc,  neurones  multivalents 
et  architectonics  dc  type  rcticulaire. 


370  BRAIN    MECHANISMS    AND    LEARNING 


SUMMARY 


1.  According  to  the  generally  accepted  view,  the  basic  process  under- 
lying any  kind  of  learning  behaviour  at  the  neuronal  level  seems  to  be  the 
persistence  of  synaptic  facilitatory  (or  inhibitory)  effects  as  a  result  of  the 
repeated  presentation  of  the  same  stimulus  or  of  that  ot  the  same  set  of 
associated  stimuli. 

2.  The  only  post-activation  facilitatory  (or  inhibitory)  residue  that 
has  so  far  been  disclosed  and  is  now  recognized  as  a  general  pre-synaptic 
process  is  the  so-called  'post-tetanic  potentiation'  (PTP).  Actually  it  would 
be  better  termed  a  'protracted  tetanic  potentiation'. 

3.  Classical  studies  of  PTP  represent  it  as  a  process  strictly  localized  in 
the  presynaptic  terminals  of  the  fibres  that  have  been  involved  in  a 
rather  strong  hypcractivation  (stimulation  at  high  frequency).  It  the 
benefit  of  the  PTP  cannot  be  transferred  from  one  kind  of  affercnts  to 
another,  if  it  remains  monosynaptic  while  learning  processes  actually 
need  the  participation  of  polyneuronic  structures,  how  can  we  here  give 
a  role  to  this  phenomenon? 

4.  The  key  seems  to  be  in  the  now  well  established  fact  that  most 
neurones  in  the  brain  of  an  animal  in  the  waking  state  are  continuously 
delivering  autogenic  repetitive  discharges.  These  maintain  in  the  axon 
terminals  a  certain  level  of  transmissive  efficacy  we  propose  to  call 
'tetanic  potentiation'  (PT).  Any  transient  increase  in  frequency  AF  will 
result  in  an  increase  APT  that  will  outlast  its  cause  by  seconds  or  minutes. 
Consequently,  the  post-synaptic  potentials  of  all  neurones  receiving 
afferents  from  those  in  which  some  A?  has  occurred  will  be  enhanced  in 
amplitude  as  long  as  the  potentiation  increment  will  persist.  This  effect 
in  its  turn  will  increase  the  firing  frequency  of  the  neurones  involved,  and, 
among  those  previously  silent,  will  induce  some  of  them  to  start  firing. 

5.  It  is  easy  to  understand  how  the  same  sequence  of  events  operating 
several  times  along  a  chain-like  polyneuronic  structure  can  result  in  a 
very  important  lengthening  of  the  final  trace  left  by  a  brief  input  hyper- 
activity. Negative  AF  due  to  a  drop  in  activity  or  to  the  intervention  of 
inhibitory  processes  can  similarly  give  rise  to  long-lasting  traces  of 
inactivation. 

6.  Network-like  characteristics  are  found  in  all  polyneuronic  structures 
of  the  brain.  There  many  neurones  are  connected  to  heterogeneous  afferent 
pathways  and  can  thus  be  activated  by  signals  of  different  sensory  quali- 
ties. A  multivalent  neurone  of  that  kind  can  obviously  transfer  to  any  of 
its  group  of  afferences  the  benefit  of  a  residual   APT  caused  by  the 


A.    FESSARD    ET   TH.    SZABO  37I 

transient  hyperactivity  of:  another  group.  If  the  common  neurone  is  an 
auto-active  one  and  the  afferent  impulses  have  no  fn-ing  effect  upon  it,  the 
transfer  is  nevertheless  possible  through  the  resulting  frequency  change 
AF  of  its  pace-maker. 

Afferent  impulses  of  one  kind  producing  no  detectable  effect  at  the 
output  of  a  network  are  thus  assumed  to  be  able  to  acquire  efficacy  if  they 
arrive  during  the  subsidence  interval  of  the  activity  traces  left  by  a 
stronger  activation  brought  about  by  another  kind  of  afferent  impulses. 

7.  Sequential  pairs  of  associated  stimuli  as  are  applied  in  classical  con- 
ditioning procedures  may  operate  in  the  way  described  above  when 
progressively  establishing  new  functional  links  within  the  central  nervous 
system. 

8.  Some  experimental  proofs  supporting  the  validity  of  the  preccdnig 
assumptions  have  been  obtained.  Auto-rhythmic  ganglion  cells  of  Aplysia 
have  been  used  to  show  the  long-lasting  frequency  changes  of  the  pace- 
maker that  survive  the  immediate  effects  of  a  brief  tetanus  applied  to  an 
afferent  tract.  A  satisfactory  test  of  the  facilitation  transfer  mechanism  as 
suggested  in  our  theory  has  been  applied  to  the  disynaptic  system  of 
neurones  that  control  the  discharges  of  electric  organs  in  Torpedo. 
Pyramidal  cells  in  Hippocampus  have  also  been  proved  to  be  able  to 
reveal  potentiation  transfers  when  activated  through  different  pathways 
that  converge  on  to  the  intermediate  polysynaptic  structures  leading  to 
them. 

9.  In  concluding,  the  necessity  of  completing  our  experimental  evidence 
with  microphysiological  explorations  of  network-like  structures  has  first 
been  emphasized  and  attention  has  been  drawn  towards  the  fact  that  our 
conception  has  been  entirely  derived  from  classical  data,  that  have  here 
been  considered  jointly  instead  of  separately:  autogenic  cellular 
rhythmicity,  post-tetanic  potentiation,  multivalent  neurones  and  net- 
work-like architectonics. 


GROUP   DISCUSSION 

EccLEs:  It  is  very  important  for  the  theory  of  learning  that  the  stimulated  line  is 
the  only  one  that  increases  in  efficacy.  But  it  is  also  important  to  show  what  Dr 
Fcssard  has  shown  —  that  interneuroncs  which  are  common  to  both  lines,  fire  and 
they  increase  the  effectiveness  of  their  synaptic  action  in  turn.  In  other  words,  you 
are  converging  through  an  intcrncurone  which  both  lines  arc  firing  but  which  is 
not  powerful  enough  for  one  of  the  lines  to  transmit  to  the  next  stage  of  the 
synaptic  relay.  This  has  to  be  built  in  to  any  theory  of  learning  or  conditioning.  I 
did  set  up  a  very  provisional  diagram  —  in  1953  —  which  did  presuppose  what  Dr 

BB 


37^  BRAIN    MECHANISMS    AND    LEARNING 

Fcssard  has  found  when  I  was  attempting  to  give  some  picture  of  the  neuronal 
mechanism  of  learning,  at  least  at  the  simplest  level. 

Fessard:  I  remember  your  diagrams. 

Gerard  :  I  hope  this  will  be  elaborated  in  the  general  discussion  on  Saturday.  I 
remind  you  that  in  Lloyd's  experiments  with  the  monosynpatic  reflex  each 
arterent  did  not  influence  the  response  induced  by  any  other  afferent  and  Dr 
Fessard's  results  seem  to  be  in  conflict  with  that  unless  you  take  into  account  the 
existence  of  interneurones. 

KoNORSKi:  Post-tetanic  potentiation  (P.T.P.)  was  first  discovered  many  years 
ago  in  neuromuscular  preparations,  hi  curarized  preparations  the  P.T.P.  is  very 
strong  and  long  lasting.  We  did  some  of  these  investigations  with  Lubinska  and 
found  that  the  P.T.P.  lasted  for  minutes.  Do  you  think  this  is  a  different  pheno- 
menon from  the  P.T.P.  found  in  C.N.S.? 

Fessard:  I  would  say  it  is  just  the  same. 

KoNORSKi :  Dr  Kozak  and  Dr  Bruner  have  shown  that  the  P.T.P.  in  neurosalivary 
preparations  (where  the  effector  is  a  salivary  gland)  is  even  more  prolonged  —  from 
10  minutes  to  half  an  hour.  So  we  see  that  the  P.T.P.  phenomena  are  general  and 
apply  to  the  C.N.S.  as  well  as  to  the  peripheral  nervous  system. 

Fessard:  As  Dr  Eccles  just  recalled,  motoneuiones  may  be  taken  as  models  of 
any  others,  but  there  may  be  strong  quantitative  diff^erences. 

Magoun:  Is  there  any  value  in  considering  the  alterations  in  the  sensitization  of 
enervation  in  this  question.  The  increment  of  excitability  in  this  case  occurs  at  the 
receptor  sites  on  the  post-synaptic  membrane  rather  than  on  the  pre-synaptic 
membrane.  As  long  as  one  is  looking  for  all  possible  instances  in  which  there  is  an 
enhancement  of  excitability  persisting  for  a  long  time,  I  wonder  if  there  would  be 
any  concepts  to  be  applied  from  the  field*  of  sensitization  of  denervation. 

Eccles.  There  are  important  facts:  for  example,  Axelsson  and  Thesleft  have 
shown  that  when  you  cut  the  nerve  to  a  mammalian  muscle  and  it  degenerates,  the 
well-known  hypersensitivity  to  acetyl-choline  in  tact  is  not  a  real  hypersensitivity 
of  the  cndplate  region,  but  simply  a  spreading  sensitivity  at  the  same  level  through- 
out the  whole  length  of  the  muscle  fibre  which  effectively  becomes  a  long, 
extended  cndplate.  This  has  been  tested  by  micro-injection  techniques. 

Magoun:  What  about  the  influences  in  the  C.N.S.  such  as  have  been  explored 
by  Stan? 

Gerard:  Dr  Luco  commented  on  that.  Would  you  like  to  add  anything? 

Luco:  Professor  Canon  did  some  experiments  on  sensitization.  If  you  cut  the 
nerve  to  the  motor  nerve  cell,  the  sensitization  is  increased.  I  want  to  add  one 
interesting  thing.  We  cut  the  post-ganglionic  fibres  of  the  superior  cervical  gang- 
lion which  innervates  the  nictating  membrane.  We  re-innervated  the  membrane 
with  cholinergic  fibres  of  the  hypoglossal  nerve,  and  the  sensitivity  to  adrenaline 
was  normalized  after  re-innervation  with  a  very  different  nerve.  In  other  words,  the 
normal  sensitivity  which  had  been  lost  was  regained  with  a  different  nerve  wluch 
normally  is  not  innervating  the  membrane. 

Gerard  :  Let  us  not  forget  the  plasticity  or  enduring  effects  of  activity  even  at  a 
simpler  level  than  the  synapse,  in  the  nerve  fibre  itself  After  brief  activity  there  is  a 
change  in  the  magnitude  and  duration  of  the  after-potentials  which  increases  from 
milliseconds  to  minutes,  and  the  heat  or  oxygen  consumption  increases  for  hours. 


A.    FESSARD    ET   TH.    SZABO  373 

It  is  unthinkable  to  nic  that  in  the  simpler  animal  one  would  get  more  enduring 
ertects  ot  activity  than  m  the  more  complex  animals.  I  remind  you  also  that  the 
spontaneous  rhythms  ni  the  membrane  potential  or  peripheral  nerves  fit  the  same 
story.  Both  in  nerves  and  in  spontaneous  beat  of  trog  brain  neurones  a  chemical 
control  to  balance  the  potassium  and  sodium  seems  to  me  to  fit  in  very  nicely. 

EccLEs:  About  Dr  Luco's  suggestion  that  we  take  post-denervation  sensitization 
into  account.  That  would  tend  to  make  the  disused  line  more  effective  than  it  used 
to  be  and  so  would  work  against  our  results  on  the  depression  induced  by  disuse. 
Furthermore,  we  have  already  controlled  this  kind  of  effect  in  the  experiment 
where  we  were  recording  intracellularly  the  synaptic  potentials  of  the  nerve  cell 
and  firing  at  it  from  two  different  paths,  one  disused,  the  other  normal. 

Luco :  The  sensitization  is  normally  increased  when  the  membrane  is  denervated ; 
the  point  is  that  another,  different  nerve  is  responsible  for  this  return  of  sensitivity. 


LASTING  CHANGES  IN   SYNAPTIC  ORGANIZATION 

PRODUCED  BY  CONTINUOUS  NEURONAL 

BOMBARDMENT' 

Frank  Morrell 

I  should  like  to  present  some  experimental  observations  which  have  led 
us  to  suggest  an  analogical  model  for  cellular  learning.  The  model  is 
interesting  in  two  respects,  (i)  Although  the  process  is  a  pathological  one, 
it  is  presumed  to  utilize  the  same  neural  pathways  available  to  physio- 
logical stimulations.  (2)  Changes  in  synaptic  organization,  cellular 
excitability  and  cellular  chemistry  have  been  demonstrated  on  a  time  scale 
comparable  to  behavioural  learning. 

For  the  past  few  years  our  laboratory  has  been  conccrnexl  with  a  study 
of  chronic  epileptogenic  lesions  produced  in  animals  by  local  application 
of  an  ethyl  chloride  spray  to  a  small  (2  mm.)  area  of  cortex  (Morrell  and 
Florenz,  1958;  Morrell,  1959).  Such  animals  develop  paroxysmal  electro- 
graphic  discharges  at  the  periphery  of  the  lesion  within  a  few  hours. 
Within  a  few  days  a  secondary  focus  of  paroxysmal  discharge  may  be 
recorded  in  the  contralateral  homologous  cortex.  Fig.  i  illustrates  such  a 
development.  In  the  tirst  24  hours  after  application  of  the  ethyl  chloride 
(Fig.  1  A),  the  electrical  record  disclosed  paroxysmal  activity  limited  to  the 
area  around  the  primary  lesion.  There  was  little  or  no  evidence  of  ab- 
normal discharge  in  an  electrode  (electrode  4)  placed  symmetrically  over 
the  cortical  region  opposite  the  lesion.  Three  days  later,  however,  in  the 
same  animal,  epileptiform  spikes  appeared  quite  prominently  in  the 
symmetrically  placed  contralateral  electrode  (Fig.  iB). 

Such  secondary  foci  have  been  observed  in  patients  with  convulsive 
disorders  (Gastaut,  1959)  and  in  animal  preparations  by  Erickson  (1940), 
Rosenblueth  and  Cannon  (1942),  Speransky  (1935),  Nims,  Marshall  and 
Nielsen  (1941),  Morrell  (1959),  Kopeloff  cf  nl.  (1954,  1955),  Pope,  Morris, 
Jasper,  Elliott  and  Penficld  (1947)  and  Roger  (1954).  In  the  terminology  of 
the  electroencephalographer,  the  area  of  secondary  discharge  has  been 
called  the  'mirror'  focus.  In  the  early  stages  of  its  development,  the 
secondary  discharge  represents  a  'reflection'  of  the  primary  discharge.  It  is 
dependent  upon  activity  in  the  primary  lesion  in  the  sense  that  it  subsides 

1  This  work  was  supported  by  the  Tcagle  Foundation  and  by  USPHS  Grant  1185. 

375 


376 


BRAIN    MECHANISMS    AND    LEARNING 


following  ablation  or  neuronal  isolation  of  the  primary  lesion.  Electro- 
graphically,  this  dependent  stage  of  homotopic  discharge  may  be  character- 
ized by  the  fact  that  secondary  spikes  appear  only  at  the  time  that  spike 
discharges  are  evident  in  the  primary  region  (and  often  only  in  response  to 
the  larger  of  the  primary  spikes)  and  have  an  appreciable  latency  following 
the  primary  discharge  when  measured  with  cathode  ray  oscillography 
(Fig.  2)- 


1-0  A  R  459 

5-7 


Fig.  I 

Electroencephalogram  of  an  unanacsthetized  rabbit  24  hours  (A)  and  3  days  (B)  after  produc- 
tion of  an  ethyl  chloride  lesion.  The  site  and  extent  of  the  lesion  is  indicated  by  the  cross 
hatched  area  on  the  diagram.  Derivations  are  bipolar  from  implanted  electrodes  over  the 
indicated  regions.  Calibration  is  50  microvolts  and  i  second. 


After  a  given  period  of  time  (24  hours  to  7  days  in  the  rabbit,  4  weeks  to 
3  months  in  the  cat;  about  8  weeks  in  the  monkey)  the  secondary  contra- 
lateral focus  becomes  independent  in  that  it  does  not  disappear  upon 
ablation  or  coagulation  of  the  prmiary  region  of  discharge.  Electro- 
graphically,  the  independent  stage  of  homotopic  discharge  is  characterized 
by  random  spikes  and  paroxysmal  bursts  which  bear  no  relation  in  time 
to  the  activity  present  in  the  primary  lesion  (Fig.  3). 


TRANK    MORRELL 


377 


Fig.  2 
Characteristics  of  the  dependent  niirnir  focus,  hi  the  ink-written  tracing  the  upper 
two  channels  record  the  primary  focus  and  the  lower  two  channels  the  mirror 
focus.  The  ethyl  chloride  lesion  is  indicated  by  cross  hatching.  Calibration:  lOO 
microvolts  and  i  second.  In  the  oscillographic  tracing  the  upper  channel  records  the 
primary  region  and  the  lower  one  the  secondary  region.  Calibration:  loo  msec. 


rv'--wu.A-vAJi/yf/l\v'/y'fV^^''''V'^^ 


2-3 


>.-wvV'Y¥^^V1J^yi^^WHVVfv^^ 


,;-wvv-^-A^-^^^''^'MW■^.,/f«VV,Y^;^^J>MtV,'JV■^-.L,"J^^ 


'''>'-"^^'M.Vv;u~Vr^<^AASA'/^.^yVW^ 


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6-7 


Yv^M/VA'V^J■■^^tVvvYVw^AjvJ^^M 'V>^rt'*>^  ~^-~'''''V'Vv^(v-a~i^-,v''\A;v>vvvJ'^ 


7- 


AiWAMvSV^^-^^i^'^'-^/^jMfil^ 


8-  I  

Fig.  3 
Electrographic  characteristics  of  tlie  independent  mirror  focus.  Electroencephalogram  of  an 
unanaesthetized  rabbit  taken  3  weeks  after  production  of  an  ethyl  chloride  lesion  in  the  area 
designated  by  cross  hatching.  Discharges  originating  in  the  primary  lesion  (electrode  2)  and 
in  the  secondary  region  (electrode  7)  are  unrelated  in  time  of  occurrence.  Note  also  that  there 
is  some  depression  of  activity  in  electrodes  just  posterior  to  the  primary  lesion  while  this  is  not 
true  of  electrodes  posterior  to  the  mirror  focus.  Calibration:  50  microvolts  and  i  second. 


378  BRAIN    MECHANISMS    AND    LEARNING 

Once  the  independent  stage  of  secondary  discharge  has  been  reached, 
local  changes  in  cellular  excitability  may  be  demonstrated  by  alterations  in 
evoked  potentials.  For  example,  one  measure  of  excitability  change  is  the 
amplitude  of  the  direct  cortical  response  (DCR)  to  the  same  electrical 
stimulus  presented  before,  and  7  days  after,  development  of  the  focus. 
Electrodes  were  implanted  in  various  cortical  regions  of  the  hemisphere 
contralateral  to  the  ethyl  chloride  lesion  (Fig.  4)  so  that  a  bipolar  stimu- 
lating electrode  consisting  of  two  75  micron  silver  wires  cemented  to- 


pic. 4 

Direct  cortical  response  tested  before,  and  7  days  after,  production  of  an  etiiyl  cliloridc  lesion. 
The  derivations  are  from  implanted  electrodes  as  indicated  in  the  diagram.  The  area  of  the 
ethyl  chloride  lesion  is  cross  hatched.  Variations  in  duration  and  configuration  of  the  evoked 
potentials  are  due  to  differences  in  inter-electrode  distance  and  in  orientation  of  the  recording 
electrode  with  respect  to  the  stimulating  electrodes.  Photographs  consist  of  ten  to  forty 
superimposed  sweeps.  Calibration:  15  msec. 


gether  and  exposed  only  at  their  tips  rested  approximately  2  mm.  away 
from  a  monopolar  steel  needle  used  as  a  recording  electrode.  The  reference 
electrode  was  a  steel  screw  in  the  calvarium.  Direct  cortical  responses  were 
tested  repeatedly  at  each  of  these  sites  before  producing  the  ethyl  chloride 
lesions.  Responses  obtained  in  each  area  are  demonstrated  in  the  first 
column  of  oscillograph  tracings.  These  tracings  were  made  by  super- 
imposition  often  to  forty  responses  and  thus  serve  to  indicate  the  stability 
and,  therefore,  reliability  of  amplitude  measurements  under  these  circum- 
stances. An  ethyl  chloride  lesion  was  then  produced  in  the  left  visual 


FRANK    MORRELL  379 

cortex  and  the  animal  was  again  tested  7  days  after  development  ot  the 
lesion  (second  column  of  tracings).  The  marked  augmentation  of  the 
directly  evoked  response  limited  to  the  contralateral  visual  cortex  is 
clearly  apparent.  A  similar  augmentation  of  the  direct  cortical  response  in 
areas  contralateral  to  a  cortical  circumscction  has  been  noted  by  Eidelberg 
Konigsmark  and  French  (1959).  These  authors  also  attribute  such  aug- 
mentation to  increased  epileptogenic  properties. 

These  data  suggest  that  the  secondary  area  of  discharge  may  be  described 
as  a  ganglionic  network  in  which  spontaneous  and  evoked  activity  have 
been  chronically  altered  as  a  result  of  experimental  alteration  of  its 
environmental  input  in  the  form  of  continuous  epileptiform  bombard- 
ment. 

The  sequence  just  described  may  be  altered  and  the  development  of  the 
mirror  focus  prevented  by  section  of  the  corpus  callosum  either  before 
production  of  the  primary  lesion  or  within  24  hours  afterwards.  A  similar 
observation  has  been  made  by  Erickson  (1940)  with  respect  to  electrically 
induced  after-discharges.  Interestingly  enough,  the  development  ot 
independent  contralateral  secondary  discharge  may  also  be  prevented  if 
the  callosal  connections  remain  intact  but  a  subpial  partial  isolation  of  the 
contralateral  cortex  is  carried  out  within  the  same  time  interval.  Such  an 
isolation  deprives  the  cortex  of  all  of  its  subcortical  connections  as  well  as 
those  relating  it  to  other  cortical  areas  of  the  same  hemisphere  (Fig.  5  A 
and  B).  This  would  suggest  that  the  enduring  changes  in  synaptic  function 
which  form  the  basis  of  the  independent  mirror  focus  require  that  at  least 
two  forms  of  input  be  available  to  the  cortical  region  concerned. 

We  may  now  proceed  to  ask  whether  the  change  in  excitability  or 
irritability  is  dependent  upon  impulses  circulating  in  closed  chains  oi 
neurones  or  whether  it  is  based  upon  structural  alterations  of  cells  within 
the  network.  As  a  first  step,  neuronal  isolation  of  the  region  of  primary 
discharge  was  carried  out  according  to  the  technique  of  Kristians'en  and 
Courtois  (1949).  Fig.  6A  illustrates  persistent,  perhaps  even  augmented, 
activity  in  the  mirror  focus  after  isolation  of  the  primary  lesion.  Note  that 
the  paroxysmal  discharge  in  the  primary  lesion  had  ceased:  (Compare 
with  Fig.  3  on  the  same  ammal.)  The  mirror  region  may  then  be  similarh' 
isolated  (Fig.  6B  and  C).  Some  residual  spiking  sometimes  persists  for 
several  minutes  in  the  isolated  mirror  region  (Fig.  6B)  but  soon  disappears 
to  be  replaced  by  electrical  silence  (Fig.  6C).  After  these  isolations  were 
performed,  the  calvarium  was  replaced  and  the  animal  returned  to  its  cage 
for  several  months.  Surface  recording  during  that  period  indicated  no 
return  of  paroxysmal  discharge.  At  the  time  for  the  definitive  experiment, 


380 


BRAIN    MECHANISMS    AND    LEARNING 


B 

Fig.  5 
Dissection  of  rabbit  brain  to  illustrate  features  of  the  c.xCra-callosal  isolation.  A  slab  of  cerebral 
cortex  in  the  hemisphere  opposite  the  ethyl  chloride  lesion  is  dissected  so  that  the  cortex  is 
separated  from  all  subcortical  connections  and  from  the  surrounding  intracortical  regions  as 
well.  The  callosal  pathway  remains  intact  and  is  the  only  connection  through  which  input  is 
available  to  the  dissected  region  (5A).  In  a  Weil  stained  cross  section  (5B)  the  integrity  of  the 
callosal  pathway  may  be  visualized.  For  photography  the  cortex  was  lifted  to  demonstrate 
the  underlying  white  matter  but  the  operative  procedure,  of  course,  is  done  in  such  a  way  as 
to  preserve  the  pial  circulation  to  the  cortical  slab. 


FRANK    MORRELL 


381 


3-5 


7-f 


-^''-^V---vw'H^'^,_/^'^^'Y^^^^^^,,/lHwV^^^ 


6-4 


I  -2 


3-5 


6-4 


|r''\,'■Vv/y*M'/lMy^V^''^***''^-''^^ 


Fig.  6 
Bilateral  cortical  isolation  in  an  animal  with  well-developed  independent  mirror  focus.  This 
is  the  same  animal  shown  in  Fig.  3.  Recordings  were  made  with  the  animal  under  40  mg.  per 
kg.  of  nembutal  anaesthesia.  Derivations  are  from  the  electrodes  indicated  in  the  diagrams. 
Isolation  of  the  primary  lesion  is  first  carried  out  (6A)  and  demonstrates  loss  of  paroxysmal 
spike  discharge  in  the  primary  region  while  the  secondary  area  continues  to  discharge  actively. 
Isolation  of  the  secondary  region  was  then  undertaken  (6B  and  C).  For  a  few  moments 
abnormal  discharge  persists  in  the  isolated  secondary  region  (B)  but  soon  disappears  (C)  to  be 
replaced  by  almost  complete  electrical  silence.  Note  that  the  electrode  positions  have  been 
changed  in  B  and  C.  Calibration:  50  microvolts  and  i  second. 


382 


BRAIN    MECHANISMS    AND    LEARNING 


a  tracheotomy  was  performed  under  ether  anaesthesia  and  the  animal 
placed  on  flaxedil  and  artificial  respiration.  Local  anaesthesia  was  used  for 
the  scalp  incision,  the  hemispheres  were  widely  exposed  and  the  pia 
arachnoid  covered  with  warm  mineral  oil.  At  the  end  of  the  experiment 
the  isolated  regions  were  serially  sectioned  to  confirm  the  completeness  of 
loss  of  neural  continuity.  The  pial  circulation  was,  of  course,  preserved 
intact  in  these  preparations.  The  appearance  of  the  whole  brain  at  autopsy, 
as  well  as  a  cross  section  through  the  isolated  region,  are  indicated  in 
Fig.  7. 


Fig.  7 

Whole  brain  at  autopsy  and  cross  section  through  tlie  isolated  regions.  The  defect  in  tlie  right 

frontal  pole  was  produced  in  the  course  of  removal  of  the  brain  at  autopsy. 


Gross  electrodes  were  placed  upon  the  surface  of  the  isolated  mirror 
region  and  adjacent  surrounding  cortex  and  one  to  four  tungsten  micro- 
electrodes  (Hubel,  1957)  were  inserted  into  the  isolated  slab  at  a  depth  of 
500  to  1000  micra.  Search  for  spontaneously  firing  units  was  rarely 
successful  so  that  one  had  to  rely  upon  multiple  placement  at  a  depth 
where  unit  discharge  might  reasonably  be  expected  in  connection  with 
surface  electrographic  paroxysms.  A  pledget  of  metrazol  placed  upon 
adjacent  normal  cortex  elicited  a  seizure  discharge  which  slowly  spread 


FRANK    MORRELL 


383 


across  the  neuronal  gap  into  the  isolated  region  (Fig.  8).  Gross  electrodes 
on  the  slab  first  recorded  volume  conducted  potentials  unaccompanied  by 
unit  discharge  and  then  suddenly  the  slab  burst  into  self-sustained  activity 
which  was  associated  with  niassive  unit  discharge.  Since  the  high  imped- 
ance of  the  microelectrodc  tip  precludes  recording  at  any  distance,  we 
must  conclude  that  the  discharge  truly  represents  ephaptic  activation  of 
ganglionic  elements  within  the  isolated  region.  We  do  not  have  time  here 
to  discuss  the  physiological  properties  of  isolated,  non-epileptic  cortex 
(see  references  Libet  and  Gerard,  1939;  Bremer,  1941 ;  Burns,  1949;  Sloan 
and  Jasper,  1950;  Bremer  and  Desmedt,  1958;  Torres,  Ziegler  and  Wissof, 


Isolated  cortex  ^A^/,         '  ^^  .,,...      .  .  ■  '-  ,   v    -  ,vVvl^,>     Vi-^s/vys 

Microelecifode 


Normol  corte)'  _: 

I  solo  ted' cortex  •   ^   *     ^         .-  1    ,         ,        1  -    -> 

Examples  of  propagation  of  abnormal  discharges  to  isolated  regions.  A  pledget  of  metrazol 
had  been  placed  on  the  normal  cortex  2  cm.  distant  from  the  isolated  region.  The  electro- 
graphic  discharge  so  induced  spreads  slowly  across  the  cortex  and  after  some  delay  was  seen 
to  invade  the  isolated  region.  Micro-electrode  tracings  are  from  tungsten  electrodes  as  des- 
cribed in  the  text.  Calibration  is  so  microvolts  and  one  second  for  the  ink-writer  tracings  and 
I  second  for  the  oscillograph. 


1958;  Morrcll  and  Torres,  1958;  Marshall,  1959).  In  our  own  experience 
we  have  never  been  able  unequivocally  to  demonstrate  transmission  of 
electrical  discharge  into  completely  neuronally  isolated  (but  otherwise 
normal,  i.e.  non-cpilcptic)  cortex.  The  ease  with  which  such  ephaptic 
transmission  can  be  demonstrated  ni  isolated  epileptic  cortex  makes  it 
clear  that  the  increased  excitability  or  irritability  has  persisted  in  the 
cellular  elements  of  the  mirror  region  despite  the  fact  that  the  spontaneous 
manifestation  of  this  irritability  was  abolished  by  the  neuronal  isolation. 
We  believe  this  to  be  crucial  observation  because  it  demonstrates  that  the 
mirror  focus  is  a  region  which  has  not  only  'learned'  to  behave  in  terms  of 
paroxysmal  discharge,  but  which  'remembers'  this  behaviour  even  after 
months  of  inactivity.  The  isolation  experiment  has  excluded  reverberating 


384  BRAIN    MECHANISMS    AND    LEARNING 

impulses  as  the  basis  of  the  changed  electrical  behaviour  and  makes  it 
it  necessary  to  search  for  structural  alterations. 

The  material  presented  thus  far  indicates  that  a  region  of  chronic 
epileptiform  discharge  in  one  hemisphere  can  induce  a  similar  pattern  of 
neuronal  activity  in  cells  of  the  opposite  hemisphere  which  w^ere  untouched 
by  the  initial  experimental  procedure  and  which  arc  related  to  the  primary 
region  by  massive  commissural  pathways.  After  a  time  these  contralateral 
alterations  become  permanently  fixed  in  local  cellular  organization  and 


Fig.  9 
Section  tlirougli  the  region  of  the  mirror  focus.  Note  the  collection  of  densely 
stained  cells  to  the  right  of  the  photomicrograph  compared  with  the  character- 
istic staining  of  normal   cortex   to   the   left.    Methyl   green   pyronin   stain. 
Magnification  ■:  75. 

persist  independently  of  the  neural  system  which  originally  established 
them.  In  addition  to  the  spontaneous  behaviour  of  these  cells,  we  have 
traced  some  measures  of  evoked  activity  which  also  indicate  a  reorganiza- 
tion of  the  synaptic  properties  within  the  altered  population.  Of  special 
interest  is  the  fact  that  these  changes  are  long-lasting  and  that  they  survive 
the  chronic  neuronal  isolation  of  the  involved  neurones,  an  isolation  which 
prevents  the  spontaneous  manifestation  of  the  alteration  which  has  taken 
place. 

I  should  like  to  conclude  by  reporting  some  preliminary  experiments 


FRANK    MORRELL  3S5 

which  iUustrate  the  use  to  which  our  model  of  neural  learning  may  be  put. 
The  experiments  involve  the  supposition  that  the  molecular  basis  of 
memory  nnght  be  found  within  the  cells  or  cell  systems  of  the  mirror 
focus. 

Among  the  most  important  known  determinants  of  membrane  respon- 
siveness is  the  distribution  of  charge  across  the  cell  boundary.  While  the 
relative  internal  and  external  concentration  of  various  ion  species  are 
known  to  produce  radical  alterations  in  membrane  potential,  these  changes 


r 


k 


Fig.  10 
Slighdy  liitjhcr  power  phoroniicrograph  thrmii^h  region  of  nnrriir  tocus.  The 
appearance  of  normal  cortical  cells  with  this  method  is  seen  in  the  lower  right 
and  upper  left  hand  corners.  Methyl  green  pyronin  stain.  Magnification  X  85. 

arc  transient  and  it  seems  unlikely  that  distribution  oi  the  relatively  per- 
meable free  ions  could  account  for  lasting  patterns  in  the  intricate  local 
distribution  of  membrane  potential.  A  much  more  likely  candidate  for 
such  permanent  patterning  is  the  configuration  of  potential  set  up  in 
ordered  sequences  of  amino  acids  or  proteins.  Yet  these  substances,  too, 
are  known  to  be  in  continual  Bux,  in  generation,  breakdown  and  re- 
generation. One  must  postulate  an  organizer  substance,  a  substance  which 
in  its  synthesis,  breakdown  and  resynthcsis  can  perpetuate  or  regenerate 
the  same  pattern  of  polarized  molecular  configurations  which  were 
previously  present.   The  search  for  an  organizer  substance  leads  one 


386  BRAIN    MECHANISMS    AND    LEARNING 

logically  to  the  nucleic  acids  and,  for  events  which  are  primarily  cytoplas- 
mic, to  the  ribonucleic  acids. 

Ribonucleic  acid  stains  (methyl  green  pyronin  method)  have  been  done 
on  sections  through  the  region  of  the  mirror  focus  in  nine  animals  after 
preliminary  electrical  studies  had  clearly  indicated  the  extent  and  distribu- 
tion of  both  primary  and  secondary  discharging  areas.  Control  sections 
were  taken  from  electrically  uninvolved  areas  of  brain  and,  in  addition, 
every  third  section  was  treated  with  ribonucleasc  to  insure  that  the  sub- 


FlG.   1  I 

Higher  pi)  werphntoinicrogrdph  denumstrating  the  characteristic  concentration 
of  pyronin  positive  material  along  the  inner  surface  of  the  membrane.  The 
stained  material  extends  far  into  the  dendrite.  Note  also  the  appearance  of  a 
bilobcd  nucleus   Methyl  green  pyronin  stain.  Magnification  ■  840. 

Stance  stained  was  ribonucleic  acid.  Fig.  9  demonstrates  a  small  nest  of 
darkly  stained  cells  surrounded  by  the  more  lightly  coloured  regions  of 
normal  cortex.  Such  densely  stained  cells  were  consistently  found  in 
areas  coincident  with  the  electrically  defined  mirror  focus.  A  slightly 
higher  power  photomicrograph  (Fig.  10)  illustrates  the  penetration  of  the 
pyronin-positive  material  into  the  dendrite  and  also  indicates  the  wedge- 
like  distribution  of  the  stained  cell  system.  Pigmented  cells  extend  through- 
out the  depth  of  the  cortex.  At  still  higher  magnification  the  extent  of 
penetration  into  the  dendrite  is  clearer  (Fig.  i  1)  and  one  may  observe  a 


FRANK    MORRELL  387 

concentration  oi  the  pyronin-positive  material  in  a  dense  layer  along  the 
inner  surface  of  the  cell  membrane.  Not  infrequently  the  cytoplasmic 
space  between  the  membrane  zone  and  the  nucleus  is  considerably  paler. 
Such  a  concentration  might  be  expected  for  an  arrangement  of  protein 
molecules  capable  of  influencing  the  distribution  of  potential  across  the 
membrane.  It  is  not  the  concentration  pattern  to  be  expected  as  a  result  of 
simple  tiecrease  in  cell  volume.  Note  also  the  suggestion  of  a  bilobed 
nucleus.  Andrew  (1955)  has  considered  the  occurrence  of  bilobed  nuclei  in 
mouse  Purkinje  cells  to  indicate  an  abortive  attempt  at  amitotic  division  in 
nerve  cells  subjected  to  certain  forms  of  stress.  The  primary  lesion  (Fig. 
1 2 A)  is  surrounded  by  cells  of  a  similar  appearance.  The  contralateral 
homologous  region  of  the  same  section  (Fig.  12B)  is  less  deeply  stained 
than  in  sections  slightly  further  away  from  the  primary  histological  lesion, 
(compare  Fig.  9).  Similarly,  the  electrical  records  indicated  that  the  most 
active  discharge  in  the  mirror  region  was  not  homotopic  with  the  centre 
of  the  ethyl  chloride  lesion  but  rather  with  its  periphery  just  as  the 
primary  electrical  discharge  is  at  the  periphery  rather  than  the  centre  o^ 
the  primary  lesion.  Adjacent  sections  treated  with  ribonuclease  show  loss 
of  almost  all  the  tinctorial  properties  of  these  cells. 

Although  these  are  still  preliminary  observations,  some  controls  have 
been  introduced  to  insure  that  the  histological  changes  are  not  artifactual. 
One  might  argue,  for  example,  that  such  nests  of  deeply  stained  cells  are 
occasionally  (although  rarely,  in  our  experience,  if  the  brain  is  properly 
fixed)  found  in  normal  brain.  These  may  be  due  to  random  variations  in 
penetration  of  dye,  fixation  of  material,  or  even  in  the  capacity  of  the  cell 
to  take  the  stain  for  reasons  other  than  those  suggested  in  our  experi- 
mental procedure.  One  might  also  consider  that  such  cells  were  damaged 
in  the  course  of  removal  of  the  brain  or  in  the  fixation  procedure  and  that 
the  deep  stain  indicates  nothing  more  than  pyknosis.  Most  of  these 
objections  may  be  countered  by  the  following  evidence:  (i)  The  densely 
staining  cell  aggregates  were  seen  in  different  cortical  zones  in  each  of  the 
experimental  animals  and  consistently  were  related  to  the  electrical  focus 
rather  than  to  any  particular  cortical  zone.  (2)  Adjacent  sections  from  the 
same  animal  indicated  that  stained  areas  could  be  superimposed,  thus 
excluding  random  staining  of  the  slide.  (3)  The  brains  were  perfused  with 
fixatives  while  the  animals  were  under  deep  anaesthesia  but  still  alive.  This 
procedure  minimized  cell  changes  due  to  poor  fixation.  Moreover,  it 
would  seem  unusual  that  fixation  artifact  would  vary  in  location  from 
animal  to  animal  in  a  manner  precisely  concordant  with  variations  in  the 
site  of  electrical  discharge.  There  remains  the  argument,  which  may  be 

cc 


388 


BRAIN    MECHANISMS    AND    LEARNING 


A 
Fig.  12 


C.--    ' 


^( 


.,«:;*-r>' 


H 
Fig.  12 
Area  of  the  primary  histological  lesion  compared  with  the  exactly  homotopic 
region  in  the  same  section.  Small  densely  stained  cells  are  seen  around  the 
primary  lesion  while  in  the  contralateral  cortex  fewer  cells  seem  to  take  the 
stain  than  in  regions  closer  to  the  area  of  maximal  electrical  discharge.  Methyl 
green  pyronin  stain.  Magnification  X  75. 


FRANK    MORRELL  389 

valid  at  least  for  the  primary  lesion,  that  the  dark  cells  arc  simply  partially 
chromatolyscd  neurones.  Yet  the  same  sort  of  cells  are  seen  in  the  mirror 
focus,  an  area  which  has  been  untouched  by  the  experimental  procedure, 
the  cortex  remaining  unexposed  until  the  brain  itself  was  removed. 
Neither  can  one  account  for  these  findings  on  the  basis  of  retrograde 
degeneration  for  such  histochcmical  changes  are  not  seen  contralateral  to 
a  simple  cortical  excision. 

The  observation  that  changes  in  ribonucleic  acid  occur  in  cell  popula- 
tions subjected  to  continuous  synaptic  bombardment  is  not  in  itself 
surprising.  Hyden  and  co-workers,  using  much  more  elegant  techniques 
(Hyden,  1943;  Brattgard  and  Hyden,  1952)  have  already  demonstrated 
increases  in  cellular  RNA  with  various  kinds  of  stimulation  (Hambergcr 
and  Hyden,  1949).  They  have  also  demonstrated  that  such  changes  occur 
transneuronally  (Hamberger  and  Hyden,  1949a).  The  intriguing  question 
raised  in  the  present  investigation  is  not  the  relation  of  RNA  to  nerve 
activity  or  inactivity,  but  rather  the  relationship  of  RNA  to  the  coding  of 
that  information  necessary  to  effectuate  permanent  alteration  of  cellular 
excitability. 

For  the  moment  it  seems  reasonable  to  present  the  working  hypothesis 
that  the  cells  of  the  mirror  focus  undergo  a  structural  alteration  and  that 
changes  in  distribution  of  RNA,  perhaps  linked  with  protein  or  phos- 
pholipids, form  the  chemical  correlates  of  this  alteration.  Snice  the  cells 
and  cell  systems  of  the  mirror  focus  have  been  shown  to  have  some  of  the 
attributes  of  learning  and  of  memory,  it  is  perhaps  not  too  far  fetched  to 
consider  that  the  complex  of  ribonucleic  acid  and  protein  represents  an 
essential  element  in  the  molecular  basis  of  memory. 


ACKNOWLEDGMENT 

I  should  like  to  express  appreciation  to  Doctors  Kenneth  Osterberg  and 
K.  L.  Chow  for  help  with  the  histochemical  material. 


GROUP   DISCUSSION 

Magoun.  I  wonder  it  Dr  Morrcll  plans  to  profit  in  his  cytochcniical  studies  from 
a  simpler  situation,  where  the  sensitization  of  denervation  can  be  detected  in 
greater  isolation  than  in  the  cortex,  such  as  in  a  post-ganglionic  relay  in  the 
peripheral  autonomic  system  which  Cannon  and  his  associates  studied  for  so  many 
years.  Study  of  the  sensitization  of  a  mirror  focus  in  epileptic  genesis  in  the  cerebral 
cortex  is  one  of  which  Dr  French  and  others  have  been  investigating  at  Los  Angeles. 
Dr  Morrell's  results  are  similar  to  theirs  and  since  he  has  made  reference  to  their 


390  BRAIN    MECHANISMS    AND    LEARNING 

work  I  Will  not  need  to  elaborate  it  here.  Dr  Doty  in  an  earlier  meeting  was 
interested  in  the  effect  of  mirror  foci  in  the  cerebral  cortex,  from  the  point  of  view 
of  cerebral  cortex  in  the  establishment  of  intracortical  conditioned  reflexes.  I 
wonder  if  he  has  now  additional  information  ? 

Doty.  The  conditions  of  our  experiments  would  not  have  permitted  the  obser- 
vation of  such  a  focus. 

Chow.  I  would  like  to  add  a  word  of  caution  about  the  histological  pictures  Dr 
MorrcU  shov/ed.  The  R.N. A.  staining  is  a  very  tricky  thing  to  study  unless 
another  stain  is  used  to  corroborate  this  result.  Another  point  is  that  in  the  last  few 
years  Dr  Ricsen,  Dr  Rush  and  I  studied  the  problem  from  another  angle,  that  is  we 
want  to  study  the  problem  of  disuse.  We  have  reared  cats,  rats,  monkeys  and 
chimpanzees  in  darkness  and  studied  the  visual,  behavioural  and  retinal  structural 
effects.  We  have  examined  the  retina  of  dark-reared  animals  with  the  conventional 
stain  and  the  R.N. A.  stain.  In  rats,  cats  and  monkeys  reared  in  darkness  the  retina 
appeared  normal  to  the  haematoxylin  and  eosin  stain,  but  with  the  Azure  B  stain 
there  was  a  reduction  in  the  content  of  the  R.N.  A.  of  the  rod  and  cones,  bipolar 
and  ganglion  cells.  In  the  chimpanzee  we  have  observed  in  two  cases,  almost 
complete  degeneration  of  the  ganglion  cell  layer.  In  these  eyes  we  did  not  stain  the 
R.N. A.  This  is  the  first  example  we  have  had  of  possible  structure  changes  in  the 
visual  system  in  higher  animals  due  to  disuse. 

MoRRELL.  We  have  not  proved  that  the  histological  changes  observed  are  due  to 
neuronal  bombardment  of  these  specific  cells.  Some  of  the  negative  observations 
are  consistent  with  those  of  Dr  Chow  in  that  the  area  opposite  the  primary  histo- 
logical lesion  is  paler  and  shows  a  loss  of  R.N.  A.  I  do  not  think  that  the  electrical 
changes  can  be  attributed  to  denervation  sensitization  since  experiments  on  the 
partially  isolated  cortex  in  which  the  coi;pus  callosum  was  intact  do  not  show  the 
characteristic  electrical  changes.  The  electrical  as  opposed  to  the  histological 
changes  in  the  mirror  focus  are,  I  think,  a  result  ot  synaptic  bombardment. 

Myers.  I  should  like  to  suggest  that  the  firing  of  some  areas  of  cortex  may  be 
more  effective  than  of  others  for  the  elicitation  of  contralateral  effects  of  the 
nature  under  study  b)'  Dr  Morrell.  Since  he  and  others  have  demonstrated  the 
importance  of  the  corpus  callosum  for  the  development  of  the  mirror  focus  it 
would  seem  desirable  that  the  areas  chosen  for  the  making  of  epileptogenic  lesions 
have  the  most  dense  interhemisphenc  interconnections.  Such  a  suggestion  may  be 
of  more  than  academic  importance  inasmuch  as  there  exists  profound  differences 
in  density  of  corpus  callosum  projection  from  different  areas  over  the  cortical 
surface.  The  visual  receptive  area  and  the  primary  projection  areas  in  general, 
including  incidentally  the  somatomotor  areas,  have  the  least  dense  while  the 
adjoining  or  so-called  associative  cortex  tends  to  have  the  most  dense  projection 
through  the  corpus  callosum. 

The  Pacella  Kopeloff^  and  Jasper  group  have  carried  out  a  number  ot  early 
studies  of  the  mirror  focus  and,  as  I  recall,  investigated  the  mirror  locus  using 
biochemical  as  well  as  electrographic  techniques.  I  believe  they  found  significant 
changes  in  the  chemistry  of  the  mirror  focus  as  compared  to  normal  tissue.  I 
wonder  if  Dr  Morrell  recalls  what  these  tmdings  might  have  been  in  relation  to  the 
present  discussion. 

Morrell.  Although  most  ot  our  lesions  were  placed  in  visual  cortex  a  good 
number  of  them  were  in  somatosensory  and  in  motor  cortex. 


FRANK    MORRELL  391 

Myers.  Again,  it  seems  that  these  three  cortical  areas  have  least  to  offer  in  terms 
ot  contralateral  firing. 

MoRRELL.  One  of  the  reasons  why  most  ot  our  lesions  have  been  made  in  sensory 
areas  is  that  epileptogenic  lesions  of  the  motor  cortex  often  produce  clinical  seizures. 
These  mav  result  in  death  of  the  animal  or  may  require  anticonvulsant  treatment, 
and  this  of  course  complicates  the  experiment. 

Myers.  Have  you  had  the  opportunity  to  study  species  variation  in  regard  to  the 
development  of  contralateral  toci  of  independent  tiring? 

MoRRELL.  I  have  not  had  time  to  delineate  species  variation  in  the  development  of 
secondary  foci.  However,  we  have  done  these  experiments  in  rabbits,  cats  and 
monkeys  and  have  been  able  to  demonstrate  ditferences  in  the  time  required  for 
the  establishment  of  mirror  toci  in  each  of  these  animals.  In  the  cat  and  monkey  it 
is  much  longer  than  m  the  rabbit.  Penfield  has  made  the  statement  that  if  a  lesion 
has  been  present  for  approximately  2  years  (monkey)  ablation  ot  the  primary  site 
docs  not  lead  to  disappearance  of  the  mirror  focus. 

Myers.  Was  Penfield's  data  related  to  cortical  areas  other  than  the  temporal  tip. 

MoRRELL.  In  motor  cortex. 

Naquet.  You  said  that  the  isolated  cortex  in  the  normal  animal  has  a  higher 
threshold  than  in  your  preparation. 

MoRRELL.  In  preparations  with  well-developed  secondary  toci  there  is,  oi  course, 
no  normal  side.  The  threshold  to  electrical  stimulation  oi  the  non-epileptic  isolated 
cortex  is  higher  than  that  in  the  adjacent  surrounding  cortex. 

Naquet.  I  agree  but  I  feel  that  we  cannot  compare  what  happens  in  the  isolated 
cortex  when  you  stimulate  electrically  to  what  happens  spontaneousK'.  I  think  we 
mav  ask  Dr  Garcia-Austt  what  he  thinks  about  it. 

MoRRELL.  There  have,  as  you  arc  all  aware,  been  great  disputes  as  to  whether 
spontaneous  rh\thms  are  present  in  completely  neuronally  isolated  cortical 
tissue.  It  is  obviously  impossible,  even  with  serial  sections,  to  be  sure  that  no 
threads  of  tissue  remain  connecting  the  cortical  slab  to  the  surrounding  brain. 
Nevertheless,  in  our  experience,  if  good  isolation  is  achieved  there  is  no  clearly 
demonstrable  spontaneous  parox\'smal  epileptiform  activity  in  the  isolated  region. 

Fessard.  Sensitization  of  isolated  slabs  of  cortex  to  acetyl-choline  is  a  fact  that 
has  been  carefully  studied  recently  in  monkeys  by  Dr  Frank  Echlin.  His  paper  will 
come  out  soon  in  the  EEG  Journal.  Have  you  heard  of  this  work?  It  impressed  me 
much  when  I  visited  Dr  Echlin  recently  in  New  York. 

Morrell.  We  have  not  placed  acetyl-choline  directlv  on  isolated  cortical  regions. 
With  electrical  stimulation  the  non-epileptic  isolated  slab  has  a  higher  threshold 
than  normal  cortex. 

LissAK.  Regarding  Dr  Fessard's  question,  some  10  years  ago  with  my  colleagues 
Dr  Endroczi  and  Dr  Hasznos  we  did  some  experiments  on  isolated  cortex.  We 
found  an  increased  sensitivity  to  acet}l-choline  and  we  determined  the  choline 
esterase  activity  too  and  wc  found  that  it  was  decreased  not  only  in  the  isolated 
cortex  but  also  to  some  degree  in  the  contralateral  mirror  part  of  the  cortex. 

Garcia-Austt.  I  would  like  to  ask  some  questions.  Wc  also  have  been  working 
with  isolated  cortical  slabs.  We  think  that  the  slabs  have  a  greater  capacity  to 
respond  with  a  seizure  to  stimulation  and  also  to  spontaneous  seizure  discharge. 
As  to  the  threshold  —  we  have  not  studied  it  as  measured  by  the  threshold  voltage 
to  give  a  seizure  —  but  we  found  that  post-discharge,  if  measured  half  an  hour 


392  BRAIN    MECHANISMS    AND    LEARNING 

after  isolation  is  more  prolonged  in  the  isolated  cortex  than  in  the  cortex  before 
isolation.  On  the  other  hand,  if  it  is  tested  within  the  first  half-hour,  it  is  very  hard 
to  get.  So  the  question  is  —  what  do  you  mean  by  threshold  and  when  were  these 
tested  in  relation  to  the  isolation  procedure?  Also  did  the  epilcptical  activity  in  the 
mirror  cortex  in  some  cases  increase  after  isolation?  Have  you  tested  the  sensitivitv 
to  mctrazol  given  intravenously  of  the  cortex  from  the  other  side  ? 

MoRRELL.  Thresholds  were  determined  by  electrical  stimulation  measured  in 
terms  of:  the  amount  of  current  required  to  establish  self-sustained  afterdischarges. 
Excitability  is  usually  depressed  immediately  after  isolation,  may  be  augmented  a 
few  hours  later  and  is  usually  depressed  again  days  or  weeks  later.  We  often  did 
find  that  spontaneous  electrical  abnormality  increased  for  a  short  period  after 
isolation  in  some  cases.  In  most  cases  it  did  not  persist  and  gradually  disappeared. 
It  is  interesting  that  the  electrical  abnormality  of  the  mirror  region  frequently 
increased  after  isolation  of  the  primary  cortical  lesion.  We  have  administered 
systemic  metrazol  to  most  of  these  animals  and  found  that  the  paroxysmal  dis- 
charges usually  did  begin  in  the  isolated  epileptic  regions.  This  is  not  surprising 
because  I  think  it  is  a  common  observation  that  seizures  induced  by  systemic 
metrazol  start  in  any  region  where  trauma  to  nerve  cells  has  been  produced. 

Gerard.  I  am  delighted  with  these  findings,  and  with  the  demonstration  of 
transmission  of  influence  across  a  cut  —  one,  incidentally,  considerably  more  than 
200  micra.  This  is  very  satisfactory.  I  do  not  know  of  another  clear-cut  case  since 
our  frog  brain  work.  On  the  question  of  spontaneity  of  the  isolated  part,  I  suspect 
that  we  have  been  too  easily  assuming  that  all  parts  will  be  alike,  I  remind  you 
that  even  with  the  frog's  brain,  where  a  traction  of  a  milligramme  bit  will  give 
regular  electrical  beats,  not  any  part  of  the  brain  will  do.  The  olfactory  bulb  is 
particularly  vigorous.  A  second  point:  h;;ive  you  to  your  own  satisfaction  excluded 
possible  secondary  effects  through  the  pia,  either  neural  or  humoral  —  like  the 
findings  of  Burn  and  the  automatic  activity  described  by  Bach,  where  effects  on 
the  slab  were  induced  indirectly  and  not  electrically?  Finally,  on  the  R.N. A.  story  I 
would  like  to  mention  work  done  by  Edith  Maynard  in  our  laboratory.  She  has 
followed  spontaneous  or  evoked  discharges  in  the  isolated  lobster  cardiac  ganglion. 
A  ganglion  soaked  in  the  R.N.A.ase  for  8  hours,  and  shown  then  to  have  no 
R.N. A.  bv  histological  tests,  continues  to  show  normal  physiological  activity.  It  is, 
however,  possible  that  the  R.N.A.ase  is  not  destroyed  by  the  fixation  process  and 
only  enters  the  cell  at  the  time  of  fixation ;  so  that  this  observation  rec]uires  further 
check.  It  is,  however,  most  interesting,  especially  considering  the  evidence  of 
Tobias  that  peripheral  fibres  soaked  in  proteoK'tic  enzymes  could  practically 
dissolve  without  significant  change  in  the  action  potentials,  whereas  with  lipases 
conduction  was  quickly  abolished  with  no  evidence  of  histological  change. 

MoRRELL.  It  is  very  difficult  to  exclude  the  effects  which  might  be  produced  by 
substances  carried  through  the  pial  vessels.  One  has  to  maintain  the  pial  circulation 
intact  in  order  to  have  a  viable  slab.  1  do  not  know  any  way  of  getting  around  this 
difficulty. 


Vf 


v^^j,  *^\c^ 


Va 


v> 


FUNCTIONAL  ROLE  OF  SUBCORTICAL  STRUCTURES 

IN  HABITUATION  AND  CONDITIONING 

R.  Hernandez-Peon  and  H.  Brust-Carmona 

Until  a  few  years  ago  it  was  generally  assumed  that  at  least  in  mammals 
the  cortex  was  necessary  for  learning  and  that  learning  was  therefore  a 
cortical  process.  Furthermore,  it  was  assumed  that  the  neural  association 
of  stimuli  during  positive  learning  takes  place  intracortically  by  means  of 
two-dimensional  cortico-cortical  connections.  However,  it  has  been 
established  ni  dogs  and  cats  that  decorticated  animals  can  learn  and  can 
retain  some  simple  responses  learned  before  decortication.  Therefore,  it  is 
evident  that  subcortical  structures  play  an  important  role  in  basic  learning 
processes.  In  the  present  paper  this  role  will  be  discussed  on  the  basis  of 
the  experimental  evidence  obtained  by  the  authors. 

HABITUATION 

If  a  non-significant  stimulus  is  repeated  even  at  intervals  ot  hours  or 
days,  a  decrement  of  response  is  observed  which  may  last  for  hours,  days 
and  years.  Recognized  as  having  a  nature  different  from  fatigue  and 
adaptation  at  the  receptor  (Griffith,  1924)  this  long-lasting  decline  of 
behavioural  responses  is  usually  referred  to  as  habituation.  As  it  has  been 
rightly  pointed  out  by  Thorpe  (1950),  habituation  represents  the  simplest 
type  of  learning.  It  involves  stimulation  of  a  single  modality,  and  it  is 
found  through  all  the  animal  scale,  from  protozoa  to  man.  Habituation  in 
the  latter  can  be  observed  both  in  effector  responses  (somatic  and  autono- 
mic) as  well  as  in  sensory  experiences.  Because  of  the  ubiquity  ot  habitua- 
tion in  organisms  of  every  grade  of  evolution,  it  seems  warranted  to 
conclude  that  learning  derives  from  some  fundamental  property  of  living 
matter,  and  that,  therefore,  learning  does  not  necessarily  require  special 
complex  neuronal  circuits.  We  consider  it  convenient  to  use  the  term 
plasticity  proposed  by  Konorski  (194H)  in  order  to  distinguish  that  property 
from  another  fundamental  phenomenology  of  living  cells,  excitability, 
which  is  related  to  very  transient  changes  produced  by  the  stimulus.  In 
animals  with  nervous  systems  in  which  'all  or  none'  signals  are  trans- 
mitted, plasticity  permits  the  storage  of  information  delivered  by  those 
signals,  whereas  excitability  is  concerned  with  their  generation  and 
transmission. 

393 


394  BRAIN    MECHANISMS    AND    LEARNING 

Habituation  is  not  only  the  primary  learning  process,  but  seems  to  be 
a  common  and  necessary  denominator  in  the  establishment  of  all  other 
more  complex  types  of  learning.  Indeed,  the  acquisition  of  any  specific 
motor  performance  is  accompanied  by  the  elimination  of  a  great  number 
of  originally  present  irrelevant  responses.  Therefore,  when  searching  for 
the  neurophysiological  basis  of  learning,  the  importance  of  understanding 
the  basic  mechanisms  of  habituation  becomes  apparent. 

Granting  that  through  specialization  of  function,  plasticity  as  well  as 
excitability  are  more  developed  in  certain  elements  of  multicellular 
organisms,  there  is  no  doubt  that  the  nervous  system  is  endowed  with  the 
privilege  of  both  properties.  There  are  two  fundamental  questions  about 
the  mechanisms  of  plastic  changes,  and  therefore  of  learning,  (i)  What  is 
the  ultimate  nature  of  plasticity  ?  (2)  Where  are  the  neurones  in  which 
these  properties  are  more  developed;  Our  total  ignorance  on  the  first 
question  cannot  be  overemphasized.  The  reason  for  this,  it  must  be  ad- 
mitted, is  that  the  right  method  for  obtaining  direct  evidence  of  plastic 
changes  has  not  as  yet  been  elaborated  and  applied  to  the  study  of  the 
nervous  system.  More  attention  has  been  devoted  to  the  second  question 
concerning  the  locus  of  learning  in  the  nervous  system.  The  outstanding 
development  of  the  cortical  mantle  in  the  human  brain,  and  its  upper 
anatomical  location  have  impressed  most  scientists  in  the  past  who  have 
granted  the  cerebral  cortex  the  highest  rank  in  the  neural  hierarchy.  Very 
often,  this  contention  has  been  upheld  to  the  point  of  assuming  that  all  the 
learning  processes  take  place  exclusively  at  the  cortical  level.  There  is 
much  evidence,  however,  to  indicate  that  many  types  of  simple  learned 
behavioural  responses  do  not  require  the  cerebral  cortex.  Lower  verte- 
brates with  no  true  cortex  as  well  as  invertebrates  which  do  not  even  have 
a  brain,  are  capable  of  learning.  But  although  it  is  evident  that  habituation 
in  lower  vertebrates  does  not  require  phylogcnetically  new  structures  such 
as  the  cortex,  it  might  be  argued  that  in  mammals  the  greatly  developed 
cortical  mantle  has  taken  over  the  basic  mechanisms  of  learning  originally 
located  in  lower  brain  structures  of  other  animals.  With  the  aim  of 
assessing  the  role  and  capacity  of  different  levels  of  the  mamnialian 
neuraxis  for  the  establishment  of  habituation  the  following  experiments 
were  performed. 

Vestibular  liahitiiatioii  in  decorticated  and  decerebrated  cats.  Following  a 
period  of  controversy,  Griffith  (1920)  established  that  post-rotatory 
nystagmus  in  man  decreases  with  repetition  of  rotation,  and  that  such 
decline  bears  a  striking  resemblance  to  the  traditional  learning  curve. 
The  same  author  observed  the  cumulative  and  long-lasting  effects  of 


R.    HERNANDEZ-PEON    AND    H.    BRUST-CARMONA 


395 


habituation  in  response  to  vestibular  stimuli.  In  one  case,  habituation 
persisted  4  years  after  the  last  experiment  during  which  the  subject  was 
rotated. 

By  means  of  electromyographic  recordings  from  the  extra-ocular 
muscles,  we  have  confirmed  in  intact  cats  that  repeated  rotation  leads  to  a 
decrease  of  the  number  and  amplitude  of  ocular  movements.  As  shown  in 

POST-ROTATORY     NYSTAGMUS 
IN    A    DECORTICATE     CAT 


-('IVjVkAAA/'.MyiA/'^ 


FOLLOWING     ACOUSTIC     STIMULATION 

I  — aMAAaAAAA/IAMAAA/\/ 


5— ajWaAa ^^-^aa^ 


[1000  >JV. 


Fig.  I 


Electromyographic  recordings  of  post-rotatory  nystagnuis  in 
a  decorticate  cat.  Recording  was  initiated  immediately  after 
stopping  rotation  which  lasted  for  1 5  seconds.  The  rotations 
were  repeated  every  minute.  The  uppermost  tracings  represent 
the  initial  control.  The  second  shows  the  reduction  of  nystagmus 
(habituation)  after  five  trials.  A  startling  acoustic  stimulus  was 
applied  and  the  nystagmus  recorded  after  the  ne.xt  rotation 
showed  recovery  (dishabituation)  but  it  was  reduced  again  after 
five  more  trials  (rehabituation). 


Fig.  I,  habituation  of  post-rotatory  nystagmus  was  also  present  in  cats 
with  bilateral  removal  of  the  neocortex,  and  usually  the  number  of 
rotational  series  needed  to  extinguish  completely  ocular  movements  was 
less  in  them  than  in  the  intact  cats. 

Since  these  experiments  demonstrated  that  the  neocortex  is  unnecessary 
for  habituation  to  vestibular  stimuli,  the  role  of  the  diencephalon  and 


396 


BRAIN    MECHANISMS    AND    LEARNING 


rostral  mesencephalon  was  tested  by  transecting  the  brain  stem  at  the  mid- 
collicLilar  level.  In  these  animals,  a  rapid  dechne  of  post-rotational  ocular 
movements  was  also  obtained  (Fig.  2).  Such  results  indicated  that  habitua- 
tion of  post-rotatory  nystagmus  does  not  require  the  thalamic  station  of 
the  vestibular  pathway  either,  and  pointed  to  the  lower  brain  stem  as  the 


Fig.  2 

Elcctroinycigrdphic  recordings  of  post-rotatory  nystagmus.  (A)  Nystag- 
mus of  the  first  experimental  rotation.  (B)  After  habituation  had  been 
established  with  thirty  rotations  an  extensive  electrolytic  lesion  which 
rendered  the  cat  unconscious  was  made  in  the  mesencephalic  tegmen- 
tum. (C)  The  first  rotation  after  the  lesion  elicited  nystagmus  which 
diminished  at  a  faster  rate  than  in  the  aw^ike  intact  animal  with  successive 
trials.  D  represents  the  recording  obtained  after  fifteen  trials  with  the  brain 
stem  lesion. 

probable  source  oi  inhibitory  mechanisms  which  prevent  the  discharge 
of  extra-ocular  motoncurones  after  repeated  vestibular  stimulation. 
Subsequent  experiments  demonstrated  that  lesions  in  the  mesencephalic 
reticular  formation  did  not  prevent  habituation  of  post-rotatory  nystag- 
mus but  that  lesions  placed  in  the  pontine  tcgmcntiun  prevented  the 
habituatory  process. 


R.    HERNANDEZ-PEON    AND    H.    BRUST-CARMONA 


397 


Tactile  habituation  at  the  spinal  cord  in  intact  cats.  The  participation  of  the 
various  levels  of  the  central  nervous  system  (including  the  lowest  one)  in 
habituation  can  be  demonstrated  only  by  studying  spinal  afferent  re- 
sponses which  might  be  modified  by  the  spinal  cord  itself. 

It  IS  known  that  repetition  of  electrical  stimuli  applied  to  the  skni 
results  in  a  significant  decrement  of  the  corresponding  sweat,  respiratory 
and  muscular  responses  (Seward  and  Seward,  1934).  By  local  electro- 
myographic recordings  Hagbarth  and  Kugelbcrg  (1958)  have  recently 
shown  that  the  abdominal   skin   reflex  also   undergoes  habituation  by 


Fig.  3 
Habituation  of  tactile  evoked  potentials  recorded  from  the  lateral  column  of  the  spinal  cord 
in  an  awake  freely  moving  cat.  The  tactile  stmiulus  (single  cutaneous  shock)  was  regularly 
repeated  at  intervals  of  10  seconds. 


repetition  of  the  corresponding  stimuli.  All  these  observations  indicate 
that  like  other  polysynaptic  reflex  responses,  spinal  reflexes  induced  by 
tactile  stimulation  can  be  diminished  in  tlie  intact  organism  by  a  process  of 
habituation. 

Since  previous  studies  have  demonstrated  that  habituation  can  occur  as 
iar  down  as  the  cochlear  nucleus  (Hernandez-Peon,  Jouvet  and  Scherrer, 
1957),  the  retina  (Palestini,  Davidovich  and  Hernandez-Peon,  1959),  the 
olfictory  bulb  (Hernandez-Peon,  Alcocer-Cuaron,  Lavin  and  Santibanez 
1957),  and  the  spinal  tifth  sensory  nucleus  (Hernandez-Peon,  Miranda  and 
Davidovich,  1959),  it  seemed  likely  that  afjereiit  neuronal  habituation  would 
also  occur  at  the  spinal  level.  With  the  purpose  of  testing  this  hypothesis, 


398  BRAIN    MECHANISMS    AND    LEARNING 

bipolar  electrodes  were  permanently  implanted  in  the  lateral  column  of 
the  upper  thoracic  segments  of  the  spinal  cord.  In  order  to  prevent  dis- 
placements of  the  spinal  cord  during  movements  of  the  vertebral  column, 
the  vertebra  to  be  perforated  was  tightly  fixed  to  the  adjacent  vertebrae  by 
means  of  a  vanadium  plate.  The  electrode  was  made  up  of  two  insulated 
stainless  steel  wires,  the  tips  of  which  were  bared  and  i  mm.  apart. 
Single  electrical  square  pulses  of  o.i  msec,  duration  and  of  intensities 
which  produced  only  tactile  sensations  when  applied  to  the  experimenter's 
skin,  were  delivered  to  the  cat's  skin.  The  cutaneous  area  whose  stimula- 
tion evoked  the  potentials  recorded  by  the  spinal  electrode  was  always 
small  and  very  localized. 


Fig.  4 
Habituatit)!!  of  spinal  potentials  (recorded  from  the  lateral  column)  evoked  by 
mild  cutaneous  shocks  regularly  repeated  at  intervals  of  lO  seconds  in  a  freely 
moving  cat.  Whereas  the  late  waves  were  greatly  reduced  or  abolished  with 
twenty-nine  trials,  the  primary  short-latency  component  remained  unaffected. 

Repetition  of  those  tactile  stimuli  led  to  a  progressive  and  oscillating 
decline  of  the  spinal  evoked  potentials  (Fig.  3)  which  eventually  could  be 
completely  extinguished.  As  shown  in  Fig.  4,  in  contrast  with  the  stability 
of  short  latency  components,  the  late  waves  of  the  evoked  responses  were 
more  susceptible  to  habituation.  Usually  the  rate  of  repetition  of  stimuli 
was  one  every  10  seconds,  but  decrement  of  response  was  also  observed 
with  longer  intervals  between  successive  stimuli.  Stimulation  at  faster 
rates  (once  every  i  or  2  seconds)  made  the  evoked  potentials  decline  more 
rapidly  than  at  slower  rates.  As  in  afferent  neuronal  habituation  in  other 
sensory  pathways,  great  individual  variation  was  observed  in  the  number 
of  stimuli  required  to  extinguish  the  spinal  evoked  potentials.  That  number 
ranged  between  dozens  and  several  hundreds. 


R.    HERNANDEZ-PEON   AND    H.    BRUST-CARMONA 


399 


Interruption  of  monotonous  stimulation  usually  led  to  restoration  of 
the  diminished  response  (dishabituation).  But  successive  series  of  stimuli 
elicited  the  same  degree  of  response  decrement  with  a  lesser  number  of 
stimuli  than  was  required  for  the  first  series.  Dishabituation  of  the  tactile 

AWAKE 


S^S  sS^m  [S^&  finsB 

B|^^^H   ^^^^^H  ^^^^^H    ^^^^^H 


ANAESTHETISED 


[5O/UY 


Sm.sec 


Fig.  5 


Releasing  etfccts  of  anaesthesia  upon  spinal  tactile  habituation.  The  upper  two  rows  show  the 
reduction  of  the  evoked  potentials  obtained  after  forty  repetitions  of  the  tactile  stimulus  in  the 
awake  animal.  Then  the  cat  was  anaesthetized  with  pentobarbital.  The  lower  two  rows  show 
the  great  stability  of  the  potentials  evoked  by  the  same  number  of  stimuli. 

spinal  potentials  was  also  observed  by  presenting  an  alerting  acoustic 
stimulus,  or  by  a  transient  increase  of  the  intensity  or  frequency  of  the 
regular  tactile  stimuli.  As  has  been  observed  in  other  sensory  pathways, 
recovery  of  the  extinguished  responses  was  obtained  by  central  anaes- 
thesia. The  spinal  evoked  potentials  were  not  only  restored  to  their 


400  BRAIN    MECHANISMS    AND    LEARNING 

original  magnitude  by  sodium  pentobarbital,  but  remained  remarkably 
stable  in  this  condition  (Fig.  5). 

Tactile  Iwbitiiation  at  the  spinal  cord  in  decorticated  cats.  After  establishing 
that  afferent  neuronal  habituation  also  occurs  at  spinal  sensory  neurones  in 
intact  cats,  the  possible  participation  of  the  cerebral  cortex  in  this  phen- 
omenon was  explored  in  cats  whose  neocortex  had  been  totally  removed 
2  or  3  months  before.  In  all  of  them,  the  spinal  evoked  potentials  also 
dechned,  sometimes  at  a  faster  rate,  with  repetition  of  the  tactile 
stimuli. 

Tactile  habituation  at  the  spinal  cord  in  decerebrated  cats.  It  being  evident 
that  the  neocortex  is  not  necessary  for  the  establishment  of  afferent  neu- 
ronal habituation  at  the  spinal  cord,  it  was  deemed  convenient  to  test 
whether  structures  in  the  forebrain,  temporal  lobe  or  diencephalon  might 
play  a  role  in  the  demonstrated  habituatory  spinal  sensory  suppression. 
With  this  aim  in  view,  the  brain  stem  was  severed  at  the  mid-collicular 
level  leaving  intact  all  the  mesencephalic  tegmentum  in  the  remaining 
brain  stem.  In  these  mesencephahc  animals,  habituation  of  tactile  evoked 
responses  at  the  spinal  cord  was  readily  observed  (Fig.  6),  and  not 
infrequently  the  number  of  stimuli  required  for  extinguishing  those 
responses  was  again  less  than  in  intact  animals.  Dishabituation  was  also 
observed  following  a  transient  increase  of  the  stimulus  intensity. 

From  the  results  just  presented  it  is  obvious  that  tactile  habituation  at  the 
spinal  cord  can  take  place  in  cats  with  only  the  sub-diencephahc  portion 
of  their  central  nervous  system.  If,  according  to  the  view  proposed  by  one 
of  us  (Hernandez-Peon,  1955,  1957,  1959),  afferent  neuronal  habituation 
at  second-order  sensory  neurones  results  from  centrifugal  inhibitory 
influences  proceeding  from  the  reticular  system  of  the  lower  brain  stem, 
the  spinal  responses  extinguished  by  habituation  in  the  mesencephalic 
preparation  should  be  enhanced  by  interrupting  the  postulated  descending 
inhibitory  path  to  the  spinal  sensory  neurones.  This  hypothesis  was  tested 
by  performing  a  high  transection  of  the  spinal  cord  in  those  decerebrated 
cats  which  had  already  been  habituated  to  repeated  tactile  stimuli. 

Tactile  habituation  at  the  spinal  cord  in  spinal  cats.  Shortly  after  severance 
of  the  spinal  cord  at  C2,  the  tactile  evoked  potentials  were  remarkably 
enhanced.  Very  often,  as  illustrated  in  Fig.  6,  not  only  did  the  evoked 
potentials  recover  the  magnitude  they  showed  before  habituation,  but  the 
enhancement  surpassed  the  original  size.  These  results  clearly  indicate  that 
a  descending  influence  which  acts  upon  spinal  sensory  neurones  originates 
in  the  lower  brain  stem  itself.  Another  conclusion  to  be  drawn  from  the 
same  results  is  that  the  electrophysiological  correlates  of  afferent  neuronal 


R.    HERNANDEZ-PEON    AND    H.    BRUST-CARMONA 


401 


habituation  at  the  spinal   cord  in   mcscnccphahc  cats  depends  on  that 
descending  influence. 

From  the  prececiing  experiments  it  is  evident  that  brain  stem  structures 
participate  in  spinal  habituation.  However,  those  experiments  do  not 
preclude  the  possibility  that  the  isolated  spinal  cord  might  also  be  capable 
of  performing  that  function.  Whether  the  spinal  cord  is  able  to  learn  is  a 


DECEREBRATED 


SPINAL 


0 


15 


20 


7\A^ 


vvr^sA 


5  msec. 


Fig.  6 
Tactile  cviiked  potenti.ils  recorded  frcnn  the  latcr.d  column  of 
the  spinal  cord.  The  left  column  shows  the  decrement  observed 
in  a  decerebrate  cat  during  a  series  of  twenty  cutaneous  shocks 
delivered  at  a  rate  of  i/sec.  The  responses  of  the  right  column 
were  obtained  in  the  same  animal  immediately  after  transect- 
ing the  spinal  cord  above  the  recording  site. 


question  whose  answer  is  of  considerable  importance  to  the  conceptualiza- 
tion of  integrative  levels  of  the  C.N.S.  in  learning  processes. 

Our  spinal  preparation  pcrnntted  us  to  investigate  this  question.  It  was 
found  that  repetition  of  tactile  stimuli  in  spinal  cats  also  led  to  a  progressive 
decline  of  the  corresponding  evoked  potentials  (Fig.  6).  And,  as  happens 
in  intact  animals,  a  transient  increase  in  the  intensity  of  the  stimulus  caused 
the  diminished  responses  to  have  a  greater  amplitude  after  the  disrupting 


402  BRAIN    MECHANISMS    AND    LEARNING 

Stimulus.  Again,  the  effects  of  repetition  of  the  tactile  stimuli  in  the  spinal 
cats  were  long  lasting,  and  appeared  to  be  cumulative. 

These  experiments  indicate  that  plastic  inhibition  can  develop  in  the 
isolated  spinal  cord  and  confirm  the  results  obtained  by  Prosser  and 
Hunter  (1936)  in  the  rat.  By  electromyographic  and  mechanical  record- 
ings they  observed  in  the  spinal  rat  fading  of  spinal  flexor  reflexes  with 
repetition  of  the  corresponding  stimuli.  Because  of  the  features  which 
prevent  the  identification  of  this  diminution  of  responsiveness  with  fatigue 
and  sensory  adaptation,  Prosser  and  Hunter,  rightly  interpreted  the 
phenomenon  as  habituation  and  assumed  that  it  involved  spinal  inter- 
nuncial  neurones  rather  than  the  first  sensory  elements  or  the  final  moto- 
neurones. 

From  the  foregoing  considerations  it  is  evident  that  in  aeidition  to  the 
supraspinal  influences  acting  upon  sensory  impulses  there  is  an  intraspinal 
mechanism  which  regulates  the  excitability  of  lower  order  sensory  neu- 
rones, and  consequently  the  entrance  of  afferent  impulses  into  the  spinal 
cord  itself  Such  a  mechanism  implies  a  local  feed-back  circuit  in  which 
spinal  interncurones  are  likely  to  be  involved.  The  interneurones  are 
activated  by  collaterals  from  spino-thalamic  fibres,  and  in  turn  they  would 
inhibit  the  corresponding  sensory  neurones.  This  hypothetical  sensory 
circuit  would  be  comparable  to  the  ventral  horn  circuit  formed  by  the 
recurrent  collaterals  of  motor  axonS  and  the  Rcnshaw  cells  which  have 
been  found  to  inhibit  the  motoneurones  (Eccles,  1957). 

CONDITIONING 

Conditioning  results  in  the  acquisition  of  a  response  (conditioned 
response)  to  a  stimulus  (conditional  stimulus)  which  previously  was  not 
effective  in  eliciting  that  response.  Conditioning  may  be  considered  to 
represent  one  of  the  simplest  types  of  positive  learning,  just  as  habituation 
represents  the  simplest  type  of  negative  learning.  From  the  neurophysio- 
logical  point  of  view,  conditioning  must  necessarily  involve  plastic 
associatii'c  pliciioiiwiia  which  must  take  place  in  some  central  region  of 
convergence  of  sensory  impulses.  Pavlov  (Pavlov,  1928)  used  the  term 
tonporary  couucctioiis  to  designate  the  process  of  neural  association,  but  we 
prefer  to  call  it  simply  plastic  association,  since  its  manifestations  can  be  so 
permanent  as  to  endure  for  the  life  of  the  individual. 

In  studying  conditioning  it  must  be  borne  in  mind  that  the  development 
of  the  conditioned  behaviour  involves  the  emergence  of  new  responses  to 
the  conditional  stimulus  {plastic  association),  as  well  as  the  disappearance  of 


R.    HERNANDEZ-PEON    AND    H.    BRUST-CARMONA  403 

inborn  and  acquired  responses  {plastic  iiihibirioit)  (Hernandez-Peon,  1957). 
Therefore,  the  total  conditioned  behaviour  varies  throughout  the  different 
stages  of  the  experimental  procedure.  It  should  also  be  emphasized  that 
the  conditioned  reaction  is  not  a  simple  replica  of  the  unconditioned 
response,  but  usually  involves  more  complex  behavioural  changes 
revealed  by  the  expectant  attitude  o{  the  animal. 

According  to  the  Pavlovian  traditional  concept,  all  processes  of  plastic 
association  and  plastic  inhibition  occur  at  the  cerebral  cortex,  in  the 
absence  of  which  conditioning  is  assumed  to  be  impossible.  There  is 
plenty  of  evidence,  however,  to  indicate  that  acquisition  and  retention  of 
conditioned  responses  in  dogs  and  cats  do  not  require  the  neocortex 
(Bromiley,  1948;  Culler  and  Mettler,  1934;  Girdcn,  Mcttlcr,  Finch  and 
Culler,  1936;  Ten  Catc,  1938;  Wing,  1946;  Wing,  1947;  Wing  and 
Smith,  1942;  Zeleny  and  Kadykov,  1938). 

Although  conditioning  in  the  decorticate  animals  provided  clear 
evidence  concerning  the  essential  role  of  subcortical  structures  in  plastic 
associative  phenomena,  the  relative  importance  of  each  ot  them  for  the 
establishment  of  conditioning  remained  to  be  shown.  By  making  sub- 
cortical lesions  in  cats,  Hernandez-Peon,  ct  al.  (Hernandez-Peon,  Brust- 
Carmona,  Eckhaus,  Lopez-Mcndoza  and  Alcocer-Cuaron,  1958)  found 
that  a  nociceptive  salivary  conditioned  response  was  eliminated  only  by 
lesions  in  the  mesencephalic  reticular  formation.  These  lesions  did  not 
interfere  with  wakefulness,  but  produced  striking  behavioural  changes  to 
be  described  later  on. 

In  so  far  as  the  mesencephalic  tegmentum  is  a  region  of  rich  afferent 
convergence,  and  since  the  above-mentioned  results  pointed  out  its 
importance  in  basic  associative  phenomena,  the  following  questions  were 
raised:  does  a  mesencephalic  lesion  equally  impair  conditioned  responses 
to  stimuli  of  different  modalities?  Does  it  affect  to  the  same  extent  both 
classical  alimentary  and  defensive  conditioned  responses?  In  an  attempt  to 
answer  those  questions  the  following  experiments  were  performed  using 
cats  in  which  two  different  responses  were  conditioned:  (i)  alimentary 
responses  to  visual  and  olfactory  stimuli  and  (2)  defensive  flexor  responses 
to  an  acoustic  stimulus. 

Cividitioued  alimeutary  responses  in  intact  cats.  The  unconditional  stimulus 
consisted  of  a  bit  of  fish.  This  was  brought  near  the  cat  by  means  of  a 
clamp  attached  to  a  thread  which  was  introduced  through  a  tube  in  the 
ceiling  of  the  cage.  The  light  of  a  lamp  placed  at  the  ceiling  and  the  sight 
and  smell  of  the  fish  were  the  conditional  stimuli.  Salivation  was  measured 
by  counting  the  drops  of  saHva  flowing  through  a  poly-ethylene  tube 

DD 


404 


BRAIN    MECHANISMS    AND    LEARNING 


permanently  implanted  in  the  parotid  duct.  The  light  was  turned  on  4 
seconds  before  presenting  the  food  to  the  animal.  A  typical  conditioned 
pattern  of  behaviour  was  established  after  ten  to  fifteen  trials  (Fig.  7).  As 
soon  as  the  light  was  turned  on,  the  cat  showed  an  orienting  reaction 
directed  towards  the  opening  through  which  the  food  was  delivered.  Then 
the  cat  stared  and  approached  the  food-clamp  upon  its  presentation.  Very 
often,  the  cat  tried  to  catch  the  food  by  rising  on  its  hindlegs.  During  the 
presentation  of  the  conditional  visual  stimuli,  one  or  two  drops  of  saliva 
flowed  thrt)ugh  the  parotid  catheter. 

CoiuHtioiicd  flexor  rc<:poiisc  in  intact  cats.  Aiter  the  establishment  of  ali- 
mentary conditioned  responses,  the  cats  were  conditioned  to  acoustic  and 


CONDITIONING  VISUAL  STIMULI 

LIGHT       and        FOOD-HOLDER 


Fk;.  7 
This  figure  illustrates  the  sequential  behavioural  response  of  a  cat  conditioned  with  visual 
stimuli  (light  and  food-holder)  and  food.  When  the  light  was  turned  on,  the  cat  oriented  its 
head  towards  the  lamp  and  when  seeing  the  food-holder  it  rose  on  its  feet  and  tried  to  catch 
the  food. 


nociceptive  stimuli  according  to  the  following  procedure:  the  animal  was 
immobilized  in  a  harness  to  which  its  legs  were  fastened.  A  buzzer  was 
rung  fc~>r  5  seconds  and  then  a  shock  was  delivered  from  a  Grass  Stimulator 
through  electrodes  attached  to  the  left  foreleg  of  the  animal.  The  shock 
evoked  a  definite  flexion  of  the  limb  and  generalized  struggling  move- 
ments. The  contraction  of  the  flexor  muscles  of  the  left  foreleg  was 
recorded  with  bipolar  intramuscular  electrodes  and  an  electromyograph. 
After  six  to  ten  buzzer-shock  associations,  the  buzzer  alone  elicited  the 
flexion  of  the  limb  and  the  struggling  reaction. 

Cofiditio}icd  alimentary  responses  in  decorticate  cats.  Salivation  and  the 
expectant  attitude  were  easily  conditioned  to  the  light  and  to  the  fish 
odour  in  cats  from  which  the  neocortex  had  been  bilaterally  removed  2  to 


R.    HERNANDEZ-PEON    AND    II.    BRUST-CARMONA  4O5 

6  months  before  (Fig.  8).  But  in  contrast  with  the  intact  annnals,  these 
cats  did  not  seem  to  recognize  the  fish-clanip  nor  could  they  reach  the 
food  easily. 

Conditioned  flexor  response   in   decorticate   cats.   In   decorticate   cats   the 
flexor   response   was   readily   conditioned   to   the   buzzer.    Usually   the 


ALiMENTARY 

REFLEX  FLEXOR     REFLEX 


BEFORE 
CONDITIONING 


CONDITIONED 


AFTER  LESION 
IN       R.F. 


mM 


BUZZfeR  , , 

ELECTRIC    SHOCK 


Fig.  8 
Conditioned  alimentary  and  flexor  responses  in  a  cat  with  the  neocortex  bilaterally  removed. 
Then  a  lesion  was  made  in  the  mesencephalic  reticular  formation  and  both  kinds  of  responses 
disappeared. 

number  of  associations  required  tor  establishing  the  conditioned  response 
was  not  greater  than  in  the  intact  cats. 

Effects  of  mesencephalic  lesions  on  the  conditioned  alimentary  and  flexor 
responses.  Once  the  conditioned  alimentary  and  flexor  responses  had  been 
established,  electrolytic  lesions  were  made  in  the  posterior  part  of  the 
mesencephalic  reticular  formation  (plane  A-2  of  the  stereotaxic  maps  of 
the  cat's  brain).  Usually  the  lesion  did  not  yield  unconsciousness,  and  the 


406  BRAIN    MECHANISMS    AND    LEARNING 

animals  awoke  when  the  anaesthetic  wore  oft,  although  two  animals 
remained  iniconscious  for  2  days. 

The  cats  were  tested  i  to  3  days  after  the  operation  and  when  they  were 
wide  awake.  All  the  alimentary  responses  conditioned  to  visual  stimuli 
were  absent.  The  orienting  reaction  and  salivation  were  no  longer  elicited 
by  turning  the  light  on,  nor  by  placing  the  fish-clamp  with  food  within 


ALIMENTARY 
REFLEX 


FLEXOR    REFLEX 


BEFORE 

CONDITIONING 


CONDITIONED 


AFTER 
LESION 
IN    R.F. 


mm— 


w— .-ySr'UA^i^llgll^ 


BUZZER 


ELECTfaC  SHOCK 


Fig.  9 
This   figure   illustrates   the   disappearance   of  alimentary   and   flexor   conditioned 
responses  consecutive  to  a  lesion  in  the  mesencephalic  tegmentum.  Notice  that  the 
brain  stem  injured  cat  does  not  seem  to  perceive  the  food  placed  within  its  visual 
field. 


the  visual  field  of  the  animal  at  short  distances  from  it,  as  illustrated  in 
Fig.  9.  Only  when  the  food  was  put  very  near  its  nose  did  the  cat  begin  to 
snift'  and  salivate,  but  it  was  unable  to  detect  the  location  of  the  food. 
However,  when  the  food  was  placed  near  its  mouth,  the  cat  eagerly  ate  it 
and  salivated  abundantly.  Also  in  these  cats  the  buzzer  did  not  elicit  the 
flexion  of  the  limb  nor  the  generalized  struggle  reaction  (Fig.  9).  And 


R.    HERNANDEZ-PEON    AND    H.    BRUST-CARMONA  407 

there  were  no  indications  that  the  conditioned  motor  response  could  be  re- 
estabhshed  by  the  buzzer-shock  associations. 

Moreover,  the  general  behaviour  of  all  these  cats  with  such  mesencepha- 
lic lesion  was  strikingly  changed.  The  most  notorious  teaturc  was  impair- 
ment of  their  vision  and  pain  reactions.  When  walking,  they  bumped  into 
objects  and  the  walls  of  the  laboratory,  i.e.  they  behaved  as  though  they 
were  completely  blind  They  were  also  unresponsive  to  painful  stimuli 
which,  both  in  the  intact  and  in  the  decorticate  cats,  evoked  crawling  and 
aggressive  behaviour. 

From  the  foregoing  results  it  is  evident  that  whereas  extensive  cortical 
removals  did  not  prevent  conditioning,  a  small  lesion  in  the  mesen- 
cephalic reticular  formation  eliminated  visual  and  acoustic  conditioned 
respc^nses.  It  must  be  emphasized  tliat  the  mesencephalic  lesion  impaired 
various  sensory  discriminations  to  different  degrees.  While  vision  was 
most  impaired,  olfaction  seemed  to  be  the  modality  least  affected.  It  is 
difficult  to  offer  a  satisfactory  explanation  for  the  surprising  blindness 
producec4  by  a  lesion  placed  tar  bcliind  the  specific  visual  pathway.  But  the 
apparent  difficulty  may  be  disposed  of,  if  one  remembers  [a)  that  the 
mesencephalic  reticular  formation  receives  photic  impulses  from  the 
retina  (French,  Vcrzeano  and  Magoun,  1953)  as  well  as  from  cortical 
visual  areas  (French,  Hcrnandcz-Pcon  and  Livingston,  1955),  and  (/>)  that 
electrical  stimulation  of  the  same  area  modifies  the  excitability  of  the 
retina  (Granit,  1955;  Hernandez-Peon,  Scherrer  and  Velasco,  1956),  the 
lateral  geniculate  body  (Hernandez-Peon,  Scherrer  and  Velasco,  1956), 
and  the  visual  cortex  (Bremer  and  Stoupel,  1959).  The  impairment  of 
vision  might  be  the  result  of  an  interference  with  the  centrifugal  mechan- 
isms which  regulate  transmission  along  the  specific  visual  pathway,  and/or 
with  the  final  integration  of  the  photic  impulses  which  result  in  conscious 
vision.  This  explanation  falls  in  line  with  the  view  proposed  by  Penfield 
(Penfield,  1958,  1959)  about  the  hij^lu'sr  level  of  sensory  iiite^^ratioii.  Accord- 
ing to  this  author,  the  final  integration  of  sensory  impulses  is  not  achieved 
at  the  cortical  level  but  at  the  'centrencephalon'  where  they  arc  finally 
conveyed.  The  anatomical  substratum  of  the  'centrencephalic  system'  is 
the  higher  brain  stem  which  includes  the  diencephalon,  the  mesencephalon 
and  probably  the  metencephalon.  Our  results  indicate  the  important  role 
played  by  the  brain  stem  in  the  integration  of  sensory  impulses  which 
accompanies  learning  processes,  and  thus  lend  experimental  support  to 
Penfield's  hypothesis. 

The  unavoidable  conclusion  that  plastic  association  during  conditioning 
takes  place  at  subcortical  levels  docs  not  preclude  cortical  participation  in 


408  BRAIN    MECHANISMS    AND    LEARNING 

certain  aspects  of  conditioning  and  learning  in  general.  The  integrity  of 
the  cortex  for  complex  discriminations  is  as  important  as  the  integrity  of 
subcortical  structures  for  some  of  the  simplest  types  of  learning  (habituation 
and  earliest  manifestations  of  conditioning).  Therefore,  all  the  levels  of  the 
central  nervous  system  appear  to  be  endowed  with  plastic  properties  which 
cannot  be  ascribed  exclusively  to  any  particular  locus  of  the  brain. 

GROUP   DISCUSSION 

Doty.  I  completely  agree  with  Dr  Hcrnandez-Pcon  with  regard  to  the  excep- 
tional importance  of  subcortical  mechanisms  in  the  establishment  and  performance 
of  conditioned  responses. 

We  can  offer  some  additional  experimental  support  (Doty,  Beck  and  Kooi, 
1959)  for  his  position.  Fig.  i  shows  extensive  brain  stem  lesions  totalling  100 


A- 8.5 


Fig. 


Lesions  in  the  central  dicnccphalon,  represented  on  plates  from  the  stereotaxic  atlas  of  Jasper 
and  Ajmone-Marsan  (1954).  See  text.  (From  Doty,  R.  W.,  Beck,  E.  C.  and  Kooi,  K.  A., 
1959.  Effect  of  brain  stem  lesions  on  conditioned  responses  of  cats.  Experitneiital  Neurology, 
I,  360). 

mm.^  anterior,  however,  to  the  mesencephalon.  This  animal  gradually  recovered 
from  a  cataleptic  stupor  during  the  first  two  post-operative  weeks,  and  Fig.  2 
shows  that  the  EEG  ultimately  returned  to  normal  levels.  The  animal  walked  after 
the  third  week  and  would  blink  to  a  visually  presented  threat.  No  other  conditioned 
reactions  could  be  observed  post-operatively.  Prior  to  surgery  this  cat  made 
discrete,  conditioned  flexions  of  a  leg  80  per  cent  of  the  time  to  a  tonal  CS  and 


R.    HERNANDEZ-PEON    AND    H.    BRUST-CARMONA 


409 


conditioned  respiratory  responses  95  per  cent  of  the  time.  During  1325  post- 
operative retraining  trials  in  twenty-six  sessions  over  a  period  of  37  days  there  was 
not  even  a  suggestion  of  a  conditioned  response  (e.g.  Fig.  3). 

On  the  other  hand,  in  another  animal  an  enormous  lesion  totalHng  113  mm.^ 
destroying  most  of  the  central  mesencephalon  (Fig.  4)  and  producing  a  profound 
catalepsy  for  the  21  days  of  survival  did  not  preclude  the  appearance  of  conditioned 
reflexes.  One  could  not  claim  the  level  of  conditioned  responsiveness  was  high  in 
this  cat,  but  neither  had  it  been  very  good  pre-operatively  (see  Doty,  Beck  and 


_RPC_ 


CAT  15,    I6AUG56 


CSI — ■ — — 1 


'^<''\v;^~,-.'vv--^'^'-  j:-^^*^ 


EKG 


t'Sl .-.     .  '  I  Sec   IjjV. 


Fig.  2 
EEG  taken  on  the  thirty-sixth  post-operative  day,  of  cat  having  lesions  shown  in  Fig.  D-6. 
(ij)  lack  of  response  to  presentation  of  CS  alone  after  twenty-six  CS-US  pairings  on  this  day 
which  brought  the  total  to  1253  pairings  since  surgery.  (/>)  the  forty-eighth  pairing  of  the 
same  day  showing  transition  to  low  voltage,  fast  activity  in  marginal  gyrus  to  the  US  but  not 
the  CS.  (From  Doty,  R.  W.,  Beck,  E.  C.  and  Kooi,  K.  A.,  1959.  Effect  of  brain  stem  lesions 
on  conditioned  responses  of  cats.  E.xpcriiiieiitiil  NciiroUii;}',  I,  360.) 

Kooi,  1959)  and  it  seems  probable  that  a  prolongation  of  life  would  have  seen  a 
more  impressive  recovery.  The  best  performance  was  six  flexion  CRs  m  a  session 
of  forty-five  trials  and  respiratory  CRs  were  then  present  25  per  cent  of  the  time. 
Equally  interesting,  in  view  of  the  importance  of  the  mesencephalic  reticular 
system  is  electrocortical  'arousal'  reactions,  in  the  return  of  low  voltage,  fast 
patterns  for  long  periods  in  the  EEG  of  this  animal  and  the  presence  of  an  'arousal' 
reaction  accompanying  conditioned  responses  (Fig.  D-io). 

Thus,  we  cannot  support  the  idea  that  the  mesencephalic  reticular  formation  is 
of  any  extraordinary  importance  in  this  type  of  conditioning.  I  am  certain  that 
differences  in  period  of  survival  and  other  details  can  account  tor  this  apparent 
contradiction  between  the  experiments  of  Dr  Hernandez-Peon  and  ourselves. 


410 


BRAIN    MECHANISMS    AND    LEARNING 


Hernandez-Peon.  Were  these  animals  unconscious  after  the  lesion  and  how 
long  did  they  remain  unconscious? 

Doty.  They  were  certainly  unconscious  tor  many  days  following  surgcr)'. 

Hernandez-Peon.  The  point  is  that  the  lesions  we  made  did  not  impair  con- 
sciousness. The  animals  awoke  and  were  able  to  walk  after  the  anaesthesia  wore  off. 
In  cats  with  larger  lesions  producing  unconsciousness,  the  long  period  of  recovery 
probably  involves  several  unknown  processes  which  may  mask  completely  the 
immediate  effects  of  the  lesion,  hi  fact  Dr  Brust-Carmona  reported  in  January  of 
this  year  that  in  cats  with  small  reticular  lesions  leg  withdrawal  can  be  conditioned 


CAT  14,  13  JUNE  56 


CSh 


a. 

I  Sec.   1 1 0.0 


CAT  14,  17  JULY56 


LEM.  i/i.  Ik  (  • 


_i______;_-_j X- 


FiG.  3 
EEG  records  from  cat  having  lesions  shown  in  Fig.  D-8.  (a)  pre-operative  record  of  condi- 
tioned respiratory  response  and  electrocortical  arousal  reaction  to  the  CS.  (/>)  first  CS  presented 
on  the  sixth  post-operative  day  produces  an  arousal  reaction  and  a  respiratory  CR.  Note  that 
record  /)  is  at  double  the  gain  of  j;  hence  the  post-operative  electrical  activity  is  remarkably 
near  normal.  (From  Doty,  R.  W.,  Beck,  E.  C.  and  Kooi,  K.  A.,  1959.  Effect  of  brain-stem 
lesions  on  conditioned  responses  of  cats.  Experimeutal  Neurology,  i,  360.) 


I  month  after  the  lesion  was  made,  but  that  lesions  in  the  subthalamic  region 
(smaller  than  Doty's)  definitely  impaired  this  type  of  conditioning. 

Palestini.  It  is  interesting  that  different  afferent  systems  may  habituate  because 
of  participation  of  different  strtictures  placed  at  different  levels  of  the  reticular 
formation.  I  want  to  mention  yet  another  possibility,  based  on  Moruzzi's  observa- 
tions. Since,  the  'cerveau  isole'  also  shows  habituation  we  may  infer  that  structures 
placed  rostrally  to  the  mesencephalon  would  also  be  capable  of  inducing  this 
phenomenon. 

Buser.  I  already  mentioned  the  observations  made  on  the  cat  with  an  extensive 
lesion  on  the  medial  thalamus.  Training  to  the  routine  motor  alimentary  condi- 
tioning (pressing  lever  for  food  at  a  given  signal)  was  carried  on  post-opcrativcly 


R.    HERNANDEZ-PEON    AND    H.    BRUST-CARMONA 


411 


for  5  months  without  the  least  success:  the  animal  revealed  itselt  completely 
unable  to  perform  the  required  task.  In  contrast,  simpler  associations  were  obtained 
very  quickly  (with  an  almost  normal  score) :  generalized  movements  then  orienta- 
tion towards  the  food  tray  at  the  signal. 

This  might  indicate,  if  still  necessary,  that,  depending  upon  the  complexity  of 
the  training  performance,  the  nervous  structures  to  miplicate  as  a  site  for  the  link 
mav  be  different.  It  is  perhaps  significant  that,  in  our  observation,  the  mesence- 
plialic  reticular  formation  was  apparently  intact  and  that  at  the  same  time  the 
ability  for  elementary  conditioning,  but  not  for  a  complex  one,  was  preserved. 


CAT  14 


Fig.  4 
Summary  of  lesions  destroying  the  mesencephalic  reticular  system.  (From  Doty,  R.  W., 
Beck,  E.  C.  and  Kooi,  K.  A.,  1959.  Effect  of  brain  stem  lesions  on  conditioned  responses  of 
cats.  Experiineiitiil  Neurology,  I,  360.) 

Segundo.  Concerning  lesion  effects  on  conditioned  responses,  I  would  like  to 
add  observations  made  by  our  group.  Small  lesions  in  mesencephalic  reticular 
formation  or  amygdaloid  complex  or  large  lesions  in  lateral  nuclear  complex  of 
thalamus  (involving  lateral  and  medial  geniculate  and  V.P.)  did  not  produce 
marked  perturbations  in  learned  or  learning  abilities.  A  lesion  that  destroyed  the 
centre-median  provoked  less  of  a  response  learned  previously.  A  comparable  loss 
was  encountered  after  a  large  lesion  of  the  head  of  the  caudate  nucleus  in  one  cat 
but,  contrastingly,  another  cat  with  a  similar  lesion  was  not  perturbed:  hence  the 
caudate  nucleus  gave  ambiguous  results  (as  it  did  in  the  self-stimulating  studies 
mentioned  by  Dr  Olds)  (Roig,  Segundo,  Sommer-Smith  and  Galeano,  I959; 
Segundo,  Roig  and  Sommer-Smith,  1959). 

When  lesion  effects  upon  conditioning  are  discussed,  the  learned  effect  should 
be  identified  since  it  is  conceivable  that  one  same  lesion  mav  affect  different 


412  BRAIN    MECHANISMS    AND    LEARNING 

responses  in  different  manners.  Moreover,  we  must  admit  the  possibility  that  an 
animal  confronted  with  a  certain  training  routine  mav  have  a  'choice'  as  to  the 
neural  structures  it  will  utilize  in  that  particular  learning  process:  this  could  be  one 
explanation  tor  the  apparently  confficting  results  of  lesions. 

Hernandez-Peon.  I  think  that  different  parts  of  the  brain  do  have  different 
roles  in  different  types  of  learning  and  even  for  a  given  type  of  learning  at  different 
stages  of  learning.  We  must  always  point  out  the  type  of  learning  and  the  stage  of 
learning  and  whether  we  are  dealing  with  positive  or  negative  learning,  hi  other 
words,  wc  have  to  take  into  consideration  the  effects  produced  by  plastic  associa- 
tion and  by  plastic  inhibition,  because  certainly  different  parts  of  the  brain  have 
more  importance  for  one  or  another  type  of  learning. 

RosvoLD.  I  should  like  to  emphasize  the  point  already  made.  If  comparisons  are 
going  to  be  made,  the  methods  used  must  be  the  same.  We  found  that  very  slight 
changes  in  the  testing  methods  can  elicit  entirely  different  behaviour. 

I  should  like  also  to  say  that  in  monkeys,  at  least,  the  effect  of  lesions  in  medialis 
dorsalis  are  not  those  one  would  expect  from  its  connections  in  the  frontal  lobe. 
For  example,  one  does  not  find  any  of  the  effects  that  one  fmds  from  frontal  lobe 
lesions.  On  the  contrary,  one  finds  that  lesions  in  the  head  of  the  caudate  nucleus 
do  give  the  effects  found  after  frontal  lobe  lesions. 

Thorpe.  I  also  would  like  to  emphasize  the  importance  ot  standardizing  the 
circumstances  in  which  these  responses  are  obtained.  Having  in  mind  the  biological 
importance  of  habituation,  I  like  (see  Thorpe,  1956)  to  distinguish  it  from  various 
other  types  of  response  waning  known  to  the  ethologist  and  to  regard  it,  from 
the  biological  point  of  view,  as  Joiio-tcrin  stiiiiiiliis-spccific  waiiiiio.  It  thus  becomes 
very  important  to  know  the  relation  ot  the  degree  of  habituation  or  dishabituation 
to  the  intensity  of  the  stimulus.  I  was,  ther'efore,  particularly  interested  to  know  of 
Dr  Segundo's  results  for  it  seems  that  information  about  the  habituation  effect  of 
different  tones  may  be  a  very  important  piece  of  evidence  in  understanding  what  is 
really  going  on.  If  in  the  case  of  spinal  habituation  wc  are  uncovering  something 
of  the  fundamental  physiological  mechanism  of  the  habituation  process,  we  might 
expect  a  very  considerable  difference  in  the  detail  of  correlation  between  the 
intensity  and  the  duration  ot  the  stimulus  and  of  the  response  as  between  intact 
and  decorticate  animals.  It  is  important  that  these  should  be  standardized.  It  also 
bears  on  the  similarity  between  habituation  and  internal  inhibition.  Pavlov,  I 
think,  at  one  time  thought  of  internal  inhibition  as  in  some  respect  connected 
with  the  absence  of  the  unconditioned  stimulus.  At  other  times  he  thought  of  it 
more  as  the  result  of  some  kind  of  competition.  The  first  view  seems  much  more 
natural  to  the  biologist  and  that  is  why  the  ethologist  thinks  ot  habituation  {loini- 
tcnii  stiiiiiihis-spccific  u'aiiiii(<)  as  characteristic  of  the  absence  of  the  consummatory 
act  or  consummatory  stimulus  situation.  If  this  innately  determined  system  is 
present  we  should  expect  the  habituation  to  be  reduced  or  absent.  On  the  other 
hand,  if  some  similar,  but  non-identical  stimulus  is  present  we  should  expect  the 
habituation  to  be  affected  in  corresponding  degree.  So  again  it  becomes  highly 
important,  in  experimental  studies  on  habituation,  to  have  specific  information 
about  the  details  of  the  stimulus  employed  and  the  relation  between  intensity  of 
the  stimulus  and  the  intensity  and  duration  of  the  effect. 


FUNCTIONS  OF  BULBO-PONTINE  RETICULAR 

FORMATION  AND  PLASTIC  PHENOMENA 

IN  THE  CENTRAL   NERVOUS   SYSTEM 

M.  Palestini  and  W.  Lifschitz 

In  investigations  of  the  pliysiology  of  the  Reticular  Formation,  the 
concept  that  this  structure  exerts  a  diffuse  ascending  and  activatuig  in- 
fluence has  predominated  until  a  short  time  ago.  Moreover,  many  experi- 
mental results  are  interpreted  as  deriving  from  the  action  ot  the  reticular 
formation  of  the  brani  stem  considered  as  a  functional  whole. 

In  this  paper,  our  nitention  has  been  precisely  to  insist  that  the  reticular 
formation  of  the  brain  stem  has  ascending  influences  which  evoke  con- 
tradictory phenomena.  Thus,  we  shall  see  that  this  structure  has  not  only 
its  well-known  desynchronizing  action  but  also  a  synchronizing  action, 
and  that  it  can  both  exert  an  influence  by  facilitating  the  cortical  potentials, 
evoked  by  sensory  stmiuli  and  by  inhibiting  them.  We  shall  discuss  these 
last  functions  in  relation  to  their  possible  independence  of  the  EEG 
pattern.  Lastly,  we  shall  reler  to  its  participation  in  sleep  and  wakefulness, 
in  habituation  and  attention. 

Part  of  this  report  (paragraphs  A,  B,  C)  is  concerned  with  experiments 
made  in  the  midpontine  prctrigeminal  preparation  (MPP)  in  the  lines 
followed  by  Moruzzi's  school.  The  following  paragraph  contains  recent 
results  obtained  in  our  laboratory  using  the  same  preparation. 

On  this  occasion,  we  shall  omit  the  technical  data,  and  summarize  the 
hndings  of  the  studies  which  formed  the  basis  for  this  paper.  The  reader 
will  tind  further  details  in  the  articles  that  have  already  been  published. 

A.    THE    MIDPONTINE    PRETRIGEMINAL    PREPARATION    AND    THE    SLEEP-WAKE- 
FULNESS    RHYTHM 

EEG  recordings  in  cats  with  electrolytic  transsections  at  midpontine 
levels  (Fig.  i)  show  a  low^  voltage  and  high  frequency  activity  that  has 
generally  been  related  to  the  waking  state  (Batini,  Moruzzi,  Palestini, 
Rossi  and  Zanchetti,  1958,  1959). 

This  desynchronized  EEG  pattern  of  the  MPP  predominates,  and  the 
periods  of  synchronized  cortical  activity  observed  are  infrequent  and 
short  lived. 

413 


414 


BRAIN    MECHANISMS    AND    LEARNING 


dors 


^'"Hirr — n '^•irr*')  ■■  •!■--■  ■■iniiiri  i.  n  ixmir"'**" — mnr^nl  r-n -rr-n  iiiiii.initn>)'*i 


1    sec 


100pV      j 


venrr 


Fig.  I 
EEG  patterns  following  midpontinc  and  rostropontinc  transscctiims 
Drawings  of  horizontal  sections  of  the  cat's  brain  stem.  Cross  hatched  areas  indicate  level  and 
extent  of  brain  stem  lesion  in  the  midpoiitine  (A)  and  rostropontinc  (B)  pretrigeminal  prepara- 
tions. EEG  patterns  typical  for  each  preparation,  as  recorded  from  right  (F.d)  and  left  (F.s) 
frontal  areas,  arc  reproduced  below  each  set  of  anatomical  drawings.  It  can  be  noticed  that 
both  types  of  transsection  result  in  the  complete  interruption  of  ascending  trigeminal  in- 
fluences. Anatomical  abbreviations  in  the  original.  Anh.  ital.  Biol.,  97,  1-12,  1959. 


M.    PALESTINI    AND    W.    LIFSCHITZ  4I5 

The  EEG  observations  at  hourly  intervals  for  no  less  than  24  consecutive 
hours  showed  that  cats  suffering  midpontine  lesions  present  a  desyn- 
chronized  activity  significantly  more  persistent  than  normal  animals. 

Such  an  experimental  hnding  makes  it  necessary  to  verify  some  variables 
and  only  thus  can  an  hypothesis  about  the  probable  mechanism  underlying 
this  lasting  electrocortical  dcsynchronization  be  postulated. 

In  fact,  the  desychronizcd  EEG  in  the  MPP  could  be  due  to  an  irritative 
action,  while  the  low  voltage  pattern  could  be  the  result  of  a  depressed 
cortical  activity.  Different  controls  effected  in  the  animals  during  the  post- 
operative survival  time  (1-9  days)  made  the  first  possibility  unlikely  while 
the  second  one  was  completely  dismissed  (Batiiii,  Moruzzi,  Palestini, 
Rossi  anci  Zanchetti,  1959). 

Some  humoral  factors  arc  known  to  play  a  role  in  EEG  activation.  For 
instance,  the  eiicct  of  adrenaline  on  the  cortical  arousal  is  widely  known. 
Nevertheless,  it  must  be  noted  that  adrenaline  does  not  act  directly  on  the 
cerebral  cortex,  but  through  the  reticular  formation.  Its  desynchronizing 
efiect  is  not  disclosed  in  the  'cerveau  isolc'  but  is  found  in  transsections 
similar  to  the  midpontine  (Bonvallet,  Dell,  Hiebel,  1953).  On  the  other 
hand,  there  is  some  evidence  of  increased  adrenaline  secretion  in  decere- 
brated animals  (Anderson,  Bates,  Hawthorne,  Haymaker,  Knowlton, 
Riosch,  Spence,  Wilson,  1957)  which  drops  below  normal  levels  in  the 
spinal  dogs.  The  above  circumstances  made  it  necessary  to  establish  the 
role  of  adrenaline  111  the  EEG  activation  of  the  MPP  (Batini,  Magni, 
Palestini,  Rossi  and  Zanchetti,  1959). 

Midpontine  cats  were  observed  for  24  hours  following  which  a  section 
at  Cj  was  performed  in  order  to  eliminate  any  brain  stem  influence  on  the 
adrenal  gland.  In  these  cases,  the  EEG  remained  desynchronized  (Batini, 
Magni,  Palestini,  Rossi  and  Zanchetti,  1959). 

The  COo  blood  increase  must  not  be  neglected  either  especially  since 
the  MPP  sometimes  presents  periodic  breathing.  In  a  group  of  cats,  the 
gaseous  composition  of  the  arterial  blood  was  measured  before  and  after 
the  midpontine  operation.  This  experiment  demonstrated  that  the  EEG 
activating  pattern  in  the  MPP  does  not  depend  on  blood  CO.^  pressure 
changes. 

Summing  up,  the  authors  of  these  experiments  stated:  'Irritative 
phenomena  or  humoral  factors  may  occasionally  contribute  to,  but  are 
not  likely  to  be  responsible  for  the  EEG  activation'  (Batini,  Magni, 
Palestini,  Rossi  and  Zanchetti,  1959). 

All  these  experimental  results  support  the  hypothesis  of  a  possible 
synchronizing  structure,  placed  behind  the  midpontine  section  in  the 


41 6  BRAIN    MECHANISMS    AND    LEARNING 

brain  stem,  wliosc  exclusion  would  provoke  an  EEG  activation.  It  is 
evident  also,  that  the  structures  rostral  to  the  midpontine  lesion  are  in- 
dispensable for  a  desynchronized  EEG  since  a  little  more  rostral  pontine 
transsection  to  the  MPP  (rostropontine  preparation)  produces  EEG 
synchronization. 


B.     SENSORY     DEAFFERENTATION    IN     THE     MIDPONTINE    PRETRIGEMINAL 

PREPARATION 

Bremer  (1935)  observed  that  sensory  affercnces  play  an  important  role 
in  the  electric  cortical  activity  of  the  'encephale  isole'  and  'cerveau  isolc' 
animals.  Results  obtained  by  Moruzzi  and  Magoun  (1949)  permitted  a 
new  interpretation  of  the  influences  that  sensory  afterences  have  upon 
cortical  activity.  They  would  act  thrcnigh  their  activating  action  on 
reticular  formation. 

Roger,  Rossi  and  Zirondoli  (1956)  have  thrown  more  light  on  the  same 
experimental  field.  They  established  that  the  electrical  activity  of  low 
voltage  and  high  frequency  of  the  'encephale  isolc'  is  suddenly  syn- 
chronized by  the  elimination  of  the  trigeminal  afterences. 

The  results  observed  in  the  MPP  would  seem  to  be  at  variance  with  the 
above-mentioned  facts.  Both  experimental  conditions  eliminate  the 
trigeminal  afterences  but,  while  Roger  ct  al.  (1956)  maintain  in  their 
preparation  the  anatomical  continuity  of  the  brain  stem,  the  MPP  excludes 
the  ascending  influence  of  the  medulla  and  the  caudal  pontine  region. 

Batini  ct  al.  (1959)  repeated  and  confirmed  the  results  obtained  by  Roger 
ct  al.  (1956).  It  was  thus  possible  to  state  that  gasserectomy  in  'encephale 
isole'  cats  determines  EEG  synchronization.  But,  if  a  midpontine  trans- 
section  is  performed  in  these  animals,  the  EEG  shows  the  characteristic 
MPP  desynchronization. 

These  results  permit  us  to  establish  another  explanation  of  these  facts 
and  to  insist,  as  we  shall  see  later,  on  a  possible  ascending  synchronizing 
influence  coming  from  the  bulbar  reticular  formation  and  from  the  caudal 
pontine  region. 

The  MPP  and  its  characteristic  EEG  pattern  ofters  a  more  satisfactory 
way  of  studying  the  importance  of  sensory  afterences  on  the  electrical 
activity  during  wakefulness.  Batini,  Palestini,  Rossi  and  Zanchetti  (1959) 
eliminated  on  successive  days  the  olfactory  and  visual  afterences  of 
animals  submitted  to  pretrigeminal  section.  Destruction  o(  the  olfactory 
bulbs  m  the  MPP  did  not  modify  the  EEG.  But  if  these  animals  suftered  a 
lesion  in  their  optic  nerves,  their  cortical  rhythms  became  synchronized. 


M.    PALESTINI    AND    W.    LIFSCHITZ  417 

However,  one  or  two  days  after  the  completion  of  sensory  deafterentation, 
the  low  voltage  and  fast  EEG  rhythms  reappeared  and  persisted  unmodi- 
fied through  the  survival  period. 

To  sum  up,  these  facts  show  that  the  whole  desynchronized  EEG 
activity  following  MPP  might  be  due  eitlier  to  the  elimination  of  some 
ascending  synchronizing  influences,  and/or  to  the  exaltation  of  a  tonic 
activity,  rostral  to  the  section.  The  latter  would  be  able  to  sustain  a 
cortical  desynchronization  when  total  deafterentation  was  done. 

The  hypothesis  based  on  a  'synchronizing  or  possible  sleep-inducing 
influences  exerted  by  a  structure  present  in  the  caudal  brain  stem'  (Batini, 
Moruzzi,  Palestini,  Rossi  and  Zanchetti,  lys-S)  has  been  strongly  reinforced 
by  recent  experimental  data. 

Chronic  midpontine  hemisections  show  desynchronization  in  the  hemi- 
sphere ipsilateral  to  the  section,  while  the  other  hemisphere  displays  both 
synchronized  and  desynchronized  periods  of  EEG  activity  (Cordeau  and 
Mancia,  1959).  These  results  can  be  explained  by  the  presence  of  some 
ascenciing  synchronizing  influence  on  the  cerebral  cortex  ipsilateral  to  the 
intact  pontine  region. 

We  want  to  mention  another  observation  here.  In  an  ingenious  experi- 
ment performed  in  cats,  the  head  circulation  was  split  into  two  difterent 
circuits  by  a  ligature  of  the  basilar  artery  at  pontine  level,  one  of  the 
circuits  corresponding  to  the  carotid  arteries  that  irrigate  the  pontine 
rostral  region,  midbrain  anci  cerebrum,  and  the  other  to  the  vertebral 
arteries  for  the  medulla  and  the  caudal  pontine  region.  In  these  conditions, 
intravertebral  administration  of  a  low  dose  of  Thiopental  produced  a 
general  arousal  reaction  in  a  previous  EEG  spontaneously  synchronized. 
These  results  can  be  interpreted  as  a  functional  and  reversible  inactivation 
by  the  drug  of  a  synchronizing  mechanism  originating  in  the  lower  brain 
stem  (Magni,  Moruzzi,  Rossi  and  Zanchetti,  1959).  The  experiments  we 
have  mentioned  support  the  idea  of  the  functional  diversity  of  the  reticular 
formation,  to  whose  well-known  desynchronizing  influence  is  now  added 
its  synchronizing  eftcct  upon  the  cortex. 

C.    MIDPONTINE    CATS    AND    WAKING    BEHAVIOUR 

The  psychophysiological  correlation  between  wakefulness  and  cortical 
desynchronization  on  one  side  and  sleep  and  synchronization  on  the  other 
has  been  recently  discussed.  Thus,  EEG  of  normal  cats  during  sleep  shows 
periods  of  desynchronization  (Dement,  1958).  Observations  made  on 
human  beings  also  show  this  type  of  EEG  during  normal  sleep  (Dement 
and  Kleitman,  1957). 


4l8  BKAIN    MECHANISMS    AND    LEARNINC 

By  means  of  an  objective  technique  consisting  of  hypnotic  mduction, 
we  have  recently  observed  in  humans  that  a  synchronized  EEG  is  recorded 
during  the  somnambuhst  phase  of  suggested  sleep,  showing  thcta  and 
even  delta  rhythms.  If  a  verbal  contact  is  established  with  the  hypnotized 
subject,  it  may  be  observed  that  he  answers  when  his  EEG  pattern 
resembles  those  recorded  during  the  waking  state  with  closed  eyes. 
Spontaneous  post-hypnotic  amnesia  for  the  meannigful  conversation  is 
shown  by  the  subject  (Dittborn,  Borlone  and  Palestini,  1959). 

The  desynchronized  EEG  patterns  in  MPP  animals  do  not  enable  it  to 
be  niferred  that  they  are  in  a  waking  state.  But  the  fact  that  these  animals 
have  a  normal  pupil  and  can  still  make  vertical  eye  movements,  make  it 
possible  to  study  some  behavioural  reactions.  In  fact,  they  have  shown  the 
capacity  to  make  an  apparently  directed  or  intentional  movement  with 

I 
L 


OLF  STIM 


I  1  I  1,1  I  1  I  I 

.5sec 

Fig.  2 

Effect  of  heterosensory  stimulation  on  visual  potentials  (MPP) 

EEG  record.  Primary  potentials  decrease  during  olfactory  extrastimulation. 

their  eyes  to  follow  an  object  passing  across  their  visual  fields.  Movements 
disappear  as  soon  as  synchronized  EEG  patterns  are  seen,  while  the  pupil 
becomes  myotic.  A  more  important  reaction  is  the  pupil  dilatation  which 
appears  in  some  cats  with  midpontnic  section  when  a  more  emotionally 
significant  stimulus  is  presented  to  them  (rat,  dog). 

In  order  to  obtain  further  information  about  waking  behaviour  in  the 
MPP  we  have  been  studying  'attention'  in  these  animals  (Palestini, 
Lifschitz  and  Armengol,  1959).  In  some,  the  cortical  potentials  evoked  by 
a  flash  decreased  when  the  MPP  was  submitted  to  a  simultaneous  hetero- 
sensory stimulation  (olfactory).  Of  course,  these  results  were  obtained 
during  a  desynchronized  pattern  of  activity  which  apparently  was  not 
modified  during  the  process  of  attention  (Fig.  2).  This  result,  compared 
with  controls,  enabled  us  to  conclude  that  the  MPP  would  be  able  to 
develop  an  alert  state  resembling  that  of  a  normal  animal. 


M.    PALESTINI    AND    W.    LIFSCHITZ  419 

In  short,  the  midpoiitinc  animal  develops  a  persistent  desynchronized 
EEG,  in  correlation  with  seemingly  wakeful  behaviour.  In  no  case  can  it 
be  stated  that  the  alert  state  is  higher  than  the  normal,  as  could  be  concluded 
from  the  EEG  pattern. 

Anatomical  analysis  of  the  midpontine  section  shows  that  it  leaves  the 
extreme  anterior  region  of  the  reticular  pontis  oralis  nucleus  intact.  This  is 
considered  to  be  one  of  the  areas  containing  the  largest  nuniber  of  cortico- 
reticular  projections  (Rossi  and  Brodal,  1956).  The  possible  participation 
of  these  projections  in  the  maintenance  of  wakefulness,  after  total  de- 
aft'erentation,  needs  further  experimental  demonstration  (Batini,  Moruzzi, 
Palcstini,  Rossi  and  Zanchctti,  1959). 

On  the  other  hand,  it  is  suggestive  to  remember  that  the  lower  brain 
stem,  which  would  exert  a  synchronizing  nifluence,  is  also  the  region 
where  the  long  axon  reticular  neurones  are  located.  These  reticular 
neurones  are  connected  with  thalamic  nuclei  (Nauta  and  Kuypers,  1958) 
from  which  synchronizing  and  hypnogenic  effects  are  obtained  by  electric 
stimulation.  With  regard  to  these  anatomo-functional  relationships 
hypothetical  consideratitMis  have  already  been  made  (Batini,  Magni, 
Palestini,  Rossi  and  Zanchetti,  1959;  Cordcau  and  Mancia,  1959).  Finally, 
the  possible  anatomo-functional  interrelations  of  structures  posterior  to 
the  midpontine  lesion  also  seem  to  be  interesting.  The  fact  that  sleep  is 
followed  by  a  decrease  in  the  muscular  tone  is  well  known.  Therefore, 
the  origin  in  the  medulla  of  an  ascending  synchronizing  influence  and  a 
descending  inhibitory  effect  on  reflex  activity  is  a  suggestive  fact  that 
needs  to  be  studied. 


D.    HABITUATION    IN    THE    MIDPONTINE   PREPARATION 

We  have  already  remarked  that  the  pretrigeminal  cat  is  able  to  follow 
with  vertical  eye  movements  an  object  passing  across  its  visual  field.  This 
is  suggestive  of  the  condition  of  'purposeful  attention'  which  together 
with  the  desynchronized  EEG  might  indicate  a  possible  vigilant  state. 
Eye  movements  are  maintained  as  long  as  the  object  is  made  to  pass  to 
and  fro  in  the  visual  field,  while  a  normal  cat  shows  a  rapid  habituation. 

The  above  observation  led  us  to  study  habituation  in  the  MPP  (Palestini, 
Lifschitz  and  Armengol,  1959).  Since  in  this  preparation  the  animal  has 
only  two  sensory  afferences,  visual  and  olfactory,  we  chose  the  visual 
cortex  to  analyse  the  behaviour  of  evoked  potentials  caused  by  repetitive 
stimulation  from  a  flash  given  at  a  frequency  of  i  per  second.  We  have 
considered  as  habituation  the  decrease  and  even  disappearance  of  an  evoked 

EE 


420  BRAIN    MECHANISMS    AND    LEARNING 

potential  produced  in  this  way  (Litschitz,  Palestini  and  Arniengol,  1959) 
with  the  possibihty  of  recuperation  to  the  previous  ampUtude  by  some 
known  dishabituating  agents  (extrastiniuhition,  rest,  changes  in  the 
characteristics  of  the  stimuh,  etc.). 

EEG  recordings  of  primary  and  secondary^  visual  responses  were  made 
before  and  after  midpontine  section.  Each  animal  was  its  own  control. 
The  preliminary  recording  was  made  on  unanacsthetized  dark-aciapted 
cats  with  permanently  nnplanted  bipolar  electrodes  in  striate  cortex  and 
gyrus  lateralis  anterior.  The  pupil  was  dilated  by  homatropine  and  the 
head  was  maintained  in  the  same  position  by  means  of  a  metal  cone. 

Midpontine  section  produced  several  changes  in  primary  and  secondary 
evoked  photic  potentials.  In  the  first  place,  an  increase  in  the  amplitude  of 
these  potentials  was  recorded.  This  phenomenon  will  be  discussed  later. 
Secondly,  a  remarkable  decrease  in  the  speed  of  habituation  of  primary 
potentials  was  noticed.  Tt  was  clear  that  it  could  be  obtained  only  after  a 
great  number  of  stimuli  and,  in  some  cases,  was  not  present  during  the 
whole  test  period  (Fig.  3).  Thirdly,  the  secondary  potential  had  a  time- 
course  of  habituation  similar  to  that  shown  by  the  primary  one  (Fig.  4). 
This  is  quite  different  from  that  to  be  seen  in  normal  animals.  In  a  previous 
communication  (Lifschitz,  Palestini  and  Armengol,  1959)  a  description 
has  been  given  of  the  rapid  habituation  of  the  secondary  potential  registered 
in  the  most  anterior  part  of  the  gyr.us  lateralis,  while  habituation  of  the 
evoked  potential  in  the  striate  area  needed  the  application  of  hundreds  and 
even  thousands  of  stimuli  to  develop.  There  is  a  very  striking  diftercnce 
between  both  potentials,  for  the  secondary  response  practically  ciisappears 
after  the  first  twenty  to  thirty  stimuli  and  even  after  only  three  to  five 
stimuli  (EGG  recordings).  Other  authors  have  also  described  this  prompt 
habituation  of  secondary  responses  (Jasper,  Ricci  and  Doane,  1958)  and 
have  stressed  their  peculiar  plasticity  which  has  specially  drawn  our 
attention.  The  difference  in  habituation  rates  between  primary  and  secon- 
dary potentials  is  altered  in  the  MP?  since,  as  we  have  already  noted, 
both  responses  have  a  similar  temporal  course  of  habituation  in  this 
preparation. 

So  far,  the  mechanisms  of  attention  and  habituation  have  generally  been 
attributed  to  inhibitory  tonic  inffuences  originating  in  central  regions  of 
the  brain  stem.  This  hypothesis  is  based  on  experiments  showing  the 
blocking  of  sensory  transmission  at  the  level  of  gracilis  nucleus  (Hernandez- 
Peon,  Scherrer  and  Velasco,  1956),  trigeminal  nucleus  (Hernandez-Peon, 

^  Wc  call  photic  secondary  responses  those  recorded  in  the  gyrus  lateralis  anterior  and 
suprasylvian  gyrus  (Buser  and  Borenstein,  1959). 


M.    PALESTINI    AND    W.    LIFSCHITZ 


421 


and  Hagbarth,  1955),  lateral  geniculate  body  (Hernandez-Peon,  Scherrer 
and  Velasco,  1956)  and  retina  (Granit,  1955;  Dodt,  1956).  Experiments  with 
anaesthetics  (Hernandez-Peon,   Guzman,   Alcaraz  and  Fernandez-Guar- 

HABITUATION 

NORMAL     CAT 

11'  FLASHES 


PRETRGEMINAL    CAT 

1»J  FLASHES 


FLASHES 


V-* 


'\yv-w>-^y  \/-**v.*--*^l  /  V^ 


100  >/V 


Fig.  3 

Change  in  habituation  rate  by  nndpontine  transscction 

Control  before  the  lesion  in  the  same  animal.  Primary  cortical  photic  potentials. 

Note  lack  of  habituation  and  potentiation  after  lesion.  EEG  records.  Time  calibration 

0.5  seconds. 


diola,  1958)  or  mesencephalic  lesions  (Hernandez-Peon,  1955)  also 
showeti  the  reticular  mesencephalic  meclianisms  as  responsible  for  these 
phenomena. 


422 


BRAIN    MECHANISMS    AND    LEARNING 


However,  data  obtained  up  to  now  show  a  possible  difference  between 
the  mechanism  of  attention  and  habituation.  The  latter  develops  slowly  at 
different  levels  of  the  specific  pathway  (Lifschitz,  Palestini  and  Armengol, 
1959),  lasts  for  hours  and  even  for  days  (Hernandez-Peon,  Guzman, 
Alcaraz  and  Fernandez-Guardiola,  1958)  and  is  generally  accompanied  by 

HABITUATION 
NORMAL    CAT 

1U   FLASHES 


PRETRIGEMINAL    CAT 

1i»  FLASHES 


AFTER    2240     FLASHES 


Fig.  4 
Lack  of  habituation  of  secondary  cortical  photic  potentials  in   inidpontine  pretrigemiiial 

preparation 
EEG  record  from  gyrus  lateralis  anterior.  Shows  fast  habituation  in  the  normal  cat  and  no 
habituation  in  the  MPP.  Time  calibration  0.5  seconds. 


a  synchronized  EEG  record  (Cavaggioni,  Gianelli  and  Santibaiiez,  1959). 
Attention,  on  the  contrary,  is  accompanied  by  immediate  reduction  in 
the  amplitude  of  the  potential  when  the  animal  is  suddenly  submitted  to 
an  extra  stimulation,  it  is  a  short-lived  process  and,  tmally,  goes  together 
with  cortical  arousal. 


M.    PALESTINI    AND    W.    LIFSCHITZ  423 

These  facts,  and  especially  the  last  mentioned,  make  us  think  of  possible 
differences  in  the  mechanisms  responsible  for  these  two  plastic  activities, 
for  it  is  unlikely  that  the  same  mechanisms  would  account  for  such  dis- 
similar characteristics.  Attention  combines  the  functional  traits  of  a 
transitory  influence  which  has  at  the  same  time  an  activating  effect  upon 
the  EEC  Habituation,  on  the  contrary,  is  the  result  of  repeated  stimula- 
tion, it  appears  slowly  and  is  maintained  for  a  longer  period. 

It  has  already  been  noted  that  state  of  attention  can  be  provoked  in  the 
MPP  when  a  heterosensory  stimulus  is  applied.  In  this  respect,  the  animal 
behaves  normally,  while  habituation  in  pretrigeminal  cats  shows  the 
above-mentioned  alterations.  In  other  words,  this  particular  kind  of  brain 
stem  transsection  seems  capable  of  dissociating  both  phenomena.  This 
suggests  that  attention  is  a  function  of  the  mesencephalic  reticular  forma- 
tion or  of  even  more  anterior  regions.  On  the  same  basis,  habituation  of 
cortical  potentials  might  be  considered  a  function  of  caudal  reticular 
mechanisms.  Anyhow,  we  should  point  out  that  this  is  probably  not  the 
only  habituating  influence,  since  we  have  sometimes  observed,  in  the  MPP, 
a  delayed  decrease  in  the  evoked  potentials.  It  can  be  said  that  this  part  of 
the  reticular  formation  acts  as  a  habituation-facilitating  mechanism. 

When  a  more  rostral  pontine  section  is  made,  a  synchronized  EEG  can 
be  observed  as  a  rule.  This  fact  differentiates  the  rostropontine  from  the 
midpontine  animal,  but  both  preparations  show  the  same  slow  type  of 
habituation  (Fig.  5).  This  points  to  the  possible  independence  of  syn- 
chronizing and  habituating  mechanisms. 

Sharpless  and  Jasper  (1956)  remark  that  there  is  no  strict  correlation 
between  the  magnitude  of  the  auditory  evoked  potentials  in  the  cerebral 
cortex  and  habituation  of  the  arousal  reaction.  Although  this  last  is  seen 
after  twenty  or  thirty  repetitions  of  the  arousal  stimulus,  the  evoked 
potentials  remain  of  the  same  size  or  increase.  These  authors  believe  it 
necessary  to  distinguish  between  habituation  of  the  arousal  reaction  and 
decrease  of  the  evoked  potentials  as  a  consequence  of  the  former.  On  the 
other  hand,  a  detailed  study  of  the  zones  of  mesencephalic  reticular  forma- 
tion that  evoke  the  arousal  reaction  and  those  that  inhibit  responses  in  the 
dorsal  cochlear  nucleus  (Jouvct  and  Desmedt,  1956)  has  induced  these 
authors  to  assume  that  each  of  these  functions  has  a  different  reticular 
organization. 

Moreover,  it  is  well  known  that  stimulation  of  the  reticular  formation 
produces  dcsynchronization  of  the  EEG,  while  different  authors  have 
observed  the  facilitation  or  diminution  of  cortical  evoked  responses  during 
stimulation  of  this  structure  (Rossi  and  Zanchetti,  1957).  All  these  facts  lead 


424 


BRATN    MECHANISMS    AND    LEARNING 


US  to  consider  the  possible  existence  of  an  independent  control  for  these 
phenomena:  size  of  potentials  and  EEG  synchronization  or  desynchroniza- 
tion. 

The  results  already  described  regarding  the  elementary  plastic  processes, 

HABITUATION 

NORMAL    CAT 

1«J  FLASHES 


ROSTROPONTINE    CAT 

•     1«»  FLASHES 


1   100  _vV 


Fig.  5 
Study  of  habituation  associated  to  a  synchronized  EEG 
Rostropontiiie  cat.    No   habituation   during   stimulation   period 
ahnost  twice  as  long  as  that  of  the  normal  cat. 

attention  and  habituation,  open  a  new  line  of  research  for  studying  the 
central  mechanism  of  Pavlovian  'internal'  and  'external  inhibition' 
(Pavlov,  1928).  The  second  concept  corresponds  to  attention  and  the  first 
to    sensory    discrimination    and    habituation.    Habituation    as    negative 


M.    PALESTINI    AND    W.    LIFSCHITZ  425 

learning  has  already  been  discussed  (Hernandez-Peon,  Jouvet  and  Scherrer, 
1957).  It  would  seem  useful  to  consider  from  this  point  of  view  the  role  of 
the  low  bulbo-pontine  structures  ni  the  origni  anci  development  of  the 
processes  of  internal  inhibition,  taking  into  account  the  Pavlovian  view  of 
the  intimate  relationship  between  the  latter  and  sleep  (Pavlov,  1928). 

E.    MIDPONTINE    PRETRIGEMINAL    PREPARATION    AND    CORTICAL    POTENTIALS 
EVOKED    BY    PHOTIC    STIMULATION 

It  is  an  accepted  fact  that  the  cortical  potentials  evoked  by  sensory 
stimuli  diminish  in  amplitude  during  spontaneous  desynchronization 
periods.  Electrical  stimulation  of  the  reticular  formation  provokes  an 
arousal  reaction  and  reduces  the  cortical  potentials  evoked  by  physio- 
logical stimulation  of  the  specihc  sensory  pathways.  On  the  other  hand  it 
has  been  observed  that  during  EEG  synchronization  the  evoked  responses 
increase  in  amphtude  (Bremer,  1953). 

The  midpontine  animal,  with  its  permanent  state  of  wakefulness,  and 
the  rostropontine  cat,  with  a  synchronized  EEG  pattern,  seemed  to  be  two 
suitable  preparations  for  studying  these  problems.  In  addition,  we  have 
assumed  that  inhibitory  influences  which  facilitate  habituation  originate  in 
the  medulla.  If  this  were  so,  midpontine  section,  separating  this  structure, 
might  reveal  a  facilitation  of  the  cortical  evoked  responses. 

Cats  with  electrodes  permanently  implanted  in  the  gyrus  lateralis  and 
gyrus  lateralis  anterior  were  used  in  these  experiments.  Primary  and 
secondary  photic  cortical  potentials  were  recorded  (EEG  anci  CRO) 
before  and  after  midpontine  lesion. 

The  secondary  potentials  recorded  in  normal  cats  showed  an  initial 
negative  deflection.  Latency,  which  was  difficult  to  measure  in  such  condi- 
tions, had  an  average  value  of  20  msec,  and  its  amplitude  was  about 
80  (iV.  Iterative  photic  stimulation  with  a  frequency  of  1  per  second 
produced  rapid  habituation  and  the  secondary  response  became  masked  by 
cortical  activity. 

The  midpontine  transsection  performed  in  the  same  animals  brought 
about  some  clear  changes.  Latency  (20  msec.)  became  very  regular  and 
easy  to  measure  and  the  amplitude  increased  notably,  reaching  sometimes 
150  [xV.  or  more.  These  results  were  obtained  with  a  dcsynchronized 
EEG  background  (Figs.  4,  6).  Similar  changes  to  those  c^escribed  in  the 
midpontine  cat  were  also  noticed  in  rostropontine  lesions,  accompanied 
in  this  case  with  cortical  synchronization. 

Pretrigeminal  section  performed  in  these  animals  also  modified  the 


426  BRAIN    MECHANISMS    AND    LEARNING 

primary  responses.  In  Fig.  7  (CRO  recording  with  bipolar  electrodes) 
some  of  these  modifications  can  be  observed,  i.e.  a  slight  change  in  the 
first  spike  and  a  marked  increase  of  amplitude  in  the  following  deflections 
which  are  precisely  those  which  arc  most  changed  by  habituation  and 
conditioned  learning  (Guzman,  Alcaraz  and  Fernandez-Guardiola,  1957; 
Hernandez-Peon,  Guzman,  Alcaraz  and  Fernandez-Guardiola,  1958). 

Studies  made  with  monopolar  electrodes  demonstrated  that  the  ampli- 
tude of  the  first  positive  deflection,  currently  designed  wave  i,  remained 
unmodified  or  increased  slightly.  Conversely,  positive  waves  3  and  4  and 
negative  wave  5  showed  a  constant  and  appreciable  increase.  We  wish  to 


NORMAL    CAT 


PRETRIGEMINAL     CAT 


NORMAL    CAT 


Fig.  6 

Oscillographic  recording  of  secondary  cortical  photic  responses 

Stimulus:  flash  i /second.  Monopolar  record  in  the  same  cat  before  (normal)  and  after  mid- 

pontine  section.  Five  responses  in  each  trace.  Downward  deflection  negative.  Time  calibration 

40  msec.  Amplitude  calibration  100  \iV. 


Stress  once  again  that  these  results  were  obtained  with  a  desynchronized 
EEG  pattern.  In  rostropontine  animals  exactly  the  same  changes  were 
seen,  but  cortical  spindles  intcrfereci  with  the  regularity  observed  in  the 
midpontine  cat. 

Since  the  potentiation  described  was  achieved  after  total  transsection  of 
the  brain  stem,  we  assume  that  it  is  the  result  of  the  elimination  of  a  tonic 
inhibitory  influence  originated  behind  the  lesion  and  as  a  consequence  of 
the  exaltation  of  facilitating  influences  situated  above  the  level  of  the 
lesion. 

Regarding  the  site  of  action  of  these  ascending  inhibitory  influences  of 
bulbar  origin,  nothing  definite  can  be  said  at  the  present  time.  Neverthe- 
less, on  the  basis  of  some  anatomical  and  neurophysiological  data,  we  may 


M.    PALESTINI    AND    W.    LIFSCHITZ 


427 


40msec 


Vi 


100  >jV 


60msec 


Fig.  7 


Oscillographic  recording  of  primary  cortical  photic  responses 
Stinuihis:  flash  i/scc.  Bipolar  electrodes.  Five  responses  in  each  trace. 

A.  Cat  unanaesthetizcd,  chronically  implanted  and  dark-adapted. 

B.  Same  cat  after  midpontine  section.  Amplification  and  sweep  rate 

as  in  A. 

C.  Same  condition  as  in  B,  but  sweep  rate  has  been  slowed  to  show 

the  last  deflection. 


428  BRAIN    MECHANISMS    AND    LEARNING 

discuss  a  priori  the  possibility  that  these  influences  may  act  upon  the  non- 
specific systems. 

Numerous  axons  have  been  recently  described  which  originate  in  the 
medulla  and  are  distributed  across  the  midbrain  tegmentum,  grey  peria- 
queductal matter,  superior  colliculus  and  pretectal  area,  non-specific 
thalamic  nuclei  and  sub-thalamic  region  (Nauta  and  Kuypers,  1958). 

From  these  diffused  axonal  projections  those  concerned  with  the  non- 
specific nuclei  seem  worthy  of  special  mention,  since  there  is  evidence  that 
intralaminar  stimulation  facilitates  specific  visual  responses  in  the  'cerveau 
isole'  animal  (Jasper  and  Ajmone-Marsan,  1952;  Jung,  1958). 

We  ascribe  similar  importance  to  periaqueductal  and  tegmental  projec- 
tions of  the  reticular  formation.  They  might  be  the  structural  bases  of 
functional  antagonistic  interrelations  between  different  levels  of  the 
reticular  formation  of  the  brain  stem  according  to  inferences  from  the 
results  discussed,  although  there  is  no  direct  demonstration. 

It  is  also  possible  that  these  inhibitory  influences  may  operate  at  a  sub- 
cortical level  of  the  specific  pathway. 

From  data  obtained  by  other  authors,  these  inhibitory  influences  might 
be  exerted  on  the  retina  by  a  centrifugal  pathway  (Granit,  1955;  Dodt, 
1956;  Hernandez-Peon,  Guzman,  Alcaraz  and  Fernandez-Guardiola, 
1957;  Palestini,  Davidovich  and  Hernandez-Peon,  1959),  in  the  geniculate 
lateral  nucleus  (Hernandez-Peon,  Scherrer  and  Velasco,  1956). 

Although  we  do  not  disregard  these  last  possibilities,  our  findings  lead 
us  to  consider  them  of  less  importance.  In  fact,  as  we  pointed  out  before, 
potentiation  of  the  primary  response  in  the  pretrigeminal  animal  has  a 
marked  and  almost  exclusive  effect  on  waves  3,  4  and  5  which  most  authors 
believe  to  have  an  intracortical  origin. 

There  is  another  point  to  which  we  should  like  to  refer  briefly.  As  we 
have  noted,  potentiation  of  the  primary  and  secondary  cortical  photic 
responses  was  obtained  either  w^ith  a  desynchronized  (MPP)  or  synchron- 
ized EEG  pattern  (rostropontine  animal).  This  observation  induces  us  to 
consider  that  there  may  be  no  causal  relationship  between  the  facilitating 
and  the  synchronizing  and  desynchronizing  influences. 

To  sum  up,  we  can  now  say  that  the  midpontine  cat  has  the  following 
characteristics: 

1.  A  predominantly  desynchronized  EEG,  generally  correlated  with  a 
wakeful  pattern,  although  we  are  not  in  a  position  to  say  that  its  alert 
state  is  greater  than  that  of  a  normal  animal. 

2.  Primary  cortical  potentials  evoked  by  a  flash  do  not  show  habitua- 


M.    PALESTINI   AND    W.    LIFSCHITZ  429 

tion  or  need  a  period  at  least  three  times  longer  than  that  required  by  the 
normal  animal  to  show  it.  Much  more  evident,  in  this  respect,  arc  the 
results  obtained  on  secondary  cortical  potentials,  since  they  show  rapid 
habituation  in  the  normal  cat. 

3.  A  significant  increase  in  the  primary  and  secondary  cortical  potentials 
evoked  by  a  luminous  stimulus.  Evidently  the  reactions  described  in 
points  2  and  3  only  refer  to  photic  cortical  responses ;  this  does  not  allow 
us  to  extend  them  to  other  sensory  responses. 

Aware  of  the  oversimplification  of  our  hypothesis  and  admitting  that 
other  structures  of  the  nervous  system  also  participate,  we  would  ascribe 
different  functions  to  two  areas  of  the  reticular  formation.  The  influences 
originated  rostral  to  the  midpontine  level  would  mainly  participate  in 
cortical  dcsynchronization,  in  the  facilitation  of  evoked  potentials,  in 
dishabituation  and  in  attention,  while  those  originated  caudal  to  this  level 
would  synchronize  the  EEG,  facilitate  habituation  and  inhibit  evoked 
cortical  potentials.  These  three  influences  ascribed  to  the  reticular  forma- 
tion of  the  medulla  lead  us  to  think  that  this  structure  should  be  regarded 
as  an  important  part  of  a  sleep  system. 


GROUP   DISCUSSION 

Adey.  I  would  like  to  discuss  a  few  aspects  of  the  study  that  Mr  Lindslcy  and  I 
have  undertaken  to  assess  the  role  of  subthalamic  areas  in  the  maintenance  ot 
reticular  excitability,  and  I  think  these  findings  bear  very  closely  on  the  papers  that 
have  been  presented  this  afternoon.  These  lesions  are  in  chronic  cats  and  monkeys 
and  they  involve  the  subthalamus,  the  dorsal  part  of  the  hypothalamus  and 
frequently  the  ventro-mcdial  part  of  the  thalamus.  These  are  chronic  lesions  and 
the  cats  were  kept  in  good  condition  for  6  weeks  to  2  months  before  they  were  used 
for  subsequent  acute  or  chronic  experiments.  It  was  found  that,  after  such  a  lesion, 
when  recording  from  the  medial  reticular  formation  of  the  rostral  mesencephalon, 
many  of  the  units  which  are  normally  present  and  respond  to  stimulation  of 
sciatic  nerve  are  no  longer  active,  and  in  fact  it  is  very  difficult  to  find  spontaneously 
firing  units.  When  one  is  detected,  it  fires  only  slowly,  and  exhibits  only  a  brief 
phasic  rise  in  firing  rate  with  each  stimulus,  in  contrast  to  the  tonic  and  sustained 
rise  in  firing  rate  induced  in  normal  reticular  units  by  repetitive  sciatic  stimulation 
in  most  cases.  Since  it  is  almost  impossible  to  assess  reticular  function  on  the  basis  of 
such  unit  studies,  we  reverted  to  macro-electrode  recordings  in  the  rostral  mid- 
brain reticular  formation  adjacent  to  the  periaqueductal  grey  matter.  After  brief 
tctanization  of  the  mid-brain  recording  electrodes  for  2  or  3  seconds,  there  is  a 
slight  facilitation  of  the  reticular  response  to  sciatic  stimulation  as  compared  with 
the  control  records,  lasting  5  to  10  minutes.  After  unilateral  coagulation  of  the 
subthalamus  there  is  slight  reduction  in  the  reticular  responses,  when  compared 
with  control  records,  but  not  very  much.  However,  after  bilateral  coagulation  the 


430  BRAIN    MECHANISMS    AND    LEARNING 

reticular  response  almost  disappears.  If  one  then  briefly  tetanizes  the  midbrain 
recording  electrode  the  response  returns  almost  to  its  original  size  and  behaves  in 
much  the  fashion  of  a  post-betanic  potentiation,  with  gradual  decay  to  a  low  level 
over  10  to  15  minutes.  This  potentiation  can  be  repeated  indefinitely.  These 
animals  have  certain  curious  behavioural  alterations  which  may  be  classified  as 
catatonic.  They  suifer  a  gross  defect  in  avoidance  behaviour,  but  in  this  respect  tend 
to  recover  over  a  period  of  months,  although  they  never  revert  to  normal.  They 
assume  these  curious  postures  even  though  they  are  apparently  alert  and  in  many 
cases  do  not  feed  spontaneously.  Now  on  the  basis  of  these  findings,  we  would 
suggest  that  cither  arising  in  the  subthalamus,  or  passing  through  it,  there  arc 
certain  tonic  facilitatory  influences  which  are  mainly  responsible  for  the  normal 
accessibility  ot  reticular  units  to  input  from  the  periphery.  We  also  have  evidence 
that  there  is  a  brief  phasic  inhibitory  aspect  to  this  activity,  much  as  Huguelin  and 
Bonvallet  have  described  but  the  overall  effect  ot  subthalamic  lesions  of  the  type 
we  have  described  is  a  loss  of  a  tonic  facilitation. 

Palestini.  We  have  postulated  in  this  paper  that  EEG  activation  patterns  and 
facilitation  of  visual  cortical  responses  appear  when  bulbo-pontine  structures  are 
left  out  of  action  by  the  section.  But  we  have  also  pointed  to  possible  inhibitory 
and  synchronizing  influences  originated  in  higher  levels,  hi  relation  to  facilitating 
mechanisms  acting  upon  reticular  formation  and  coming  from  upper  segments  we 
had  only  considered  corticoreticular  relationships.  Now  Dr  Adey  has  presented  us 
a  new  possibility  of  facilitating  influences  which  seems  quite  important  to  us. 

Olds.  I  would  like  to  address  myself  to  Dr  Adcy's  material,  to  ask  whether  there 
was  any  particular  part  of  the  reticular  formation  in  which  recording  electrodes 
should  be  placed  in  order  for  this  eifect  to  be  obtained.  I  would  say  that  the  area  he 
describes  as  having  his  lesion  is  very  similar  to  regions  where  we  get  very  rapid 
self  stimulation  and  I  am  just  wondering  if  the  part  of  the  tegmentum  used  for 
recording  is  also  the  part  that  gives  us  very  rapid  self-stimulation  which  would  be 
the  vcntro-latcral  part  of  the  tegmentum. 

Adey.  First  of  all,  the  recordings  were  all  made  in  the  paramedian  part  of  the 
dorsal  reticular  formation  adjoining  the  peri-aqueductal  grey-matter  at  the 
rostral  mesencephalic  level.  As  far  as  the  subthalamic  lesions  goes,  it  is  my  impres- 
sion that  it  is  a  region  very  heavily  traversed  by  a  rhinonccphalic  descending  flux 
which  arises  from  the  pyriform  cortex,  the  amygdala.  It  is  also  the  main  descending 
area  for  fluxes  through  the  corpus  striatum  and  particularly  from  the  globus 
pallidus.  We  have  not  looked  specifically  in  the  ventro-lateral  tegmentum. 

Galambos.  As  Dr  Adey  has  said,  the  main  outflow  region  of  the  limbic  system 
is  to  this  midbrain  reticular  formation.  I  am  not  exactly  clear  where  the  prctri- 
geminal  section  cuts  through  the  midbrain  but  wonder  whether  it  might  destroy 
the  caudal  part  of  the  nucleus  of  Bechtercw  which  is  a  specific  midbrain  terminus 
for  the  limbic  outflow.  As  I  understand  Dr  Palestini's  view,  he  interprets  the  lack 
of  habituation  of  the  visual  cortical  response  after  the  lesion  to  absence  of  impulses 
from  regions  caudal  to  the  cut.  Could  it  be  that  his  lesion  destroys  a  part  of  the 
nucleus  of  Bechterew  and  thus  prevents  inflow  to  the  midbrain  from  the  limbic 
structures  more  rostrally  located? 

Palestini.  Prctrigeminal  transection  is  made  at  a  midpontine  level  and  leaves 
intact  the  anterior  part  of  the  pons  and  midbrain  structures.  Previous  research  has 
given  some  data  about  the  possible  importance  of  nucleus  pontis  oralis  in  the 


M.    PALESTINI    AND    W.    LIFSCHITZ  43 1 

maintenance  of  this  permanent  waking  EEC  rhvthm,  which  is  better  observed  when 
this  nucleus  is  less  destroyed. 

LiFSCHiTZ.  I  think  it  is  interesting  to  compare  results  communicated  by  Dr 
Jouvet  to  this  symposium  to  our  own,  because  it  appears  that  we  are  speaking  in 
favour  ot  two  different  inhibitory  or  synchronizing  influences,  one  coming  from 
the  caudal  part  of  the  brain  stem,  and  the  other  trom  higher  structures.  It  is  possible 
that  both  influences  act  hi  these  processes,  perhaps  at  different  moments.  During 
habituation  an  internal  inhibition  develops  which  is  different  trom  internal  inhibi- 
tion of  inhibitory  or  negative  conditioned  reflexes.  It  is  quite  possible  that  one  of 
these  is  acting  in  one  type  of  internal  inhibition  and  not  hi  the  other. 

About  Dr  Galambo's  remark,  I  think  that  the  data  we  have  from  Moruzzi 
stating  that  the  'cerveau  isole'  gets  habituated  is  against  the  idea  of  an  action  coming 
from  rhinencephalic  structures.  In  this  case  pathways  coming  trom  the  rliinen- 
cephalon  to  the  midbrain  have  been  also  severed,  but  there  is  a  different  result  in 
habituation. 


CHANGES  IN  CORTICAL  EVOKED  POTENTIALS  BY 
PREVIOUS  RETICULAR  STIMULATION 

Miguel  R.  Covian,  Cesar  Timo-Iaria  and  Ricardo  F.  Marseillan 

It  is  a  well-established  fact  that  the  central  nervous  system  possesses 
mechanisms  by  means  of  which  the  afferent  inflow  can  be  influenced,  and 
that  an  important  role  in  these  mechanisms  is  played  by  the  reticular 
formation  of  the  brain  stem.  Reticular  stimulation  has  been  shown  to 
affect  the  sensory  discharge  at  various  levels  in  the  central  nervous  system. 
On  the  other  hand  on  a  background  of  continuous  electrical  activity  there 
arises  in  the  cortex  on  peripheral  stimulation  a  primary  response  —  only 
in  the  correspondent  receptor  areas  —  and  a  number  of  waves  which 
follow  it  and  spread  to  a  somewhat  wider  area.  The  primary  response  is 
the  one  which  has  been  studied  in  most  detail ;  it  occurs  regularly  on  any 
kind  of  peripheral  stinuilation  and  is  the  most  closely  connected  with  the 
arousing  of  sensation. 

The  literature  is  contradictory  regarding  the  interaction  between  those 
nerve  elements  which  determine  development  of  the  primary  responses 
and  the  central  core  of  the  brain  stem  which,  receiving  impulses  coming 
from  all  sensory  channels,  is  an  adequate  region  for  the  integration  of  these 
different  impulses. 

In  the  present  paper  the  influence  of  previous  stimulation  of  the  reticular 
formation  upon  the  cortical  evoked  potential  obtained  by  a  tactile  stimulus 
is  studied  in  an  attempt  to  understand  the  interaction  between  the  specific 
and  non-specific,  diffuse  projection  systems. 

METHODS 

Experiments  of  this  type  were  performed  upon  twenty-four  cats.  The 
animals  were  anaesthetized  with  initial  (60  mg.  kg.)  and  maintenance  doses 
of  chloralose  given  intravenously.  The  somatic  sensory  area  of  the  left 
cortex  was  exposed  by  craniectomy  and  reflection  of  the  dura  and  covered 
by  mineral  oil.  A  unipolar  electrode  connected  to  a  Dumont  double  beam 
oscilloscope  through  a  Grass  AC  pre-amplifier  registered  the  electrical 
activity  of  the  cortex  with  negativity  upwards  in  all  records.  Photographic 
records  of  the  evoked  potentials  were  taken  either  in  individual  sweeps  or 

433 


434 


BRAIN    MECHANISMS    AND    LEARNING 


ill  three  or  five  superimposed  sweeps.  One  concentric  electrode  consisting 
of  32  gauge  enamelled  stainless  steel  wire  enclosed  within  a  22  gauge 
stainless  steel  sheath  was  placed  stereotaxically  in  the  brain  stem  reticular 
formation.  Bipolar  stimulation  was  performed  between  the  tip  of  the 
inner  conductor  and  a  bare  collar  of  0.5  mm.  wide  encircling  the  lower 
end  of  the  insulated  sheath.  The  distance  between  the  tip  and  collar  was 
approximately  1 .0  mm.  The  electrical  stimuli  were  short  square  waves  of 


Fig.  I 


Diagram  showing  the  experimental  arrangement. 


0.2  msec,  duration,  i/sec,  voltage  variable,  delivered  by  a  Grass  stimulator 
through  an  isolation  unit  and  preceding  the  skin  stimulation  at  intervals 
of  100  and  50  msec.  Tactile  stinuilation  was  apphed  to  hair-covered  areas 
of  the  right  foreleg  by  a  small  camel's-hair  brush  mounted  on  a  lever 
rigidly  attached  to  the  moving  armature  of  an  electromagnet  device  the 
coil  of  which  was  energized  by  a  pulse  of  4  msec,  duration,  i/sec.  by  way 
of  a  Grass  stimulator.  The  main  features  of  the  experimental  arrangement 


M.    R.    COVIAN,    C.    TIMO-IARIA    AND    R.    F.    MARSEILLAN  435 

arc  shown  in  Fig.  i.  At  the  end  of  the  experiment  an  electrolytic  lesion  was 
made  in  the  brain  stem  reticular  formation  with  a  direct  current  ot  2-3  mA 
during  15  sec.  The  animal's  head  was  perfused  with  formalin  through  one 
carotid  artery  and  electrode  position  was  later  determined  from  serial 
sections  stained  by  Toluidine  blue. 


RESULTS 

The  stimulation  of  the  right  forepaw  evoked  (Fig.  2)  the  characteristic 
surface  positive-negative  primary  responses  in  the  corresponding  area  of 
the  somatosensory  cortex.  With  previous  stimulation  of  the  brain  stem 


Fig.  2 
Cortical  evoked  potential  in  somatosensory  area  by 
tactile  stimulation.  Time  200  cps.  Calibration :  see  uV 
—  same  calibration  for  all  other  records. 


reticular  formation  at  100  msec,  interval  and  1.5  volts,  the  negative  com- 
ponent disappeared  and  a  slight  reduction  of  the  positive  one  was  observed 
(Fig.  3).  In  Figs.  4  and  5  the  same  phenomenon  is  presented  when  the 
stimulation  was  made  at  50  msec,  interval  and  1.5  volts. 

It  can  be  seen  in  Fig.  6  in  superimposed  sweeps,  in  the  lower  record  the 
evoked  potential  and  in  the  upper  one  the  effect  of  reticular  formation 
stimulation,  at  100  msec,  interval  and  4  volts. 

FF 


436 


BRAIN    MECHANISMS    AND    LEARNING 


Fig.  3 
Disappearance    of  the    negative    component   of  the 
cortical  evoked  potential  by  previous  reticular  stimu- 
lation (loo  msec,  interval,  2  volts).  Time  200  cps. 


Fig.  4 
Cortical  evoked  potential.  Time  200  cps. 


M.    R.    COVIAN,    C.    TIMO-IARIA   AND    R.    F.    MARSEILLAN 


437 


IlG.    S 

Disappearance  of  the  negative  component  by  previous 
reticular  stimulation  (so  msec,  interval,  i.s  volts). 
Time  200  cps. 


Fig.  6 
Superimposed  sweeps.  Lower  record:  cortical  evoked 
potential.    Upper   record:    cortical  evoked  potential 
obtained  100  msec,  after  brain  stem  reticular  stimu- 
lation. 


43^ 


BRAIN    MECHANISMS    AND    LEARNING 


VOLTAGE    SERIES    AT    100    MSEC.    INTERVAL 


One  voltage  series  was  made  when  the  interval  between  stimuli  was 
100  msec.  In  Fig.  7  are  represented  the  results  obtained.  It  can  be  seen  that 
at  2  volts  there  was  no  modification;  at  3  volts  the  negative  potential 
began  to  decrease  and  the  positive  one  remained  unchanged.  At  4  and  5 
volts  the  dimniution  of  the  negative  potential  was  more  marked  and  no 
change  was  observed  on  the  positive  potential. 


2v 


3v 


4v 


5v 


Fig.  7 
Voltage  series  at  loo  msec,  interval.  Time  200  cps.  Calibration:  500  [iV. 


VOLTAGE    SERIES    AT    50    MSEC.    INTERVAL 

The  same  voltage  series  was  repeated  at  50  msec,  interval  between 
stimuli  and  the  results  arc  summarized  in  Fig.  8.  It  can  be  observed  that  at 
2  volts  there  is  already  a  decrease  oi  the  negative  potential  which  is  more 
marked  at  3  and  5  volts.  Regarding  the  positive  wave  a  little  increase  was 
seen. 

In  all  the  previous  experiments  the  negative  wave  underwent  significant 
changes,  while  the  positive  wave  remained  almost  unchanged.  Only  when 


M.    R.    COVIAN,    C.    TIMO-IARIA    AND    R.    F.    MARSEILLAN 


439 


very  high  voltage  reticiUar  stimulation  (<S  volts)  was  used  did  both  waves 
disappear,  as  shown  in  Figs.  9  and  10  in  superimposed  sweeps  at  100  and 
50  msec,  interval. 

Control  cxpcriiiiciits.  The  possibility  of  spreading  current  to  the  medial 
lemniscus  was  ruled  out  by  the  following  experiment:  a  concentric 
electrode  was  placed  on  the  medial  lenniiscus  at  co-ordinates  As,  L5,  H3. 
Its  stimulation  determined  an  evoked  potential  in  the  cerebral  cortex. 


2v 


3v 


5v 


Fig.  8 
Voltage  series  at  50  msec,  interval.  Time  200  cps.  Calibration:  500  liV. 


While  the  evoked  potential  in  somatosensory  area  was  being  recorded  by 
stimulation  of  the  forepaw  in  the  usual  way,  electrolytic  lesions  were  made 
by  a  5  mA  direct  current  until  the  evoked  potential  disappeared.  At  this 
point  the  stimulation  of  the  medial  lemniscus  did  not  evoke  any  potential 
in  the  cerebral  cortex,  but  the  stimulation  of  the  brain  stem  reticular 
formation  at  co-ordinates  A3,  L2.5,  H2  evoked  a  cortical  pcnential  as 
before.  This  evoked  potential  by  single  shock  reticular  stimulation  was 
very  similar  to  that  obtained  in  the  same  conditions  by  Buser  and  Borenstein 


440  BRAIN    MECHANISMS    AND    LEARNING 

on  the  associative  cortex.  In  Fig.  lo  this  type  of  response  can  be  seen  in 
superimposed  sweeps. 

On  the  other  hand,  after  local  destruction  of  the  reticular  formation,  no 


Fig.  9 
Disappearance  of  the  cortical  evoked  potential  by  pre- 
vious reticular  stimulation  at  I  GO  msec,  interval  and 
8  volts. 


Fig.  10 
Same  as  Fig.  y  but  stimulation  at  50  msec,  interval 
and  8  volts. 

evoked  potential  was  obtained  by  its  stimulation  and  oi  course  the  cortical 
evoked  potential  after  tactile  stimulus  was  not  now  influenced  by  the 
stimulation  at  that  point  ot  reticular  brain  stem. 


M.    R.    COVIAN,    C.    TIMO-IARIA    AND    R.    F.    MARSEILLAN  44I 

COMMENTS 

The  activity  in  sensory  systems  is  subject  to  modification  by  central 
regulatory  mechanisms  and  background  states,  sufficiently  pronounced  to 
be  capable  of  influencing  perception  and  so  to  be  of  interest  for  psychology. 
Upon  the  arrival  at  the  cortex,  afferent  discharge  may  show  variation 
related  to  spontaneous  cortical  activity  (Bishop,  1944),  to  cortical  thalamic 
cxcitabiUty  cycles  (Chang,  1950,  195 1)  or  to  influence  of  other  afferent 
stimuli  (Gellhorn  et  al,  1954).  The  possibility  that  not  only  spontaneous 
but  also  some  electrical  and  chemically  evoked  cortical  potentials  can  be 
abolished  during  electrocortical  arousal  has  been  pointed  out  by  a  number 
of  investigators.  Disappearance  of  recruiting  potentials  has  been  observed 
by  Moruzzi  and  Magoun  (1949)  and  later  confirmed  by  other  investi- 
gators (Jasper,  Naquet  and  King,  1955)  and  it  has  been  reported  that  local 
strychnine  waves  can  be  blocked  during  sensory  arousal.  It  has  also  been 
demonstrated  more  rccendy  that  intermediary  stages  of  afferent  trans- 
mission are  also  subject  to  influence  by  regulatory  mechanisms.  Reticular 
inhibition  of  the  medullary  relays  in  sensory  paths  was  shown  by 
Hernandez-Peon  and  Hagbarth  (1955)  and  by  Hernandez-Peon  and 
Scherrcr  (1955)  in  experiments  on  the  trigeminal  nucleus  and  by 
Hernandez-Peon,  Scherrer  and  Velazco  on  nucleus  gracilis. 

While  some  authors  reported  no  interaction  between  the  mechanisms 
that  give  origin  to  the  primary  cortical  response  and  those  which  give  rise 
to  spontaneous  periodic  activity  (Morison  and  Dempsey,  194- ;  Moruzzi 
and  Magoun,  1949;  Jasper,  1949)  other  investigators  observed  some  kind 
of  interaction  (Jasper  and  Ajmonc-Marsan,  1952;  Bremer,  1954). 

The  present  experiments  support  the  findings  that  show  that  reticular 
formation  is  capable  of  exerting  a  clear  influence  upon  cortical  evoked 
potentials.  The  pathway  used  in  this  case  by  the  stimulus  ot  the  reticular 
formation  to  reach  the  cortex  seems  to  be  the  slower  one  as  described  by 
Adey,  Scgundo  and  Livingston  (1957),  which  shows  rapid  fatigue,  fails  to 
follow  repetition  rates  faster  than  2-3  stimuli  per  second  and  which 
conducts  exclusively  or  predominandy  in  an  upward  direction.  The 
possibility  of  spreading  current  to  the  medial  lemniscus  is  rejected  by  the 
results  of  the  control  experiments.  The  positive-negative  evoked  potential 
in  the  cortical  forepaw  projection  areas  is  unequally  affected  by  the 
previous  reticular  stimulation.  There  is  a  different  susceptibility  of  the 
positive  and  negative  components  of  the  primary  response,  the  negative 
being  the  more  susceptible.  Parma  and  Zanchetti  (1956)  observed  a 
reticular  blocking  of  cortical  potentials  evoked  by  thalamic  stimulation. 


442  BRAIN    MECHANISMS    AND    LEARNING 

In.  some  conditions  they  obtained  a  reduction  of  the  negative  component 
whereas  the  positive  potential  remained  conipletely  unaffected.  Gauthier, 
Parma  and  Zanchetti  (1956)  observed  that  the  primary  response  ehcited  by 
peripheral  stimulation  is  defniitcly  decreased  during  cortical  arousal  but 
they  did  not  give  any  detail  regarding  the  influence  upon  the  positive  and 
negative  component  ot  the  response.  Appclberg,  Kitchell  and  Landgren 
(1959)  studying  the  reticular  influence  upon  thalamic  and  cortical  poten- 
tials evoked  by  electrical  stimulation  of  the  cat's  tongue  observed  a  con- 
siderable reduction  of  both  components  of  the  primary  response.  They 
did  not  mention  any  difference  in  the  behaviour  of  the  positive  and 
negative  components.  This  fact  could  be  attributed  to  the  different 
parameters  of  stimulation  of  the  reticular  formation  used.  Changes  in  two 
components  of  the  primary  response  evoked  by  tactile  stimulation  were 
observed  by  Narikashvili  (1957)  related  with  the  recruiting  response: 
when  the  primary  response  preceded  or  coincided  with  the  rising  slope  of 
a  recruiting  response  potential,  the  negative  spike  of  the  evoked  potential 
was  increased  (the  positive  was  blocked) ;  if  the  primary  response  arose 
when  the  potential  of  the  recruiting  response  was  fully  developed,  then  its 
positive  component  was  increased  and  the  negative  was  blocked.  He 
observed  also  that  the  EEG  desynchronization  had  less  effect  on  the  primary 
response:  it  suppressed  the  negative  component  or  had  no  effect. 

Buser  and  Borcnstein  (1957)  working  in  cats  anaesthetized  with  chlora- 
lose  report  the  existence  of  induced  potentials  in  association  cortex  areas  by 
single  stimulation  of  the  reticular  formation  and  its  inhibitory  effects  on 
the  secondary  response.  The  conflicting  results  obtained  by  different 
investigators  regarding  potentials  evoked  in  the  cerebral  cortex  by  stimu- 
lation of  the  reticular  formation  could  be  attributed  to  the  multisynaptic 
interneuronal  organization  of  this  system  that  makes  it  more  susceptible 
to  anaesthetic  blockade,  but  this  susceptibility  varies  with  the  different 
anaesthetics.  Contrary  to  Buser  and  Borenstein,  response  to  reticular 
stimulation  in  primary  areas  and  inhibition  of  the  primary  response  was 
obtained  in  the  present  work. 

French,  Verzeano  and  Magoun  (1953)  reported  a  different  sensitivity  of 
the  waves  of  the  primary  response  to  anaesthetics.  They  observed  that  the 
initial  event  of  the  primary  response  was  never  diminished  by  anaesthesia 
(ether  or  nembutal) ;  on  the  contrary  it  was  sometimes  augmented,  while 
the  second  cortical  deflection  usually  diminished  in  amplitude  and  Anally 
disappeared.  Feldberg,  Malcolm  and  Smith  (1957)  observed  that  the 
intraventricular  injection  of  small  doses  of  tubocurarine  in  cats  under 
chloralose  caused  definite  changes  in  the  primary  response  evoked  by 


M.    R.    COVIAN,    C.    TIMO-IARIA    AND    R.    F.    MARSEILLAN  443 

contralateral  stimulation  of  the  peroneal  nerve.  The  evoked  cortical 
response  showed  an  accentuation  ot  the  positive  and  an  attenuation  or 
disappearance  of  the  negative  waves. 

Purpura  and  Grundfcst  (1956)  obtained  similar  depressing  effects  by 
intracarotid  injection  of  tubocurarine.  By  topical  application  of  gamma 
aminobutyric  acid  (GABA),  Iwama  and  Jasper  (1957)  observed  an  imme- 
diate and  reversible  depression  in  the  surface  negative  component  of  the 
primary  evoked  potential  in  somatosensory  cortex  of  the  cat  m  response  to 
thalamic  stimulation. 

The  positive  and  negative  components  of  the  primary  response  are 
post-synaptic  events.  The  negative,  which  seems  to  signal  the  depolariza- 
tion of  the  apical  dendrites,  appeared  in  the  findings  here  reported  most 
sensitive  to  the  action  of  the  reticular  formation.  It  represents  the  activa- 
tion of  a  larger  number  of  neuronal  units  than  the  fnst  one.  This  multi- 
synaptic  arrangement  would  be  more  susceptible  to  the  action  of  the 
unspecific  extralemniscal  system  than  it  is  to  the  anaesthetics.  The  alterna- 
tive of  an  interaction  at  a  subcortical  level  has  to  be  taken  into  account. 


GROUP   DISCUSSION 

Olds.  We  have  material  on  chronic  stimulation  o(  the  reticular  torniation  and 
its  effect  on  self-stimulation.  It  seems  very  interesting  in  the  light  of  this  inhibition 
of  the  negative  component.  We  have  an  animal  selt-stimulating  with  electrodes  in 
the  medial  forcbrain  bundle  and  we  gradually  turn  up  a  stimulus  m  the  dorso- 
medial  reticular  formation  —  the  sine  wave  stimulus  —  up  to  10  micro-amperes 
which  is  subthreshold  for  any  effect  which  we  could  observe  from  this  stimulus 
alone,  self-stimulation  comes  to  a  complete  halt.  Going  the  other  way,  the  situation 
is  peculiarly  just  the  reverse,  if  one  now  has  the  animal  responding  to  escape  from 
the  tegmental  stimulus  and  he  now  begins  to  augment  stimulation  in  the  medial 
forcbrain  bundle  electrode  just  gradually  raising  the  level,  the  rate  of  the  escape 
response  is  increased.  Just  what  this  peculiar  interaction  may  mean  I  have  no  idea 
but  it  seems  interesting  enough  to  put  on  the  record  at  this  time. 

Naquet.  Did  you  try  to  stimulate  the  lemniscus;  Some  years  ago,  in  1954, 
working  with  Drs  Magoun  and  Eve  King,  we  obtained  the  same  results  as  you, 
when  we  stimulated  the  sciatic  nerve  or  the  radial  nerve.  But  when  v/e  stimulated 
the  lemniscus,  the  stimulation  of  the  reticular  formation  provoked  sometimes  a 
facilitation  of  the  evoked  potentials  recorded  after  the  thalamic  relay.  I  think  this 
facilitation  was  confirmed  by  Dumont  and  Dell  (ipS^)  and  Bremer  and  Stoupel 
(1958).  When  they  applied  a  shock  on  the  optic  nerve,  the  stimulation  of  the 
reticular  formation  gives  some  facilitation  on  the  response  record  at  the  level  of 
the  cortex.  When  a  flash  is  used,  the  stimulation  of  the  same  point  of  the  reticular 
formation  provokes  a  reverse  effect  or  no  effect. 

Hernandez-Peon.  Perhaps  the  different  results  obtanied  concerning  facilitation 
and  depression  of  the  sensory  evoked  potentials  may  be  due  to  the  placement  of  the 
stimulating  electrodes.  There  is  also  a  difference  in  the  results  obtained  by  an 


444  BRAIN    MECHANISMS    AND    LEARNING 

electric  shock  applied  in  the  central  sensory  pathway  or  by  using  a  physiological 
stimulus  applied  to  the  receptor.  I  would  like  to  add  that  it  was  reported  some  time 
ago  by  Dr  Purpura  that  dendritic  potentials  which  are  supposed  to  arise  in  the 
cortex  are  depressed  during  reticular  stimulation  or  during  arousal. 

Magoun.  Local  cortical  responses,  along  with  other  surface-negative  phases  of 
evoked  cortical  potentials,  are  most  susceptible  to  EEG  arousal  by  reticular 
stmiulation  or  by  natural  alerting  to  attention.  The  conclusion  that  an  inhibition  of 
dendritic  depolarization  is  the  key  feature  of  EEG  arousal  needs  some  qualification, 
however.  Drs  Eidelberg  and  Feldman  tested  this  with  thioscmicarbazide  which 
blocks  the  formation  of  GAB  A  to  the  point  of  generating  seizure  discharge  in  the 
nervous  system.  In  this  circumstance,  surface-negative  recruiting  responses  became 
verv  much  augmented,  as  do  negative  phases  of  other  evoked  cortical  potentials. 
However,  these  augmented  surface-negative  phases  could  still  be  abolished  by 
reticular  stimulation.  This  suggests  that  if  an  active  inhibition  is  involved  here,  it  is 
one  that  is  independent  of  GAB  A  biochemistry.  Additionally,  in  this  connection, 
when  the  surface-negative  phase  is  blocked  in  EEG  arousal,  one  does  not  see  an 
inverted,  surface-positive  potential,  as  in  the  situations  in  which  Drs  Purpura  and 
Grundfest  proposed  a  hyperpolarizing  potential  to  be  unmasked. 

EccLES.  The  GAB  A  is  not  just  blocking  an  excitatory  surface  dendritic  potential 
and  leaving  an  inhibitory  one.  Grundfest  has  published  records  which  show  that  a 
better  interpretation  is  that  GABA  is  simply  eliminating  surface  excitatory  poten- 
tials and  leaving  the  excitatory  potentials  deeper  down  on  the  apical  dendrites  and 
somas,  which  of  course  would  give  rise  to  surface-positive  potentials. 


RECHERCHES    SUR   LES  MECANISMES  NEUROPHYSIO- 
LOGIQUES  DU  SOMMEIL  ET  DE  L'APPRENTISSAGE 

NEGATIF 

Michel  JouvejI'^' 

introduction 

On  pent  distingucr  dc  fa^e^ii  theoriquc  deux  grandcs  varictcs  d'inter- 
actions  dialectiques  entre  rorganisme  ct  Ic  milieu  cxterieur:  Tune  d'ordre 
synchronique,  I'autre  d'ordre  diachronique. 

Elles  peuvent  s'illustrer  par  I'opposition  dcs  jeux  de  bridge  et  d'echccs  — 
...  dans  unc  partic  d'echecs,  n'importe  quelle  position  donnce  a  pour 
caractcre  singulier  d'etre  afFranchie  dc  ses  antecedents  ...  cclui  qui  a  suivi 
toute  la  partie  n'a  pas  Ic  plus  legcr  avantage  sur  le  curieux  qui  vient 
inspecter  la  partic  au  moment  critique  ...  (Pouillon,  1956). 

Il  en  est  ainsi  de  la  grande  majorite  dcs  reponses  du  systeme  nervcux 
etudiees  en  cours  d'experiences  aigues,  sur  dcs  animaux  anesthcsies  ou 
menie  curariscs.  Les  fluctuations  dcs  reponses  sont  alors  tenues  pour 
aleatoires  ct  nc  dependent  point  de  1'  'histoirc'  de  I'animal.  Il  en  est 
cgalement  ainsi  de  I'ctude  de  la  plupart  dcs  reflexes  absolus.  La  liaison 
cntre  Torganismc  ct  Ic  milieu  cxterieur  est  d'ordre  synchronique. 

Par  contre,  'dans  unc  partic  de  bridge,  il  est  toujours  capital  de  savoir  ce 
qui  s'est  passe  avant  le  coup  a  jouer  ...  on  nc  comprcnd  pas  pourquoi,  a  la 
dixieme  levee  par  cxcmplc,  le  jeu  se  prcscnte  de  telle  manierc  si  Ton  n'a  pas 
suivi  Ics  neufs  levees  prccedcntcs  ...  '  (Pouillon,  1956).  C'est  cxacteincnt 
cc  qui  sc  passe  au  sein  dcs  liaisons  diachroniques,  lors  de  la  confrontation, 
en  experimentation  chroniquc,  de  I'organisme  avec  unc  quclconque 
variation  du  milieu  cxterieur. 

Dans  le  cadre  dc  ccs  liaisons  diachroniques  deux  grandcs  varictcs  de 
reponses  du  systeme  nervcux  apparaissent: 

L'une  se  traduit  par  Fapparirioii  d'une  rcponse  motrice  ou  vegetative  a 
un  stimulus  ontologiquemcnt  sigmtiant  (la  reaction  d'attention  ou 
d'oricntation)  ou  a  toute  variation  nouvclle  du  milieu  cxterieur  (eftet  dc 
nouvcaute,   dc   surprise).    Cctte   rcponse   survient   cgalement   lorsqu'un 

1  Charge  de  recherches  au  CNRS  —  Institut  de  Physiologie,  Faculte  dc  Medecine  de  Lyon. 

-  Ce  travail  a  beneficie  d'une  subvention  partielle  de  TOffice  of  Scientific  Research  and 
Development  conitnand,  United  States  Air  Force,  attribuee  par  son  Service  Europeen,  sous 
contrat  AF  61  (052)  109. 

445 


446  BRAIN    MECHANISMS    AND    LEARNING 

Stimulus  indifferent,  par  association  rcpctee  avec  un  stimulus  absolu, 
dcvient  historiquement  signifiant,  (lors  du  conditionnement  classique  dc 
type  pavlovien  par  exemple).  C'est  Vappreiitissage  positij. 

L'autre  modalite  de  reactivite  nerveuse,  au  contraire,  s'accompagne  dc 
la  (iisparitioji  d'une  reponse  motrice  ou  vegetative.  Il  en  est  ainsi  lors  de 
I'cxtinction  dc  la  reaction  d'attention  ou  d'invcstigation,  lorsque  sont 
repetes  frcquemment  a  I'etat  de  veillc  des  stimuli  'indifFcrents',  ou  bien 
lorsque  sont  rcpctcs  au  cours  du  sommeil  des  stimuli  indiftcrents,  capables 
au  debut  d'entrainer  un  cveil  (extinction  de  la  reaction  d'cveil). 

Enfin  cette  modalite  de  reactivite  caractcrise  cgalement  I'extinction  du 
reflexe  conditionne  lorsque  le  signal  conditionnc  est  rcpetc  scul  (inhibition 
interne  par  extinction). 

Cette  varictc  de  liaison  diachroniquc,  plus  clcmentaire  que  I'appren- 
tissage  positif  puisqu'il  ne  concerne  en  general  qu'un  scul  recepteur, 
apparait  bien  ainsi  comme  I'une  des  formes  les  plus  simples  d'apprentissage, 
Yappreiitissin^c  ucgatij  (dont  nous  nc  considerons  ici  que  les  formes  les  plus 
simples). 

L'usagc  tend  actuellement  a  donner  a  cette  varicte  de  liaisons  Ic  tcrmc 
d'liahitiiatioii  (Dodge,  1923;  Humphrey,  1933;  Thorpe,  1944;  Konorski, 
1948).  Il  recouvre  ceux  d'inhibition  interne  (Pavlov,  1929),  d'extinction 
ou  d'adaptation  negative  (Hilgard  et  Marquis,  1940). 

Ccs  processus  d'apprentissage  ncgatif,  dont  I'importance  est  capitale, 
ont  un  caractere  commun  dont  Pavlov,  dans  la  quinzieme  des  lemons  sur 
I'Activite  Nerveuse  Supcrieure,  soulignat  le  premier  la  singularite:  leiir 
relatkvi  ctroitc  avec  le  sommeil.  On  se  rappelle  I'experience  classique  au 
cours  de  laquelle  Pavlov  decrivit  I'endormissement  d'un  chien  au  cours  de 
I'extinction  d'un  reflexe  conditionnc.  L'ctude  de  I'activite  clectrique 
ccrcbrale  a  revclc  cgalement  la  frequence  des  phcnomenes  de  sommeil 
electroencephalographique  qui  accompagne  ccs  processus  d'Appren- 
tissage  ncgatif  (Fessard  et  Gastaut,  1956). 

Pour  cette  raison,  I'etude  des  mecanismes  de  I'endormissement  est 
capitale  car  elle  pent  nous  donner  des  renseignements  utiles  conccrnant 
I'apprentissage  ncgatif.  C'est  pourquoi  nous  exposerons,  tout  d'abord,  les 
rcsultats  de  recherches  conccrnant  le  sommeil. 

I  —  OBSERVATIONS  MONTRANT  l'eXISTENCE  DE  DEUX  SYSTEMES  INHIBI- 
TEURS,    TELENCEPHALIQUE   ET    RHOMBENCEPHALIQUE,    ENTRANT   EN    JEU    AU 

COURS    DU    SOMMEIL 

Si  Ton  applique  a  I'etude  des  mecanismes  du  sommeil  la  methode  des 
sections  ctagces  du  ncvraxe,  c'est  au  niveau  de  la  partie  du  systeme  ncrveux 


MICHEL  JOUVET  447 

cii  relation  avec  le  milieu  exterieur  (par  ses  afterenccs  et  efterences  prin- 
cipales)  que  les  fluctuations  de  I'activitc  electrique  de  I'encephale  doivent 
etre  niises  en  correlation  avec  les  signes  soniato-vegetatifs  du  sommeil.  Car 
rcndorniissement  traduit  une  forme  de  comportemcut  total  de  I'organisme, 
ct  doit  done  etre  juge  par  rapport  a  son  eiii'iroiiiicDtciit. 

On  sait  ainsi,  depuis  Goltz  (1892)  que  le  chien  decortique  est  capable  de 
sommeil.  On  sait  egalcment  qu'un  chat  mesencephalique  chronique 
presente  des  fluctuations  periodiques  de  vigilance  (Bard  ct  Macht,  1958; 
Rioch,  1954),  celles-ci  deviennent  plus  difficiles  a  percevoir  dans  le  cas 
de  preparations  pontiques  chroniqucs  (Rioch,  1954).  Enfm,  I'observation 
d'une  moelle  epiniere  isolee  par  une  section  sous-bulbairc,  ne  revele 
aucune  periodicite  dans  le  sens  d'un  rythme  nycthemeral  (Magoun,  1954). 

Ainsi,  a  chaque  'niveau  d'intcgration'  du  tronc  cerebral,  il  devient 
possible  d'observer  des  fluctuations  de  vigilance,  en  tcrnw  cc  comportemcut. 
Notre  but  a  cte  d'en  etudier  les  correlations  electriques. 

Les  recherches,  que  nous  rapportons  brievement,  ont  etc  effect uees  sur 
trente  chats  chroniques  etudies  plusieurs  semaines  et  porteurs  d'clectrodes 
corticales,  sous-corticales  et  intra-musculaires  (Jouvet  et  Michel,  1958; 
Jouvet  et  col.,  1959,  b,  c,  d). 

Certains  animaux  ont  cte  totalcment  ou  partiellement  decortiqucs, 
tandis  que  d'autres  ont  subi  une  section  totale  ou  sub-totale  du  tronc,  a  la 
jonction  mesodienccphalique. 

L'activite  electrique  cerebrale  recueillie  sur  un  appareil  EEC  a  plume 
a  etc  mise  en  correlation  avec  les  critcres  peripheriques  du  sommeil: 
posutre  de  I'animal,  pupilles  et  membranes  nictitantes,  temperature  rectale, 
EKG,  respiration,  ct  surtout  activite  E.M.G.  des  muscles  de  la  nuque  qui 
nous  a  semble  etre  un  des  temoins  les  plus  tideles. 

(i)  Chez:  Ic  chat  intact  ciidormi  —  On  pent  distinguer  deux  stades  elec- 
triques bien  difterents.  Le  premier  est  bien  connu  (Rheinbergcr  et  Jasper, 
1937;  Hess  ct  col.,  1953). 

\ —EiidorDiisscment  ct  sommeil  hut  (Figs,  i,  II;  2,  II)  —  L'endor- 
missement  est  marque  par  I'apparition  de  fuseaux  envahissant  d'abord  le 
cortex  et  le  diencephale,  puis  la  formation  reticulce  (F.R.)  mesencephalique. 

Ensuite  le  sommeil  lent  est  caracterise  par  I'apparition,  au  niveau 
du  cortex  ct  des  structures  diencephalomtfsencephahques,  d'ondes  lentes 
de  2  a  4  cycle-secondc  de  grande  amplitude,  tandis  que  l'activite  hippo- 
campique  ventrale  presente  des  pointes  tres  breves  et  de  haut  voltage. 
L'activite  pontique  demeure  rapide.  Lc  seuil  d'eveil  par  stimulation 
directc  de  la  F.R.  est  pusl  eleve  lors  de  la  presence  d'ondes  lentes  que  lors 
du  stade  des  fuseaux. 


448 


BRAIN    MECHANISMS    AND    LEARNING 


fM6.  ^  , 

c««. 

FR. 
H. 


u 


Fig.  I 

ANIMAL    INTACT    CHRONIQUE  —  I      Eveil 

II  Phase  telencepha- 

liquc 

III  Phase  paradoxale. 
Remarquer,  au  cours  de  la  phase  paradoxale,  la 
supression  totale  du  tonus  musculaire  des  muscles 
de  la  nuque  (E.M.G.),  Ic  ralentisseinent  du  rythme 
cardiaque  (E.K.G.),  les  niouveiuents  des  yeux  (O.G.) 
—  (Jouvet,  Michel  et  Courjon  —  C.R.  Soc.BioL,  1959, 
sous  presse).  Calibrage:  i  seconde  —  50^v.  pour 
touts  les  figures. 


MICHEL  JOUVET 


449 


Au  cours  de  ce  stadc,  raiiimal  s'cst  mis  en  posture  de  somnieil,  les 
membranes  nictitantes  viennent  rccouvrir  les  pupilles  qui  sont  en  niyosis 
—  la  nuque  flechit  jusqu'a  ce  que  repose  la  tete.  Parallclement,  I'activite 
electrique  des  muscles  de  la  nuque  diminue  progressivement  jusqu'a  un 
certain  niveau  de  base  alors  qu'en  general  I'activite  des  autres  groupes 
musculaires  est  nulle. 

B  —  La  phase  paradoxale  (Figs,  i.  III,  2,  III)  —  Elle  tait  toujours  suite  a 
une  phase  de  sommcil  profound  et  n'apparait  jamais  d'emblee  apres  un 


CSM 
CA 

H.V. 


i-u.  , 

FR.>«(A,) 

FR.p. 
EMG. 


%\m^'^'t^A-^/i/.\ 


^lh^4,^V-r'^'w*'W^VT<''•*wv>^v^ 


ii#A^nwimi»'*r*#«»»'^  1'*^  ***>***  *<Awy»» 


■^V^  ^i-vHw^ 


I  II  III 

Fig.  2 

ANIMAL    INTACT,    CHRONIQUE  —  I       Evcil 

II  Phase  tclcncephaliqiie  dii  somnieil 

III  Phase  paradoxalc  —  apparition  de  fuseaux  au  niveau  de  la 
F.R.  pontique  (F.R.P.)  et  activite  rythnnque  au  niveau  de 
I'hippocanipe  dorsale. 

Hv,  Hd:  Hippocanipe  ventrale,  dorsale. 

F.R.m:  F.R.  niesencephalique 

Noter  la  vitcsse  reduite  d'cnreiristrenient. 


trace  de  veille.  Elle  debute  soudainement  et  se  caracterise  par  une  activite 
cortico-mesodiencephalique  rapide  et  de  bas  voltage  identique  a  celle 
dc  I'eveil.  L'hippocampe  ventral  presente  egalement  mie  activite  rapide. 
L'hippocampc  dorsal  pent  presenter  une  activite  rythmique  lente  identique 
a  celle  decnte  par  Green  et  Arduini  (1954)  au  cours  de  I'eveil.  En  meme 
temps,  I'activite  rhombencephalique  est  le  siege  de  fuseaux  de  6  a  8  c/s, 
d'apparition  synchrone  avec  I'activite  rapide  corticale.  Cette  phase 
s'accompagne  immediatement  d'une  disparition  complete  dc  I'activite 


450 


BRAIN    MECHANISMS    AND    LEARNING 


E.M.G.  des  muscles  enregistrcs.  Elle  dure  en  general  lo  a  15  minutes. 
Soit  spontancment,  soit  sous  I'influencc  d'une  stimulation  exterieure, 
I'activitc  pent  revenir  au  stade  antcrieur  du  sommeil  avec  rcapparition 
de  fuseaux  ou  d'ondcs  lentes  mcsodiencephalo-corticales,  disparition  des 
fuseaux  rhombencephaliques  et  reapparition  d'une  Icgerc  activite  muscu- 
laire,  ou  bien  il  pent  y  avoir  un  reveil  generalise  de  I'animal. 

Au  cours  dc  la  phase  paradoxale,  la  posture  de  I'animal  est  celle  du 
sommeil,  il  n'y  a  plus  aucun  tonus  musculaire  postural  et  —  si  la  tete  ou  un 
membre  de  I'animal  sont  en  surplomb  —  ils  pendent  alors,  flasques,  soumis 
uniqucment  a  la  pcsanteur.  Les  membranes  nictitantes  recouvrent  presque 


B 


,^■■11    .^t^    i4   ^^«*fc\  ^»lN»»H^I|».|»'ttH-l***"*^ 


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w.vVirV'V«(+*'V^»*V"**lN**'«^/^**W 


»v-H»'MMVrt>*-'''*irs«*«'^*'*«^  I 


t 


ANIMAL    DECORTIQUE    CHRONIQUE  ■ 


Fig.  3 

I  Eveil 

II  Endormissement 

III  Narcose  au  Nembutal  (35  mg./kg.) 

Remarquer  I'absence  totale  de  fuseaux  ou  d'ondes  lentes  au  niveau  des  formations  sous- 
corticales  diencephaliques  (1-2),  mesencephaliqucs  anterieures  (3-4)  ou  posterieures  (5-6). 
tandis  que  I'hippocampe  (7)  presente  une  activite  caracteristique  (Jouvet  et  Michel,  195  8) 


entierement  les  pupilles  qui  sont  en  myosis,  tandis  que  les  globes  oculaires 
sont  frequemment  anime's  de  secousses  rapides,  ainsi  que  les  vibrisses;  plus 
rarement,  on  pent  constater  de  breves  secousses  des  machoires  et  de  la 
queue.  Le  rythme  respiratoire  est  plus  ample  et  plus  rapide,  tandis  que  le 
rythme  cardiaque  se  ralcntit  et  que  I'arythmie  respiratoire  se  precise. 

Le  seuil  d'eveil  (en  decibels)  par  une  stimulation  auditive  augmente  par 
rapport  au  stade  d'ondes  lentes.  Il  est  de  meme  pour  le  seuil  d'eveil  par 
stimulation  directe  de  la  F.R.  mesenccphalique.  Enfin,  les  rcponses 
cvoquees  auditives,  corticales  ou  reticulaircs  ont  leur  amplitude  tres 
diminuee  par  rapport  au  stade  lent  du  sommeil. 

Cette  phase,  que  nous  avons  retrouvee  chez  chaque  animal,  se  repete 


MICHEL  JOUVET  45 1 

pcriodiqucnicnt,  survcnant  en  general  a  3  ou  4  reprises  au  cours  d'cnregis- 
trement  continu  dc  2  heures  de  sonimeil. 

(2)  Chez:  un  animal  dccortiqiic  total  {Figs.  3,4)  —  An  cours  de  rcndorniisse- 
ment  ct  du  somnicil  profond,  les  formations  centrales  rhonibo-meso- 
diencephaliques  prcsentcnt  continuellcnient  inic  activite  rapide,  identique 
a  ccllc  observee  au  cours  de  I'etat  de  veille;  tandis  qu'au  niveau  du  rhinen- 
cephale  apparaissent  des  pointes  breves,  I'activitc  E.M.G.  est  nioderee 


ER»n(lM  

TK. 
EM6. 


^^^HW**!^!!    *lW^^i»    Sill'  'Wi^^i^i  W  ii>Hwi"  1^  '»■  II    w    '    I    ""^    "•f'*%fm'» 


Fig.  4 
—  Phase  paradoxale  (rhoinbcncephalique)  du  sonimeil  chez  un  chat  dcconiqiic  chroniqiie 

Apparition  de  fuscaux  au  niveau  du  nucleus  pontis  caudalis  (F.R.F.)  et  disparition  du  tonus 
niusculaire  (E.M.G.). 

Le  trace  inferieur  fait  suite  au  trace  supericur. 

Vitesse  d'enregistremeiit  7  in,  s/sec. 

(Fig.  3B).  Cette  activite  rapide  et  de  bas  voltage  persiste  durant  la  pcriode 
entiere  de  survie  de  I'animal  (jusqu'a  3  niois).  La  narcose  profonde  au 
Nembutal  (35  mg.  kg.)  n'entraine  aucune  variation  du  trace  sous-cortical, 
mais  par  contrc  provoque  I'apparition  d'une  activite  caracteristique  au 
niveau  de  I'hippocampc  (Fig.  3C).  Cette  absence  de  variation  du  trace 
sous-corticale  a  cte  confirmee  reccmmcnt  par  Sergio  et  Longo  (1959)  chez 
le  lapin  dccortique. 

Cette  phase  est  suivic  d'une  'phase  paradoxal,  marquee  par  I'apparition 

GG 


452 


BRAIN    MECHANISMS    AND    LEARNING 


de  bouffccs  d'activitc  rythmiques  dc  fuscaux  a  6-8  c/s,  de  gpande  ampli- 
tude, se  rcpctant  de  fa(jon  rcguliere  au  niveau  de  la  formation  rcticulce 
politique  (Fig.  4). 

En  mcme  temps  que  s'installe  cette  activite,  deux  ordres  de  phcno- 
mencs  apparaisscnt: 

—  d'une  part,  une  activation  rhinencephalique  (activite  rapidc),  tandis 
que  les  formations  mcso-dicncephaliqucs  continuent  a  tester  rapides; 

—  d'autre  part,  une  disparition  totale  de  toute  activite  tonique  muscu- 
laire. 


I 


- 1 

-  —  a. 

H.     ,  '  ' 


F«(*i)i 


Fig.  5 
Persistance  d'ondes  lentes  au  niveau  reticulaire  mcsencephalique  (F.R.),  lors  de 
la  premiere  phase  du  sommeil  (A)  chez  un  animal  dccortique  subtotal  (I)   ou 
porteur  d'une  section  incomplete  du  tronc  cerebral  (II)  —  B:  etat  de  veille. 


Animal  dccortique  subtotal  (Fig.  5)  —  II  sutiit  dc  respecter  une  surface  trcs 
minime  du  neocortex  pour  retrouvcr,  au  cours  de  la  premiere  phase  du 
sommeil,  1' invasion  des  formations  meso-diencephaliques  par  des  fuseaux 
et  des  ondes  lentes.  Le  'stadc  paradoxal'  s'objcctive  de  la  mcme  fa^on  que 
prccedemment  decrit:  apparition  de  'fuseaux'  pontiques  mais,  cctte  fois, 
les  formations  meso-diencephaliques  redevicnnent  rapides  ainsi  que  la 
surface  corticale  restante. 

(3)  Animal  mcsencephalique  (Fig.  6)  —  L'activite  electrique  des  formations 
corticales  et  dicncephaliques,  situees  en  avant  de  la  section,  prcsentent 


MICHEL  JOUVET  453 

contiuuelleuient  I'aspcct  classiquc  dccrit  au  niveau  du  'ccrveaii  isolc' 
(Bremer,  1935),  encore  que  de  breves  et  indiscutables  phases  d'activation 
apparaissent  au  niveau  du  cortex  lors  dc  stimulations  olfactives  identiques 
a  celles  decrites  par  Arduini  et  Moruzzi  (1953). 

CA      '  ■ 

■TV(MJ  I  .  '. 


Jif 


1 1  jjj,;.^»-.vu...w.(^,iyA''^^"w''-*««Jx'r-*~^--*^ 


H'jto  N»T  ^^  »*«'\/v<iv«*^A^ 


>.»V<**J 


Fig.  6 
animal  mesencephalique  chronique  — 
En  avaiit  de  la  section,  fuseaux  et  ondes  lentes  au  niveau  du  cortex 
(C.S.M.  -  CA)  et  du  thalamus  (Th)  au  cours  de  la  veille  (I)  et  de 
rarcheo-somnieil  (II).  Par  centre  I'activitc  reticulaire  mesencephalique 
reste  rapide  (F.R.ni)  tandis  qu'une  activite  de  fuseaux  apparait  au 
niveau  de  la  F.R.  pontique  (F.R.P.)  au  cours  de  la  phase  rhomb- 
encephalique  du  soniincil  (archeo-sonnncil)  (II).  et  que  Tactivite 
E.M.G.  disparait. 

E}i  arricrc  dc  la  sccrioii,  par  contrc,  I'activitc  mesencephalique  reste 
constammcnt  rapide.  Scule  pent  s'objectiver  la  phase  "paradoxale'  qui 
correspond,  selon  nous,  a  r'archeo-sommeil'  de  I'animal  mesencc'phaliquc; 
fuseaux    pontiques,    absence    totale    d'activite    E.M.G.    d'autant    plus 


454  BKAIN    MECHANISMS    AND    LEARNING 

rcmarquable  qu'a  I'ctat  de  veillc  Ic  tonus  inusculairc  est  augmente  ct  sc 
traduit  par  une  riche  activite  E.M.G. 

Si  la  section  du  tronc  n'est  pas  totale  et  qu'il  persiste  une  mince  lame  de 
tissu  cerebral  central  reliant  les  etages  meso  et  diencephaliques,  les  deux 
premiers  stades  decrits  sur  I'animal  normal  se  retrouvent  et  le  stade  para- 
doxal s'accompagne  alors  d'unc  activation  meso-diencephalo-corticale  et 
rhinencephalique  (Fig.  5). 

Ccs  rcsuhats  coinhiiseiir  done  a  adiiicttrc  deux  iiii'caux  dc  soninwil  fort 
difjcrciits.  Le  premier  'niveau'  concerne  I'endormisscment  et  le  sommeil 
profond  de  ranimal  normal.  Il  necessite  obligatoirement  la  presence,  au 
moins  partielle,  du  necortex  puisqu'il  y  a  nue  absence  totale  d'activite  lente 
sous-corticale  chez  I'animal  decortiquc  total,  ou  en  arriere  d'une  section  du 
tronc  cerebral.  Cette  activite  lente  traduit  un  phenomene  d'inhibition 
puisque  le  seuil  d'eveil  par  stimulation  directe  de  la  formation  reticulee 
s'elcve  lors  de  ce  stade.  Il  est  done  legitime  dc  parler  de  sommeil  telen- 
ccphalique  a  propos  de  cette  phase. 

Le  deuxieme  'niveau'  que  traduit  le  stade  paradoxal  depend  d'un  mecan- 
isme  totalement  different. 

I  —  L'allure  identiquc  dcs  'fuseaux'  rencontres  chez  I'animal  intact  et 
chez  les  animaux  dccortiqucs  et  mcsenccphaliques  chroniques,  la  meme 
periodicite,  les  memes  phenomenes 'musculaires  permettent  d'assimiler  la 
'phase  paradoxale'  de  ranimal  intact  endormi  a  1'  'archeo-sommeil'  de 
I'animal  mesencephalique  ou  decortiquc. 

L'apparition  d'une  activite  de  'fuseaux'  au  niveau  du  noyau  reticularis 
pontis  caudalis  (R.P.C.)  s'accompagne  immcdiatement,  de  fa^on  absolue, 
d'une  disparition  totale  de  toute  activite  tonique  musculaire,  dont  on 
connait  la  dependance  par  rapport  au  systeme  Gamma.  Il  est  logique  de 
supposer  que  le  stade  paradoxal  represente  la  mise  en  jeu  d'un  mecanisme 
nihibiteur  agissant  caudalement  sur  le  systeme  Gamma.  On  sait  qu'un 
tel  controle  supra  spinal  est  possible  au  niveau  de  cette  structure  (Eldred  et 
Col.,  1953).  La  cause  de  l'apparition  periodique  d'un  tel  mecanisme  reste 
encore  inconnue,  mais  il  semble  qu'elle  soit  independante  des  variations  du 
milieu  exterieur. 

II  —  Le  declanchemcnt  d'une  activite  rapide  ccrcbrale  en  avant  du  rhom- 
boencephale,  au  cours  de  cette  phase,  pose  de  nombrcux  problemes.  La 
presence  d'une  activite  rapide  corticale  au  cours  du  sommeil  a  cte  signalee 
au  niveau  du  scalp  par  Rimbaud,  Passouant  et  Cadilhac  (1955)  et  par 
Dement  (1958)  chez  le  chat,  et  Dement  et  Kleitman  (1957)  chez  I'hommc. 
Ces  derniers  auteurs  dccrivent  egalement  les  memes  mouvements  rapides 


MICHEL  JOUVET 


455 


dcs  yeux  ct  apportent  dc  nombrcux  arguments  qui  permettent  de  supposer 
que  cette  activitc  rapide  accompagne  le  rcve  chez  I'homme. 

Pour  CCS  auteurs,  cette  activite  rapide  representerait  un  stadc  inter- 
mediaire  entre  la  veille  et  Ic  sommeil.  Nous  pensons  plutot  qu'il  s'agit 
d'un  stade  de  sommeil  plus  profond,  etant  domie  I'elcvation  du  seuil 
d'cveil  et  les  phenomcnes  periphcriques. 


Fig.  7 
Schema  des  2  systcmes  inhibitcurs  entrant  en  jeii  an  coiirs 

du  sommeil. 
I  —  Lc  svsteme  inliibiteiir  telcncephalique  agissant  siir  le 

S.R.A.A. 
II  —  Le  systemc  inhibiteiir  rhonibeneephalique  agissant  sur 
le  systemc  Gamma. 


C'est  pourquoi  uiic  telle  activite  rapide  cercbrale,  accompagnee  de  tous 
les  phenomenes  vegetatifs  et  somatiques  du  sommeil  protoud,  apparai 
bicn  paradoxalc. 

Ces  donnces  permettent  ainsi  d'admcttre  que  deux  mc'canisnies  inhibi- 
tcurs diftl'rents  entrent  en  jeu  au  cours  du  sommeil  (Fig.  7) : 

Le  premier  mecanismc  represente  le  misc  en  jeu  d'un  systemc  rostral 
inhibiteur,  agissant  sur  le  systemc  rcticulaire  activatcur  ascendant  (Moruzzi 
et  Magoun,  1949).  Au  sein  dc  cc  systemc,  le  neo  cortex  represente  un 
maillon  essentiel,  puisquc  sans  lui  les  phenomcnes  de  synchronisation  ou 
les  ondes  lentes  diencephalo-mesencephaliqucs  n'apparaissent  plus. 


456  BRAIN    MECHANISMS    AND    LEARNING 

Ce  systeme  entraine  un  etat  d'inhibition  des  structures  centrales  du 
tronc,  mais  laisse  cependant  persistcr  unc  certaine  activite  tonique  muscu- 
laire  pcriphcrique. 

Le  deuxieme  mecanisme  represente  la  inise  en  jeu  d'un  systeme  cuadal 
inhibiteur  agissant  sur  le  systeme  Gamma.  Il  se  traduit  par  I'apparition 
d'une  activite  caracteristique  au  niveau  de  la  F.R.  politique  et  traduit 
I'archeo  sommeil  pcriodique  de  I'animal  dccortiquc  et  mesenccphalique 
—  Chez  I'animal  intact,  il  dcclanche  egalemcnt  I'apparition  d'une  activite 
paradoxalement  rapide  des  structures  rostrales  du  nevraxe.  Il  est  probable 
que  ce  stade  depend  du  milieu  interieur.  Enfm,  il  est  possible  qu'il  soit  le 
support  de  I'activitc  onirique. 

Ai'cc  ces  diffcrciits  iiit'caiix  dc  soiniiicii  nous  nous  troui'oiis  ainsi  cii  possession 
d'tiii  instrument  de  travail  precieux  puisque  nous  pouvons  mettre  en  evidence, 
a  chaque  niveau  d'intcgration  du  S.N.  les  processus  de  base  veille-som- 
meil  qui  se  traduisent  par  des  aspects  clectriques  particuliers.  C'est  sur  ces 
mccanismes  de  base  qu'il  est  logique  de  tester  les  processus  de  base  de 
I'apprentissage,  en  particulicr  les  plus  simples,  ccux  de  I'apprentissage 
negatif,  puisqu'il  est  fort  probable  qu'ils  nicttcnt  en  jeu  des  processus 
inhibiteurs. 


II  —  L  HABITUATION    DE    LA    REACTION    D  EVEIL 

Il  est  d'observation  courante  que  nous  nous  habituons  facilement  a 
dormir  dans  un  endroit  bruyant;  le  passage  de  trains  nocturnes,  par 
exemple,  qui  nous  reveille  chaque  fois  les  premieres  nuits,  rapidement  ne 
trouble  plus  notre  sommeil.  Les  stimuli  auditifs,  qui  excitent  notre  oreille, 
restent  cependant  les  memes.  A  leur  'indifference  diachronique',  a  leur 
probabilite,  notre  systeme  nerveux  ne  reagit  plus  par  I'eveil. 

Il  reste  a  determiner  qu'il  n'y  reagisse  plus  ou  qu'il  y  reagisse  par  de 
I'inhibition. 

L'habituation  de  la  reaction  d'eveil  apparait  commc  Texprcssion  dc  la 
plasticitc  ccrcbrale  au  niveau  des  mccanismes  de  base,  rcgulatcurs  de 
rclcctrogcnesc. 

La  Constance  dc  ce  phenomcnc  chez  de  nombreuses  espcces  animales,  la 
relative  facilite  de  son  etude  electrique  ont  permis  son  etude  des  I'avcne- 
ment  de  rclectrocnccphalographie  (Ectors,  1936;  Rheinberger  et  Jasper, 
1937;  Clark  et  Ward,  1945).  Enfm  recemment,  ce  sujet  a  fait  I'objet  d'une 
etude  trcs  complete  par  Sharpless  (1954),  Sharpless  et  Jasper  (1956). 


MICHEL  JOUVET  457 

(A)  Les  aspects  E.E.G.  de  riiahitiiatiou  dc  la  reaction  d\'i>eil:  Les  rcsultats 
auxqucls  nous  faisons  bricvcmcnt  allusion  sont  pour  la  plupart  incdits 
(Jouvct  ct  Michel,  1959  a).  (L'habituation  dc  la  reaction  d'evcil  a  cte 
etudiee  chcz  des  preparations  chroniques  intactcs,  dccortiquccs  ou  mesen- 
cephaliqucs  qui  ont  scrvi  a  nos  rcchcrches  sur  Ic  soninicil.  Des  stimuli 
auditifs  ctaient  employes  pour  provoquer  I'cveil). 

Chez  I'animal  intact,  la  traduction  E.E.G.  de  l'habituation  ne  pcrmct  pas 
d'elucider  les  niccanismes  de  bases  de  cc  processus,   mais  cllc  niontrc 

FR 

Fig.  8 
Habituation  de  la  reaction  d'cveil  — 

—  Evcil  cortical  (C.S.M.  —  CA)  et  rcticulaire  (F.R.)  lors  dc  la  presentation  au  conrs  du  sonmiei 
d'un  train  de  dies  a  12/sec. 

—  Absence  de  reveil  lors  de  la  6cme  presentation  des  stimuli  acoustiques,  augmentation  des 
reponscs  corticales  acoustiques. 

ccpendant  qu'il  obeit  aux  lois  de  I'apprentissage  et  qu'il  ne  s'agit  pas  d'un 
phcnomcnc  dc  fatigue  ou  d'adaptation  des  recepteurs  (Sharplcss,  1954). 

L'habituation  est  ainsi  specijiqiie  pour  un  stimulus  donne  —  puisque  la 
preuve  meme  de  ce  phenomcne  est  obtenue  en  induisant  apres  habituation 
un  reveil  par  un  stimulus  acoustique  difjereiit,  mais  moins  intense,  ce  qui 
permet  d'eliminer  le  facteur  'profondeur'  du  sommeil  (Fig.  10)  (voir  aussi 
Sharpless  et  Jasper,  1956). 

Get  apprcntissage  negatit  pent  persistcr  dun  jour  a  I'autre,  puisqu'il  est 


458 


BRAIN    MECHANISMS    AND    LEARNING 


plus  rapide  d'habituer  I'eveil  d'un  animal  a  un  stimulus  le  2eme  et  le  3 erne 
jour  que  le  premier.  Les  courbcs  obtenues  ainsi  cvoquent  celles  de  tout 
apprentissage  (Fig.  10,  I). 

Enfni,  cet  apprentissage  negatif  est  cgalement  susceptible  d'etre  inter- 
tompu:  par  le  temps,  par  I'intervention  d'un  stimulus  nouveau  (Sharpless, 
1954),  ct  enfm  et  surtout  par  conditionnement  (Fig.  10,  II). 

C'est  ainsi  qu'un  animal  qui  s'habitue  apres  six  repetitions  d'un  son  de 
500  c/s.  conservera  ensuite  longtemps  une  reaction  d'evcil  si  ce  son  a  ete 
associe  a  des  chocs  douloureux. 


Fig.  9 
Schema  des  mecanismes  possibles 
de   I'habituation    de    la    reaction 
d'eveU. 

1  —  DeafFerentation  specifique. 

2  —  Deafferentationnon  specifique 

au    niveau    des    coUaterales 
destinces  au  S.R.A.A. 

3  —  Processus    inhibiteur    priini- 

tivemenr  rcticulaire. 

4  —  Systeme     inhibiteur     extra- 

reticulaire. 


Tous  ces  caractcres  prouvent  bicn  que  nous  sommes  en  presence  d'un 
reel  processus  d'apprentissage  negatif.  L'analyse  des  activitcs  electriques 
corticales  et  sous-corticales  demontre  que  le  processus  survicnt  en  meme 
temps  aux  etages  corticaux  et  sous-corticaux. 

(B)  —  Observations  tnontraiit  riiitcrveiitioii  d'un  systcnw  inhibiteur  tclcn- 
ccplialique  an  cours  de  F habituation  de  la  reaction  d'eveil:  Depuis  les  travaux  de 
Moruzzi  et  Magoun  (1949)  (Magoun,  1950),  on  sait  que  la  condition 
necessaire,  sinon  suffisante  a  un  eveil  du  cortex  [arousal)  est  I'activation  du 
systeme  reticule  activateur  ascendant  (S.R.A.A.).  Le  problcme  qui  se  pose 


MICHEL  JOUVET  459 

devant  I'habituation  de  la  reaction  d'cveil  concerne  done  les  mecanismes 
rcsponsablcs  de  I'absencc  d'activation  rcticulaire. 

A  priori,  quatre  mecanismes  hypothetiques  peuvent  etre  mis  en  cause. 
Les  deux  premiers  supposent  une  dcaffcrentation  specifique  ou  non  speci- 
fique;  les  deux  autres,  Tintervention  de  processus  d'inhibition   active 

(Fig- 9). 

(i)  —  Le  premier  mccanisme  consisterait  dans  un  'blocage'  dcs  afFcrences 
sensorielles  (deafFerentation  specifique)  responsables  de  I'eveil  au  niveau  des 
premiers  relais  specifiques  (noyau  cochlcaire  dans  le  cas  des  stimuli 
acoustiques) :  le  systcme  nerveux  ne  serait  alors  plus  excite. 

On  sait  qu'un  tel  controlc  des  afterenccs  est  possible  aussi  bien  dans  des 
conditions  experimentales  aigues  (Habgarth  et  Kerr,  1954;  Galambos, 
1956)  que  chroniques  (Hernandez-Peon  et  Scherrer,  1955;  Hernandez- 
Peon,  Scherrer  et  Jouvet,  1956). 

Ce  controle  des  afferences  acoustiques  suppose  cependant  un  etat  eleve 
d'excitation  centrale  obtenu  par  stimulation  d'aires  corticales  (Jouvet  et 
col.,  1956),  des  parties  latcrales  du  tegmentum  (Jouvet,  Desmedt,  1958) 
dans  des  conditions  aigues.  Dans  des  conditions  chroniques,  il  s'accom- 
pagne  d'une  activation  de  I'ecorce  (Hernandez-Peon  et  col.,  1956). 

Ce  controle  semble  done  deja,  a  priori,  difficile  sur  un  animal  endormi. 
Un  argument  formel  permet  enfin  d'eliminer  definitivement  I'interven- 
tioii  d'un  tel  mccanisme:  la  constatation  de  reponses  soit  cochleaires,  soit 
corticales  (d'amplitude  augmentee  par  rapport  a  I'atat  de  veille)  (Fig.  8), 
alors  que  Taninaal  ne  se  reveille  plus  a  des  stimuli  acoustiques. 

Il  est  ainsi  etabli  que  le  processus  dccrit  sous  le  nom  d"habituation 
neuronale  afferente'  (Hernandez-Peon,  Jouvet  et  Scherrer,  1957)  n'entre 
pas  en  jeu  au  cours  de  I'habituation  de  la  reaction  d'cveil. 

(2)  —  Un  deuxieme  mccanisme  possible  consisterait  dans  une  'deafteren- 
tation'  du  S.R.  A.  A.  (deafferentation  non  specifique)  par  I'intervention  d'un 
mccanisme  inhibiteur  hypothctique  agissant  au  niveau  des  collatcrales 
issues  des  voies  specifiques  et  destinces  au  reseau  reticulaire  (Starzl, 
Taylor  et  Magoun,  1951;  French,  Verzcano  et  Magoun,  1953). 

Ainsi,  selon  la  suggestion  de  Sharplcss  (1954)  'This  inhibition  must  he 
exerted  on  coUateral  pathways  between  specific  auditory  system  and  the  fiial 
common  pathu'ay  of  the  reticuhn  activatuig  system  ...  ' 

Selon  cette  hypothesc,  le  S.R.  A.  A.  ne  serait  plus  mis  en  jeu  au  cours  de 
I'habituation  par  les  stimuli  du  mondc  exterieur,  les  afferences  specifiques 
—  a  elles  seules  —  n'etant  pas  capablcs  d'entraincr  un  cveil  (Lindsley  et 
col.,  1950;  French,  Verzcano  et  Magoun,  1953;  French  et  col.,  1952) 

La  possibilite  d'un  tel  mccanisme  est  infirmce  par   la  constatation   de 


460 


BRAIN    MECHANISMS    AND    LEARNING 


rcpoiiscs  cvoqiiccs  retiailaires  de  grande  amplitude  an  coiirs  dii  somnicil  physio- 
logiqiic,  diiraiit  riiahitiiatiflii  de  la  reaction  d'eveil  (Fig.  11).  Ccs  reponses 
peuvent  cependant  disparaitrc  lors  dc  la  narcosc  barbiturique  (voir 
egalcmcnt  Arduini  ct  Arduini,  1954). 


IV- 


Courbe  d'habituation  dc  la  reaction  d'cvcil  a  des  stimuli  acoustiques  chez  le  ineine 

animal  an  cours  de  4  seances  successives  a  un  jour  d'intcrvallc.  Lcs  pomts  blancs  reperent 

la  duree  de  I'Arousal  provoquc  par  un  stimulus  acoustique  different  et  nioins  fort  aprcs 

habituation. 

A  —  Habituation  a  un  son  de  500  c/s. 

B  —  Deshabituation,  apres  que  le  son  ait  etc  associe  10  fois  a  des  chocs  douloureux  sur  la 

patte.  II  persiste  toujours  une  mininie  activation. 
Habituation  de  la  reaction  d'cveil  a  un  son  de  2000  c/s  chez  un  animal  dccortiquc  subtotal 
ct  prive  de  ses  aires  acoustiques. 

Habituation  cfe  la  reaction  d'cveil  a  un  son  de  1000  c/s  chez  un  animal  aux  voies  speci- 
fiques  sectionnees  au  niveau  tlu  mcsenccphale. 


Il  rcste  done  lcs  deux  autres  hypotheses  a  examiner: 

(3)  —  soit  I'existence  d'un  niccanisnie  inhibiteur  autoehtone  reticulaire, 
expression  de  la  plasticite  des  neurones  du  S.R.A.A.  responsables  de 
I'evcil, 

(4)  —  soit  I'intervention  dun  mecanisnie  inhibiteur  extra  reticulaire 
agissant  sur  le  S.R.A.A. 


MICHEL    lOUVET 


461 


L' existence  de  difterents  niccaiiismcs  dc  sommeil  propres  a  chaque 
niveau  du  tronc  cerebral  (voir  chapitre  precedent)  permet  de  tester  ces 
deux  dernieres  hypotheses. 

Ainsi,  au  niveau  du  couple  S.R.A.A.  —  systeme  inhibiteur  rcticulaire 
rhonibencephalique,  I'ctude  de  I'habituation  de  la  reaction  d'evcil  (eveil 


S^2^ 


II 


Fig.  II 
Reponscs  cvoquees   rcticuhiires   (F.R.)    a   des   dies   lors   de   I'cveil   (I)    cC   du 
sommeil  (II). 

L'activite  spontanee  du  cortex  (C.  A.)  est  egalcincnt  cnregistree  a  vitesse  lente 
de  balayage  (oscilloscope). 


de  rarcheo-soninieil)  permet  de  tester  l'activite  autochtone  des  formations 
reticulaires  (en  dehors  de  toute  participation  neocorticale). 

Les  resultats  expcrimentaux  prouvent  alors  qu'il  est  impossible  d'habitur 
la  reaction  d'cveil  chez  I'animal  mesencephalique  chronique  ou  decortique 
chronique  —  I'animal  se  reveillant  constamment,  et  pour  un  temps  tres 
long,  a  chaque  stimulus  acoustique  (Fig.  12). 


462 


BRAIN    MECHANISMS    AND    LEARNING 


Les  mccanisnies  elementaircs  de  plasticitc,  rcsponsables  de  I'habituation, 
ne  seniblent  done  pas  avoir  iin  siege  reticulaire  mcsencephaliquc  ou  meme 
thalamique. 

Par  contre,  dcs  qu'apparaissent  les  signes  E.E.G.  d'lntercaction  S.R.A.A. 


•  •  •  • 


Fk:.  12 
Absence     d'habituation     chcz     un     .iniinal     incsenccphalique 
chronique  (I)  ct  decortiquc  (II). 

Chaque  point  represente  la  durcc  du  rcvcil,  au  cnurs  dc  4  seances 
success! ves  pour  i  et  3  seances  pour  II. 


—  systcme  diffus  inhibiteur  telenccphalique,  —  des  courbes  d'habituation 
peuvent  etre  obtcnucs  (animal  intact,  decortique'  subtotal,  a  section 
incomplete  du  tronc  cerebral  respectant  les  projections  inhibitrices  cortici- 
fuges  (Fig.   TO,  III,  IV).  CV.sY  <]ojic  au   Sy.^tciiw   hiliihitciir  Telenccphalique 


MICHEL  JOUVET  463 

qti'il  revieiit  iriiiliibcr  le  S.R.A.A.  au  corns  dc  V habituation  dc  la  reaction 
d'eveil.  Ce  systcmc  n'est  probablcmcnt  pas  I'apanagc  dune  aire  determince 
de  I'ccorcc,  puisque  I'habituation  rcstc  possible  aprcs  ablation  dcs  aires 
specifiques  acoustiques  (Sharpless,  Jasper,  1956)  (Fig.  10,  III). 

Le  cortex  frontal  joue  cependant  un  role  important  puisque  I'habitua- 
tion devient  tres  lente  aprcs  son  ablation  presquc  complete.  (Ce  pheno- 
mene  est  a  rapprocher  dcs  constations  de  Konorski  (1956)  —  qui  remarque 
un  ralcntissement  considerable  dc  processus  d'inhibition  chez  Ic  chien 
apres  ablation  des  lobes  frontaux). 

Le  systcme  inhibiteur  pcut  egalement  etre  mis  en  jcu  par  dcs  afFcrcnces 
non  specifiques  puisque  I'habituation  est  possible  aprcs  section  dcs  voies 
acoustiques  au  niveau  du  tronc  (Sharpless  et  Jasper,  1956)  (Fig.  10,  IV). 

Ces  affcrences  empruntent  alors  nccessairement  le  S.R.A.A.  Il  est 
possible  qu'ellcs  empruntent  les  voies  decrites  par  Scheibel  et  Scheibel, 
1957;  Nauta  et  Kuypers,  1957,  Brodal  et  Rossi,  1955,  et  qu'ellcs  soicnt 
responsablcs  ces  difterentes  modalites  de  conduction  au  sein  du  S.R.A.A. 
qui  ont  etc  dc'montrees  elcctrophysiologiqucment  (Adey  et  col.,  1957). 

Ainsi,  I'habituation  de  la  reaction  d'eveil  necessite  ime  part,  meme 
minimc,  d'ecorce  cerebrale.  La  delimitation  de  ce  systeme  inhibiteur 
agissant  sur  le  S.R.A.A.  est  difficile  dans  le  cas  dc  I'habituation  de  la 
reaction  d'eveil  car  I'aspect  E.E.G.  dc  sa  mise  en  jeu  est  masque  par 
I'activitc  de  sommeil.  C'est  pourquoi  I'ctude  de  ses  modalites  d'action  au 
cours  d'autres  phenomenes  d'apprentissage  negatif  est  importante.  Tel 
est  le  case  de  I'habituation  de  la  reaction  d'orientation. 


ni  —  L  HABITUATION    DE   LA    REACTION    D  ORIENTATION 

L'habituation  ou  extinction  de  la  reaction  d'orientation,  (ou  reflexe 
d'investigation,  ou  reflexe  de  'Qu-est-cc-que  c'est  que  ^a?'  Pavlov,  1929) 
prcsentc  de  tres  nombreuses  analogies  avec  I'habituation  dc  la  reaction 
d'eveil.  Cependant,  dans  le  cas  de  la  reaction  d'orientation  le  'gradient 
d'excitation'  est  moins  important.  Ce  n'est  plus  le  passage  du  sommeil 
profond  a  un  reveil  cortical  mais  le  passage  d'uii  etat  'relaxc'  de  I'animal  et 
de  son  trace  E.E.G.  cortical  a  un  etat  d'attention  spccifique  dont  le 
composantes  motrices,  pupillaircs,  psycho-galvaniques,  cardiaques, 
vasculaires,  respiratoires,  et  entin  electrocncephalographiqucs  ont  fait 
I'objet  de  tres  nombreux  travaux  (Anokhin,  1956;  Asratian,  1955; 
Berlyne,  1950;  Pavlov,  1929;  Rusinov,  1957;  Sokolov,  1953).  Un 
Congrcs  recent  lui  a  etc  specialement  consacre  (Moscou,  1957)  (voir 
egalement  Heissler,  1958). 


464  BRAIN    MECHANISMS    AND    LEARNING 

Qu'elle  soit  induite  par  uii  stimulus  nouvcau  (cffet  de  nouvcaute 
(Bcrlyne,  1950)  ou  par  un  signal  ontologiqucment  ou  historiquement 
signifiant  (conditionnement),  on  pcut  adnicttrc  que  la  reaction  d'orienta- 
tion  s'accompagne  au  niveau  du  systcnie  nerveux  d'une  augmentation 
d'amplitude  du  message  specifiquc,  dcs  I'etape  sous  corticale,  (Hernandez- 
Peon,  Schcrrer  et  Jouvet,  1957;  Galanbos,  1956)  chcz  I'animal  ou  chez 
riiomme  (Jouvet,   1957).  Cette  augmentation  porte,  avant  tout,  sur  la 


'J^u^^MHf*l^ 


B   Wf'f^l^^WjjV'^^^^^^^^^^ 


I       luMili  11" 


Fig.  13 
Rcponses  du  cortex  acoustique  a  des  dies. 
A.B.  —  Lors  de  reaction  d'orientation  (arousal). 

C  —  Extinction  de  la  reaction  d'orientation  (absences  d'arousal). 
Augmentation  des  reponses. 
D.E.  —  Inhibition  supra-liminale  —  La  presentation  des  dies  induit  des  ondes  lentes 
corticaics  (nienic  si  le  trace  de  base  est  rapide  (comparer  avec  B). 

phase  rapide,  surface  positive  de  la  reponse  et  certains  resultats  experi- 
mentaux  permettcnt  de  supposer  que  la  mise  en  jeu  du  S.R.A.A.  pourrait 
jouer  un  role  dans  cette  facilitation  (Dumont  ct  Dell,  1958;  Bremer  et 
Stoupel,  1958).  Cette  augmentation  d'amplitude  de  la  reponse  s'accom- 
pagne egalement  d'une  rcpartiton  plus  etendue  des  reponses  evoquces  au 
niveau  des  structures  sous-corticales  (Galambos  et  col.,  1956;  Yoshii,  1956) 
ou  du  cortex  (Jouvet  et  col.,  1956,  1957)  et  d'une  activation  de  I'ecorce 
dont  la  duree  est  le  meilleur  index  pour  objectiver  la  diminution  progres- 
sive de  I'activation  du  S.R.A.A.  au  cours  de  I'extinction  de  la  reaction 
d'orientation. 


MICHEL  JOUVET  465 

LES     ASPECTS     E.E.G.     DE     l'eXTINCTION     DE    LA     REACTION    d'oRIENTATION 

(Fig-  13) 

Deux  phases  distinctes  caracterisent  ce  processus  chez  Faiiiiiial  intact 
(Jouvet  et  col.,  1956,  1957;  Rollback,  1958;  Marsallon,  1959). 

(A)  —  Au  cours  dc  la  premiere  (Fig.  1  3  A,  B,  C)  (Fig.  14,  I),  I'activation 
corticale  induite  par  Ics  stimuli  (lumierc  suivic  dc  train  de  dies)  diminuc 
progressivemcnt  et  disparait.  Parallelement,  les  reponses  corticales  (7//<^'- 


C.i.fA 


C.A. 

C.5./A. 


II 


^MrrJyf^iW^  jilfyi 


V'VJw^r^^vwH^'^.Av^AvsJ.^  mir 


Fig.  14 
I  —  Reaction  d'orientatioii  a  la  prcsentatiiui  d'unc  liiinicrc  ct  d'un  train 

de  dies  a  8/sec. 
II  —  Inhibition  supra-liniinale  —  la  6enie  presentation  des  stimuli  au  cours 
de  la  3cme  seance  induit  des  ondcs  lentcs  corticales  (CA-CSM)  et 
reticulaires(FR),  augmentation  importante  des  reponses  corticales  alors 
que  les  reponses  du  noyau  cochleaire  (N.C)  ne  varicnt  pas. 

mentent  d'amplitude  aux  depens  surtout  de  leur  phase  lente  negative  et 
secondaire  positive.  En  meme  temps,  toute  re'action  motrice  de  I'animal 
disparait. 

(B)  —  Si  la  repc'tition  des  stimuli  est  poursuivie  (une  fois  par  minute 
environ),  et  si  ceux-ci  sent  presentes  sur  un  trace  cortical  d'eveil,  ils 


466  BRAIN    MECHANISMS    AND    LEARNING 

induisent  alors  des  ondcs  lentes  corticalcs  ct  sous  corticalcs  (Fi^.  13  D,  E) 

(Fig-i4,n). 

Ce  phenoinene  aboutit  cnhn  a  un  veritable  endormissement  (inhibition 
supra-liniinale  de  repetition)  dc  I'aninial-objective  sur  I'E.E.G. 

Che^  raiiiiiial  dccortiquL'  total,  aucune  variation  des  reponses  sous-corti- 
calcs  n'apparait  au  cours  de  la  repetition  des  stimuli.  La  reaction  d'orienta- 
tion  ne  pent  s'habituer  (Popov,  191 1;  Kvassov,  1956).  Enfni,  la  repetition 
dc  stimuli  'indiffcrents'  n'est  pas  capable  d'induirc  de  phenomenes  d'archco- 
sommcil  E.E.G.  aussi  bien  chez  I'animal  decortique  que  mesenccphalique. 

Les  structures  centrales  du  tronc  cerebral  ne  semblent  done  ^^s  primitivc- 
mcut  rcsponsables  de  I'installation  du  sommeil  au  cours  de  I'inhibition 
supra-liminale  de  repetition,  commc  I'hypothese  en  a  c'tc  soulevee 
recemmcnt  (Moruzzi,  1959;  Gastaut,  1957).  L'intcrvention  d'un  systhne 
iuliibitciir  tckiiccphalique  tn^issaiit  sur  le  S.R.A.A.  est  done  Ci^ak'iiiciit  indispen- 
sable a  Y extinction  de  la  reaction  d'orientatioii  et  a  l' apparition  de  phenoinene 
d'endorinissenient  (inhibition  supra-maxiniale). 


HYPOTHESES        CONCERNANT        LES        MLCANISMES        NEUROPHYSIOLOGIQUES 
d'action   du   SYSTEME  INHIBITEUR  TELENCEPHALIQUE 

L'apparition  de  variations  elcctriques  caracteristiques  chez  Tanimal  a 
cortex  intact,  au  cours  des  processiTs  d'apprentissagc  negatif,  alors  qu'au- 
cune  fluctuation  ne  s'observe  chez  les  animaux  dccortiques  ou  nu'sen- 
cephaliques,  conduit  a  abandomier  I'hypothese  qui  fait  de  I'habituation  de 
la  reaction  d'orientation  ou  de  la  reaction  d'eveil  un  processus  priniitivc- 
ment  reticulaire  (Gastaut,  1957)  car  aucim  mecanisme  inhibiteur,  capable 
d'apprentissagc  ne  semble  entrer  en  jeu  au  niveau  des  formations  rc'ti- 
culees  mesencephaliques  et  thalamiques  dcconnectees  du  neocortex. 
(Dans  le  cas  —  il  est  vrai  —  d'apprentissagc  positif,  certains  resultats 
contradictoires  de  conditionnement  obtenus  chez  des  animaux  decortiques 
peuvent  s'expliquer  —  selon  nous  —  par  le  fait  qu'une  partie  trcs  minime 
de  neocortex  soit  restec  en  place  (Lebedinskaia,  1935);  d'autre  part,  il  se 
pent  que  ccrtaines  lesions  rcticulaires  qui  enipechent  Tctablissement  de 
liaisons  diachroniques  (Hernandcz-PeeSn  et  col.,  1958)  agissent  par  I'inter- 
ruption  des  voics  corticifuges). 

Les  donnces  clectrophysiologiqucs  contu-ment  done  I'hypothese  de 
Pavlov  sur  le  role  capital  du  cortex  (La  misc  en  jeu  d'un  freinage  de 
I'ecorce  sur  le  S.R.A.A.  a  etc  mise  en  evidence  recemment,  en  experience 
aigue,  au  niveau  du  reflexe  monosynaptiquc  (Hugelin  et  Bonvallet,  1957, 
a,  b).  L'inhibition  corticifuge  serait  alors  mise  en  jeu  par  I'excitation  de  la 


MICHEL   JOUVET  467 

formation  reticulce  et  agirait  en  manicrc  dc  'feed  back'  imnicdiat.  Une 
telle  modalite  operationnellc  semblc  incompatible  avec  Ics  processus 
d'apprentissage  ncgatif). 

Chez  I'animal  a  cortex  intact,  Taugmentation  importante  de  la  phase 
lente  negative  et  positive  de  la  rcponse  corticale  aux  stimuli  apparait 
comme  un  processus  important,  puisqu'elle  precede  toujours  I'extinction 
complete  de  V'aroiisaF  et  I'apparition  des  ondes  lentes  reticulaires  (dont  on 
sait  I'origine  corticale). 

De  nombreux  arguments  permettent  d'attribuer  ces  phases  secondaires 
negative  et  positive  a  une  reponsc  corticifuge,  expression  de  I'activitc 
d'lnterneurones  corticaux  (Bremer,  1934;  von  Euler,  Magoun  et  Ricci, 
1957),  ou  expression  de  I'actii'itc  di:^  dendrites  de  I'ecorce  (Roitback,  1953, 
1955;  Purpura  et  Grundfest,  1956;  Clare  et  Bishop,  1955)  etc.  Quelle  que 
soit  sou  orioiiie,  cerre  phase  secoiulaire  senihle  represeiiter  la  traduction 
d'wie  oude  d'iuliibitio}i  ai^issaut  sur  le  S.R.A.A.  Au  cours  de  I'apprentissage 
negatif,  tout  se  passe  comme  si  les  processus  plastiques  ou  'integratifs' 
reticulaires  (Fessard,  1954),  dont  certaines  modahtes  ont  etc  mises  en 
evidence  au  cours  du  conditionnemcnt  (Buser,  Hernandez-Peon  et  Jouvet, 
1958),  ctaient  sous  la  dependance  d'inHux  inhibiteurs  corticifuges,  dont 
I'aspect  au  niveau  de  I'ecorce  est  rcpresente  par  la  phase  secondairc  de  la 
reponsc,  les  fuseaux  et  les  ondes  lentes. 

Ainsi,  sous  Tinfluence  de  la  repetition  de  stimuli  'indifterents'  un  change- 
ment  d'excitabilite  de  I'ecorce  apparait  selon  un  processus  qui  teste  encore 
a  etre  determine.  L'intervcntion  du  rhinenccphale  est  possible  puique  Ton 
sait  que  sa  stimulation  est  capable  d'induire  un  ralentissement  de  I'activitc 
corticale  (Segundo  et  col.,  1954);  celle  du  'systeme  diffus  thalamique'  pent 
egalement  etre  invoquec  puisquc  de  nombreux  arguments  expcrimentaux 
montrent  qu'il  est  responsable  des  phenomenes  de  synchronisation  et  des 
potentiels  negatifs  observes  au  niveau  de  I'ecorce  (Jasper,  1949,  I954  J  Li  et 
col.,  1956). 

Mais  quel  que  soit  Ic  determinisme  de  cc  changement  diachronique 
d'excitabilite  corticale,  une  ctape  indispensable  a  tout  phenomcne  d'ap- 
prentissage negatif  est  representee  par  I'inhibition  corticifuge  diffuse 
agissant  sur  le  S.R.A.A. 

Elle  a  pour  coroUaire,  au  niveau  de  la  formation  reticulce,  I'apparition 
d'ondes  lentes,  soit  spontanees,  soit  accompagnant  la  reponse  rcticulaire 
(Fig.  15).  La  propagation  de  I'activitc  lente  corticale  au  sein  du  S.R.A.A. 
semble  s'effectuer  seloii  des  processus  origiiiaux,  et  se  fait  en  general  avec  un 
certain  delai  par  rapport  au  cortex  car  son  installation  est  lente.  Parmi 
toutes  les  hypotheses  possibles  pour  cxpliquer  I'influence  inhibitrice  de 

HH 


468  BRAIN    MECHANISMS    AND    LEARNING 

I'ecorce  sur  le  S.R.A.A.,  il  se  pourrait  —  selon  la  suggestion  de  Scheibel 
(1957)  —  que  des  effets  electroniques  induits  par  I'ecorce  puissent  agir  sur 
le  S.R.A.A.  afiii  dc  modifier  la  propagation  des  messages  au  niveau  des 
voies  pauci  et  multisynaptiques  de  la  formation  reticulee,  selon  des 
mecanismes  semblables  a  ceux  decrits  par  Barron  ct  Matthews  (1938)  au 
niveau  de  la  moelle. 


.CA. 


XR. 


Fig.  15 
I  —  Reponses  du  cortex  acoustique  monopolaire  et  de  la  formation  reticulee  bipolaire  a  un 
signal  acoustique. 

1  —  Lors  du  reflexe  d'orientation. 

2  —  Lors  de  I'extinction  du  reflexe. 

Apparition  d'une  onde  positive  secondaire  corticale  et  d'une  reponse  secondaire  reticulaire. 
Calibrage:  2o:milli-secondes,  50  microvolts. 


La  premiere  phase  du  sommeil,  ou  phase  tclcncephaliquc,  semblc  mettre 
enjeu  des  processus  analogues.  Ccttc  phase  acqiiisc  au  coiirs  dc  revolution  et 
de  la  teleucephalisation  tradiiirait  aiusi  la  repouse  de  Fecorce  aux  stinuili 
iridiffereiits  que  coustitue  iiotre  ein^irointenient  lorsque  nous  nous  endornious. 


RESUME 


I  —  Les  processus  d'apprentissage  negatif  apparaissent  comme  Tune  des 
formes  les  plus  simples  de  liaisons  diachroniques.  lis  se  traduisent  par  la 
diminution,  puis  la  disparition  d'une  reponse  du  systcme  nerveux  a 
certains  stimuli,  lorsquc  ceux-ci  sont  longucment  rcpctes  sans  cffet  nocif 
pour  I'organisme. 


MICHEL  JOUVET  469 

Par  ses  rapports  etroits  avcc  rcndormisscnicnt  et  le  sommcil,  I'apprcn- 
tissagc  ncgatif  posscdc  unc  singularitc  dynamiquc  qui  I'opposc  a  I'apprcn- 
tissage  positif;  c'est  pourquoi,  Tctudc  des  mecanismcs  du  sommcil  doit 
etre  abordcc  en  premier. 

II  —  Les  correlations  E.E.G.  des  variations  veille  —  sommeil  ont  ainsi 
cte  etudiees  sur  trois  series  d'animaux  chroniques  (intacts,  decortiqucs  et 
mcsencephaliques).  Des  arguments  experimentaux  sont  apportcs  en 
faveur  de  I'existence  de  deux  systemes  inhibiteurs  mis  en  jeu  au  cours  du 
sommeil : 

Le  premier  systeme  necessite  le  cortex.  Son  action  inhibitrice  se  traduit 
par  I'apparition  de  'fuseaux'  et  d'ondes  lentes  au  niveau  du  cortex,  du 
dienccphale  et  de  la  F.R.  mcsenccphalique,  alors  que  I'activite  de  la  F.R. 
pontique  demeure  rapidc  ct  qu'il  pcrsiste  un  certain  tonus  musculaire. 
Les  ondes  lentes  meso-diencephaliqucs  sont  absentes  chez  I'animal  decor- 
tique  et  n'apparaissent  pas  en  arricre  d'une  section  du  tronc  cerebral 
pratiquee  a  la  limite  posterieure  du  diencephale. 

Le  deuxieme  systeme  s'accompagne,  chez  toutes  les  preparations 
chroniques,  de  I'apparition  de  'fuseaux'  au  niveau  de  la  F.R.  pontique  en 
meme  temps  que  disparait  totalement  le  tonus  musculaire  et  qu'apparait 
une  activitc  rapide  generalisee  aux  structures  rostrales  du  nevraxe  (phase 
paradoxale  du  sommeil).  C'est  sur  I'interaction  de  ces  deux  systemes 
inhibiteurs,  tclencephalique  et  rhombencephalique,  et  du  S.R.A.A.  que  les 
processus  de  base  de  I'apprentissage  negatif  ont  etc  etudies. 

III  —  L'habituation  de  la  reaction  d'evcil  ne  pent  s'expliquer  par  une 
deafterentation  specifique  ou  non  specifique  puisque  des  reponses  evoquecs 
de  grande  amplitude  continuent  a  etre  cnregistrces  au  niveau  des  voies 
specifiques  ou  de  la  F.R.  au  cours  du  sommeil. 

Il  ne  s'agit  pas  non  plus  d'un  processus  inhibiteur  primitivement 
reticulaire  car  on  ne  pent  habituer  la  reaction  d'eveil  auxdepens  de  la 
phase  paradoxale  du  sommcil  chez  I'animal  dccortique  ou  mcsenccphali- 
que. 

Des  arguments  en  faveur  dc  Tintcrvcution  du  systeme  inhibiteur  tclen- 
cephalique sont  exposes. 

IV  —  L'habituation  de  la  reaction  d'orientation  subit  les  memcs  lois  que 
celles  de  la  reaction  d'eveil.  Elle  ne  pent  etre  obtenue  chez  I'animal  dccor- 
tique chronique.  Chez  I'animal  intact,  cc  processus  s'accompagne  de 
correlations  E.E.G.  qui  objcctivent  la  misc  en  jeu  du  systeme  inhibiteur 
tclencephalique  (ondes  lentes  corticales  et  rcticulaires). 


470  BRAIN    MECHANISMS    AND    LF.ARNINf; 

V  —  Dcs  hypotheses  sont  cniin  cniiscs  pour  cxpliqucr  Ic  mode  d'action 
du  systcmc  mhibitcur  tclcnccphahquc  au  niveau  du  S.R.A.A.,  ct  le  role 
probable  des  dendrites  de  I'ccorcc  est  cvoque  a  ce  sujet. 


Research  on  the  Neurophysiological  Mechanisms  of  Sleep  and  on 
Some  Types  of  Negative  Learning 

SUMMARY 

Negative  learning  (habituation,  extinction  ot  the  orientating  reflex)  is 
one  of  the  simplest  types  of  learning  since  it  involves  usually  excitation 
from  only  one  receptor.  It  may  be  defined,  after  Thorpe,  as  an  activity  of 
the  central  nervous  system  whereby  innate  responses  to  certain  stimuli 
w^aiic  as  the  stimuli  are  repeated  for  long  periods  without  unfavourable 
result.  It  has  been  shown  that  habituation  cannot  be  explained  by  fatigue 
or  'adaptation'  at  the  receptor  level  and,  since  Pavlov,  the  relationship 
between  habituation,  extinction,  'internal  inhibition'  and  sleep  are  well 
known. 

Since  the  problem  oi  filling  asleep  is  intimately  related  with  negative 
learning,  we  shall  consider  first  some  experimental  facts  which  suggest 
that  two  different  mechanisms  at  least  act  during  sleep.  Then,  we  shall 
describe  some  evidence  concerning  the  intervention  of  one  of  these 
mechanisms  during  two  types  of  negative  learning:  the  habituation  of  the 
arousal  reaction  and  the  habituation  of  the  orientation  reaction. 

I.  observations  postulating  the  existence  of  two  inhibitory  systems, 

TELENCEPHALIC    AND    RHOMBENCEPHALIC,    ACTING    DURING    PHYSIOLOGICAL 

SLEEP 

Since  sleep  involves  the  total  behaviour  ot  the  organism,  its  mechanisnr 
has  to  be  studied  in  relation  to  environment.  Thus,  in  brain  transsection 
techniques,  we  must  mainly  analyse  that  part  of  the  nervous  system  which 
is  in  relation  with  the  external  world  through  its  main  afferent  and  efferent 
pathways. 

It  is  well  known  that  a  neodecorticated  animal  can  sleep.  A  sleep-waking 
rhythm  has  also  been  shown  to  occur  in  chronic  mesencephalic  cats,  but 
there  is  no  such  pcrit>dicity  at  the  isolated  spinal  level. 

We  recorded  the  electrical  correlates  of  such  sleep-waking  rhythm  in 
three  types  of  chronic  preparations:  normal,  neodecorticated  and  mesen- 
cephalic cats  bearing  chronicallv  implanted  multipolar  electrodes  in  various 
cortical  and  subcortical  locations. 


MICHEL  JOUVET  471 

The  electrical  activity  of  the  brain  was  recorded  and  correlated  with  a 
number  of  somatic  signs  of  sleep:  sleep  posture,  aspect  of  pupils  and 
nictitating  membranes,  rectal  temperature,  respiratory  rhythms,  E.K.G. 
We  found  that  one  of  the  best  signs  of  sleep  was  the  E.M.G.  of  the  nucchal 
muscles. 

1.  Normal  dns  (Figs.  1-2).  Two  opposite  E.E.G.  patterns  were  observed 
during  physiological  sleep: 

A.  The  first  sta(^c  is  well  known  (drowsiness  and  sleep).  Spindles  and 
slow  waves  were  recorded  at  tlic  cortical,  diencephalic  and,  later,  at  the 
mesencephalic  reticular  level.  The  ventral  hippocampus  may  show  a 
'spike-like'  activity.  In  contrast,  the  electrical  activity  at  the  pontine 
reticular  level  remained  fast.  During  this  stage,  the  E.M.G.  of  nucchal 
muscles  decreased  but  did  not  disappear.  The  threshold  of  arousal  by 
stimulation  of  the  mesencephalic  reticular  formation  was  found  to  be 
higher  during  the  slow  wave  activity  than  during  spindle  activity. 

B.  The  second  sra(^c  or  'paradoxical  staoc'  (Fig.  i,  III,  2,  III):  It  begins 
suddenly  (always  after  the  first  stage)  and  is  characterized  by  a  low 
voltage  fast  electrical  activity  at  the  cortico-diencephalo-mcsencephalic 
level  comparable  with  the  arousal  pattern.  But  the  pontine  reticular 
formation  usually  presents  a  spindle  activity. 

Behaviourally,  the  cat  was  soundly  asleep  and  there  was  a  total  disap- 
pearance of  any  E.M.G.  activity.  Some  very  rapid  jerks  of  the  vibrissae 
and  movements  of  the  eyes  were  frequently  seen.  Spontaneously,  or 
induced  by  any  stimulus,  the  cat  may  go  back  to  the  first  stage  of  sleep  or 
awaken. 

During  the  paradoxical  stage,  the  threshold  oi  arousal  (by  direct 
stimulation  of  the  R.F.)  was  higher  than  during  the  slow  wave  stage. 

2.  Ncodccorticatcd  Cat  (Figs.  3-4).  In  such  preparations,  the  mesodicn- 
cephalic  activity  remained  constantly  fast  with  a  low  voltage.  Neither 
spindles  nor  slow  wave  could  be  recorded,  week  after  week,  during  the 
wake-slccping  cycle,  even  after  injection  of  narcotic  doses  of  Nembutal. 

Diiriii<i  the  paradoxical  sta(^e,  a  'spindling  activity'  was  recorded  at  the 
pontine  reticular  formation  level.  Concomitantly  the  liippocampus 
showed  an  arousal  type  ot  activity. 

The  same  behavioural  phenomena  as  are  found  in  normal  cats  occurred 
during  this  last  stage. 

Suhtotally  ueodecorticated  cats  (Fig.  5) :  If  a  very  small  part  of  frontal  or 
ten;poral  cortex  was  left  intact  during  the  decortication,  the  patterns  ot 


472  BRAIN    MECHANISMS    AND    LEARNING 

electrical  activity  during  the  two  stages  of  sleep  were  the  same  as  in  intact 
animals. 

Mesencephalic  cats  (Fig.  6) :  RostraUy  (i.e.  in  front  of  the  transsection),  the 
cortex  and  the  diencephalon  had  the  'cerveau  isole'  type  of  electrical 
activity  with  monotonous  spindles  and  slow  waves  which  might  persist  for 
several  days. 

Catidally  (behind  the  transsection),  the  mesencephalic  reticular  formation 
presented  continuous  fast  activity  and  no  slow  wave  or  spindle  could  be 
recorded.  Only  the  paradoxical  stage  was  present:  rhythmic  'spindles'  at 
the  rhombencephalic  level  during  which  the  cat  had  a  behavioural  sleep 
posture  with  complete  atonia.  This  stage  would  thus  appear  as  an  'archeo- 
sleep'  for  a  preparation  which  possessed  only  an  archeo-encephalon 
related  to  the  external  world. 

If  the  transsection  of  the  brain  stem  was  not  total,  slow  waves  were 
recorded  at  the  mesencephalic  reticular  formation  and  the  patterns  of 
electrical  activity  during  the  two  stages  of  sleep  were  usually  similar  to 
those  of  the  intact  animal  (Fig.  5).  These  facts  lead  to  the  following  con- 
clusions (Fig.  7) : 

Sta{ie  I  of  sleep : 

Since  the  threshold  of  arousal  was  raised  during  the  slow  wave  activity 
in  the  reticular  formation,  this  slow  _activity  must  be  inhibitory.  Since  no 
slow  activity  could  be  recorded  at  the  mesencephalic  level  in  a  totally 
neodecorticated  cat,  or  behind  a  total  transsection  of  the  brain  stem,  one 
may  conclude  that  the  inhibitory  slow  waves  arc  a  descending  activity 
and  that  they  require,  at  least,  the  integrity  of  a  small  part  of  the  cortex. 
Thus,  the  first  stage  of  sleep  would  appear  to  be  the  result  of  the  activity 
of  some  telencephalic  inhibitory  system  acting  upon  the  ascending 
activating  reticular  system. 

Sta(^e  2  or  paradoxical  staqe: 

[a)  Since  the  behavioural  aspects  of  the  paradoxical  stage  are  the  same  in 
intact,  decorticated  and  mesencephalic  cats,  and  since  during  this  phase  a 
peculiar  activity  appears  at  the  pontine  reticular  formation  level,  one  may 
conclude  that  this  rhombencephalic  region  is  directly  related  to  this  stage. 
This  structure  appears  to  act  caudally  and  suppresses  totally  the  tonic 
muscular  activity.  It  is  suggested  that  this  effect  could  be  mediated  through 
the  supra  spinal  control  of  the  Gamma  system. 

{b)  The  appearance  of  a  fast  activity,  at  the  mesodiencephahc  and  cortical 
levels  during  this  stage  is  paradoxical  since  the  level  of  sleep  is  deeper  than 
in  the  first  stage  and  not  intermediary  between  sleep  and  waking.  Such  a 


MICHEL  JOUVET  473 

cortical  activity  has  already  been  found  in  cats  and  human  beings  (Demcnt- 
Kleitnian)  and  some  arguments  suggest  that  it  could  reflect  a  dream 
activity. 

Since  negative  learning  is  concerned  with  the  occurrence  of  sleep,  its 
aspects  (habituation  of  the  arousal  in  sleeping  cats,  and  habituation  of  the 
orientation  reflex  in  awake  cats)  were  studied  in  relation  to  the  telen- 
cephalic  inhibitory  slow  waves  (stage  i)  and  the  rhombencephalic  spindle 
activity  (stage  2). 

II.    THE    HABITUATION    OF   THE   AROUSAL 

Repetition  of  a  specific  tone  which  initially  produces  long  lasting 
arousal  of  a  sleeping  cat,  fails  to  do  so  after  several  trials.  A  study  of  the 
effects  of  variations  of  the  stimulus  and  of  the  effects  of  total  neodecortica- 
tion  and  transscction  of  the  brain  stem  upon  this  habituation  phenomenon 
has  led  to  the  following  conclusions  (Fig.  9) : 

(1)  Habituation  of  the  arousal  docs  not  depend  on  changes  (i.e.  'block- 
age', 'inhibition')  occurring  in  the  specific  auditory  pathways  or  m  the 
non-specific  ascending  pathways  (mesencephalic  reticular  formation) 
since  cochlear,  reticular  (Fig.  11)  and  cortical  auditory  potentials  (Fig.  8) 
of  great  amplitude  were  recorded  during  complete  habituation  of  the 
arousal. 

(2)  Habituation  of  the  arousal  does  not  depend  on  some  intrinsic 
inhibitory  reticular  mechanism  since  it  is  not  possible  to  obtain  habituation 
of  arousal  (as  judged  on  the  arousal  from  stage  2  of  sleep)  in  chronic 
mesencephalic  or  neodecorticated  cats  (Fig.  12). 

(3)  Habituation  of  the  arousal  may  be  obtained  in  cats  with  subtotal 
transscction  of  the  brain  stem  cir  in  subtotally  decorticated  cats.  The 
smaller  the  cortical  surface  left  intact,  the  longer  is  the  process  of  habitua- 
tion (Fig.  10). 

(4)  These  results  suggest  that  the  habituation  of  the  arousal  reaction 
depends  on  the  entry  in  action  of  a  rostral  inhibitory  system  (in  which  the 
neocortex  is  an  essential  relay)  which  acts  downwards  upon  the  ascending 
activating  system. 

III.    HABITUATION    OF    THE    ORIENTATING    REFLEX 

Novel  indifferent  stimuli  (light  and  intermittent  tone)  evoke  an  orienta- 
ting reflex  in  an  awake  cat.  They  rapidly  tailed  to  do  so  if  repeated 
(habituation  of  the  orientating  reflex).  If  these  stimuli  were  repeated  still 
further,  a  stage  of  behavioural  sleep  may  be  obtained  (Pavlovian  internal 
inhibition). 


474  BRAIN    MECHANISMS    AND    LEARNING 

(i)  During  the  habituation  of  the  orientating  reflex  in  intact  cats,  a 
marked  enhancement  of  the  secondary  negative  and  positive  phase  of  the 
cortical  (Figs.  13-15)  evoked  potentials  of  the  indifferent  stimuli  was 
observed,  and  a  similar  enhancement  of  a  secondary  wave  could  be 
recorded  at  the  reticular  level  (Fig.  15).  This  phenomenon  precedes  the 
appearance  of  induced  bursts  of  spindles  and  slow  waves  at  the  cortical, 
diencephalic  and  fmally  at  the  reticular  level,  and  it  leads  to  the  appearance 
of  stage  I  of  sleep  (Figs.  13-14). 

(2)  Habituation  of  the  orientating  reflex  did  not  occur,  or  at  least  was 
irregular,  in  neodecorticated  cats.  Repetition  of  stimuli  did  not  induce 
changes  of  the  subcortical  evoked  potentials  and  did  not  induce  sleep. 

(3)  Repetition  of  indifferent  stimuli  failed  to  induce  the  'archeo-sleep' 
in  a  mesencephalic  cat. 

(4)  It  is  suggested  that,  during  habituation  of  the  orientating  reflex, 
indifferent  stimuli  may  trigger  the  inhibitory  telencephalic  system  which 
acts  upon  the  reticular  activating  system. 


CONCLUSION 

(i)  There  exists  a  rostral  mhibitory  system  (in  which  the  neocortex 
plays  a  foremost  role)  which  acts  upon  the  reticular  activating  system 
during  the  first  stage  of  sleep.  Its  electrical  manifestation  is  the  appearance 
of  spindles  and  slow  waves  first  at  the  corticodiencephalic  and  later  at  the 
mesencephalic  levels.  This  system  is  plastic  and  can  be  triggered  by 
repetition  of  indifferent  stimuli  during  habituation  of  the  arousal  and  of 
the  orientating  reflex. 

It  is  suggested  that  the  late  component  of  the  cortical  evoked  response 
and  the  triggered  slow  waves  which  are  recorded  during  habituation 
(and  which  may  represent  a  cortical  dendritic  activity)  are  the  electrical 
manifestation  of  the  corticofugal  inhibitory  influence. 

(2)  There  exists  also  a  caudal  inhibitory  system  (in  which  the  reticular 
formation  of  the  pons  plays  a  major  role)  which  is  responsible  for  the 
second  stage  of  sleep  (paradoxical  stage).  This  system  acts  caudally  on  the 
motor  outflow,  inhibiting  the  muscular  tone  and  triggering  an  'arousal- 
like' activity  in  the  structures  rostral  to  the  pons.  When  this  system  is 
active,  a  'spindling'  activity  is  recorded  at  the  pontine  reticular  level  in 
intact,  decorticated  and  mesencephalic  cats  (in  which  this  activity  may 
represent  the  entry  in  action  of  some  archeo-sleep  mechanism).  This 
activity  cannot  be  induced  by  repetition  of  stimuli  and  there  is  no  evidence 


MICHEL  JOUVET  475 

that  this  caudal  inhibitory  system  could  be  responsible  for  any  negative 
learning  in  mesencephalic  and  ncodccorticated  cats. 

(3)  Habituation  of  the  arousal  reaction  and  of  the  orientating  reHex 
necessitates  the  intervention  of  an  active  telcncephalic  inliibitory  system. 

GROUP   DISCUSSION 

Magoun.  I  wonder  if  Dr  Jouvct's  findings  resemble  those  of  Hugelin  and 
lionvallct,  who  have  proposed  the  existence  of  a  negative  feedback  from  the  cortex 
to  the  lower  brain  which  checks  the  latter's  ficilitating  effects  upon  motor  activity. 

They  proposed  that  EEG  arousal,  evoked  by  reticulo-cortical  stimulation,  in- 
duced a  recurrent  inhibition  of  brain  stem  activity.  Can  the  inability  of  your 
decorticate  animal  to  display  slow  waves  in  the  thalamus  in  sleep,  be  attributed  to 
elimination  of  such  corticifugal  inhibition ;  Have  you,  or  have  the  group  in  Pisa,  in 
studies  of  the  slow  wave  activity  of  the  'cerveau  isole',  ever  stimulated  the  cortex  to 
sec  whether  it  is  possible  to  block  slow  wave  activity  in  the  thalamus  ?  Can  reduction 
of  spindle  activity  in  the  thalamus  of  the  'cerveau  isole'  be  used  to  test  the  cortici- 
fugal inhibition  oi  brain  stem  activity  proposed  by  Hugelin  and  Bonvallet? 

JouvET.  I  am  aware  of  the  experiments  oi  Hugelin  and  Bonvallet  and  of  their 
hypothetic  negative  feed  back.  But  I  consider,  for  the  following  reasons,  that  the 
mechanism  which  would  act  during  the  first  stage  of  sleep  is  quite  different: 

(i)  The  time  course  oi  these  two  inhibitory  mechanisms  is  very  different. 

In  Hugelin  and  Bonvallet's  experiments  the  inhibitory  action  of  the  cortex  takes 
place  in  a  very  short  time  (several  milliseconds),  hi  our  chronic  experiments, 
recording  directly  at  the  reticular  level,  we  could  usually  observe  the  appearance 
of  the  slow  waves  manv  minutes  after  the  beginning;  ot  slow  activity  at  the  cortical 
level. 

(2)  But  the  main  objection  is  this:  according  to  Hugelin  and  Bonvallet,  one 
may  get  inhibition  ot  the  reticular  formation  by  stimulation  of  the  reticular 
formation  itself  (negative  feed  back).  In  our  cases,  when  we  stimulated  the  reticular 
formation  at  the  beginning  or  during  sleep,  we  always  got  arousal,  as  is  well 
known.  If  the  inhibitory  action  of  the  cortex  was  driven  by  the  reticular  formation 
(as  suggested  by  Hugelin  and  Bonvallet)  we  would  have  expected  an  augmentation 
of  slow  waves. 

I  cannot  answer  you,  concerning  the  stimulation  of  the  cortex  in  the  'cerveau 
isole'  preparation,  because  we  have  not  done  it. 

Naquet.  This  winter  while  doing  some  experiments  on  anoxia  in  the  decere- 
brate cat  with  Fernandez-Guardiola  I  found  during  the  recover\'  period  after 
anoxia  some  spindles  on  the  anterior  lobe  of  the  cerebellum. 

JouvET.  I  also  recorded  on  the  cerebellum  and  I  found  this  spindle  activity,  but 
with  much  lower  voltage. 

Naquet.  Don't  you  think  they  come  from  the  cerebellum  = 

JouvET.  I  don't  think  so,  but  I  have  no  definite  proof  up  to  now. 

Naquet.  Have  you  tried  to  explore  the  habituation  for  click  stimuli  in  the 
cochlear  nucleus  in  your  mesencephalic  cat? 

JouvET.  I  could  never  obtain,  even  in  a  series  of  intact  animals,  a  consistent  decrease 
of  acoustic  evoked  potentials  at  the  cochlear  nucleus  level  bv  repetition  of  clicks 


476  BRAIN    MECHANISMS    AND    LEARNING 

(afferent  neuronal  habituation).  So  I  considered  that  this  phenomenon  was  not  a 
good  index  to  objectivate  negative  learning  in  other  types  of  preparation,  such  as 
decorticated  or  chronic  mesencephalic  cats. 

Palestini.  I  would  like  to  mention  experimental  data  strongly  suggesting  the 
presence  of  a  hypnogenic  structure  in  the  caudal  brain  stem.  I  want  to  point  out  also 
that  slides  showing  the  mesencephalic  lesions  done  by  Dr  Jouvet  suggested  that 
the  connections  with  cerebellum  and  hippocampus  are  not  severed  and  it  is 
possible  that  they  may  be  in  the  brain  stem  reticular  formation.  Lastly,  the  increase 
in  the  positive  wave  has  been  found  in  conditioning  and  also  after  pre-trcgiminal 
section  in  cats. 

Jouvet.  If  I  understood  the  work  of  the  Moruzzi  school,  these  authors  postulate 
the  existence  of  both  a  group  of  tonically  ascending  excitatory  cells  in  the  upper 
pons  and  an  ascending  synchronizing  mechanism  in  the  lower  pons  or  behind. 

From  our  results,  it  seems  that  a  lower  pontine  mechanism  acts  mostly  caudally 
(on  the  motor  outflow)  because  wc  observe  a  striking  absence  of  EMG  activity 
during  the  'paradoxal  stage'  of  sleep.  There  must  be  some  relationship  between  the 
fact  activity  we  observe  during  this  stage  of  sleep  and  the  rather  continuous  fast 
activity  shown  by  the  MPP  cat.  Did  someone  record  at  the  pontine  level  in  this 
type  of  preparation? 

BusER.  How  long  after  the  decortication  did  you  make  your  recording  and  ob- 
serve the  absence  of  slow  waves ;  Could  there  not  be  any  secondary  effect  (degenera- 
tion) which  actually  would  be  responsible  for  the  disappearance  of  thalamic  slow 
patterns  after  decortication. 

Jouvet.  There  have  been  some  papers  about  EEC  in  decorticate  animals,  mainly 
those  of  Morison  and  Bassett  (1945),  and  Kennard  (1943)-  These  papers  were 
concerned  with  acute  experiments.  In  sUch  conditions  these  authors  could  record 
spindles  at  the  thalamic  level  immediately  after  the  decortication.  In  our  chronically 
decorticate  cats  we  could  not  get  any  spindles  or  slow  waves  when  we  began  to 
record  (usually  6  to  12  hours  after  the  decortication).  This  fact  has  been  recently 
confirmed  by  Sergio  and  Longo  in  Rome,  working  on  chronic  rabbits. 

In  some  cats,  at  the  subcortical  level,  we  could  record  slow  waves  and  spindles 
during  sleep,  but  a  careful  anatomical  and  histological  control  shows  us  cortical 
cells  left  in  place.  This  fact  eliminates,  in  part,  the  possibility  of  some  degeneration 
or  hypcrsensitization  effects. 

Segundo.  The  following  observations  illustrate  the  participation,  as  demon- 
strated by  the  possibility  of  either  'habituating'  or  'conditioning'  the  response,  of 
learned  issues  in  the  determination  of  arousal. 

(A)  Habituation.  Habituation  of  arousal  from  sleep  was  described  by  Sharpless 
and  Jasper  and  similar  attenuation  was  shown  recently  to  involve  recovery  from 
animal  'hypnosis',  a  condition  that  behaviourally  and  clcctrographically  resembles 
natural  sleep  (Sharpless  and  Jasper,  1956;  Silva,  Esiable  and  Segundo,  I959)- 
Further  studies  by  Apelbaum  and  collaborators  on  EEC  'arousal'  habituation  have 
shown  that,  if  a  cat  was  primarily  'habituated'  to  a  'basic'  tone  of  200  c.p.s.  and 
then  series  of  other  tones  (202-500  c.p.s.)  were  presented,  the  responsiveness  of  the 
animal  to  the  latter  was  modified  in  a  characteristic  manner.  Initially,  tones  close  to 
200  (e.g.  202,  205,  210,  220  c.p.s.)  did  not  induce  EEG  'arousal',  whereas  tones 
removed  from  200  (230-500  c.p.s.)  did.  As  more  series  were  applied  to  each  cat,  the 
remaining  tones  gradually  became  inoperant  following  a  succession  in  which  tones 


MICHEL  JOUVET  477 

closer  to  the  'basic'  frcqucncv  lost  ctficacy  earlier.  Finally,  all  'test'  tones  were 
inopcrant.  These  observations  confirmed  that  specificity  of  habituation  ot  EEG 
'arousal'  is  not  absolute,  involving  a  certain  degree  of 'generalization'  (5-20  c.p.s. 
in  200  c.p.s.).  Secondly,  the  biased  progress  of  habituation  to  'test'  tones  indicated 
that  after  having  learned  not  to  respond  to  one  pitch,  learning  not  to  respond  to 
similar  frequencies  was  facilitated.  Obviously,  the  process  determining  habituation 
of  EEG  'arousal'  to  a  given  pitch  affects  also  mechanisms  subserving  'activation'  to 
other  tones,  in  a  manner  related  strictly  to  the  frequency  arrangement  upon  the 
pitch  continuum  (Apelbaum,  Silva,  and  Frick  1959)  Apelbaum,  Silva,  Frick  and 
Segundo,  /;;  preparation). 

(B)  Coiiditiotiiii^.  Tones  reinforced  (during  wakefulness)  by  various  absolute 
stimuli  have  been  presented  to  naturally  sleeping  cats.  The  following  conclusions 
could  be  drawn. 

(i)  The  effectiveness  of  each  sound  in  provoking  arousal  (EEG  and  behavioural) 
depended  on  the  absolute  excitation  currently  associated  with  it:  reinforcement 
with  centre  median  or  mesencephalic  reticular  stimulation  conferred  marked 
arousing  potency  (Segundo,  Roig  and  Sommer-Smith,  1959);  reinforcement  with 
painful  subcutaneous  stimulation,  less  so  (Galeano,  Roig,  Segundo  and  Sommer- 
Smith,  1959);  reinforcement  with  cessation  of  painful  subcutaneous  stimulation  or 
with  application  of  amvgdaloid  or  caudate  stimulation,  little  or  no  efficiency 
(Roig,  Segundo,  Sommer-Smith  and  Galeano,  1959;  Segundo,  Galeano,  Sommer- 
Smith  and  Roig,  this  voltiDic). 

(ii)  Certain  discriminatory  capabilities  subsist  during  natural  sleep  and  enable  the 
animal  to  differentiate  positive  (usually  reinforced)  from  negative  (usually  non- 
reinforced)  stimuli;  awakening  takes  place  on  presentation  of  the  former  but  does 
not  occur  after  the  latter.  A  degree  of  generalization  exists,  however,  and  is  greater 
for  the  EEG  'arousal'  response  than  for  the  behavioural  reaction;  namely,  if  200 
c.p.s.  are  reinforced  (and  210,  225  and  250  are  not  reinforced)  EEG  'arousal'  will  be 
produced  by  200,  210,  225  and  250  c.p.s.  tones;  behavioural  arousal  on  the  other 
hand  only  bv  200  and  210  c.p.s.  (Segundo,  Roig  and  Sommer-Smith,  1959). 

(iii)  Conditioned  inhibitory  stimuli  tend  to  have  'hypnogenic'  qualities.  Fig.  i 
illustrates  this  'depressant'  influence  of  'negative'  excitations  contrasting  with  the 
arousing  potencv  of  the  'positive'  stimulus  (tone)  (Segundo,  Roig  and  Sonnner- 
Smith,  1959). 

Consequently,  and  confirming  observations  from  everyday  life,  learned  issues 
participate  in  determination  of  awakening. 

Hernandez-Peon.  Drs  George  Bach-y-Rita  and  H.  Brust-Carmona  in  my 
laboratory  have  done  some  experiments  on  mesencephalic  cats  recording  from  the 
cochlear  nucleus  and  they  observed  a  significant  reduction  of  the  auditory  poten- 
tials by  repeating  the  same  acoustic  stimulus  which  has  similarities  to  the  same  kind 
of  habituation  observed  in  the  intact  cat.  We  think  that  it  is  possible  to  obtain 
habituation  in  the  mesencephalic  cat.  Dr  Jouvet  showed  desynchronized  tracings 
in  the  mesencephalic  reticular  formation  both  in  the  intact  cat  during  deep  sleep  and 
in  the  mesencephalic  cat  which  he  believes  to  be  permanently  awake.  How  does  he 
decide  when  the  desynchronized  tracing  represents  sleep  and  when  wakefulness? 

Jouvet.  We  use  many  indexes  of  behavioural  sleep,  including  the  classical 
posture  of  the  cat,  the  aspect  of  the  pupils,  the  nictitating  membranes,  the  rhythm 
of  respiration,  the  heart  rate,  the  drop  of  rectal  temperature.  But  we  think  that  the 


47S 


BRAIN    MECHANISMS    AND    LEARNINC; 
EFFECT  OF  COND.  INH.  STIM. 


CONT. 


S-M   CO.      ■wKw^miMMiiOiiim'^wi  i»i»«iiVt>»i«>«> 


AFTER        COND.        INH.       STIM.      (BUZZ.) 


^/4j^^*)**^f^/,^<iw^;^v^^  .  M^^l'\r4^tf,%U<^WAM 


AFTER      COND.      STIM.  (T) 


Fk;.  I 
Contrasting  cticcts  of 'negative'  and  'positive"  stimuli.  During  training  the  following  stimuli 
were  presented  to  this  animal :  (i)  Absolute  direct  electrical  excitation  of . . .  (effects  not  depicted 
in  this  figure).  (2)  Conditioned  or  'positive':  a  1600  c.p.s.  tone  (currently  reinforced  by  i)-  (3) 
Conditioned  inhibitory  or  'negative' :  a  buzzer  (when  tone  was  preceded  by  buzzer,  the  former 
was  never  reinforced).  EEG  from  sensory  motor  cortex.  Upper  line:  control.  Middle  line: 
repeateci  application  of  buzzer  ('negative'  excitation)  produced  a  condition  that  bchaviourally 
and  electrographically  resembled  sleep;  two  successive  stages  are  shown  (left,  right).  Lower 
line:  application  of  tone  ('positive'  excitation)  provoked  immediate  arousal.  Abbreviations: 
BUZZ.,  Buzzer;  COND.,  Conditioned;  CONT.,  Control;  INH..  Inhibitory;  STIM.. 
Stimulus;  T.,  Tone. 

Calibration:  100  u  v  i  sec.  (unpublished  figure  from  work  by  Scgundo,  Roig  and  Soinmer- 
Sniith,  1959). 


MICHFL   jOUVET  479 

best  index,  just  as  iii  man,  w  ould  be  the  muscle  tone.  In  cats,  the  best  place  to  record 
it,  is  the  nucchal  muscles.  We  never  use  the  EEG  alone  to  decide  if  the  animal  is 
sleeping,  but  we  correlate  the  EEG  and  these  indexes.  That  is  the  advantage  of  the 
polygraphic  recording. 

Grastyan.  Fast  activity,  during  sleep  was  first  described  by  Kleitman  and 
Dement  who  found  it  to  be  characteristic  ot  dreaming.  Dement  has  also  found  it  in 
cats.  It  was  surprising  to  find  at  the  same  time  that  a  continuous  slow  activity  in  the 
hippocampus  existed,  in  this  stage  of  the  sleep.  We  have  never  seen  so  continuous 
and  marked  slow  waves  in  an  aroused  animal.  We  have  tried  to  influence  and 
artificially  elicit  this  activity  and  found  that  in  deep  sleep,  stimulation  of  the 
reticular  formation  by  a  mild  electrical  stimulus  has  provoked  this  dream-like 
activity,  without  any  sign  of  a  behavioural  arousal.  We  observed  as  you  did,  that 
the  cat  loses  his  tone,  but  I  cannot  agree  with  you  that  this  stage  represents  a 
deeper  stage  of  sleep  than  that  oi'  the  slow  activity.  The  first  evidence  is  that 
stimulation  of  the  reticular  formation  could  induce  this  activity.  If  we  stimulated 
with  strong  stimuli  we  got  a  full  arousal.  I  think  that  the  fast  activity  observed  on 
the  neocortex  sleep  is  a  partially  aroused  state  of  the  nervous  system,  a  stage  between 
the  deepest  sleep  and  full  arousal. 

JouvET.  As  far  as  I  know,  it  was  first  reported  in  1955  by  Rimbaud,  Passouant 
and  Cadilhac  that  it  is  possible  to  record  fast  activity  during  behavioural  sleep  in 
cats.  The  problem  of  the  level  of  sleep  is  ditiicult.  If  we  use,  as  a  measure  of  this 
level,  the  threshold  of  behavioural  arousal  by  stimulation  of  the  reticular  forma- 
tion, we  found  a  higher  threshold  during  the  paradoxal  stage  than  during  the  first 
stage  oi  sleep.  We  don't  know  what  is  the  behavioural  interpretation  of  this 
paradoxal  stage.  We  are  faced  with  a  very  peculiar  pattern  of  nervous  activity. 
There  is  some  evidence  which  permits  us  to  think  that  this  activity  represents 
dreams.  But  dreams  are  perhaps  a  routine  activity  of  the  brain  during  sleep,  the 
function  of  which  is  unknown 

REFERENCE 

Apelbauin,  J.,  Silva.  E.  E.  and  Frick,  O. :  Frequency  discrimination  and  "armisar  reaction. 
18.  XXI  International  Congress  of  Physiolot^ical  Sciences.  Buenos  Aires,  August  y-15, 
I'jyj.  Abstracts  of  Communications. 


CORPUS  CALLOSUM   AND  VISUAL  GNOSIS 


Ronald  E.  Myers 


A  full  account  oi  brain  mechanisms  in  Icarmng  must  be  concerned  at 
the  same  time  with  definition  of  structure  and  function.  Yet,  an  essential 
lack  of  knowledge  of  both  the  anatomy  anti  physiology  of  learning  needs 
at  once  to  be  confessed,  clarification  of  these  problems  having  up  to  now 
been  approached  only  in  their  more  gross,  macro  context. 


Normal 


After  Mid-Chiasma 
Section 


Fig.  I 


Optic  chiasnia-section  results  in  uTiii.itcr.il  restriction  of  retm.il  .iffereiit  stmuiiatioii. 

The  present  discussion  will  unfortunately  carry  us  only  a  short  step 
closer  to  our  goal  of  understanding.  We  shall  be  concerned  with  a  side 
issue  —  that  of  characterizing  the  mechanism  of  exchange  of  information 
between  the  two  brain-halves  and  this  only  as  it  involves  visual  learning. 

Cats  were  used  as  subjects  in  the  experiments  to  be  described.  All  of 
these  cats  were  first  subjected  to  mid-sagittal  transection  of  the  crossing 

481 


482  BRAIN    MECHANISMS    AND    LEARNING 

retinal  fibres  at  the  optic  chiasnia.  This  altered  the  rctino-ceutral  relations 
such  that  excitations  from  each  eye  were  conducted  in  an  afferent  sense 
only  to  the  brain-half  on  the  same  side,  as  illustrated  in  Fig.  i.  Thereafter, 


Fig.  2 
Chiasma-sectioned  cat  with  one  eye  masked.  A  shifting  of  tlie  nia^k  troiu  one 
eye  to  the  other  results  in  a  shift  of  retinal  afferent  stimulation  from  one  brain- 
half  to  the  other. 

by  occluding  one  or  the  other  eye  it  was  possible  in  these  cats  to  determine 
which  of  the  two  brain-halves  was  to  receive  afferent  visual  stimulation 
during  any  given  visual  experience.  A  simple  rubber  mask  was  used  as 
shown  in  Fig.  2  to  be  applied  only  during  periods  ot  training  or  testing. 


RONALD    E.    MYERS 


483 


The  chiasma-sectioned  cats  were  taught  visual  pattern  discrimination 
responses  through  one  eye.  In  this  procedure,  the  food-deprived  and 
monocularly  masked  animals  were  placed  in  an  enclosed  darkened  training 
box  (see  Fig.  3).  The  box  presented  at  one  end  two  transilluminated 
translucent  visual  patterns  held  in  separate,  swinging  doors  situated  side 
bv  side.  The  different  sets  of  paired  patterns  used  in  the  experiments  are 


Fig.  3 
Training  box  used  for  establishment  of  pattern  discrimination  responses.  A  cat 
is  introduced  into  starting  chamber  at  the  right  end  of  the  bo.x.  Lifting  of  doors 
contained  in  the  mid-panel  admits  the  cat  to  the  choice  chamber  to  the  left.  The 
animal  chooses  by  pushing  on  the  swinging  doors  containing  the  patterns. 
Correct  choice  is  rewarded  by  a  morsel  of  food  (see  insert). 


portrayed  m  Fig.  4.  A  push  on  the  door  containing  one  pattern  of  a  pair 
was  arbitrarily  and  consistently  rewarded  by  the  hungry  animal  fmding 
food  beyond;  a  push  on  the  door  containing  the  second  pattern  of  the  pair 
was  punished  by  the  door  not  opening,  an  annoying  buzzer  sounding,  and 
sometimes  a  verbal  reprimand  being  given.  Following  each  such  choice 
occurrence,  the  animals  were  trained  to  return  to  the  opposite  end  of  the 
box  and  were  removed  from  the  choice  situation  by  intervening  panels 
n 


484 


BRAIN   MECHANISMS   AND   LEARNING 


a 


b 


I 


n 


ni 


lY 


Y 


Fig.  4 
Pairs  of  test  patterns  used.  In  describing  a  discrimination 
taught  to  an  animal  the  positive  pattern  is  hstcd  first.  For 
example,  in  discrimination  I-ab,  the  positive,  rewarded 
pattern  is  a  circular  flat  patch  of  white  against  a  black  back- 
ground while  the  negative  pattern  is  a  similar  square  patch. 


RONALD    E.    MYERS  485 

being  lowered.  The  choice  situation  was  then  programmed  for  the  next 
response  by  the  patterns  being  exchanged  or  not  exchanged  between  the 
doors  according  to  a  predetermined  chance  sequence;  the  appropriate 
stimulus  door  being  baited ;  and  the  intervening  panels  again  lifted  allow- 
ing access  to  the  choice  chamber.  The  cats  were  subjected,  in  general,  to 
40  such  training  experiences  or  'trials'  each  day.  After  a  period  of  such 
training,  usually  from  a  few  days  to  a  few  weeks  according  to  the  diffi- 
culty of  the  response,  the  animals  achieved  the  criterion  of  learning  on  a 
given  discrimination,  choosing  the  'correct'  pattern  34  or  more  times  in 
40  trials.  After  the  animals  had  learned  the  discriminations  they  were  over- 
trained usually  up  to  400  additional  trials  to  stabilize  performance. 

A  successful  or  high  level  performance  by  the  animal,  assuming  ade- 
quate control  for  undesired,  non-visual  clues,  may  be  interpreted  to  mean 
that  the  animal  can  see,  that  he  perceives  a  difference  between  the  two 
discriminanda,  and  that  his  response  to  the  stimuli  is  in  keeping  with 
antecedent  experience  or  conditioning  in  the  training  situation.  This  latter 
capacity  of  specifying  objects  in  relation  to  prior  experience  may  be 
defined  as  (Gliosis  from  the  Greek  word  meaning  kiiowk'dge,  and  implies 
contribution  from  intact  memory  mechanisms.  The  specification  of 
objects  in  terms  o( gnosis  must  be  set  off  from  their  specification  in  terms 
o(  dimensions,  location  or  movement  or  in  terms  o(  colour,  brightness  or  the 
like.  Our  primary  interest  in  this  paper  will  be  with  I'isncil gnosis. 

PROBLEM  I.  IS  THERE  A  SYSTEM  OF  GNOSTIC  INTERCOMMUNICATION  BETWEEN 

THE    BRAIN-HALVES? 

Nine  chiasma-scctioned  cats  were  used  in  this  first  experiment.  Four 
were  taught  only  a  single  discrimination  through  one  eye  (see  Table  I). 
Cat  Mnun  may  be  described  as  illustrative  of  this  group.  Mmm  was  taught 
and  overtrained  on  discrimination  I-ab  while  using  the  right  eye.  Final 
performance  through  this  eye  was  39  correct  in  40  trials.  Did  this  cat 
know  using  the  left  eye  the  pattern  discrimination  he  had  been  taught 
using  the  right  eye?  First  performance  through  the  right  eye  was  38 
correct  in  40  trails.  This  initial  performance  through  the  untrained  eye 
compared  very  favourably  with  the  final  performance  through  the 
trained  eye. 

The  remaining  five  of  the  chiasma-scctioned  cats  were  taught  two  or 
more  separate  discriminations,  usually  one  through  each  eye.  Cat  Bgw 
may  be  taken  as  generally  illustrative  of  all  these  animals.  Bgw  was  taught 
pattern  discrimination  Ill-ab  while  using  his  left  eye.  After  criterion  of 


486  BRAIN    MECHANISMS    AND    LEARNING 

learning  had  been  reached  and  he  had  been  overtrained  80  trials  on  this 
response  the  mask  was  reversed  and  B(^w  was  taught  a  second  discrimina- 
tion, Il-ab,  while  using  the  right  eye.  After  this  second  response  had  been 
similarly  established  and  overtrained  80  trials,  the  cat  received  further 
blocks  of  overtraining  using  alternately  the  left  and  right  eyes.  In  the 
end  Bgw  experienced  400  overtraining  trials  through  each  eye,  each  on  its 
own    respective    discrimination.    Final    overtraining    performance    with 

Table  I 

INTEROCULAR    TRANSFER    IN    CATS    WITH    OPTIC    CHIASMA    SECTIONED 


Number  correct  on 

Number  correct  on 

Cut 

Eye 
trained 

Discrimination 

final  40  trials 
with  trained  eye 

first   40   test   trials 
with  untrained  eye 

Mmm 

R 

I-ab 

39 

38 

Bgw 

L 
R 

Ill-ab 
Il-ab 

40 
38 

39 

37 

Css 

L 
R 

Il-ab 
Ill-ab 

39 

40 

33 
39 

Bsh 

L 
R 
R 

Ill-ab 

IV-ab 

Il-ab 

40 
40 
36 

39 

27 
34 

Sll 

R 
L 

Ill-ba 
V-ab 

40 
40 

34 
39 

Brn 

R 
L 

Ill-ab 
IV-ab 

40 
39 

38 
30 

Kns 

R 

IV-ab 

39 

21 

Pll 

R 

Il-ab 

38 

34 

Hrl 

R 

IV-ab 

38 

35 

discrimination  Ill-ab  was  40  correct  in  40  and  with  discrimination  Il-ab, 
38  correct  in  40. 

On  tests  of  cross-availability  of  knowledge  run  through  the  'untrained' 
eyes  B^iw  chose  the  correct  pattern  39  times  out  of  40  on  transfer  testing 
with  discrimination  Ill-ab  and  37  times  out  of  40  on  testing  with  dis- 
crimination Il-ab.  The  few  errors  made  were  scattered  throughout  the 
test  session  and  were  not  necessarily  made  during  the  first  trials. 

Examination  of  Table  I  reveals  that  in  all  instances  but  three  the  per- 
formance using  the  untrained  eye  compares  favourably  with  that  using 


RONALD    E.    MYERS  487 

the  trained  eye.  The  three  exceptional  cases  {Bsh,  Brii,  and  Kiis)  will  be 
discussed  later  (under  Problem  V)  as  examples  of  figural  equivalence 
effects  affecting  level  of  interocular  transfer. 

From  the  above  study  it  was  concluded  that  there  exists  a  well-ordered 
system  of  intercommunication  between  the  brain-halves  exhibiting  a 
competence  sufficient  to  handle  experiential  or  gnostic  information. 

PROBLEM   II.    WHAT  IS   THE   NEURAL   BASIS   FOR   THE  VISUAL   GNOSTIC   INTER- 
COMMUNICATION   PROCESS? 

The  corpus  callosum  seemed  a  most  likely  structure  subserving  such  a 
function  because  of  its  very  large  size  and  its  relation  as  commissural 
linkage  par  excellence  between  the  cerebral  hemispheres.  Conversely,  it 
was  difficult  to  delineate  any  other  well-defined  commissural  system  that 
would  likely  be  capable  of  such  differentiated  and  complex  contribution  as 
would  seem  necessary  for  the  gnostic  transfer  activity.  None  the  less, 
review  of  the  relatively  few  carefully  controlled  studies  of  corpus  callosum 
function  yielded  surprisingly  few  hints  of  defects  following  its  total 
destruction  or  absence  in  man  or  animal. 

Despite  this  disappointingly  negative  story  derived  from  the  literature, 
interocular  transfer  tests  were  extended  to  cats  having  section  of  both  the 
optic  chiasma  and  the  corpus  callosum.  Cat  Mniw,  described  above  as 
having  demonstrated  high  level  transfer  of  discrimination  I-ab  from  the 
right  eye  to  the  left  eye,  was  one  of  six  cats  used  in  the  present  study  and 
may  serve  as  an  illustrative  case. 

Following  section  of  corpus  callosum^  and  a  post-operative  recovery 
period  of  21  days,  Aliniii  was  taught  discrimination  Ill-ba  while  using  the 
right  eye  and  Il-ab  while  using  the  left  eye.  He  was  then  given  400  over- 
training trials  on  each  of  these  responses  through  the  respective  'trained' 
eyes.  Final  performance  during  overtraining  was  40  correct  in  40  with 
discrimination  Ill-ba  and  38  correct  in  40  with  discrimination  Il-ab.  On 
tests  of  transfer  to  the  'untrained'  eyes  performance  on  discrimination 
Ill-ba  was  20  correct  in  40  trials  and  on  discrimination  Il-ab  19  correct  in 
40  trials.  Performance  was  seen  to  drop  from  the  consistent  high  level 
obtained  through  the  trained  eye  to  a  chance  level  through  the  untrained 
eye.  This  remarkable  result  was  similarly  observed  on  tests  run  with  the 
other  animals  in  this  series  in  all  instances  but  three  (sec  Table  II). 

In  one  of  these  exceptional  instances,  performance  was  significantly 

'  Along  with  section  of  the  fibres  of  the  corpus  callosum  there  was  always,  in  this  study, 
concomitant  section  of  a  contingent  of  fibres  of  the  psalterium  because  of  the  hitter's  close 
apposition  to  the  inferior  surface  of  the  corpus  callosum  in  its  posterior  extent. 


488 


BRAIN    MECHANISMS    AND    LEARNING 


poorer  than  chance,  and  in  the  other  two  it  was  significantly  better  than 
chance.  The  first  cat,  Brd,  was  taught  discrimination  I-ab  through  the  right 
eye  and  Ill-ba  through  the  left  eye.  Performance  on  transfer  tests  of 
discrimination  I-ab  through  the  left  eye  was  only  13  correct  in  40.  This 
below  chance  performance  indicated  not  only  lack  of  transfer  but  revealed 
also  a  definite  preference  for  the  negative,  I-b  pattern.  Inspection  of  the 
patterns  of  the  two  responses  made  it  seem  likely  that  the  preference  for 
I-b,  while  using  the  left  eye  was  due  to  its  resemblance  to  the  positive 
pattern  of  discrimination  Ill-ba  already  established  through  this  eye. 

Table  II 

INTEROCULAR   TRANSFER   IN    CATS    WITH    OPTIC    CHIASMA    AND    CORPUS    CALI OSUM 

SECTIONED 


Cat 

Eye 
trained 

Discriwiihitioii 

Number  correct  on 

final  40  trials 

with   trained  eye 

Number  correct  on 

first  40  trials 
with  untrained  eye 

Slv 

R 

I-ab 

40 

20 

Mmm* 

R 
L 

Ill-ba 
Il-ab 

40 
38 

20 
19 

Brd 

R 
L 

I-ab 
Ill-ba 

40 
40 

13 
20 

Knt 

R 
L 

Il-ab 
Ill-ab 

35 
40 

19 
20 

Bgw* 

L 

V-ab 

40 

34 

Hnr 

R 
L 

V-ab 
Ill-ab 

40 
40 

28 
20 

*  Priiir  training  experience  (see  Table  I). 

Bij^w  appeared  to  recall  discrimination  V-ab  on  tests  through  the  un- 
trained right  eye.  This  cat  had  earlier  been  taught  discrimination  Il-ab 
through  this  same  eye  (see  Bgw,  Table  I).  The  preference  for  pattern  V-a 
expressed  during  the  transfer  testing  may  have  been  due  to  a  previously 
unsuspected  similarity  between  this  pattern  and  positive  pattern  Il-a  of 
discrimination  Il-ab.  This  interpretation  was  strongly  supported  when 
subsequent  work  with  a  normal  cat  showed  a  near  100  per  cent  generaliza- 
tion from  discrimination  Il-ab  to  discrimination  V-ab.  In  such  a  generaliza- 
tion the  cats  presumably  responded  to  some  general  feature  of  the  two  sets 
of  patterns  such  as  smallness  versus  largeness  or  concentration  versus 
diffuseness  (see  Fig.  4). 


RONALD    E.    MYERS  489 

Hiir  failed  to  show  any  evidence  of  transfer  of  discrimination  Ill-ab 
from  the  left  eye  to  the  right;  however,  tests  of  transfer  of  discrimination 
V-ab  from  the  right  eye  to  the  left  showed  a  performance  better  than 
chance  (28  40).  Figural  equivalence  effects  may  again  have  accounted  for 
the  partial  transfer  although  these  figures  have  not  been  tested  in  this 
respect.  That  the  apparent  transfer  was  due  to  effects  other  than  a  central 
neural  intercommunication  was  strongly  indicated,  however,  by  the  great 
ease  with  which  Hiir  was  thereafter  taught  the  inverse  discrimination  V-ba 
with  the  untrained  left  eye.  Cat  Miiiiii  has  also  evidenced  no  cross  inter- 
ference after  corpus  callosum  section  when  the  two  eyes  were  separately 
taught  inverse  discriminations  (Ill-ab  and  Ill-ba). 

The  considerations  just  described  led  to  the  conclusion  that  the  apparent 
transfer  of  the  learned  responses  between  the  eyes  seen  in  the  instances 
of  Bj^'N'  and  Hfir  and  the  depression  of  performance  below  a  chance  level 
seen  in  the  instance  oiBrd  were  related  not  to  the  contribution  of  a  com- 
missural linkage  other  than  the  corpus  callosum  between  the  brain  halves 
but  to  figural  generalization  effects  arising  from  similarities  between 
patterns  of  the  separate  discriminations  taught  the  separate  eyes. 

From  the  foregoing  experiment  it  is  clear  that  the  cross-availability  of 
information  between  the  two  hemispheres  in  regard  to  the  significance  of 
complex  visual  pattern  stimulation  occurs  through  the  corpus  callosum. 
In  the  absence  of  corpus  callosum  visual  learning  and  recall  may  occur 
independently  in  the  two  hemispheres  given  independent  sensory  stimula- 
tion. One  hemisphere,  under  the  circumstances,  may  support  learned 
visual  responses  conflicting  completely  with  responses  subsumed  by  the 
other  hemisphere  without  cross-interference. 

Subsequent  work  (Sperry,  Stamm  and  Miner,  1956)  has  shown  that 
cats  with  optic  chiasma  and  corpus  callosum  sectioned  must  relearn  anew 
with  one  eye  pattern  discriminations  learned  with  the  other  eye,  the 
curves  of  relearning  through  the  'untrained'  eye  tending  to  reduplicate 
even  in  detail  the  learning  curves  obtained  during  initial  learning  through 
the  'trained'  eye.  This  latter  experiment  tends  to  further  accentuate  the 
interpretation  that  no  information  leaks  across  the  mid-line  relative  to 
visual  pattern  discriminative  learning  in  the  absence  of  corpus  callosum. 

PROBLEM     in.     TO     WHAT     EXTENT     DOES     GNOSTIC     INTERCOMMUNICATION 
RESULT    IN    CONTRALATERAL    MEMORY    TRACE    ESTABLISHMENT? 

During  the  monocular  training  in  the  chiasma-sectioned  cat,  a  stable 
and  lasting  change  is  induced  in  the  'trained'  hemisphere  receiving  the 


490  BRAIN    MECHANISMS    AND    LEARNING 

direct  afferent  stimulation.  This  change  has  been  called  the  memory  trace. 
Its  stability  is  attested  to  by  the  uniformity  of  performance  found  day  after 
day  during  the  periods  of  overtraining  of  the  learned  responses.  Its 
persistence  is  attested  to  by  the  fact  of  imaltered  performance  on  testing 
after  periods  free  of  training  of  up  to  a  year. 

The  effects  of  the  monocular  training  on  the  'untrained'  hemisphere  not 
receiving  the  relevant  direct  afferent  excitations  are  not  known.  Is  a  trace 
system  developed  in  this  second  hemisphere  independent  of  that  induced 


AAA 


Fig.  5 
The  normal  cat  can  consistently  discriminate  the  positive 
central  pattern  (an  equilateral  triangle)  from  any  of  the 
closely  similar  surrounding  patterns  (Sperry,  Miner  and 
Myers,  1955).  Compare  this  with  the  comparative  coarseness 
of  the  discriminations  depicted  in  Fig.  4  some  of  which 
begin  to  tax  the  discriminative  capacity  of  the  chiasma- 
sectioned  cat. 


in  the  first  hemisphere  receiving  direct  stimulation?  If  so,  how  do  the  two 
trace  systems  compare  in  terms  of  definition  or  capacity  r 

Explorations  of  these  questions  have  been  carried  out  in  two  ways : 
(i)  by  transfer  testing  of  chiasma-sectioned  animals  who  have  had  ablation 
of  cortex  from  the  'trained'  hemisphere  subsequent  to  training,  (2)  by 
transfer  testing  of  chiasma-sectioned  animals  who  have  had  complete 
transection  of  corpus  callosum  subsequent  to  training.  In  this  study  two 
underlying  assumptions  have  been  made:  (i)  the  memory  trace  system 


RONALD    E.    MYERS 


491 


of  pattern  visual  learning  resides  within  or  is  dependent  upon  cortex,  and 
(2)  transection  of  corpus  callosum  completely  removes  one  hemisphere 
from  the  sway  of  the  other  as  regards  aid  and  abetment  in  visual  gnosis. 
The  consequence  of  'trained'  cortical  ablation  on  contralateral  mne- 
monics may  be  dealt  with  first.  Fourteen  chiasma-sectioned  cats  were 
monocularly  taught  one  or  both  of  the  two  discriminations,  Ill-ab  and 
Il-ab.  Discrimination  Ill-ab  is  an  'easy'  discrimination  while  discrimination 
Il-ab  is  relatively  much  more  'difficult'  as  determined  by  the  number  of 
trials  needed  for  the  animals  to  learn,  the  general  level  of  sustained  pcr- 


Table  III 


PERFORMANCE   WITH    UNTRAINED   EYE   ON   DISCRIMINATION   III-AB   AFTER 
DESTRUCTION    OF    CONTRALATERAL    'tRAINEd'    CORTEX 


re. 

t  perfonuaiii 

e  on 

succes 

sive 

days  as  nimiber 

correct  in  sets  0 

f40 

Eye 

Cat 

tested 

Lesion  type 

1st 

2nd 

3rd 

Msy 

L 

R ;  minimal 

37 

— 

— 

Msf 

L 

R;  minimal 

37 

— 

Grs 

L 

R;  minimal 

20 

3<'> 

40 

Fst 

R 

L;  moderate 

30 

3S 

38 

Pin 

R 

L;  moderate 

-27 

40 

— 

Crw 

R 

L;  moderate 

28 

3-1 

38 

Spc 

L 

R;  moderate 

3i 

38 

— 

Csw 

L 

R;  moderate 

40 

— 

— 

Sch 

L 

R;  moderate 

37 

— 

— 

Chr 

L 

R;  moderate 

39 

— 

— 

Nkm 

R 

L;  extensive 

7/10 

* 

Knm 

R 

L;  extensive 

37 

^ 

— 

My  11 

L 

R;  extensive 

-7 

37 

40 

Nkm  refused  to  run  after  10  test  trials,  having  erred  in  the  last  3. 


formaiicc  during  overtraining,  and  the  general  behaviour  of  tlic  aiumals 
in  the  training  situation.  It  may  be  stated  parenthetically  tliat  the  visual 
capacity  of  the  chiasma-sectioned  cat  as  determined  by  the  difficulty  ot 
discriminations  that  may  be  learned  is  vastly  inferior  to  that  of  tlie  normal 
cat  (sec  Fig.  5). 

After  the  monocularly  trained  discriminations  had  been  established  and 
stabilized  by  overtraining,  cortex  was  surgically  removed  from  the 
'trained'  hemisphere.  The  cortical  removals  were  of  three  general  types  as 
illustrated  in  Fig.  6.  The  minimal  type  lesion  comprised  removal  of  cortex 
generally  recognized  as  the  striate  or  primary  visual  receptive  cortex;  the 


492 


BRAIN    MECHANISMS    AND    LEARNING 


Msy 


Chr 


Myn 


Fig.  6 
Stylized  diagrams  depicting  extent  of  cortical-removal  from  the  'trained' 
hemisphere  in  the  three  lesion-types.  Variations  in  extent  of  lesion  within 
a  group  were  minor. 


RONALD    E.    MYERS 


493 


moderate  type  lesion,  removal  of  the  striate  plus  adjoining  cortex  generally 
believed  to  be  visual  in  import;  and  the  maximal  type  lesion,  removal  of 
all  cortex  exclusive  of  the  anterior  pole  containing  the  sensorimotor 
cortex.  The  deep-lying  ganglionic  masses  as  well  as  piriform  cortex  were 
left  undamaged  by  these  procedures. 

After  a  post-operative  recovery  period  of  at  least  12  days,  performance 
levels  were  tested  for  the  first  time  through  the  opposite  untrained  eye. 
The  results  obtained  with  discrimination  Ill-ab  are  given  in  Table  III  and 
with  discrimination  Il-ab  in  Table  IV.  If  the  results  of  Table  III  arc  con- 
sidered together  regardless  of  lesion  type  represented,  about  half  revealed 
high  level  performance  on  the  first  day  of  testing  and  the  remainder  a  high 
level  performance  by  the  second  day.  Fig.  7  represents  in  graphic  form 
performance  of  two  of  these  cats  showing  greater  (C/;r)  and  lesser  {Alyii) 

Table  IV 

PERFORMANCE    WITH     UNTRAINED    EYE    ON    DISCRIMINATION    II-AB    AFTER 
DESTRUCTION    OF    CONTRALATERAL    'tRAINED'    CORTEX 


Eye 
tested 

Lesion  type 

Test  performance  on 

siiccessit'e  days  as  number 

correct  in  sets  of  40 

Cnt 

1st 

2nd 

jrd 

4th 

Chr 

Myn 

Bhf 

L 
L 
L 

R;  moderate 
R;  extensive 
R;  extensive 

25 
18 

2} 

25 
21 

25 
21 

32 
25 

degrees  of  interocular  transfer.  The  general  outcome  bespeaks  good  recall 
on  the  tests  through  the  untrained  eye  following  cortical  extirpation 
from  the  contralaterally  lying  'trained'  hemisphere.  However,  if  this 
outcome  is  closely  compared  to  that  obtained  on  transfer  testing  after 
chiasma-section  alone  (without  the  superimposed  cortical  removal)  it  is 
clear  that  the  cortical  removal  resulted  in  some  decrement  in  contralateral 
recall  (contrast  discrimination  Ill-ab,  Table  I  with  discrimination  Ill-ab, 
Table  III). 

The  numbers  of  cats  included  in  this  study  trained  on  the  more  difficult 
discrimination  Il-ab  have  been  few  but  results  obtained  have  been  con- 
sistent. Reference  to  Table  IV  shows  that  in  all  instances  performance  on 
the  first  day  of  testing  did  not  differ  greatly  from  chance  and  that  through 
subsequent  days,  performances  only  gradually  improved.  Fig.  8  represents 


494 


BRAIN    MECHANISMS    AND    LEARNING 


curves  of  Clir  and  Myii  on  discrimination  Il-ab  depicting  initial  learning 

through  one  eye  and  relearning  through  the  second  eye  post-operatively. 

Four  chiasma-sectioned  cats  were  used  to  explore  the  induced  gnostic 

capabilities  of  the  'untrained'  hemisphere  as  tested  following  post-training 


20r 


o 


o 
o 


<v 

£ 

3 


0 


0 


Chr 


Sets 


5 
of 


10 


15 


twenty   trials 


20r 


o 
u 


(V 

£ 

3 


0 


0 


Myn 


Sets 


5  10  15 

of    twenty    trials 

Fig.  7 
Performance  of  Chr  and  Myn  with  discrimination  Ill-ab. 
The  soHd  Hne  represents  initial  training  with  one  eye,  while 
the  dashed  line  represents  performances  achieved  through  the 
second,  untrained  eye.  C/;r illustrates  immediate  recall  through 
the  untrained  eye,  while  Myn  gives  evidence  of  considerablc 
saving  in  relearning  through  the  untrained  eye. 


corpus  callosum  section.  Performance  levels  as  post-operatively  tested 
through  both  the  trained  and  untrained  eyes  are  given  in  Table  V.  Krni 
and  B(7(('  may  be  taken  as  illustrative  cases.  Kriii  was  taught  and  over- 
trained on  discrimination  Ill-ba  and  V-ba  while  using  the  left  and  right 


RONALD    E.    MYERS 


495 


eyes  respectively.  Krm  achieved  perfect  scores  on  tinal  overtraining  with 
both  responses.  The  corpus  callosum  then  was  surgically  divided  in  its 
entire  antero-posterior  extent  through  a  left  sided  craniotomy.  After  a 


^  20r 
o 

^_ 
o 
o 

E 

Z3 


o 
o 


.a 

E 

Z3 


,o--o_         p 


Chr. 


0  5  10.  15 

Sets   of   twenty    trials 


^  20 
o 

CD 


10- 


Myn 


0  5  10  15 

Sets  of   twenty    trials 

Fig.  8 
Performance  of  Chr  and  Myn  with  discrimination  Il-ab  on 
initial  training  through  one  eye  (sohd  Hne)  and  on  rclcarning 
through  the  second  eye  (dashed  line).  Training  and  testing 
procedures  with  this  response  were  not  strictly  comparable 
owing  to  need  for  variable  encouragements.  Therefore,  only 
the  initial  trials  through  each  eye  are  represented.  Neither 
cat  shows  definite  indication  of  immediate  recognition 
through  the  untramed  eye.  On  the  contrary,  only  slight 
saving  is  suggested  in  relearning  in  the  case  of  Chr  and  no 
saving  in  the  case  of  Myn. 


post-operative  recovery  period  of  22  days  tests  were  carried  out  through 
first  the  trained  and  then  the  untrained  eye  on  both  responses.  Performances 
through   trained   eyes   on  both  discriminations  yielded  perfect  scores. 


496  BRAIN    MECHANISMS    AND    LEARNING 

Performances  through  untrained  eyes  were  2S  correct  in  40  on  tests  with 
discrimination  Ill-ba  and  20  correct  in  40  on  tests  with  discrimination 
V-ba. 

In  both  of  these  latter  instances  of  transfer  testing  a  strongly  persevera- 
tive  mode  of  responding  occurred  in  which  the  animal  pushed  always  or 
nearly  always  on  the  door  of  one  side  regardless  of  which  pattern  it 
contained.  Because  such  positional  perseveration  tends  to  cc^ntinue  and  to 
obscure  test  results,  KrDi  was  next  tested  through  the  untrained  eyes  on 
both  discriminations  under  conditions  of  'polarity  reversal'   in  which 

Table  V 

PERFORMANCES  THROUGH  TRAINED  AND  UNTRAINED  EYES  IN  CATS  WITH  POST-TRAINING  SECTION 

or    CCJRPUS    CALLOSUM 


Cat 


Discrimiuatiou 


Eye  tested 


Pre-operative 
performance 
{correct  in  .^o) 


Post-operative 

performance 

[correct  in  sets  of  40) 


Krni 

Byr 
Sll 

Bgw 


Ill-ba 
V-ba 
Ill-ba 
Ill-ab 
V-ba 
Ill-ba 
Il-ab 


Trained  (L) 
Untrained  (R) 
Trained  (R) 
Untrained  (L) 
Trained  (R) 
Untrained  (L) 
Trained  (R) 
Untrained  (L) 
Trained  (L) 
Untrained  (R) 
Trained  (L) 
Untrained  (R) 
Trained  (R) 
Untrained  (L) 


40 

40 

40 
38 
39 
34 
40 
39 
40 
39 
38 
37 


40 


20* 

20/ 

20t 

40 

— 

28* 

20/ 

20t 

39 

— 

20* 

40 

40 

— 

36 

— 

40 

— 

32 

— 

3« 

40 

35 

35 

39 

36 

27 

28 

36 


30 


Left-sided  craniotomy  in  all  cases. 

*  Exhibited  strong  positional  perseveration. 

f  Number  correct  in  20  trials  run  with  polarity  reversal. 

reward-punishment  values  of  the  stimuli  were  reversed.  Under  these 
circumstances  the  animal  chose  the  previously  rewarded  correct  pattern 
20  times  in  20  in  both  instances  despite  its  new  association  with  punish- 
ment. This  peculiar  effect  of  polarity  reversal  on  positional  perseveration 
has  also  been  clearly  observed  and  described  in  work  with  interocular 
transfer  in  the  pigeon  (Levine,  1945).  Subsequent  to  the  polarity  reversal 
testing  Knii  performed  discrimination  V-ba  well  through  the  untrained 
eye. 

Bgw  was  similarly  taught  and  overtrained  on  discriminations  Ill-ab  and 
Il-ab  while  using  the  left  and  right  eyes  respectively.  Prior  to  corpus 


RONALD    E.    MYERS  497 

caJlosum  section  this  cat  (as  well  as  Byr  and  Si!)  was  tested  for  contralateral 
recognition  of  each  discrimination  using  the  untrained  eye  during  which 
high  level  performances  were  obtained.  Corpus  callosuni  section  was  then 
carried  out  and  subsequent  retention  tests  were  run  through  both  the 
trained  and  untrained  eyes.  Again  corpus  callosum  section  caused  no 
essential  change  in  performance  level  through  the  trained  eyes.  However, 
on  tests  run  through  the  untrained  eyes  a  slight  but  definite  low^ering  of 
performance  was  seen  in  the  case  of  discrimination  Ill-ba  and  a  very  large 
and  sustained  lowering  in  performance  in  the  case  of  discrimination  Il-ab. 

Several  important  points  emerged  from  these  studies.  The  good  contra- 
lateral recall  of  the  easier  discrimination  Ill-ab  made  it  clear  that  the 
'trained'  hemisphere  could  induce  lasting  memory  traces  in  the  opposite 
hemisphere,  traces  that  subsequently  may  have  an  existence  of  their  own 
apart  from  transcallosal  influences  of  the  first  hemisphere.  Some  lack  of 
definition  or  relative  incapacity  in  this  secondary  trace  mechanism  was 
hinted  at,  however,  by  the  depression  of  initial  recall  of  this  easier  response 
occasionally  seen  through  the  untrained  eye.  The  near  failure  of  recall  of 
the  more  difficult  discrimination  Il-ab  through  the  untrained  eye  insists 
that  when  the  differentiation  handled  is  of  greater  subtlety  the  effects 
across  the  midline  through  the  corpus  callosum  are  not  sufficient  to  induce 
a  clearly  defined  secondary  memory  trace  in  the  hemisphere  not  receiving 
the  sensory  stimulation.  The  degree  of  success  or  failure  obtained  in 
contralateral  trace  establishment  seems,  then,  to  depend  in  large  part  on 
the  difficulty  of  the  discrimination  handled. 

The  impairment  of  recall  through  the  untrained  eye  seen  with  lesions  of 
the  'trained'  cortex  or  with  post-training  section  of  the  corpus  callosum 
was  not  seen  on  similar  tests  run  with  these  same  discriminations  in  cats 
with  chiasma-section  alone  (compare  results  of  Tables  III  and  IV  with 
those  of  Table  I,  or  compare  pre-  and  post-operative  transfer  performances 
of  cats  B(^ii>,  Byr  and  Sll  of  Table  V).  The  removal  of  critical  cortex  from 
the  initially  trained  hemisphere  or  the  transection  of  corpus  callosum 
subsequent  to  training  apparently  removes  an  influence  which  normally 
aids  and  abets  performance  through  the  untrained  hemisphere  at  the  time 
of  testing.  Two  contributions  of  the  trained  hemisphere  to  mnemonics 
tested  through  the  opposite  untrained  hemisphere  must  then  be  distin- 
guished. One  must  occur  prior  to  the  disruption  of  the  influence  of  the 
trained  hemisphere  presumably  at  the  time  of  initial  training  and  results  in 
the  induction  of  the  secondary,  somewhat  less  well-defined  memory 
mechanism.  The  second  contribution  appears  to  occur  at  the  time  of 
actual  testing  of  the  contralateral  mnemonics  and  results  in  the  facilitation 


498  BRAIN    MECHANISMS    AND    LEARNING 

of  correct  response  above  and  beyond  that  sustained  by  the  more  or  less 
incapable  contralateral  memory  trace  itself. 

No  gross  differences  were  seen  among  the  cortical  lesion  types  in  their 
effects  on  performance  level  through  the  opposite,  'untrained'  neural 
apparatus,  as  may  be  seen  from  Tables  III  and  IV.  Differences  in  perform- 
ances were  far  greater  within  than  between  lesion  types,  and  greater 
deficits  were  not  necessarily  seen  with  greater  lesions.  This  approximate 
equivalence  of  the  lesion  types  would  support  the  concept  that  neural 
tissue  beyond  the  more  restrictive  removals  contributes  little  towards  the 
maintenance,  and  possibly  also  the  development,  of  stable  contralateral 
memory  effects. 

It  may  be  noted  from  Table  V  that  corpus  callosum  section  subsequent 
to  training  did  not  affect  performance  on  any  discrimination  on  tests 
through  the  initially  trained  eye.  This  was  true  whether  the  eye  (and 
hence  the  hemisphere)  that  underwent  the  tests  was  on  the  same  side  or 
the  side  opposite  to  that  utilized  in  the  surgical  approach  to  the  corpus 
callosum.  From  this  it  is  apparent  that  the  unilateral  cerebral  insult 
incident  tci  the  surgical  approach  to  corpus  callosimi  did  not  compromise 
the  performance  of  either  intrahemispheric  mechanism  for  visual  dis- 
criminative response.  Furthermore,  this  lack  of  effect  of  corpus  callosum 
section  on  the  levels  of  learned  performance  through  either  hemisphere 
speaks  for  a  bilateral  competence  in  visual  learning  and  recall  speaking 
against  the  concept  of  unilateral  cerebral  dominance  in  visual  learning 
for  the  cat. 


PROBLEM  IV.  IS  THE  VISUAL  GNOSTIC  INTERCOMMUNICATION  A  GENERAL  OR 
LOCALIZED    FUNCTION    OF    THE    CORPUS    CALLOSUM? 

The  question  of  functional  localization  of  the  visual  gnostic  intercom- 
munication process  was  investigated  by  extending  transfer  tests  to  cats 
having  varying  extents  of  the  anterior  or  posterior  corpus  callosum  tran- 
sected. The  cats  involved  along  with  the  nimiber  of  millimetres  of  corpus 
callosum  sectioned  in  each  are  given  in  Tables  VI  and  VII.  The  percentage 
figures  given  in  parentheses  represent  the  part  of  the  total  antero-posterior 
extent  of  the  corpus  callosum  included  in  each  section.  Each  cat  in  the 
series  following  post-operative  recovery  was  monocularly  taught  and 
standardly  overtrained  on  discrimination  Ill-ab.  Final  level  of  performance 
in  all  cases  was  38  or  more  correct  in  40.  In  the  last  column  of  the  tables 
are  given  performances  on  the  first  consecutive  days  of  transfer  testing. 

As  may  be  seen  from  Table  VI  section  of  up  to  75  per  cent  (12.0  of 


RONALD    E.    MYERS 


499 


16.0  mm.)  ot  the  corpus  callosum  anteriorly  did  not  affect  the  level  of 
transfer  of  simple  discrimination  Ill-ab.  When,  however,  the  section 
extended  to  section  of  the  anterior  87  per  cent  (15.0  of  17.2  mm.)  transfer 


Table  VI 


INTEROCULAR    TRANSFER    IN     CATS    WITH     OPTIC     CHIASMA 
AND    ANTERIOR    CORPUS    CALLOSUM    SECTIONED 


Test 

performances 

through 

untrained  eye 

Cnt 

Extent  of 

section 

{correct  in 

40) 

1^-3 

mill. 

(70%) 

Day  1 

Day  2 

Btt 

32. 

38 

Brd 

11.4 

nun. 

(75%) 

39 

40 

Til 

11.7 

mm. 

(77%) 

37 

38 

Grv 

15.0 

mm. 

(87%) 

24 

13 

was  almost  completely  disrupted.  On  the  other  hand,  Table  VII  shows 
that  encroachments  greater  than  about  45  per  cent  (6.2  of  14.0  mm.) 
posteriorly  nearly  completely  abolished  transfer  while  smaller  posterior 
lesions  tended  in  most  instances  to  compromise  somewhat  the  early 
transfer  test  performances. 

Table  VII 


INTEROCULAR    TRANSFER    IN    CATS    WITH    OPTIC    CHIASMA 
AND    POSTERIOR    CORPUS    CALLOSUM    SECTIONED 


Test 

performances 

throng 

h  untrained  eye 

Cat 

Extent  oj  section 

{correct  in 

40) 

4.8  mm.  (26%) 

Day 

1 

Day  2 

Cnt 

33 

38 

Cto 

5.3  mm.  (37%) 

35 

39 

Wld 

7.3  mm.  (42°,,) 

33 

38 

Blk 

6.2  mm.  (44°,,) 

22 

20 

Blc 

9.0  mm.  (53°o) 

23 

28 

Gbb 

1 1.8  mm.  (68"n) 

21 

25 

Fig.  9  illustrates  graphically  the  rate  of  learning  of  the  response  through 
first  one  eye  and  then  through  the  second  eye  in  the  case  of  the  four  cats 
having  the  maximal  expanses  of  the  corpus  callosum  sectioned.  It  may  be 

KK 


500 


BRAIN    MECHANISMS    AND    LEARNING 


seen  that  these  cats  with  maximal  lesions  gave  indication  cither  of  no 
saving  or  only  slight  saving  ni  relearnuig  through  the  second  eye. 

In  summary,  transection  of  broad  expanses  of  corpus  callosum  anteriorly 
did  not  halt  transfer  while  relatively  much  smaller  lesions  posteriorly 
interfered  completely,  speaking  for  a  clear-cut  posterior  localization  of  the 
visual  gnostic  exchange  activity.  Further,  a  second  important  point 
emerges  from  a  close  consideration  of  these  cases.  Cat  Brd  transferred 
discrimination  Ill-ab  with  only  the  posterior-most  4.0  mm.  of  the  corpus 


^   10  - 


Sets  of  twenty  triols 


Sets   of   twenty   trials 


20 

• 

» 

•'A 

...«•*■•.•••■•* 

r 

10 

■*9sg;« 

\ 

v  /  \ 

r 

'  BIK. 

^( 

3 

5 

10 

15 

20 

Sets   of  twenty  trials 


Fig.  9 


,  10  15 

Sets   of   twenty  trials 


Graphs  comparing  rates  of  learning  through  the  two  eyes  on  discrimination  Ill-ab  in  four  cats. 
Initial  learning  through  the  right  eye  is  represented  by  the  solid  line  and  relearning  through 
the  left  eye  by  the  broken  line.  Extent  of  destruction  of  corpus  callosum  in  each  case  may  be 
seen  by  reference  to  Tables  I  and  II.  Gbh  showed  no  saving  in  relearning  with  the  untrained 
eye  while  some  slight  saving  is  suggested  from  the  curves  of  Gry,  Blk,  and  Blc.  Cat  Ghh  was 
trained  and  tested  by  an  individual  different  from  the  one  handling  Gry,  Blk  and  Blc. 

callosum  preserved.  Cat  Cto  transferred  the  same  discrimination  with  the 
selfsame  strand  of  posterior  fibres  severed  but  more  anterior  fibres 
preserved.  These  latter  two  cases  taken  together  point  up  an  equipoten- 
tiality  or  equivalence  of  function  of  different  fibre  strands  within  the 
broader  posterior  segment  of  the  corpus  callosum  given  over  to  the  realm 
of  visual  gnostic  intercommunication. 


PROBLEM  V.  WHAT  ROLE  CAN  ENVIRONMENTAL  INFLUENCES  PLAY  IN  DEFINING 
THE  DEGREE  OF  INTEROCULAR   TRANSFER   IN   THE   CHIASMA-SECTIONED   CAT? 

Earlier,  several  exceptional  instances  were  seen  of  depressed  level  of 
interocular  transfer  in  the  chiasma-sectioned  cats.  Examination  of  Table  I 


RONALD    E.    MYERS  5OI 

shows  that  discriniination  IV-ab  was  involved  in  all  such  instances.  It  was 
at  first  thought  that  the  reduction  in  contralateral  recall  might  be  a  reflec- 
tion of  some  peculiarity  in  this  discrimination  such  as  a  too  close  similarity 
between  the  two  patterns  of  the  pair  resulting  in  an  inordinate  difficulty 
in  their  differentiation.  This  interpretation  seemed  unlikely,  however, 
since  no  such  difficulty  was  reflected  in  the  initial  learning  curves  of  the 
cats  trained  on  this  response.  Furthermore  one  cat,  Hrl,  was  seen  to 
transfer  this  response  at  a  relatively  high  level.  A  second  cat,  Kiis,  who  at 
first  exhibited  a  strong  positional  perseveration  on  transfer  testing,  later 
revealed  a  good  transfer  performance  on  testing  with  polarity  reversal. 
This  latter  case  must,  however,  remain  inconclusive.  There  remained  for 
clarification  the  depressed  transfer  performances  of  cats  Bsh  and  Bni  on 
discrimination  IV-ab. 

Reference  once  again  to  Table  I  shows  that  both  Bsh  and  Bni  had  earlier 
been  taught  discrimination  Ill-ab  through  the  same  eye  that  had  been 
used  for  the  transfer  testing  of  discrimination  IV-ab.  It  seemed  possible 
from  inspection  that  the  depression  of  transfer  performance  with  discrimina- 
tion IV-ab  may  have  resulted  from  resemblances  between  its  }iei^ative 
pattern,  IV-b,  and  the  positive  pattern,  Ill-a,  of  the  antecedent  discrimina- 
tion Ill-ab.  Thus  was  it  first  suggested  that  a  degree  of  conflict  in  the 
experience  of  the  two  eyes  of  the  chiasma-sectioned  cat  may  result  in 
interference  with  interocular  transfer. 

The  final  investigation  to  be  reported  was  designed  to  test  this  hypo- 
thesis, and,  if  it  be  true,  to  determine  the  extent  to  which  conflict  may 
hincier  transfer.  Failure  to  resolve  conflict  between  such  monocularly- 
learned  responses  would  indicate  a  defnnte  limitation  in  corpus  callosum 
function. 

Patterns  iii-a  and  iii-b  were  constructed  such  that  iii-a  closely  resembled 
Ill-a  and  iii-b  closely  resembled  Ill-b  (see  Fig.  lo).  Quite  closely  con- 
flicting discriminations  could  then  be  created  by  making  pattern  Ill-a 
positive  for  one  response  and  iii-b  positive  for  the  other.  Three  chiasma- 
sectioned  cats  were  used  in  this  study  and  were  taught  discriminaton 
Ill-ab  through  one  eye,  and,  after  120  trials  of  overtraining,  the  closely 
conflicting  discrimination  iii-ba  through  the  other  eye.  Such  conditioning 
was  alternated  back  and  forth  between  the  eyes  until  each  eye  immediately 
performed  its  own  response  correctly  on  each  new  presentation.  These 
monocularly  established  responses  were  then  further  stabilizeci  by  the 
usual  periods  of  overtraining  (400  trials  seen  with  each). 

The  patterns  of  the  discrimination  taught  through  one  eye  were  then 
presented  for  the  first  time  to  the  other  eye  for  tests  of  interocular  transfer; 


502 


BRAIN    MECHANISMS    AND    LEARNING 


the  patterns  of  discrimination  Ill-ab  may  serve  as  illustration.  Ideally,  one 
of  two  possibilities  might  have  obtained  on  these  transfer  tests:  the  cat 
might  have  chosen   pattern   Ill-a   preferentially   because   of  the   cross- 


a 


b 


IE 


LLL 


Fig.  10 
The  two  pairs  of  test  patterns  used  in  conflict 
conditioning.    The   similarity   between   the  two 
i(  and  b  patterns  is  easily  seen. 

availability  of  information  through  the  corpus  callosum  tending  to 
establish  such  a  response  tendency  in  the  contralateral  mechanism  being 
tested;  alternatively,  the  cat  might  have  chosen  pattern  Ill-b  because  of  its 

Table  VIII 

INTEROCULAR    TRANSFER    FOLLOWING    TRAINING    OF    CONFLICTING    DISCRIMINA- 
TIONS   THROUGH    THE    SEPARATE    EYES 


Cat 

W 

zz 

Siiz 

P 

z 

Eye  tested 

L 

R 

R 

L 

L 

R 

Discrimination  tested 

Ill-ab 

iii-ba 

Ill-ab 

iii-ba 

Ill-ab 

iii-ba 

Number  correct  in  40 

test  trials 

I 

0 

0 

9 

7 

— 

Number  correct  in  40 

test  trials  with  pola- 

rity reversed 

0              0 

0             21 

1 

close  resemblance  to  the  positive,  rewarded  pattern  of  discrimination  iii-ba 
which  had  just  been  taught  through  the  eye  being  tested.  Reference  to 
Table  VIII  reveals  that  all  cats  tended  very  strongly  to  choose  pattern 


RONALD    E.    MYERS  503 

Ill-b,  the  pattern  regularly  punished  during  training  through  the  opposite 
trained  eye.  Some  cats  chose  this  pattern  40  times  in  40  trials  despite  its 
association  with  punishment.  Tested  through  one  eye  they  chose  the  one 
pattern;  tested  through  the  other  eye  they  chose  the  second  pattern.  One 
hemisphere  thus  did  not  seem  to  benefit  from  the  experience  of  the  other 
under  conditions  of  moderate  conflict.  Stated  in  other  terms  the  inter- 
hemisphcric  communication  process  lacked  the  capacity  of  bringing  about 
a  differentiation  of  the  two  conflicting  responses  within  a  hemisphere. 
From  the  extreme  degree  o(  perseveration  observed  on  the  test  trials  of 
transfer  it  was  concluded  that  the  effects  of  direct  sensory  experience  are  a 
great  deal  more  forceful  in  learning  than  the  effects  of  information  trans- 
mitted between  the  hemispheres  through  the  corpus  callosum. 


ACKNOWLEDGMENTS 

The  investigations  were  carried  out  while  the  author  was  associated 
with  the  laboratory  of  R.  W.  Sperry.  Support  was  received  in  turn  from 
the  Abbott  Memorial  Fund  of  The  University  of  Chicago,  Frank  P. 
Hixon  Fund  of  the  California  Institute  of  Technology,  United  States 
Public  Health  Service  and  National  Science  Foundation  Grant  #G-388o. 


GROUP   DISCUSSION 

Chow.  Can  you  teach  a  cat  these  two  discrimination  problems,  through  the 
same  eye; 

Myers.  Yes,  under  certain  circumstances  cats  can  consistently  be  taught  the 
conflicting  discriminations  through  one  eye.  However,  under  other  circumstances 
they  seem  never  to  differentiate  between  the  two  closely  conflicting  sets  of  patterns 
and  have  to  be  retaught  each  response  with  each  reversal  of  the  stimulus  pairs. 

RosvoLD.  I  should  like  I^r  Mvers  to  mention  some  of  his  work  on  tactile  dis- 
crimination in  relation  to  visual  discrimination  since  it  gives  a  clearer  picture  of 
corpus  callosum  function. 

Myers.  The  question  of  whether  corpus  callosum  functions  in  tactual  as  well  as 
visual  transfer  is  of  great  interest.  The  contribution  of  Bykov  mentioned  in  the 
discussion  of  Dr  Segundo's  paper  served  as  a  first  beautiful  demonstration  of  the 
central  importance  of  corpus  callosum  in  the  bilateral  dissemination  of  information 
bearing  on  tactual  learning.  A  second  contribution  in  the  area  of  touch  was  made 
b}-  Stamm  and  Sperry  who  showed  that  the  relatively  slight  degree  of  transfer  of 
tactile  discrimination  learning  that  occurs  from  one  paw  to  the  other  in  the  cat  is 
interfered  with  by  prior  section  of  the  corpus  callosum  (Stamm  and  Sperry,  1957). 
Dr  Ebncr,  in  our  laboratorv  at  Walter  Reed,  has  found  immediate  high  level 
transfer  of  tactile  discrimination  learning  between  the  hands  in  normal  monkeys 
and  complete  failure  in  corpus  callosum-scctioned  animals  (Ebner  and  Myers, 
i960).  Similarly,  a  comparable  interference  with  intermanual  transfer  of  latch-box 


504  BRAIN    MECHANISMS    AND    LEARNING 

solving  occurs  after  corpus  callosum  section  in  the  chimpanzee  (Mvcrs,  i960).  The 
accumulation  of  information  thus  far  seems  to  indicate,  rather  definitely,  a  tactile 
gnostic  intercommunicative  function  for  the  corpus  callosmn  similar  to  that  seen 
for  visual  gnosis. 

RosvOLD.  Did  you  ever  test  for  the  locus  of  tactile  functions  in  the  corpus 
callosum  ? 

Myers.  No. 

RosvoLD.  Have  you  any  inkling  of  what  function  the  anterior  corpus  callosum 
may  have.  Wc  have  some  suspicion  that  it  enters  into  delayed  response  behaviour, 
hi  some  animals  with  anterior  section  only,  there  seems  to  be  an  impairment  of 
memory  function. 

Myers.  No,  I  have  no  information  specifically  related  to  anterior  corpus  callosum 
function. 

Segundo.  Would  Dr  Myers  comment  on  the  publications  of  Akelaitis  who, 
with  the  purpose  of  avoiding  generalization  of  epileptic  seizures,  sectioned  the 
corpus  callosum  in  a  number  of  patients  (Akelaitis,  1941).  Were  those  patients 
studied  as  to  their  discriminative  capacities,  and,  if  so,  which  were  the  results  of  this 
analysis  ? 

Myers.  These  patients  were  subjected  to  a  host  ot  examinations  exploring  their 
sensory,  motor,  and  intellectual  capacities  both  pre-  and  post-operatively.  Accord- 
ing to  these  tests  the  corpus  callosum  transection  resulted  in  no  clear-cut  and 
consistent  deficits.  But  I  believe  there  is  no  conflict  between  these  apparently 
negative  human  results  and  the  results  we  have  reported  here.  Akelaitis  tested 
visual  function  in  his  patients  by  testing  recognition  of  different  visual  objects  in 
opposite  homonymous  fields  of  the  same  eye  thus  separately  testing  visual  recogni- 
tion through  the  separate  hemispheres.  Such  recognition  was  found  to  be  bilater- 
ally undisturbed  and  he  concluded  that  corpus  callosum  did  not  function  in  visual 
recognition.  However,  he  failed  to  take  into  account  the  tact  that  past  experience 
through  each  hemisphere's  own  afferent  sensory  systems  could  independently  have 
established  the  basis  for  recognition  of  those  common  objects  in  each  homonymous 
field  apart  from  presence  or  absence  of  corpus  callosum.  Had  we  taught  our 
chiasma-sectioned,  callosum-sectioned  cats,  their  visual  response  without  a  mask 
and  later  tested  first  through  one  and  then  through  the  other  eye  for  recognition  of 
the  discriminanda  I  doubt  whether  the  cats  would  have  had  difficulty  in  responding 
correctly  through  either  eye.  The  central  point  to  be  made  is  that  for  cross  recogni- 
tion tests  to  be  critical  as  tests  of  corpus  callosum  function  the  situation  or  experi- 
ence to  be  tested  must  be,  in  some  sense  or  other,  novel  or  imflimiliar  to  the  subject. 

Olds.  About  the  last  experiment,  is  it  possible  that  the  animal  did  not  learn  the 
discrimination  you  thought  he  learned  —  you  assume  he  learned  that  when  the 
vertical  bar  was  solid  it  was  positive  and  when  it  was  split  it  was  negative.  It 
seems  the  animal  might  have  learned  that  when  the  patch  is  on  one  eye  vertical  is 
positive  and  when  the  patch  is  on  the  other  eye  vertical  is  negative.  Does  that  seem 
a  possible  interpretation? 

Myers.  That  must  be  considered  a  definite  possibility  against  which  no  ultimate 
control  can  be  conceived,  bound  as  one  is  in  this  experiment  to  use  two  different 
receptive  fields.  However,  the  slight  interference  with  transfer  seen  with  mildly 
conflicting  discriminations  would  be  hard  to  explain  on  this  basis.  The  configura- 
tion of  results  of  later  experiments  not  vet  published  also  speak  against  the  idea  of  the 


RONALD    E.    MYERS  5O5 

responses  being  contingent  on  the  eve  masked  or  the  particular  receptor  stimulated. 

Gerard.  Downer  reported  in  monkeys  unilateral  responses  as  far  as  pattern 
vision  was  concerned  but  I  believe  colour  discriminations  crossed  over.  Have  you 
anv  information  on  thisf 

Myers.  Downer  reported  that  interocular  transfer  of  colour  as  well  as  of  pattern 
discrimination  was  prevented  by  prior  section  of  optic  chiasma  and  corpus  callosum 
in  monkevs.  He  further  maintained  that  after  chiasma  section  alone  the  memory 
mechanism  for  colour  discrimination  learning  achieved  bilateral  expression  while 
that  for  pattern  discrimination  remained  primarily  of  unilateral  potential.  He  has 
published  tliis  work  only  as  an  abstract  (Downer,  1958)  and  did  not  describe  the 
basis  for  this  conclusion.  His  interpretations  seem  to  go  in  the  same  direction  as  ours 
to  suggest  that  the  more  simple  task  finds  more  effective  bilateral  expression  than 
more  diflicult.  However,  we  found  bilateral  memory  development  for  more 
simple  pattern  discrinnnation  responses. 


ANATOMICAL  AND  ELECTROGRAPHICAL  ANALYSIS 
OF  TEMPORAL  NEOCORTEX  IN  RELATION  TO 
VISUAL    DISCRIMINATION    LEARNING    IN    MONKEYS^ 

Kao  Liang  Chow 

Our  knowledge  of  brain  functions  relating  to  behaviour  has  advanced 
rapidly  in  recent  years.  One  of  the  central  issues  in  this  area,  that  of  the 
neural  mechanisms  of  memory  and  learning,  however,  remains  experi- 
mentally elusive.  This  problem  may  be  approached  from  two  directions. 
One  is  to  use  a  simple  preparation,  such  as  a  protozoan  or  a  synaptic 
junction  and  to  study  any  physictvchcmical  changes  resulting  from 
repeated  excitation  or  exercise.  The  other  is  to  use  an  animal  with  a  well- 
developed  brain  in  which  learning  can  be  dehned  behaviourally  and  to 
analyse  at  a  gross  level  the  neural  structures  involved.  There  are  difficulties 
in  both  approaches.  Thus,  one  wonders  how  to  identify  learning  in  the 
simple  organism  and  how  to  extrapolate  from  any  mechanisms  detected 
there  to  a  more  complex  brain.  If  one  starts  with  the  second  type  of 
system,  on  the  other  hand,  there  is  only  hope  but  no  guarantee  that  sucli 
analysis  will  eventually  reach  the  basic  learning  mechanisms  at  a  neuronal 
or  molecular  level.  Also,  it  is  not  clear  whether  there  are  one  or  more 
neural  mechanisms  underlying  the  various  types  oi  learning  tliat  are 
dehned  behaviourally. 

The  following  material  illustrates  the  second  type  of  approach.  The 
neural  correlates  of  learning  and  retaining  visual  problems  have  been 
analysed  at  a  gross  level.  In  rhesus  monkeys,  the  cortex  of  the  middle  and 
inferior  temporal  gyri  have  been  shown  to  be  concerned  with  visual 
discriminations  (Chow  and  Hutt,  1953  ;  Riopelle  ct  ai,  1953  ;  IVibram  and 
Mishkin,  1955).  After  bilateral  ablation  of  this  cortical  area,  a  monkey  will 
learn  to  choose  one  from  a  pair  of  visual  stimuli  (such  as,  red  or  green 
colours,  triangular  or  square  patterns)  in  order  to  get  food,  but  at  a  slower 
rate  than  normal,  unoperated  annnals.  Or,  if  a  monkey  has  earlier  learned 
to  solve  these  problems  the  forgetting  produced  by  the  surgical  ablation 
can  be  reversed  by  relearning.  This  detrimental  effect  is  specific  to  the 
temporal  cortex;  lesions  in  other  neocortical  areas  do  not  affect  visual 

'  Studies  reported  m  this  paper  were  suppiirted  by  research  grant  B-801  (C3)  trmn  the 
National  histitute  of  Neurological  Diseases  and  Blindness,  National  histitute  of  Health,  and 
the  Wallace  C.  and  Clara  M.  Abbott  Memorial  Fund  of  the  University  of  Chicago. 

507 


508  BRAIN    MECHANISMS    AND    LEARNING 

discriminations  fMishkin  and  Pribram,  1954;  Pribram  and  Barry,  1956; 
Wilson  and  Mishkin,  1959).  And  this  temporal  lesion  is  specific  to  the 
visual  tasks;  it  docs  not  affect  other  learning  problems,  such  as  somesthetic 
discrimination  (Wilson,  1957;  Pasik,  ct  a\.,  1959).  After  establishing  such  a 
functional  localization,  i.e.  visual  discrimination  to  temporal  cortex,  the 
next  step  would  be  to  analyse  the  neural  mechanisms  involved.  Since  one 
does  not  know  what  ultimate  cellular  or  molecular  mechanisms  to  look 
for,  the  studies  conducted  so  far  have  dealt,  at  a  gross  level,  with  diverse 
aspects  of  the  phenomenon,  each  designed  to  answer  a  particular  question. 
For  example,  attempts  to  clarify  the  nature  of  the  visual  defect  following 
temporal  ablations  have  been  reported  (Mishkin  and  Hall,  1955;  Chow 
and  Orbach,  1957;  Orbach  and  Fantz,  1958). 

The  experiments  here  reported  were  designed  to  investigate  the  anato- 
mical pathways  necessary  for  the  retention  of  visual  discriminations,  and 
the  function  of  isolated  temporal  and  visual  cortices  in  monkeys.  Also,  the 
effect  of  local  epileptic  after-discharges  on  learning  and  retention,  as  well 
as  any  consistent  electroencephalographic  (EEG)  changes  in  the  temporal 
and  visual  areas  during  learning,  have  been  studied. 

CORTICO-CORTICAL    AND    SUBCORTICO-CORTICAL    PATHWAYS 

The  finding  that  the  temporal  cortex  is  implicated  in  visual  learning  and 
retention  indicates  the  presence  of  more  or  less  direct  inter-communica- 
tions between  temporal  and  visual  areas.  In  the  monkey,  the  only  known 
cortico-cortical  pathways  of  the  striate  area  are  short  axon  fibres  to  and 
from  the  adjacent  parastriate  region  (Mettler,  1935;  Clark,  1941).  From 
there,  post-synaptic  fibres  secondarily  transmit  visual  impulses  to  other 
cortical  areas.  Similarly,  the  anterior  temporal  cortex  receives  subcortical 
fibres  from  the  n.  pulvinaris  medialis,  and  it  sends  fibres  back  to  this 
nucleus  (Chow,  1950;  Whitlock  and  Nauta,  1956).  Therefore,  the  tem- 
poral cortex  may  receive  visual  impulses  or  may  exert  influences  on  the 
visual  area  through  either  one  of  these  two  routes,  or  both.  In  earlier 
studies,  I  interrupted  the  cortico-cortical  pathways  by  bilaterally  ablating 
the  parastriate  cortex,  and  the  subcortical  pathways  by  bilaterally  destroy- 
ing the  n.  pulvinaris  medialis  (Chow,  1952,  1954).  All  these  animals 
retained  pre-operatively  learned  visual  discriminations  as  did  normal 
controls.  In  other  words,  these  lesions  did  not  duplicate  the  effect  of 
bilateral  removal  of  the  temporal  cortex.  I  have  not  been  able  to  destroy 
completely  in  these  animals  the  parastriate  cortex  or  the  pulvinar  (it 
should  be  noted  that  only  the  posterior  part  of  the  n.  pulvinaris  medialis 


KAO    LIANG    CHOW 


509 


projects  to  the  temporal  region).  It  can  be  argued  that  a  small  remnant 
of  tissue  may  be  responsible  for  the  lack  of  detrimental  effects,  thus 
illustrating  the  great  plasticity  of  the  system. 

In  order  to  remedy  the  inadequacy  of  the  lesions  described  above,  three 
other  types  of  surgery  were  carried  out  in  a  series  of  monkeys.  First,  both 
the  parastriatc  cortex  and  the  pulvinar  were  ablated  in  two  monkeys. 
This  was  done  in  the  hope  that  these  two  lesions  would  overlap  enough  to 
prevent  effective  communication  between  the  visual  and  temporal  areas. 
Second,  the  temporal  cortex  was  undercut  parallel   to  the  surface  to 


NO.  3 


Fig.  I 
Reconstruction  of  lesions  of  monkey  No.  3  who  had  ablations  of  both  the  parastriatc  cortex 
and  the  posterior  n.  pulvinaris  inedialis.  Solid  black,  area  of  destruction;  hatching,  surrounding 
degenerated  zone;  R,  right;  L,  left;  PM,  n.  pulvinaris  niedialis;  PL,  n.  pulvinaris  lateralis; 
MD,  n.  niedialis  dorsalis;  LG,  lateral  geniculate  body;  MG,  medial  geniculate  body. 

eliminate  all  subcortical  projection  fibres  in  four  animals.  Third,  in  another 
four  monkeys,  the  temporal  cortex  was  cross-hatched  to  eliminate  the 
intracortical  and  the  arcuate  fibres.  This  last  operation  was  applied  after 
failure  to  circumscct  the  temporal  region.  Two  monkeys  with  ablation  of 
the  temporal  cortex  were  included  to  serve  as  controls. 

Pre-operatively  all  animals  were  adapted  to  the  testing  situation  by 
applying  a  red  and  green  discrimination.  They  were  then  trained  on  two, 
siiiiukaiicoiis  visual  pattern  discriminations:  black  circle  v.  black  square; 
and  black  and  white  vertical  striations  i>.  horizontal  striations.  The  animals 
were  required  to  choose  the  positive  stimulus  to  receive  a  food  reward, 
and  to  disregard  the  negative  stimulus.  The  non-correction  method  was 


510 


BRAIN    MECHANISMS    AND    LEARNING 


used.  Thirty  trials  were  given  each  day,  until  a  criterion  of  90  per  cent 
correct  responses  in  a  one-day  session  was  reached.  The  animals  were  then 
subjected  to  bilateral  one-stage  operation.  Fourteen  days  later  they  were 
tested  for  retention  of  these  visual  discriminations. 

The  brains  of  all  animals  were  examined  histologically,  and  the  lesions 
reconstructed.  Fig.  i  is  of  the  reconstruction  of  a  brain  with  both  para- 
striate  and  pulvinar  ablations.  The  cortical  lesion  was  not  complete,  but 
the  posterior  part  of  n.  pulvinaris  mcdialis  was  largely  removed.  A  second 
monkey  had  similar  lesions.  The  cortical  regions  subjected  to  the  other 

Tablh  I 


PRE-  AND  POST-OPERATIVE  LEARNING  SCORE  OP  MONKEYS  WITH  DIFFERENT 

TYPES   OF  TEMPORAL   NEOCORTICAL   OPERATIONS.    NUMBER   OF  TRIALS   TO 

CRITERION,  EXCLUDING  CRITERION  TRIALS.  NUMBERS  IN  ITALICS,  LACK  OF 

POST-OPERATIVE    RETENTION 


Monkey 
no. 

V'isiiiil  Dis 

rimination 

Type  of 
operation 

Circle 

V.  square 

Vertical  v. 
horizontal 

Ablation 

I 

Pre-op 

90 

180 

Post-op 
120 
240 

Pre-op    Post-op 

120           120 

50           270 

Parastriate  and 
pulvinar 

3 
4 

120 
150 

120 
30 

180           120 
210             60 

Cross-hatching 

S 
6 

7 
8 

210 

150 

60 

120 

240 

150 

90 

120 

300           420 
240           330 
210           270 
150           120 

Under-cutting 

9 
10 
II 
12 

330 
300 
120 
I  So 

120 

120 

30 

30 

120             90 
150             90 
210               0 
240             60 

three  types  of  surgery  (ablation,  cross-hatching,  undercutting)  were  all 
restricted  to  the  middle  and  inferior  temporal  gyri  rostral  to  the  vein  of 
Labbc.  The  locus  and  size  of  the  lesion  in  individual  monkeys  showed 
minor  variations.  Retrograde  degeneration  appeared  only  in  the  posterior 
part  of  n.  pulvinaris  medialis.  In  general,  the  cortex  above  the  plane  of 
undercutting  showed  no  damage.  The  subpial  vertical  hatching  cut 
beyond  the  thickness  of  the  cortex,  invading  to  some  extent  the  underlying 
white  matter.  The  cortex  between  the  cuts  seemed  to  be  normal  in 
appearance. 


KAO    LIANG    CHOW  51 1 

Tabic  I  summarizes  the  results.  The  numbers  of  trials  to  criterion 
(excluding  the  criterion  trials)  in  pre-opcrative  learning  and  post-operative 
testing  of  all  monkeys  are  included.  The  numbers  ni  italics  indicate  that 
after  operation  the  animal  did  not  retain  but  relearned  a  specific  discrim- 
ination. It  is  clear  that,  beside  a  few  exceptional  cases,  only  cross-hatching 
lesion  produced  an  effect  resembling  that  of  ablating  the  temporal  cortex. 
Animals  with  either  the  combined  parastriate  and  pulvinar  lesion  or  with 
the  undercutting  showed  good  retention ;  the  degree  of  saving  is  com- 
parable to  that  of  normal  animals  (Chow,  1958).  Thus,  whatever  the 
neural  mechanisms  are  involved,  the  interchange  of  information  between 
the  visual  and  temporal  areas  for  the  discriminations  used  depends 
primarily  on  cortico-cortical  pathways. 

The  present  results  may  be  compared  with  those  of  studies  by  Sperry. 
He  found  no  motor  defects  after  cross-hatching  the  sensorimotor 
cortex  in  monkeys  when  the  cuts  did  not  penetrate  beyond  the  depth  of 
the  cortex  (Sperry,  1947).  Also,  cats  showed  a  normal  rate  of  learning  and 
good  retention  of  visual  discriminations  after  multiple  subpial  cuts  of  the 
visual  area  (Sperry,  Minor  and  Myers,  1955).  Different  neural  organiza- 
tions between  the  primary  projection  areas  and  the  association  areas  may 
be  implicated  to  account  for  the  different  results. 

ISOLATED    TEMPORAL    AND    VISUAL    CORTICES 

One  of  the  inherent  weaknesses  of  using  the  ablation  method  is  that 
one  removes  the  structure  to  be  studied.  A  more  rational  way  of  studying 
the  function  of  a  cortical  area  is  to  leave  this  region  intact,  but  to  remove 
all  other  cortex.  To  study  the  role  of  the  temporal  cortex  in  visual  learn- 
ing, one  needs  a  decorticated  monkey  with  sparing  of  only  the  temporal 
and  visual  areas.  A  series  of  behaviourally  testable  monkeys  was  prepared 
which  more  or  less  met  this  requirement.  The  animals  were  subjected  to 
three  separate  operations  with  long  recovery  and  training  periods  between. 
The  first  operative  stage  was  used  to  cut  one  optic  tract  (left  side),  the 
corpus  callosum,  the  hippocampal  commissure,  and  to  ablate  one  tem- 
poral cortex  (left  side).  Extensive  decortication  of  the  contralateral  (right) 
side,  sparing  the  temporal  and  visual  areas,  was  done  during  the  second 
operation.  The  orbital  and  medial  cortical  tissue  and  the  retrosplenial  area 
were  variably  preserved.  Monkeys  after  this  second  operation  were 
suitable  for  studying  the  visual  function  of  the  temporal  cortex  in  isola- 
tion. The  third  operation  was  performed  to  remove  the  remaining  tem- 
poral cortex  (right  side).  Such  a  monkey  had  by  and  large  only  one  visual 
area  to  deal  with  visual  tasks. 


512 


BRAIN    MECHANISMS    AND    LEARNING 


Six  monkeys,  four  experimental  and  two  control  animals,  were  used. 
Three  or  4  months  after  the  first  operation,  they  were  adapted  to  the 
testing  situation  with  the  red  and  green  discrimination.  Because  of  the 
homonymous  hemianopsia,  many  devices  were  needed  to  help  the 
animals  overcome  this  defect.  The  animals  were  then  trained  on  the  two 
visual  pattern  discriminations  described  in  the  preceding  section.  After 
they  had  acquired  these  two  habits,  the  two  controls  were  operated  upon 
for  the  removal  of  the  rcmaming  temporal  cortex.  They  forgot  these  two 
habits  following  this  operation  but  relearned  them.  Thus,  the  effect  of 


Ca  3 


Ca  I 


Fig.  2 

Reconstruction  of  lesions  (solid  black)  of  one  experimental  monkey  (Ca  3)  and  one  control 

animal  (Ca  i).  R,  right;  L,  left. 


bilateral  temporal  lesions  on  retention  of  visual  discriminations  were  not 
augmented  by  the  additional  interruption  of  one  optic  tract,  the  hippo- 
campal  commissure,  and  the  corpus  callosum.  For  the  four  monkeys  in 
the  experimental  group,  they  retained  the  two  discriminations  after  the 
extensive  unilateral  decortication  of  the  second  operation.  They  lost  these 
habits  after  the  third  operation  (temporal  lesion),  but  reacquired  the  two 
problems  with  further  training.  Table  II  summarizes  the  results.  Fig.  2 
shows  the  reconstruction  of  lesions  of  one  experimental  and  one  control 
animal. 

In  addition,  the  four  experimental  monkeys  were  given  a  more  complex 


KAO    LIANG    CHOW 


513 


task,  the  visual  discrimination  Icarning-sct  problem,  to  assess  the  capacity 
of  the  isolated  temporal  and  visual  areas.  Two  of  the  animals  were  trained 
on  this  problem  after  the  tirst  operation,  retested  after  the  second  opera- 
tion, and  again  after  the  third  operation.  The  other  two  animals  were 
given  this  problem  only  after  the  third  operation. 

Table  II 

POST-OPERATIVE  LEARNING  AND  RETENTION  OF  VISUAL  DISCRIMINATIONS. 
NUMBER  OF  TRIALS  TO  CRITERION,  EXCLUDING  CRITERION  TRIALS.  C  .  S, 
CIRCLE  I',  square;  V.H,  vertical  U.  HORIZONTAL  STRIATIONS ; 
FIRST  OPERATION,  SECTION  OF  THE  LEFT  OPTIC  TRACT,  THE  CORPUS 
CALLOSUM,  AND  ABLATION  OF  THE  LEFT  TEMPORAL  CORTEX;  SECOND 
OPERATION,  DECORTICATION  OF  THE  RIGHT  HEMISPHERE  SPARING  THE 
TEMPORAL  AND  VISUAL  AREAS;  THIRD  OPERATION,  ABLATION  OF  THE 
RIGHT    TEMPORAL    CORTEX 


Monkey 

Test 

1st  operation 

2nd   operation 

jrd  operation 

no. 

Ca3 

C.S 

390 

30 

360 

V.H 

390 

90 

480 

Ca  4 

C.S 

210 

30 

180 

V.H 

180 

60 

210 

Ca  5 

C.S 

90 

30 

60 

V.H 

180 

0 

210 

Ca  6 

C.S 

180 

30 

210 

V.H 

240 

60 

360 

Ca  I 

C.S 

120 

— 

120 

V.H 

120 

— 

150 

Ca2 

C.S 

330 

— 

300 

V.H 

270 

— 

330 

The  learning-set  problem  involves  a  series  ot  467  two-choice,  visual 
object  discriminations.  The  preliminary  sixty-seven  problems  were  pre- 
sented either  titty,  or  twenty-four,  or  six  times  per  problem.  Three  trials 
per  problem  were  given  for  the  last  400  problems.  After  such  a  long  series 
of  problems  a  normal  monkey  would  make  a  random  choice  on  the  first 
trial,  but  learn  to  choose  correctly  on  the  second  trial  (Harlow,  1949).  The 
results  of  the  four  experimental  animals  are  presented  in  Fig.  3.  Both 
monkeys  lost  the  previously  established  learning-set  after  the  second 
operation.  They  reacquired  the  learning-set  through  re-training,  but 
reached  a  final  level  lower  than  that  achieved  previously.  The  third 
operation  which  more  or  less  left  only  one  visual  area  intact,  rendered  all 
four  monkeys  incapable  of  learning  or  reacquiring  the  learning-set 
(Chow,  1954a).  These  animals,  however,  could  still  learn  any  one  object 
discrimination  to  criterion  within  ninety  trials. 


514 


BRAIN    MECHANISMS    AND    LEARNING 


These  results  add  further  evidence  for  the  role  of  the  temporal  cortex  of 
monkeys  in  vision.  That  this  cortical  area  is  not  necessary  for  simple  visual 
learning  is  also  evident.  The  level  of  achievement  on  the  learning-set 
problem  is  positively  correlated  with  the  level  of  phylogenetic  develop- 
ment of  the  animal  (Shell  and  Riopelle,  195X).  The  present  finding  indi- 
cates the  indispensable  role  of  the  temporal  cortex  for  such  a  complex  task. 
Different  neural  mechanisms,  at  least  at  a  gross  level,  must  be  sought  in  the 
two  types  of  visual  learning. 


%    100 

CA 

3 

CA 

4 

90 

SO 

70 

60 
SO 

i 

CA      5 


CA     6 


F1234  PI  23     y  4 


PROBLEM        BLOCKS 

Fig.  3 
Formation  of  leaming-set.  Percentages  of  correct  responses  on  the  second 
trial  are  plotted  as  a  function  of  problem  blocks.  Monkeys  Ca  3  and  Ca  4 
were  trained  after  the  third  operation  only.  Monkeys  Ca  5,  Ca  6  were 
trained  after  the  first  operation  (interrupted  line),  tested  after  the  second 
operation  (dash-dot  line),  and  re-tested  after  the  third  operation 
(straight  line).  P,  preliminary  sixty-seven  problems;  i  to  4,  successive 
100  problem  blocks;  cross,  percentages  correct  responses  on  the  third 
trials  of  the  last  one  hundred  problems. 


EEG   CHANGES   IN   VISUAL   AND   TEMPORAL   CORTICES   DURING 
LEARNING 

Most  of  the  Studies  on  electroenccphalographic  changes  of  the  brain 
during  learning  deal  with  the  problem  of  functional  localization  (Gastaut, 
1958;  Rusinov  and  Rabinovich,  1958;  Morrell,  1959;  Galambos,  1959). 
As  with  the  ablation  method,  such  studies  are  a  necessary  first  step.  Once 
an  electrographic  change  is  localized  to  a  neural  structure,  unless  the 
genesis  of  the  potentials  is  understood  the  mechanism  of  learning  remains 
difficult  of  translation  into  neuronal  terms.  Furthermore,  in  order  to 
establish  such  a  correlation,  the  electrographic  changes  should  follow  the 
behavioural  changes  as  expressed  in  learning  curves.  Except  in  a  few  cases, 
such  a  correlation  has  not  been  convincingly  reported  (Yoshii,   1956; 


KAO    LIANG    CHOW  515 

Beck,  Doty  and  Kooi,  1958;  Galambos,  1959).  The  present  study  empha- 
sizes this  point.  The  problem  of  functional  localization  is  not  of  primary 
interest.  The  search  here  centres  on  detecting  systematic  EEG  alterations 
in  cortical  areas  known  to  be  concerned  with  visual  discrimination 
learning  in  the  monkey. 

Records  have  been  obtained  to  date  on  six  young  monkeys.  Each 
animal  lived  continuously  in  a  monkey  chair  throughout  the  5  to  6  months 
experimental  period.  The  first  2  months  were  used  to  tame  the  animal 
which  was  held  loosely  in  the  chair  so  that  it  could  turn  around,  scratch 
its  head,  lift  the  leg  to  scratch  the  back,  etc.  The  animals  continued  to 
grow  and  remained  in  excellent  health.  They  were  adapted  to  the  testing 
situation  and  trained  to  be  quiet  before  each  trial  so  that  a  relaxed,  waking 
EEG  baseline  could  be  obtained.  Eight  pairs  of  bipolar  electrodes  made 
with  30  gauge  nichrome  wire,  insulated  except  for  the  tip,  were  implanted 
in  the  temporal  and  visual  areas.  Additional  placements  of  electrodes  in 
the  lateral  geniculate  body,  the  midbrain  reticular  formation,  and  the 
hippocampus  will  not  be  reported  here.  After  the  completion  of  the 
experiment,  the  brains  were  studied  histologically.  The  electrodes  were  in 
the  middle  and  inferior  temporal  gyrus,  and  the  lateral  surface  of  the 
visual  areas.  The  electrode  sites  showed  either  slight  cortical  depression  or 
some  scarring  of  the  tissue,  caused  by  direct  injury  or  by  the  repeated 
electric  shocks  (see  next  section). 

The  test  situation  is  shown  111  Fig.  4.  Either  two  or  three  successive, 
two-choice  visual  discriminations  (red  v.  green;  black  triangle  v.  circle 
on  grey  background;  black  and  grey  vertical  i>.  horizontal  striations) 
were  presented  to  the  animals.  The  training  was  conducted  in  a-dark- 
room  with  a  specially  constructed  photic  stimulator  as  the  light  source. 
The  light  was  continuous  between  trials  but  changed  to  flashes  (5-10 
c.p.s.)  before  each  trial.  Thus,  the  animal  saw  the  visual  stimuli  only 
through  the  flickering  light,  which  may  serve  as  a  'tracer  stimulus' 
(Galambos,  1959,  p.  334).  Each  trial  consisted  of  presenting  one  visual 
stimulus.  If  it  was  a  positive  stimulus,  the  moiikey  was  required  to  push 
open  the  door  of  the  stimulus  box  to  get  a  food  reward  within  5  seconds. 
For  a  trial  with  the  negative  stimulus,  the  door  was  locked  and  the  animal 
was  required  not  to  push  the  door  within  5  seconds.  A  piece  of  food  was 
handed  to  the  animal  if  it  did  not  push  the  door  when  the  negative  stimulus 
was  presented  three  times  in  succession.  A  trial  was  given  in  the  following 
way:  the  opaque  screen  was  in  front  of  the  monkey  to  conceal  the  stimulus 
box.  The  EEG  machine  was  turned  on,  continuous  light  was  changed  to 
flashes,  the  opaque  screen  was  removed  and  the  stimulus  was  exposed 

LL 


5i6 


BRAIN    MECHANISMS    AND    LEARNING 


outside  the  animal's  reach  for  2  seconds.  The  stimukis  box  was  then  pushed 
forward,  and  the  animal  was  allowed  to  respond.  Thirty  trials  (fifteen 
positive  and  fifteen  negative  trials)  were  executed  each  day  until  the 
animal  reached  a  criterion  of  90  per  cent  correct  in  a  one-day  session.  The 
EEG  was  recorded  for  every  trial  with  a  Grass  4-channcl  model  III 
machine. 

The  six  monkeys  learneci  a  total  of  fourteen  visual  discriminations.  The 
plot  of  percentage  of  correct  responses  in  successive  daily  sessions  showed 


Fig.  4 
Photograph  to  show  the  testing  situation.  A,  monkey  in  chair,  with  the  black  screen 
around  the  chair  removed  to  show  the  electrode  wires;  B,  opaque  screen  moved  to  one 
side  to  expose  the  stimulus  box;  C,  the  flickering  light  passing  through  the  box  to 
illuminate  the  visual  stimulus  attached  to  the  box  frontal  panel;  D,  the  photic  stnnulator; 
all  controls  are  operated  manually. 


the  typical  postively  accelerated  learning  curves.  The  number  of  trials 
ranged  from  90  to  180.  EEG  recordings  of  eleven  discriminations  were 
suitable  for  analysis. 

The  normal  EEG  of  the  visual  area  showed  the  fast,  low  voltage  arousal 
pattern  mixed  with  4-5  per  second  relaxation  waves.  Occasionally  there 
were  some  alpha-like  waves.  The  temporal  leads  showed  periodical 
(every  2-3  seconds)  bursts  of  waves  (100  (jv.  and  12-16  per  second)  super- 
imposed on  the  arousal  and  relaxation  record.  These  bursts  were  very 


KAC)    LIANC;    CHOW 


517 


regular  and  appeared  in  all  records.  When  the  training  started,  photic 
driving  was  prominent  in  the  visual  area.  This  driving  habituated  rapidly, 
usually  within  the  first  thirty  trials.  It  very  rarely  appeared  in  the  temporal 
tracings. 

By  inspection,  the  visual  area  EEG  of  each  trial  throughout  the  learning 


-'■\x:-:i'W'M\r'^im\\wh\m\\^\m^^^ 


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V    H     53%  LV  I  ^  I 


19 


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Fig.  5 
EEG  records  of  four  negative  trials  taken  from  the  second  day  of  training.  Monkey  C2  made 
53  per  cent  correct  responses  on  vertical  and  horizontal  striation  discriminations  on  that  day, 
but  responded  incorrectly  to  these  four  trials.  Trials  6  and  19  show  the  decreased  amplitude  of 
temporal  cortical  EEG,  and  trials  19  and  5  show  photic  driving  in  the  visual  area  tracings. 
The  break  in  the  upper  tracings  of  light  flashes  indicates  the  presentation  of  the  stimulus.  The 
arriiw  shows  the  animal  reaching  the  stimulus.  LT,  left  temporal;  LV,  left  visual;  calibration, 
SO  uv.  and  I  sectind. 

process  was  judged  as  showing  or  not  showing  photic  driving.  For  the 
temporal  lobe,  the  disappearance  of  the  periodical  bursts  accompanied  by 
a  decreased  amphtude  of  the  entire  record  was  seen  after  exposure  of  the 
visual  stimuli.  No  other  EEG  alterations  were  recognized.  These  changes, 
however,  were  not  consistent,  being  present  in  one  trial  and  absent  in  the 
next.  Also,  these  changes  occurred  mostly  during  negative  trials.  Fig.  5 


5l8  BRAIN    MECHANISMS    AND    LEARNING 

shows  the  EEG  records  of  four  negative  trials  taken  from  the  second  day 
of  training  of  monkey  Ci.  The  EEG  tracings  show  the  four  possible 
combinations  of  alterations  (visual  area:  photic  driving  or  not  driving; 
temporal  area:  decreased  amplitude  or  not  decreased  amplitude)  in  four 
trials.  Fig.  6  was  taken  from  another  monkey,  who  responded  correctly  to 
the  negative  trials.  Again,  the  four  combinations  appeared  in  the  four 

4 


M  2 
TC      96% 


/t^-^t\jwJ('l-^A\;'/t'l\j^f^/^i,/^/{f^'^-'^''^^~'''''>'''''^f^^ 


5 

LV 
.   LT 


L V  LV  t. 

Fig.  6 
EEG  records  of  four  negative  trials  taken  from  the  fourth  day  of  training.  Monkey  M2 
reached  criterion  on  triangle  and  circle  discrimination  on  that  day,  and  made  correct  responses 
(not  reaching  the  stimulus)  to  these  four  trials.  Trials  4  and  5  show  the  decreased  amplitude  of 
temporal  EEG,  and  trials  5  and  2  show  photic  driving  in  the  visual  area  tracings.  The  break  in 
the  upper  tracing  of  light  flashes  indicates  the  presentation  of  the  stimulus.  LT,  left  temporal; 
LV,  left  visual;  calibration,  50  lav.  and  i  second. 


trials.  Similar  examples  could  also  be  chosen  from  positive  trials.  Thus,  it 
may  be  misleading  to  use  sample  records  demonstrating  EEG  changes 
during  learning.  Some  quantitative  measurements  are  necessary  to  estab- 
lish consistent  trends.  Fig.  7  presents  such  an  analysis  of  two  monkeys' 
EEG  records  on  two  visual  discriminations.  Tracings  from  the  temporal 
and   visual  areas   were   plotted   separately,   with   postive  trials  (vertical 


KAO    LIANG    CHOW 


519 


C2 


VH 


d 

- 

'd 

1   ;' 

1     ^' 

i; 

6 

0 

lb 

^P 

0 

10 
5 

1 

2 

TEMP 


VIS 


Ml  R-  G 


TEMP 


VIS. 


POS. 
NEG. 


Fig.  7 
Graphs  of  monkey  C2  on  vertical  and  horizontal  striations 
discrimination  and  monkey  Ml  on  red  and  green  discrimi- 
nation to  indicate  number  of  trials  of  temporal  cortical 
EEG  (TEMP)  showing  a  decreased  or  no  decreased  ampli- 
tude, and  of  visual  area  tracings  (VIS)  showing  photic 
driving  or  no  photic  driving,  i  to  5  refers  to  successive 
daily  sessions  of  thirty  trials  each,  with  the  corresponding 
percentages  of  correct  responses  indicated  below.  Each 
pair  of  vertical  continuous  bars  are  the  fifteen  daily  posi- 
tive trials,  and  each  pair  of  vertical  interrupted  bars,  the 
fifteen  daily  negative  trials.  The  first  bar  of  each  pair 
indicates  the  number  of  trials  of  no  decreased  amplitude 
EEG  (TEMP)  or  of  no  photic  driving  (VIS).  The  second  bar 
of  each  pair  indicates  the  number  of  trials  that  show 
decreased  amplitude  EEG  (TEMP)  or  photic  driving 
(VIS).  A  few  trials  are  eliminated  because  of  movement 
artifacts.  The  connected  curves  depict  systematic  EEG 
changes  occurring  only  in  negative  trials.  POS,  positive 
trials;  NEG,  negative  trials;  d,  decreased  EEG  amplitude; 
P,  photic  driving. 


520  BRAIN    MECHANISMS    AND    LEARNING 

continuous  bars)  separated  from  the  negative  trials  (vertical  interrupted 
bars).  In  the  graphs  of  temporal  tracings,  the  first  bar  of  each  pair  indicates 
the  number  of  trials  that  showed  no  decreased  amplitude,  and  the  second 
bar,  the  number  of  trials  that  showed  a  decreased  amplitude.  For  the  visual 
area  EEG,  the  first  bar  is  the  number  of  trials  with  no  photic  driving,  the 
second  bar,  the  number  of  trials  with  photic  driving.  The  percentage  of 
correct  responses  during  the  daily  session  was  indicated  at  the  bottom  of 
the  graph. 

These  graphs  show  that  consistent  changes  occurred  only  in  negative 
trials,  but  not  in  positive  trials.  This  probably  reflected  the  fact  that  the 
animals  were  initially  trained  to  reach  for  the  stimulus  every  time.  The 
number  of  negative  trials  showing  a  depressed  amplitude  in  the  temporal 
EEG  increased  as  the  animal  started  to  learn,  but  returned  to  the  hiitial 
level  when  criterion  was  reached.  Such  transient  changes  occurred  in 
eight  out  of  eleven  cases  of  discrimination  learning.  A  similar  change  in  the 
number  of  trials  showing  photic  driving  was  illustrated  in  one  oi  the 
graphs  for  the  visual  area.  Such  visual  area  EEG  changes  appeared,  how- 
ever, in  only  three  out  of  eleven  cases.  Thus,  it  seems  that  the  only  signi- 
ficant electroencephalographic  alterations  in  this  study  were  contmed  to 
the  temporal  cortex  which  is  known  to  be  related  to  visual  learning.  The 
fict  that  the  EEG  change  is  transitory  argues  against  it  being  a  direct 
neural  expression  of  the  learning  process.  Rather,  it  probably  represents 
some  alerting  or  attention  factor.  When  the  animal  began  to  be  aware  of 
the  problem  it  had  to  concentrate  not  to  respond  to  the  negative  stimulus. 
Once  that  was  learned   little  effort  was  needed  to  respond  appropriately. 


LEARNING  AND  RETENTION  DURING  ELECTROGRAPHIC  AFTER- 
DISCHARGES 

The  same  six  monkeys  in  the  same  testing  situation  described  in  the  last 
section  were  used  later  to  study  the  effect  of  local  EEG  after-discharges  of 
the  temporal  cortex  on  learning  and  retention.  Presumably,  seizure  after- 
discharges  disrupt  neuronal  circuits.  The  present  experiment  was  designed 
to  show  whether  or  not  some  such  neuronal  circuits  are  necessary  for 
learning  and  memory  processes. 

The  after-discharges  were  induced  either  unilaterally  or  bilaterally  by 
bipolar  electrical  stimulation  of  the  temporal  cortex.  A  Grass  stimulator 
was  used  to  deliver  monophasic  square  wave  stimuli  (3-5  ms.  50  c.p.s., 
4-25  volts).  Each  trial  was  presented  as  follows:  The  EEG  was  turned  on, 
the  light  was  changed  to  flashes,  the  EEG  was  turned  oft,  the  electrical 


KAO    LIANG    CHOW 


521 


shock  was  turned  on  for  5  seconds.  The  EEG  was  turned  on  again  and  the 
opaque  screen  was  removed  to  expose  the  stimulus  for  2  seconds.  If  there 
were  EEG  after-discharges  during  the  two-second  period,  the  stimulus 
box  was  pushed  forward  for  the  animal  to  respond.  If  no  after-discharges 


C2 


%  100 

T 

r 

90 

,' 

80 

/ 

70 

J 

0 

y 

^-^     ~^ 

12      3     4      5 


M2 


VH    ; 


2      3     4      5 


BILAT. 
UNILAT. 


Fig.  8 
Learning  curves  of  four  monkeys  on  four  visual  discrimin- 
ations, first  during  bi-tcmporal  seizure  after-discharges  (con- 
tinuous line)  and  later  during  unilateral  temporal  seizure 
(interrupted  line).  Percentages  of  correct  responses  are  plotted 
against  successive  two-day  results  (thirty  trials).  I  to  5  refers 
to  thirty  trial  blocks.  T.C.,  triangle  v.  circle;  V.H.,  vertical  v. 
horizontal  striations;  BILAT,  bilateral  temporal  after-discharges; 
UNILAT,  unilateral  temporal  after-discharges. 


appeared,  the  stimulus  box  was  not  pushed  forward  and  the  trial  was 
discounted  (less  than  lo  per  cent  of  the  total  trials).  Fifteen  shock  trials 
were  given  every  day  with  at  least  5  minutes  interval  between  trials.  The 
seizure  after-discharges  in  the  temporal  cortex  were  similar  to  those 


522 


BRAIN    MECHANISMS    AND    LEARNING 


described  by  French,  etc.  (French,  Gcrnaudt  and  Livingston,  1956; 
Konigsmark,  Abdullah  and  French,  195!^),  and  will  not  be  detailed  here. 
In  the  present  study  the  stimulus  strength  was  so  adjusted  that  the  after- 
discharges  of  about  60  per  cent  of  the  trials  lasted  8-10  seconds.  They  were 
localized  to  the  temporal  cortex,  and  did  not  spread  to  visual  areas. 
Following  unilateral  stimulation,  the  after-discharges  appeared  very  rarely 
in  the  contra-lateral  temporal  cortex  (less  than  5  per  cent  of  trials). 

Four  monkeys  were  trained  on  four  discriminations.  Fig.  8  shows  the 
learning  curves.  The  monkeys  responded  at  a  chance  level  in  150  trials 
when  trained  during  bilateral  temporal  after-discharges,  but  learned  the 
problem  during  unilateral  EEG  discharges.  The  animals  reached  for  the 
stimulus  in  every  trial  during  bi-tcmporal  after-discharges.  Their  general 
behaviour  during  this  period,  however,  appeared  to  be  normal.  They 
could  pick  up  small  pieces  of  food  from  among  inedible  objects.  Some- 
times the  animals  seemed  to  be  bewildered  and  glanced  around,  but  this 
did  not  prevent  them  from  reacting  to  the  task. 


Table  III 

RETENTION  TEST  RESULTS  OBTAINED  DURING  EEG  AFTER-DISCHARGES  IN  THE  TEMPORAL  CORTEX. 
PERCENTAGE  OF  CORRECT  RESPONSES  IN  THIRTY  TRIALS.  (tHE  FIGURES  IN  ITALICS  ARE  BASED  ON 
FIFTEEN  TRIALS.)  R.G,  RED  I'.  GREEN;  T.C,  TRIANGLE  I'.  CIRCLE;  V.H,  VERTICAL  V.  HORI- 
ZONTAL   STRIATIONS;    S,    SHOCK    TRIALS;    NS,    NO    SHOCK    TRIALS;    BILAT.,    BILATERAL;    UNILAT., 

UNILATERAL 


Monkey 

Cx 

Q 

M, 

Mo 

M, 

M, 

Problem 

R.G   T.C 

V.H 

R.G 

V.H 

R.G 

T.C 

V.H 

R.G   T.C 

V.H 

R.G 

Bilat. 

S 

53 

50 

60 

53 

43 

57       60 

67 

60 

NS 

97 

97 

97 

97 

93 

97       97 

93 

93 

Unilat. 

S 

97      93 

93 

s? 

9J 

100 

97 

;  00       gj 

100 

NS 

100      97 

97 

S? 

100 

100 

97 

100     100 

93 

The  ability  of  the  monkeys  to  perform  the  learned  visual  discrimina- 
tions during  either  bilateral  temporal  or  unilateral  temporal  after- 
discharges  was  also  tested.  Each  discrimination  was  tested  in  two  days. 
Each  daily  session  consisted  of  fifteen  trials  with  electric  shocks  and  fifteen 
trials  without  shocks  presented  in  a  balanced  order.  Each  trial  was  given  in 
the  same  manner  described  before.  For  no-shock  trials,  the  animal  merely 
waited  for  5  seconds.  The  results  are  summarized  in  Table  III.  It  is  clear 
that  the  animals  failed  to  retain  the  learned  habits  under  the  condition  of 


KAO    LIANG    CHOW  523 

bi-temporal  after-discharges,  but  performed  perfectly  under  uni-temporal 
after-discharges. 

As  a  control,  they  were  also  tested  either  immediately  after  bilateral 
shocks  to  the  visual  areas,  or  during  the  shock  period.  Because  of  the 
difficulty  of  eliciting  consistent  seizure  after-discharges  in  the  visual  areas 
(the  EEG  tracings  usually  flattened  out  for  a  short  period  after  shocks  to 
the  visual  areas),  the  latter  procedure  w2ls  used.  The  results  w^ere  entirely 
negative.  The  animals  performed  the  discriminations  correctly  under  these 
conditions.  Thus,  electric  shocks  to  the  visual  areas  do  not  affect  the 
monkey's  retention  of  visual  habits. 

Several  investigators  have  reported  that  electrical  stimulation  of  sub- 
cortical structures  rendered  cats  and  rats  incapable  of  learning  (Buchwald 
and  Ervin,  1957;  Glickman,  1958;  Ingram,  1958;  Thompson,  1958).  The 
data  presented  here  show  that  only  bilateral  temporal  EEG  after-discharges 
prevent  a  monkey  from  learning  or  from  retaining  visual  discriminations. 
Whatever  neural  circuits  may  be  responsible  for  these  discriminations, 
they  are  located  in  the  two  temporal  lobes  and  can  be  temporarily  dis- 
rupted by  abnormal  neuronal  discharges.  These  results  may  be  relevant  to 
elucidating  the  effects  of  unilateral  stimulation  of  the  temporal  cortex  in 
conscious  human  patients.  Such  stimulations  have  been  variously  reported 
to  elicit  illusions,  hallucinations,  recall,  and  to  cause  transient  amnesia 
(Penfield  and  Jasper,  1954;  Bickford  cr  ai,  1958;  Mullen  and  Pentield, 
1959)- 

SUMMARY 

Previous  investigations  have  established  that  a  restricted  area  of  tem- 
poral neocortex  in  the  monkey  concerns  with  the  learning  and  remem- 
bering of  visual  discriminations.  This  paper  reports  four  studies  illustrating 
how  this  problem  is  analysed  at  the  present  time.  These  studies  are  far 
from  uncovering  the  mechanisms  of  learning  and  retention  at  a  neuronal 
level,  but  they  show  what  specihc  questions  may  be  asked  and  answered 
experimentally.  To  ask  meaningful  questions  about  learning  phenomena 
that  can  be  identified  behaviourally  and  tested  empirically,  constitutes  one 
approach  to  the  understanding  of  the  neural  mechanisms  of  learning. 

GROUP   DISCUSSION 

Galambos.  Dr  Chow  has  referred  to  'brain-disorganization'  experiments  from 
which  much,  I  feel,  is  to  be  learned.  Besides  his  anatomical  methods  there  are  two 
physiological  ways  in  which  these  disorganizations  can  be  created.  Shocks  applied 
to  the  temporal  lobes  and  elsewhere  create  after-discharges,   highly  abnormal 


524  BRAIN    MECHANISMS    AND    LEARNING 

electrical  activity  that  presumably  reflects  a  profound  disorganization  of  the 
neurones  under  the  electrodes.  Besides  this  Bures  employs  another  method,  the 
spreading  depression  technique,  which  yields  an  electrical  record  from  the  affected 
brain  region  that  is  entirely  flat  rather  than  abnormally  active.  Appropriate  use  of 
tliese  physiological  methods  along  with  the  anatomical  ideas  for  disorganizing 
cortex  Dr  Chow  referred  to  should  give  valuable  additional  information  on  the 
brain  function  in  acquisition  and  retention  of  learned  responses. 

Chow.  I  have  talked  about  this  with  Dr  Van  Harreveld  and  he  told  me  that  in 
the  monkey  you  cannot  produce  spreading  depression  very  regularly. 

EccLES.  I  think  Dr  Chow  is  too  hard  on  hmiselt  in  interpreting  this  seeming 
inconsistency  between  the  learning  process  and  the  EEC  results.  What  I  should  like 
to  think  happens  in  the  learning  process  is  a  simplification  in  the  neural  pathways. 
Originally  a  great  deal  of  neural  activity  is  concerned,  a  lot  of  it  of  no  value  to  the 
learning  but  it  is  wandering  through  large  areas,  giving  vou  this  large  depression 
of  the  EEC 

Chow.  This  is  very  possible. 

MouELL.  From  the  standpoint  of  electrophysiology  the  behavioural  learning 
curve  must  surely  be  considered  a  very  coarse  kind  of  measure.  Even  if  these 
variously  recorded  electrical  events  are  related  to  learning  in  some  fundamental 
manner,  I  would  not  expect  them  to  follow  the  same  time-course  as  the  learning 
curve. 

RosvOLD.  We  have  evidence  that  can  substantiate  Dr  Chow's  point  that  the 
connections  are  cortico-cortical. 

Will  the  monkey  learn  anything  at  all  during  the  period  of  after-discharge  ?  Dr 
Chow  demonstrated  clearly  that  he  could  not  learn  the  visual  discrimination 
problem.  I  am  wondering  whether  the  Animal  can  learn  anything  at  all. 

What  was  your  stimulation  technique  because  we  were  not  able  to  disturb 
the  retention  ot  the  visual  discrimination  problem  —  by  strong  stimulation  in  the 
temporal  lobes. 

Chow.  I  am  using  bipolar  electrodes  to  stimulate  the  temporal  cortex,  and  not 
recording  with  EEC  I  only  test  them  when  the  EEG  shows  after-discharge 
bilaterally.  They  are  wire  electrodes  insulated  except  at  the  lip  with  3  or  4  mm. 
separation  between  electrode  tips.  The  stimulus  is  3  ms.  square  waves  50  cycles  per 
second,  for  5  seconds. 

With  respect  to  whether  this  effect  is  specific  to  the  task  or  not  i  have  not  looked 
into  the  problem.  That  is  a  question  of  functional  localization,  which  is  not  the 
purpose  of  this  study. 

BusER.  I  still  believe  in  electrophysiology  as  an  index  of  neuronal  activity  and 
neuronal  activity  is  the  basis  of  learning.  Maybe  the  test  ^•ou  are  using  is  not  a 
good  one  or  the  process  taking  place  is  not  uni-directional.  Is  it  more  complex  than 
the  total  behavioural  phenomenon  you  are  observing?  Did  you  happen  to  record 
evoked  potentials  to  optic  stimulation  in  the  temporal  region  of  the  monkey,  an 
observation  which  could  be  correlated  with  your  results  from  ablation  techniques? 

Chow.  I  did  not  make  any  recording  of  evoked  potentials  in  the  temporal  or 
visual  areas  of  the  monkey. 

As  to  your  first  question,  I  think  one  should  pose  meaningful  questions  to  be 
answered  by  the  EEG  technique.  Just  implanting  electrodes  and  recording  the 
EEG  to  see  what  happens  is  not  very  satisfying. 


KAO    LIANG    CHOW  525 

AsRATYAN.  I  think  that  some  of  our  data  pubhshed  in  1937  in  Russia  may  be  of 
interest  to  Dr  Chow.  That  is  why  I  want  Dr  Chow  to  become  acquainted  with 
these  facts.  We  divided  the  brain  cortex  of  the  dog  into  three  isolated  parts, 
namely,  the  frontal,  occipital  and  temporal  parts,  by  surgical  extirpation  of  ribbons 
of  cortical  tissue  between  main  parts  of  brain  cortex.  Let  me  show  the  operation 
schematically  on  the  blackboard.  We  cut  only  the  cortex  tissue,  but  as  it  was 
shown  later  by  histological  control  degeneration  of  subcortical  white  tissue  took 
place  also.  So,  these  cortical  parts  were  iully  isolated  from  each  other  and  con- 
nected with  each  other  only  through  subcortical  structures.  We  were  able  to 
elaborate  conditioned  defensive  motor  reflexes  to  the  visual  as  well  as  to  the  audi- 
tory stimulus.  After  repeated  cortical  operation  during  which  wc  extirpated  cither 
the  isolated  occipital  or  temporal  regions,  the  visual  or  auditory  reflexes  were 
correspondingly  abolished. 

Chow  (in  answer  to  a  question  from  Dr  Naquet).  In  this  expernncnt  the  only 
control  I  had  w^as  to  stimulate  the  visual  area  either  uni-  or  bilaterally  or  one 
electrode  on  each  occipital  area  and  to  test  on  retention.  I  have  not  tested  on 
learning.  Whether  you  tested  immediatelv  after  or  during  stimulation  of  the  visual 
areas  there  is  no  detrimental  effect  on  retention  ot  the  visual  discriminations. 

Segundo.  In  support  ot  Dr  Buser's  defence  ot  the  usctulness  ot  electrographic 
recording  in  the  study  of  learning,  I  would  mention  that,  in  our  experience,  the 
EEG  provided  more  sensitive  criteria  than  pertormance.  First,  EEC  effects  appeared 
earlier  than  behavioural  effects  during  establishment  and  disappeared  later  during 
extinction  of  learned  responses.  Secondly,  when  studying  very  wild  cats,  animals 
gave  little  behavioural  evidence  of  'learning'  but  electrographicallv  yielded 
obvious  siuns  of  conditioning. 


OBSERVATIONS   SUR  LE  CONDITIONNEMENT 
INSTRUMENTAL  ALIMENTAIRE  CHEZ  LE  CHAT^ 

P.    BUSER   ET    A.    ROUGEUL 

Avec  la  collaboration  dc  Melle  D.  Giraud^ 

Introduction 

On  s'interroge  encore,  et  sans  doute  Ic  probleme  ainsi  pose  n'a-t-il  pas 
de  solution  simple,  quant  aux  roles  respcctifs  du  cortex  cerebral  —  con- 
sidere  partiellement  ou  dans  sa  totalite  —  et  de  diverses  structures  sous- 
corticales  dans  les  mccanismes  d'integration  sensorimotrice  dont  pro- 
ccdent  I'acquisition  puis  I'cxecution  d'un  mouvement  conditionne. 

Au  nombre  des  sources  d'inforniation  dont  on  dispose,  I'analyse 
clectrophysiologique,  telle  qu'elle  a  etc  receninient  etendue  a  ce  domaine, 
apporte,  il  va  de  soi,  un  ensemble  de  renscignements  essentiels  sur  les 
modifications  globalcs  ou  localisees  que  Ton  peut  deceler  au  niveau  des 
centres,  et  du  cortex  en  particulier,  dans  les  diverses  situations  d'un 
conditionnement  moteur. 

L'interet  de  cette  methode  ne  saurait  toutcfois  en  laisser  ignorer  d'autres, 
celle  en  particulier  d'eliminations  ou  de  destructions  localisees  du  nevraxe; 
classique,  sans  doute  plus  globale  et  moins  analytique,  elle  reste  neanmoins 
essentielle  pour  decider  de  Timportance  d'une  structure  determinee  dans 
I'organisation  fonctionnclle  d'une  certaine  reaction  motrice  conditionnee. 

Tel  fut  notre  probleme.  Soumettant  des  chats  a  un  type  classique  de 
conditionnement  'instrumental'  —  type  'reward  training'  de  Hilgard  et 
Marquis  (1940)  —  nous  nous  sommes  pose  la  question  du  role  du  cortex 
moteur  dans  I'enchainement  des  processus  qui  conduisent  I'animal  a 
accomplir  un  mouvement  'volontairc'  pour  un  signal  determine.  Certes, 
les  documents  clectrophysiologiques  sur  le  cortex  moteur  (modification 
de  son  trace  spontane,  etude  des  reponses  evoquces  qui  s'y  developpent, 

^  Le  present  travail  a  beneficie  d'une  subvention  partielle  de  V  'Office  for  Scientific  Research 
of  the  Air  Research  and  Development  Command,  U.S.  Air  Force',  attribuee  par  son  Service 
europeen  sous  contrat  AF  61  (052),  103. 

'^  Nous  tenons  a  remercier  egalement  Melle  G.  Giacobini  et  Mme  S.  Laplante,  pour  leur 
aide  au  cours  des  interventions,  comme  aussi  dans  la  preparation  des  controles  histologiques 
post-mortem. 


528  BRAIN    MECHANISMS    AND    LEARNING 

niodalitcs  dc  niisc  en  jcu,  cgalcmcnt,  du  tractus  pyramidal)  ctaicnt  prccisc- 
ment  loin  dc  fairc  dcfaut,^  qu'il  s'agissc  dc  tionnccs  rccucillics  sur  animaux 
portcurs  d'clcctrodcs  iniplantccs  (Chow,  Dement  ct  John,  1957;  Beck, 
Doty  ct  Kooi,  1958;  Morrcll,  1958;  John  ct  Killam,  1959;  Scgundo  ct 
col.,  1959;  Zuckcrmann,  1959;  pour  references  antcrieures,  voir  Buser  et 
Roger,  1957;  Fessard  et  Gastaut,  1958),  ou  d'autrcs  obtcnucs  sur  prepara- 
tions aigucs  (voir  Discussion). 

Toutcfois,  la  solution  au  problcme  ainsi  pose  n'etait  pas  inclusc; 
envisageant  des  lors  les  rcsultats  d'ablations,  il  nous  apparut  que,  a  I'exccp- 
tion  dc  quelqucs  travaux,  dont  ceux  de  I'ccolc  dc  Konorski  (Konorski  ct 
col.,  1952;  Brutkowski  et  col.,  1955,  1956;  Stgpien  et  Stgpieii,  1958, 
1959^  i960)  realises  sur  le  chien  dans  des  conditions  comparables,  mais  non 
identiques  aux  notrcs,  scul  le  comportcment  moteur  spontanc,  tonus  et 
locomotion,  avait  etc  analyse  chez  les  carnivores,  souvent  d'ailleurs  avec 
unc  grande  precision,  aprcs  dc  tclles  eliminations  corticalcs  (Olmsted  et 
Logan,  1925;  King,  1927;  Langworthy,  1928;  Laughton,  1928;  McKibben, 
1929,  parmi  d'autrcs). 

Cette  absence  dc  documents  dans  le  sens  souhaite  a  dicte  le  present 
travail. 

Techniques 

Les  experiences  portent  actuellcment  sur  22  animaux,  tons  adultes;  un 
certain  nombre  d'entre  eux,  normaux,  ont  servi  dc  temoins;  d'autrcs  ont 
subi  divcrses  ablations  d'aires  corticalcs. 

Mode  opcratoirc 

Toutcs  les  ablations  out  etc  pratiquccs  ascptiqucment,  sous  narcose  au 
Nembutal,  par  aspiration  menagec,  avec  conservation  des  volets  osscux; 
rhemostasc  ctait  rcalisee  au  moyen  d'epongc  de  gelatine  (Spongel). 

Les  ablations  d'aires  motrices  ont  toujours  etc  bilatcrales  ct  extensives. 
Ellcs  portaient  sur  toute  la  region  sensorimotricc  pericruciec  ct  I'aire 
somatiquc  II,  et  debordaient  sur  les  gyrus  proreus,  marginal,  suprasylvien 
ct  cctosylvien  scion  des  contours  dont  les  details  scront  indiqucs  ci- 
dessous.  Ellcs  s'etendaient  sur  uiie  profondeur  sut^isante  pour  doniier  la 
certitude  d'avoir  climinc'  la  substance  grisc  des  sillons.  Par  ailleurs,  les 
voics  olfactivcs  primaircs  (lobe  olfactif  en  particulier)  ont  toujours  etc 
respectces. 

'  Un  certain  nonibrc  dc  ccs  donnccs,  obtcnucs  par  notre  groupc,  ct  colics  en  particulier 
recueillics  par  nous-niemes  sur  Ic  chronique  (Rougeul,  1958)  ont  etc  presentees  au  cours  du 
Symposium.  II  nous  a  paru  preferable,  pour  I'homogeneite  du  sujet  traite,  de  n'en  pas  faire 
ctat  dans  le  cadre  dc  cct  article  a  objcctif  limitc. 


p.    BUSER    ET    A.    ROUGEUL 


529 


D'autrcs  ablations  out  etc  rcalisccs,  dcstinces  a  servir  de  coiitrole:  soit 
destructions  isolces,  toujours  bilaterales,  de  divers  territoircs  (gyrus 
proreus,  aires  visuelles,  aires  auditives),  soit  elnninatioii  subtotale  du 
neocortex,  ne  laissant  subsister  que  les  regions  pericruciees  et  prefrontales. 

CoiuHtiomicniciir 

Tous  les  annnaux  et  plus  specialement  ceux  porteurs  d'ablations  etaient 
niaintenus  dans  des  conditions  aussi  fiivorables  que  possible  (semi-liberte), 
permettant  d'observer  a  volonte  leur  coniportenient  spontane. 


1-IG.   I 

Appuis  conditionnc  norniaux. 
TA:  chat  normal;  VA:  animal  a  ablations  frontalc  et  pcricrucicc  particllc;  BE:  animal  a 
ablation  du  cortex  temporal  et  de  I'an-e  somatiqiie  II  (voir  Fig.  6). 


Les  epreuves  d'apprentissage  c'taient  eftectuees  quotidiemienient  a 
heure  tixe,  toutes  precautions  etant  prises  pour  que  les  animaux  se  trouvent, 
d'une  seance  a  I'autre,  dans  des  etats  de  faini  pratiquenicnt  coniparables. 
La  duree  de  chaque  seance  n'a  jamais  depasse  30  minutes  (ro  cssais). 

Le  dispositif  d'apprentissage  'instrumental'  est  d'un  type  relativement 
classique,  s'apparentant  plus  particulicrement  a  celui  recemment  utilise 
egalement  pour  le  chat  par  Stamm  et  Sperrv  (1957):  le  mouvement  de 
bascule  d'un  levier  declenche  automatiquement  I'ouverture  d'un  volet, 
demasquant  ainsi  un  plateau  portant  de  la  nourriture  (Fig.  i) ;  I'animal,  qui 
est  maintenu  par  un  hamac  dans  une  position  determinee,  apprend  a 
eftectuer  le  geste  d'appui  a  un  signal  donne;  ce  signal  consiste  en  une 
succession  de  stimuli  brefs  acoustiques  (pips  a  frequence  donnee)  ou 
lumineux  (eclairs)  a  la  cadence  de  un,  ou  deux  par  seconde,  selon  les  cas. 


530  15RAIN    MECHANISMS    AND    LEARNING 

La  Stimulation  est  poursuivic  a  cc  rythmc  jusqu'a  raccomplissemcnt  du 
moiivcmcnt;  cii  cas  d'abscncc  d'appui,  cllc  n'cst  pas  prolongce  au-dcla  de 
20  sccondcs  (pour  Ics  animaux  norniaux) ;  cllc  Ic  sera  davantage  pour  dcs 
animaux  portcurs  dc  lesions. 

L'expericnce  sc  fait  en  chanibre  rclativcmcnt  insonorisee,  un  iond 
sonore  continu  permcttant  en  outre  de  masquer  de  manicre  satisfaisante 
d'eventuels  bruits  accidentcls;  cet  amenagement,  theoriqucmcnt  insufFi- 
sant,  s'cst  avcrc  neannioins  conveiiir,  I'experiencc  nous  ayant  montre  que 
dans  dc  tellcs  epreuves  la  susceptibilite  dcs  animaux  a  des  cfFets  d'inhibition 
cxterne  est  tres  rcduitc. 


Et'ahiatioii  des  rcsiiltats 

Au  cours  de  chaque  session,  sur  animal  normal  ou  porteur  de  lesions, 
on  procede  a  une  evaluation  aussi  approchee  que  possible  de  la  latence  dcs 
reponses :  temps  qui  scparc  pour  chaque  essai  Ic  premier  signal,  du  debut  dc 
I'appui  sur  le  Icvier.  On  releve  cgalemcnt  le  nombre  dcs  appuis  eventuelle- 
ment  eftectues  entre  les  cssais  ('appuis-crreurs'). 

A  partir  dc  ces  domiecs  immcdiates,  on  a  procede  a  d'autres  estimations 
(moyennes  de  latcnces,  etc....),  qui  scront  dc'taillccs  ci-dessous.  Enhn,  Ton 
note  toutes  les  manifestations  dc  comportement  anormal  que  Ton  pent 
observer  chez  les  animaux  operes  au  cours  dcs  seances  de  travail. 


Coiitrolc  port-iiiortciii 

Tous  les  animaux  ont  etc  maintenus  pendant  dcs  periodes  de  2  a  6  mois, 
les  survies  les  plus  longues  ctant  ccllcs  d'animaux  portcurs  d'ablations  et 
dont  la  recuperation  c'tait  rc'gulieremcnt  suivic.  Avant  le  sacrifice,  une 
analyse  electrophysiologiquc  dcs  reponses  en  divers  points  du  nevraxe 
ctait  cffectuee,  de  prc'fcrencc  sous  anesthesie  au  chloralose:  exploration  du 
cortex,  prccisant  le  nouvel  aspect  dc  la  topographic  des  projections  scnso- 
ricllcs  apres  ablation;  etude,  cgalemcnt,  par  introduction  d'unc  electrode 
au  niveau  pontique,^  dc  la  pcrsistancc  —  ou  dc  la  disparition  —  d'unc 
activitc'  pyramidale  chez  les  animaux  a  ablation  sensorimotrice.  Ultericure- 
ment,  le  cervcau  etait  perfuse  au  serum  physiologique,  puis  au  formol.  Le 
cas  cchcant,  une  etude  topographiquc  de  retendue  dc  I'ablation  etait 
cffectuee,  d'abord  macroscopiquement,  puis  sur  coupes  frontales,  apres 
coloration  dc  Nissl. 

1  Scion  une  technique  rcccmnicnt  utilisce  pcHir  rexploration  du  tractus  pyramidal  sur  la 
prcparaticMi  aiguc  (Ascher  ct  Buser,  1958). 


p.    BUSER   ET    A.    ROUGEUL  531 

Resultats 

On  cnvisagera  succcssivcmcnt  quclqucs  aspects  de  I'apprentissagc  chez 
les  animaux  nonnaux,  pour  ensuitc  considcrer  les  eftets  dcs  ablations. 

I.    MODALITES    d'aPPRENTISSAGE    CHEZ    LE    CHAT    NORMAL 

Chez  ranimal  intact,  Ic  debut  du  'dressage'  s'efFectue,  scion  les  cas,  soit 
en  anienant  passivement  la  pattc  sur  le  levier  pendant  le  signal,  soit  en 
procedant  'par  imitation'. 

La  premiere  methode,  par  mouvement  passif,  dans  laqucllc  on  associe  au 
signal  une  sensation  complexc,  a  composante  exteroceptive  et  probable- 
ment  surtout  proprioceptive,  s'apparentc  directement  au  conditionnemcnt 
du  deuxieme  type.  Nous  lui  avons  assez  vite  prcfcre  —  sauf  pour  les  sujets 
de  controle  avcugles  —  une  technique  impliquant  une  participation  de 
I'animal  pcut  —  ctre  plus  en  rapport  avec  1'  'intelligent  behaviour' 
(Konorski,  1950);  il  suffit  en  cft'et  d'appuycr  avec  la  main  sur  le  levier, 
pendant  le  signal,  pour  qu'au  bout  d'un  certain  temps,  le  chat,  trcs 
attentif  en  gc'ncral,  tente  de  faire  lui-meme  I'operation.  Get  apprentissagc 
par  imitation  rc5ussit  plus  vite  que  Ic  precedent  ct  presentc  cet  avantage  que 
le  sujet  eftcctue  d'emblee  des  mouvcments  efticaces,  alors  que  le  dressage 
par  dcplaccment  passif  conduit  frcqucmment  a  des  actcs  incomplets  (souleve- 
ments  de  la  patte,  sans  appui  reel  sur  le  levier). 

Lc  'temps  mort'  qui  s'ecoule  ainsi  entre  le  debut  du  dressage  et  les 
premiers  mouvemcnts  conditionnes  varie  selon  le  sujct  de  1  a  6  jours,  a 
raison  d'une  session  de  10  essais  par  jour. 

L'animal,  ayant  appris  a  executer  le  mouvement,  I'cftcctue  certes 
frequemment,  surtout  au  debut,  en  I'absence  de  stimulation  condition- 
nante.  Ccs  appuis-erreurs  se  rarefient  au  fur  et  a  mesurc  que  le  sujet 
diftcrcncic  les  simples  conditions  ambiantes  du  moment  de  I'application 
des  stimuli. 

Ei'ahiation  ct  caracrcristiqiics  des  pcrfoniuviccs  obtciiiics  pour 
nil  si{iiial  positij 

On  s'cst  d'autre  part  ct^orce  d'evaluer  quantitativement  les  performances 
de  l'animal  en  utilisant  commc  donnee  aiscmcnt  accessible  la  latcnce  du 
mouvement,  temps  qui  separe  I'appui  franc  du  debut  de  la  serie  des 
signaux  conditionnants.  Ces  valeurs  sont  notees  pour  chaquc  session  et 
trois  types  de  graphiques  en  scront  deduits.^ 

1  On  ne  tient  compte  dans  la  statistiquc  ni  dcs  gcstes  inefficaces,  ni  des  cas  de  performances 
accidcntcllenient  mauvaises  liees  a  des  causes  identifiables  (mauvais  etat  passager  de  I'aninial, 
oestrus  chez  les  femelles,  etc..) 
MM 


532 


BRAIN    MECHANISMS    AND    LEARNING 


100 

% 

90 


80 


70 


60 


50 


AO    - 


30   - 


20  - 


10  - 


0   _ 


"~r~ 
10 


— r- 
30 


20 


Fig.  2 
Repartition  statistiquc  dcs  latcnces  d'appuis  conditionnes  correspondant  a  lo  sujcts  norniaiix. 
Pour  cliaque  animal,  le  polygene  correspond  aux  latences  de  lOO  appuis,  realises  apres  stabili- 
sation du  conditionncment  (voir  tcxte). 


p.    BUSER   ET    A.    ROUGEUL  533 

(a)  Stadstiqiic  lics  latciiccs 

Unc  fois  etabli  un  conditionncincnt  stable,  c'est-a-dirc  lorsque  les 
latcuces  restent  dans  les  inenics  liniites  et  ne  s'ameliorent  plus  seiisiblemcnt, 
on  considcrc  la  distribution  de  leurs  valeurs  pour  lOO  cssais  (soit  lo  jours). 
Pour  unc  presentation  simple  des  resultats,  on  a  choisi  une  fois  pour  toutes 
un  intervalle  de  classes  dc  2  secondes,  le  temps  o  ctant  celui  du  premier 
signal  conditionnant.  Il  ressort  ainsi  que  (Fig.  2),  pour  rensemble  des  chats 
niM-niaux,  les  latcnces  sont  relativement  peu  dispersecs  autour  dc  la  valcur 
modalc  qui  sc  situc,  scion  Ic  sujet,  entrc  i  et  4  secondes.  Les  polygoncs 
tcmoigncnt  d'unc  bonne  similitude  d'un  animal  a  Tautrc;  il  est  de  plus 
apparu  que,  pour  un  sujet  donnc,  a  conditionncmcnt  stabilise,  cette 
distribution  nc  variait  pas  sensiblement  au  cours  du  temps.  L'allurc  des 
polygoncs  laisse  tuialemcnt  apparaitrc  unc  rupture  dc  pente  du  cote  des 
latcnces  elevces,  telle  qu'au-dela  d'unc  certainc  valcur  sc  situc  une  zone  dc 
plus  grande  ciispcrsion,  mais  ou  la  frequence  ne  dcpasse  jamais  5  pour-cent. 

Des  lors,  la  plus  grande  latencc  corrcspondant  a  plus  dc  5  pour-cent  des 
rcponscs  pouvait,  sans  trop  d'arbitraire,  represcnter  pour  chaque  animal  unc 
liiuitc  supericure  caracterisant  son  domaine  propre  de  latcnces  courtes  et 
peu  dispersecs.  C'cst  cette  valcur  que  nous  avons  considerce  dans  la 
construction  des  polygoncs  d'evolution  des  latcnces. 

(b)  Evolution  des  latcuces 

Unc  autre  statistique  a  pu  ctrc  ctablic,  destinee  cette  tois  a  apprecicr  les 
modalites  dynamiqucs  dc  I'apprentissage  pour  chaque  animal  a  partir  du 
debut  des  sessions. 

Considcrant  les  valeurs  des  latcnces  obtcnues  au  cours  dc  chaque  seance 
quotidienne  de  to  cssais,  on  rctient: 

—  d'unc  part,  le  nombre  des  appuis  eftcctivcment  obtcnus  dans  la  limite 
fixee  comme  durce  niaximalc  des  stimulations,  c'est-a-dire  20  secondes 
(Fig.  3,  courbe  grisc); 

—  d'autre  part,  Ic  nombre  d'appuis  a  latencc  courte,  c'cst-a-dirc  realises 
dans  des  temps  infericurs  a  la  limite  qui  aura  etc  prcalablcmcnt  dcterminee 
a  partir  dc  la  repartition  statistique  (Fig.  3,  courbe  noire). 

Les  deux  polygoncs  ainsi  traces  a  partir  des  points  caracteristiqucs  de 
chaque  session,  rcsument  assez  concretcment  I'cvolution  chronologique 
des  performances:  apprcntissage  brut,  c'cst-a-dirc  pourccntage  des 
mouvements  obtcnus  (courbe  grisc) ;  proportion,  d'autre  part,  des  appuis  a 
execution  rapidc  (courbe  noire).  On  y  remarque  aisement  rexistence  d'un 


534 


BRAIN    MECHANISMS   AND    LEARNING 


temps  mort,  trcs  reduit  pour  certains  aiiiinaux,  ct  n'exccdant  pas  6  jours  en 
general;  I'ascension  rapide  de  la  courbe  d'apprentissage  brut,  qui  ordinaire- 
nient  se  niaintient  telle  tout  au  long  des  sessions  n'impliquant  aucune 
source  particulicre  d'inhibition  interne;  la  croissance  cgalenient  rapide, 
enfm,  dc  la  proportion  des  appuis  precoces,  mais,  fait  attendu,  sa  plus 
grande  variabilite. 


Fig.  3 

Polygoncs  d'cvolution  des  latcnces  chcz  3  aniinaux  normaux.  Abscisses:  jours  de  conditionnc- 
ment  successifs;  ordoiinccs:  nonibres  d'appuis  realises  au  cours  d'une  seance  quotidicnnc  de 
10  essais. 

Contours  gris  et  noirs:  nombres  d'appuis  dont  les  latenccs  sont  respectivenicnt  infcrieures 
a  20  secondes  et  inferieures  a  la  'latencc  liniite',  valeur  indiquee  pour  chaquc  animal  ct  deduite 
de  la  statistique  des  delais  (voir  texte). 


(c)  Ei'aliicitioii  dc  la  tciidiincc  aiix  \ippiiis-crrciirs' 

On  a  choisi  de  considercr,  pour  chaque  session,  le  nonibre  d'intervalles 
entre  deux  essais,  pour  lesquels  //;/  appui-erreur  au  iiioiiis  aura  etc  effectue. 
Le  polygone  ainsi  obtenu  (Fig.  4)  est  alors  compare  a  cclui  des  appuis  de 
courte  latcnce  (courbe  noire  de  revaluation  b).  Cette  confrontation  entre 
extremes  —  tendance  a  I'appui  spontanc  et  tendance  au  conditionnement 
optimal  —  fait  asscz  nettement  ressortir  que,  chez  I'animal  normal  (Fig.  4, 
L,  M,  Icre  image),  sc  devcloppe  toujours  initialement,  et  quel  que  soit  le 
mode  d'apprentissage,  une  phase  d'hyperactivite  pendant  laquelle  les 
appuis-errcurs  dominent  nettement. 


p.    BUSER    ET    A.    ROUGEUL 


535 


Mal^rc  unc  rarcfiiction  ultcricurc,  souvcnt  asscz  brusque,  Ics  deux 
courbes  conservent  uii  certain  parallelisine  clans  leur  evolution,  la  tendance 
aux  appuis  a  courte  latence  et  cclle  a  des  appuis-erreurs  etant  sans  doute 
conditionnees  par  le  nienie  mccanisnic.  La  quasi  inipossibilite  d'obtenir. 


Fic.  4 
Courbes  d'appuis-crreurs  corrcspondaiit  a  des  animaux  norinaux  (a  gauche)  ct  portcurs  d'abla- 
tions  scnsoriniotrices  larges  (a  droite). 

—  abscisses:  jours  post-opcratoircs;  I'origme  des  graphic^ucs  coincide  avec  le  premier  jour 

d'apprentissage. 

—  ordonnces  fpolygone  noir:  noiubres  d'appuis  a  latence  cgale  ou  infericure  a  la  latence 
pour  cha-  <!  liniite-polygone  blanc:  nombres  d'intervalles  au  cours  duquel  un  appui- 
que  jour        [^erreur  au  nroins  a  etc  cffectue  (voir  tcxtc). 

Les  points  signalent,  en  debut  d'apprentissage,  le  nonibrc  d'appuis  a  latence  longue  (niais 
inferieure  a  20  secondcs). 


chez  le  chat,  unc  diffc'renciatic^n  parfixite  entre  I'environnenient  et  le 
signal  conditionnant  —  fait  d'ailleurs  bien  connu  —  est  a  nientionner  une 
fois  encore. 

Ccs  diverses  statistiques  subissent,  on  le  verra  ci-dessous,  des  modifica- 
tions significatives  aprcs  ablations  cortico-frontales. 


536  BRAIN    MECHANISMS    AND    LEARNING 

II.    REPERCUSSION    DE   l' ABLATION    BILATERALE   DU    CORTEX   SENSORIMOTEUR 

Lcs  dix  chats  dc  cc  groupc  sc  rcpartissciit  en  trois  categories: 

icr  oroiipc:  cinq  ont  subi  rcliniination  totale  bilateralc  du  cortex  sensori- 
moteur  (PA,  RA,  ZA,  BO,  CA). 

A  I'exanien  clcctrophysiologiquc  (sous  ancsthesie  au  chloralosc) 
precedant  le  sacrifice,  aucune  activitc  typique  des  aires  extirpces  n'a  pu 
ctre  decelee  pour  une  stimulation  tactile,  ni  au  voisinage  des  lesions  corti- 
cales,  ni  au  niveau  correspondant  au  tractus  pyramidal,  ou  des  reponses 
reverberces  sont  normalement  observees  dans  ces  conditions  (Adrian  et 
Moruzzi,  1939;  Ascher  et  Buser,  1958). 

Le  controle  anatomique  post-mortem  a  rcvelc  des  lesions  comparables, 
incluant  les  territoires  suivants  (Fig.  5,  I):  gyrus  sigmoide  anterieur  et 
posterieur,  gyrus  proreus,  coronalis,  avec  empictements  a  peu  pres  equiva- 
lents dans  tons  les  cas  sur  les  circonvolutions  latcrale  anterieure,  supra- 
sylvienne  anterieure,  ectosylvienne  anterieure  et  orbitairc. 

En  premiere  approximation,  ces  animaux  constituent  done  un  lot 
homogene  prive  a  la  fois  des  aires  motrices  pyramidales,  somatiques  I  et 
somatiques  II,  ainsi  que  des  lobes  prcfrontaux. 

Jcmc  (groupc:  chcz  trois  animaux,  une  partie  ou  la  totalitc  des  aires  soma- 
tiques II  avait  cte  cpargnce  (Fig.  5,  IT). 

L'examcn  electrophysiologique  a  eftcctivement  revele  la  presence  chez 
deux  dc  ces  sujets  (MA,  TA),  dc  potentiels  evoques  dans  une  zone  tres 
reduite,  laissee  intacte,  du  gyrus  ectosylvicn  anterieur;  toutefois,  I'cxplora- 
tion  du  tractus  pyramidal  n'a  montrc  aucune  reponse  au  stimulus  tactile 
dans  un  cas  (MA)  et  sculement  des  rc'ponses  tres  atypiques  dans  I'autre 
(TA).  Le  troisieme  sujet  (CE),  qui  avait  conserve  la  totalite  des  aires 
II,  n'a  accidentellcment  pas  fait  I'objet  des  controles  ante-mortem 
habituels. 

jeme  {^roiipe:  deux  chats  n'ont  subi  que  des  ablations  partiellcs.  Chez  I'un 
(CU),  la  lesion  fut  strictement  limitec  au  cortex  pericrucie  superficiel. 
La  region  premotrice  (g.  proreus),  ainsi  que  le  tcrritoire  de  I'aire  II  furent 
laisscs  intacts  (Fig.  6).  Chez  le  second  (VA),  relimination  a  touchc  tout  le 
pole  frontal  (g.  proreus  et  g.  coronalis)  et  s'est  ctendue  en  surface  jusqu'au 
sulcus  cruciatus.  Lcs  aires  somatique  I,  somatique  II  et  la  partie  profonde  de 
I'aire  motrice  furent  conservces;  dans  les  deux  cas,  des  reponses  pyrami- 
dales normales,  ainsi  que  des  potentiels  evoques  somesthesiques  corticaux, 
furent  observes  au  moment  du  controle  electrophysiologique  ante- 
mortem. 


p.    BUSER   ET    A.    ROUGEUL 


537 


Fig.  5 
Report,  sur  des  schenias  des  faces  lateralcs  et  mcdianes  du  cerveau  du  chat,  du  contour  des 
ablations  pratiquees  dans  les  groupcs  I  (5  chats)  et  II  (2  chats). 


538 


BRAIN    MECHANISMS    AND    LEARNING 


Fig.  6 
Contours  des  ablations  du  groupe  III  (CU,  VA)  et  des  ablations  controles 
(UA,  NA,  BE). 


p.    BUSER   ET   A.    ROUGEUL 


539 


Fig.  6 


540  BRAIN    MECHANISMS    AND    LEARNING 

Coiiiporteiiiciit  spoiitaiic 
Lcs   cinq   aniniaux   du   premier   groupc   prcseiitaient   tous   le   memc 
ensemble  d'anomalies,  dont  nous  n'evoqucrons  ici  que  lcs  traits  essentiels, 
un  certain  nombre  de  travaux  anterieurs  relatifs  a  divers  types  d'ablation 
en  ayant  deja  dctaille  les  diffcrents  aspects  (voir  ci-dessous) : 

—  Perte  de  vivacitc,  acquisition  d'unc  ccrtaine  placidite  et  docilitc; 
existence  neanmoins  d'une  hyperactivitc  sans  but  (deplaccments  incessants 
mais  lents) ; 

—  Troubles  du  tonus  postural  et  dcs  reflexes  de  redressement,  hyper- 
tonic dcs  cxtenscurs  d'une  part  et  perte  de  la  rcactitui  de  placement  tactile 
de  I'autre.  Ces  alterations  sont  vraisemblablemcnt  a  Torignie  dcs  troubles 
de  la  locomotion :  circumduction  des  pattcs  posterieures,  marche  en  ciseaux, 
marchc  sur  les  poignets  flechis,  glissades,  arrets  en  position  anormale, 
ditiiculte  de  marche  sur  une  planche  etroite. 

—  Trembles  durables  de  la  prise  de  nourriturc:  les  animaux  se  montrent 
tres  voraces,  mais  out  une  ccrtaine  ditiiculte  a  saisir  lcs  aliments  dans  Icur 
guculc  (morsure  du  bord  du  plat). 

—  Mouvements  de  Icchage  'dans  le  vide'  determines  par  toutc  stimula- 
tion tactile  du  corps  (sauf  de  la  tcte). 

Le  deuxieme  groupc  a  prcsente  dcs  tableaux  du  mcme  type,  mais  in- 
complcts,  lcs  anomalies  cftcctivemcnt  presentees  variant  scion  le  sujet. 

Lcs  deux  chats  du  troisicme  groupc  se  sont  montres  apparemment 
normaux,  misc  a  part  une  pcriode  transitoire  de  troubles  toniqucs  associes 
a  une  perte  dc  placing  chez  I'un  d'eux  (CU). 

Docilitc,  anomalies  dc  ralimentation  et  Icchage  dans  le  vicie  out  etc 
analyses  en  detail  chez  le  chat  par  Schaltcnbrand  et  Cobb  (193 1),  Bard  et 
Rioch  (1937),  Bard  et  Mountcastlc  (194N),  aprcs  ablation  bilatcralc  dc  la 
totalitc  du  neocortex;  par  Olmsted  et  Logan  (1925),  Magoun  et  Ranson 
(1938),  aprcs  ablatic^ns  frontales.  Dcs  troubles  du  tonus  et  dc  la  locomotion, 
analogues  a  ceux  que  nous  avons  constates,  out  etc  rcconnus  aprcs  ablation 
soit  dcs  aires  prcirontales  (Olmsted  et  Logan,  1925;  King,  1927;  Lang- 
worthy,  1928),  soit  dcs  aires  motrices  (Laughton,  1928;  McKibben,  1929), 
soit  aprcs  section  des  pyramidcs  (Marshall,  1936;  Liddcll  ct  Philips,  1944)> 
soit  cntm  aprcs  ablation  bilatcralc  isolee  dcs  aires  somatiqucs  I  ct  H,  chez  le 
chien  cette  fois  (St^^picii  ct  St^pich,  1958). 

Coiuiitiotniciiicnt  niotciir  aliiiicntairc 
Envisagcant  I'etude  expcrimcntalc  des  capacitcs  d'apprcntissage  moteur 
chez  lcs  animaux  portcurs  d'ablations,   le  premier  rcsultat  global  qui 


p.    BUSER   ET   A.    ROUGEUL  54I 

s'inipose  est  que  le  conditionnement  —  ou  le  reconditionncnicnt  —  s'est, 
avec  le  dispositif  utilise,  niontrc  possible  dans  tous  les  cas. 

Ceci  pose,  I'interet  se  portc  sur  le  fait  que  cet  apprentissage  des  aniniaux 
opercs  diftcrc  dc  cclui  des  nonnaux  sous  deux  aspects  concernant,  I'un  les 
caracteristiques  chronologiqucs  du  conditionnement,  I'autre  la  niodalitc 
nienie  d'execution  du  mouvenaent. 

L'apprentissage  prc-opcratoire  subi  par  deux  de  ces  animaux  n'ayant 
paru  avoir  aucunc  niflucncc  decisive  ni  sur  I'cvolution  des  performances  ni 
sur  les  rcsultats  tniaux,  nous  nc  fcrons  aucune  distinction  cntre  condition- 
nement et  reconditionncnicnt,  dans  le  cadre  dc  cet  article. 

I  —  Aspect  cliroitolooi<iiif  dc  rapprciitisSiH^e 

[a]  La  plupart  des  animaux  ont  prcscnte  un  'temps  mort'  d'obtcntion 
des  premieres  performances  se  tenant  dans  les  limites  normales  (i  a  5 
jours,  pour  les  groupes  I,  II  et  a  fortiori  III).  Cepcndant,  trois  sujets  (2  du 
groupe  I,  I  du  groupe  II)  ont  necessite  des  temps  caractcristiquement  plus 
longs  (u  a  24  jours) ;  aucune  explication  sure  ne  nous  semble  pouvoir  etre 
proposee  pour  cette  difference  des  durces  de  dressage.  En  eftet,  ni  la  pre- 
sence ou  I'absence  des  aires  somatiqucs  II,  ni  I'existence  d'un  apprentissage 
pre-operatoire  ne  paraisscnt  influcr  sur  cette  duree.  De  meme,  il  ne  sc 
dcssinc  aucune  correlation  cntre  la  longueur  du  repit  accorde  apres 
I'operation  et  ce  'temps  mort'.  Par  contre,  il  semble  que  I'etat  frequent 
d'liypotonic  avec  fitigabilite  post-operatoire,  variable  en  duree  et  en 
intensite  scion  le  sujet,  soit  a  prendre  en  consideration:  il  est  probable,  en 
effet,  que  si,  par  le  fait  de  cette  fatigabilite,  ranmial  se  trouve  au  debut  dans 
de  mauvaiscs  conditions  de  travail,  il  developpe  une  inhibition  interne 
retardatricc  dc  Tapprcntissagc  (flit  signale  du  reste  par  Konorski). 

(/))  L'examen  des  delais  des  mouvements  conditionnes  montre  par 
contre  un  fait  qui  s'est  revele  tres  general  pour  rensemble  des  aniniaux 
ayant  subi  I'ablation  totale  (groupe  I)  ou  subtotale  (groupe  II)  du  cortex 
scnsorimoteur. 

La  distribution  des  latences  evaluee  pour  une  periode  oii  les  performances 
sont  stabilisees  (on  considere  ici  coninie  stabilise  un  conditionnement  qui 
ne  s'ameliore  plus  apres  6  semaines  a  2  mois  d'apprentissagc)  laisse  en  eftet 
apparaitrc  (Fig.  7)  une  dispersion  tres  nettement  supericure  a  la  normale 
(valeurs  attcignant  40  secont4es). 

Tantot  on  retrouve  encore  un  groupement  unimodal  des  latences 
courtes  avec  un  mode  qui  ne  correspond  toutefois  qu'a  une  proportion 
reduite  d'appuis.  Tantot,  au  contraire,  la  repartition  devient  franchement 
plurimodale  avec  des  sommets  successifs. 


542  BRAIN    MECHANISMS    AND    LEARNING 

La  determination  de  la  latciicc  liiiiite,  scion  la  nicthode  adoptee  pour  les 
norniaux,  si  ellc  restc  possible  dans  le  premier  cas,  devient  plus  arbitraire 
dans  le  second;  toutcfois,  si  Ton  fait  intcrvenir  ici  encore  une  valeur 
dcduite  du  premier  groupemcnt,  celui  des  latences  les  plus  breves,  on  pent, 
malgrc  tout,  dans  cette  seconde  situation,  cvaluer  les  performances  les 
meilleures  de  I'animal.  Chez  les  sujets  du  groupe  III,  la  statistique  des 
latences  revet  une  allure  normale. 

(r)  Les  polygones  de  performances,  traces,  comme  pour  les  normaux,  a 
partir  des  prcccdentes  evaluations  de  latences,  illustrent  un  aspect  typique 
du  conditionnement  de  ces  animaux,  c'cst-a-dire  sa  grande  irregularite: 


30 

/o 

20 
10 


T 1 1 ; 1 1  r 

0     2  10  20  30  40 

sec 

Fig.  7 
Repartition  statistique  des  latences  d'appuis  conditionnes  correspondant  a  7  chats  porteurs  de 
lesions  bilatcrales  totales  ou  subtotalcs  (groupes  I  et  II)  de  I'aire  sensorimotrice  (comparer  avec 
la  Fig.  2). 

plus  encore  que  la  repartition  statistique  globale  des  latences,  I'allure 
gcncrale  des  performances  quotidiennes  fluctue  enormcment  d'un  jour  a 
I'autre,  contrastant  ainsi  avec  celle  des  normaux  (Fig.  8).  Ces  fluctuations 
paraissent  du  reste  refleter  les  alterations  des  modalitcs  memes  d'execution 
du  mouvement  volontaire,  dont  il  sera  fait  ctat  ci-dessous. 

(r/)  Les  courbes  d'appuis-erreurs,  quoique  assez  differentes  d'un  animal  a 
I'autre,  ont  toutes  —  pour  les  groupes  I  et  II  —  une  caracteristiquc  com- 
mune qui  est  la  rarete  de  ce  type  de  mouvement  en  debut  d'apprentissage 
(Fig.  4,  CA,  CE,  MA  2eme  image);  elles  s'opposent  ainsi  nettement  a 
celles  relevces  pendant  la  meme  periode  pour  les  animaux  normaux,  chez 
lesquels  ces  appuis-erreurs  sont  particulierement  frequents.  De  plus,  I'animal 
a,  davantage  qu'un  normal,  tendance  a  n'effectuer  le  mouvement  que  lors 
des  stimulations  et  non  en  leur  absence;  ainsi  ne  peut-on  guere  attribuer 


p.    BUSER   ET    A.    ROUGEUL 


543 


I'irregularitc  du  conditiomienicnt  a  dcs  troubles  de  Tattcntion,  ni  vraisem- 
blablement  a  des  troubles  de  la  memoire. 

2  —  Modalitcs  d' execution  du  uiouveiiieiit^ 

L'obscrvation  des  animaux  dcs  groupes  I  et  II  rcvcle  qu'ils  sont  parfaite- 
nient  susceptibles,  au  cours  dcs  essais,  d'effectuer  occasionncllement  le 
mouvement  demande  d'unc  fa(;on  normalc  ct  dans  un  delai  normal. 


i8s 


CA   10- 

i 

ui 

1    1 

1  1 

5- 

^^K 

i^ 

1 

M 

ki 

0. 

-.iW 

■Wp 

HPm 

HyH 

16 


32 


Fig.  8 


47 


Polygones  d'evolution  des  latences  chez  des  chats  porteurs  d'ablations  ct 
appartenant  au  groupe  I.  Meme  signification  des  contours  que  pour  la  Fig.  3.  Ici, 
les  chiffres  portes  en  abscisses  dcsignent  les  jours  post-operatoires,  Ic  premier 
chiffre  correspondant  au  premier  jour  d'apprentissage. 

Toutcfois,  la  plupart  du  temps  lous  adoptcnt,  sans  exception,  pendant  les 
seances  de  travail,  un  comportement  qui  Icur  est  special,  comportcment 
anormal  qui  consiste  en  deux  types  de  conduites: 

—  unc  hyperactivite  automatique  d'unc  part, 

—  des  phases  de  'desoricntation'  dc  I'autre. 

(a)  L'actii'ite  autoiundqiie  sc  reduit  du  rcste  a  unc  sculc  attitude,  evoquant 
celle  du  chat  satisfait  qui  pietine  sur  place  en  ronronnant;  cettc  activite 
frappe  ici,  toutcfois,  par  son  exuberance  ct  son  caractcrc  de  perseveration 
(Fig-  9). 

'  Un  film  a  etc  prcsente,  realise  grace  au  precieux  concours  du  Docteur  Verdeaux  que  nous 
enons  a  remercier  ici. 


544 


BRAIN   MECHANISMS   AND    LEARNING 


Fig.  9 
Exemplc  individuel  dc  rcponse  motricc  d'un  animal  du  groupc  I. 
Meme  sujet  que  sur  la  Fig.  i  (TA)  24  jours  apres  ablation  sensorimotrice  bilaterale  subtotale. 
Images  successives  au  cours  des  30  premieres  secondes  de  stimulation.  On  devine  le  pietine- 
ment  repete  accompagne  de  rotation  progressive  de  I'animal  vers  le  levier. 


p.    BUSER   ET   A.    ROUGEUL  545 

On  s'intcrrogc  quant  a  la  relation  qui  pcut  exister  entre  cettc  activite, 
apparcninicnt  automatiquc,  ct  Ic  niouvement  conditionnc  d'appui  sur  le 
Icvier.  Il  ne  senible  pas  que  cos  gcstcs  rcpctcs  representent  simplcnicnt  des 
tcntativcs  d'appui  inadcquatcs.  En  eftct,  si  dans  certains  cas  ils  sont 
dcclcnchcs  par  Ic  signal,  ct  par  consequent  conditionne's,  ils  sc  dcveloppent 
tout  autant  dans  la  plupart  des  cas  pendant  de  longucs  pc'riodcs,  entre  les 
stimulations,  sans  que  I'animal  n'appuic  alors  aucunement  sur  le  levier 
(on  a  signale  ci-dcssus  la  relative  rarett'  des  appuis-erreurs).  D'autre  part, 
si  certains  animaux  seniblcnt  "utiliser'  ces  pietinements  pour  tnialenient 
atteindre  le  levier  et  I'actionncr,  d'autrcs  cessent  brusquenient  de  pietiner 
avant  d'efFectucr  I'appui  franc  sur  le  levier.  Dans  cc  dernier  cas,  on  saisit 
nettenient  rexisiencc  de  deux  niouvements  distincts,  sc  substituant  Tun  a 
I'autrc  ct,  le  fait  est  possible,  antagonistes. 

(b)  Lcs  phases  dc  dcsoricfitatiou  se  caractcrisent  ainsi:  il  survient  trequeni- 
nient  qu'apres  plusieurs  reponses  a  latence  convenable,  raiiinial  paraisse,  a 
I'cssai  suivant,  brusquenient  et  totalenient  dcsoriente:  tout  en  nianifcstant 
son  inte'ret  pour  les  signaux,  il  eftectue  des  gestes  d'appui  dans  le  vide,  et, 
seniblant  incapable  d'utiliser  le  levier,  prcsente  une  attitude  de  quete 
anxieuse  dans  toutes  les  ciirections.  La  cessation  des  signaux  ramene  le 
caline,  mais  le  ineine  comportcnient  pent  reparaitre  au  cours  dc  plusieurs 
essais  successifs. 

Parfois  la  phase  de  dt'sorientation  ne  dure  qu'un  temps  reduit  au  cours  de 
I'cssai,  et  le  mouvcment  conditionnc,  necessairement  alors  a  longuc 
latence,  tinira  par  etrc  cftcctuc'. 

Signalons  que  ccs  divers  symptomes,  tres  accuses  dans  le  groupe  I,  ne 
sont  que  legercment  attc'nuc's  dans  le  groupe  II.  Quant  aux  sujets  du 
groupe  III,  ils  out  manifeste  de  temps  en  temps  une  le'gerc  tendance  a 
I'activite  automatique. 

Experiences  de  coiitrole 

Outre  les  deux  animaux  envisages  ci-dessus,  constituant  le  groupe  III 
(VA  et  CU),  trois  chats  out  subi  a  titre  de  controle  des  ablations  diverses, 
mais  toujours  bilatcrales,  dc  territoires  corticaux  (Fig.  6). 

—  BE:  ablation  des  gyri  suprasylvien,  cctosylvicn,  y  compris  I'aire 
somatique  II,  avec  en  outre  interruption  des  radiations  optiques. 

—  UA:  ablation  de  la  quasi  totalite  du  neocortex  en  arricre  du  sulcus 
cruciatus,  y  compris  les  aires  somatiqucs  I  et  II. 

NA  —  ablation  bilate'rale  et  totale  des  aires  visuelles. 

L'apprcntissage,  ainsi  que  les  modalites  d'exccution  du  mouvcment,  se 


54<5  BRAIN    MECHANISMS    AND    LEARNING 

sont  dans  1 'ensemble  revcles  norniaux,  a  I'exception  de  certains  troubles 
particulicrs  au  type  de  lesion,  qui  ne  reproduisent  en  aucun  cas  le  tableau 
typique  des  ablations  sensorimotrices  totales  ou  subtotales.  En  fait,  il  n'y 
a  guerc  a  citcr  qu'un  certain  retard  d'apprcntissage  chcz  Ics  aniniaux  avcu- 
gles  non  prealablcnient  dresses  (UA  et  BE)  et  dans  le  cas  de  I'ablation  la 
plus  ctendue  (UA)  une  tendance  a  des  acccs  de  rage  probablement  declcn- 
clics  par  (Bard  et  Moutcastle,  1948)  des  lesions  non  neocorticales  (ablation 
du  gyrus  cingulairc:). 

Discussion 

Il  est  intcressant  tout  d'abord  de  chercher  a  degager  les  traits  les  plus 
caractcristiques  du  coniportenient  des  aniniaux  porteurs  d'ablations 
sensorimotrices  largcs,  dans  les  conditions  d'expcrimentation  auxquelles  ils 
furent  souniis  ici. 

Deux  constatations  s'imposent:  d'une  part,  la  possibilitc  de  principe, 
pour  ces  sujets,  d'effcctucr  le  mouvement  appris  —  non  point  un  geste 
quelconque  de  la  patte,  mais  un  appui  precis  a  objectif  determine  — 
suivant  le  mode,  qualitatif  et  chronologique,  des  normaux:  d'autre  part, 
I'existence  d'un  certain  nombre  dc  facteurs  de  perturbation  qui  sont  a 
I'origine  de  la  grande  irrc'gularite  des  performances  et  sur  la  nature 
desqucls  on  s'interrogc. 

A  notre  avis,  deux  causes  paraisscnt  cssentiellcment  jouer:  I'hyper- 
activite  automatique  d'une  part,  la  tendance  a  la  desorientation  de  I'autrc. 

On  a  souligne  ci-dessus  que  I'hyperactivite  ne  s'cxerc^ait  pratiquement 
jamais  sur  le  Icvier,  ce  qui  correspond  a  la  rarcte  des  appuis-erreurs,  mais 
apparaissait  comme  une  suite  de  mouvemcnts  'automatiques',  apparem- 
ment  distincts  du  geste  appris. 

Dans  la  mesure  ou  se  dessinc  ainsi,  asscz  paradoxalemcnt,  une  relative 
'hypokinesic  volontaire',  on  est  tente  de  conclure  a  une  maniere  de  conflit 
entre  les  deux  groupes  de  mouvements  —  hypothetiquement  d'ailleurs, 
leurs  rapports  precis  ne  nous  apparaissant  pas  actuellcmcnt  assez  claire- 
ment  — .  Il  ne  fait  pas  de  doutc  en  tout  cas,  et  la  smiple  observation  des 
aniniaux  le  montre,  que  le  pietinement  persistant  rcpresente  une  des 
raisons  de  I'irregularite  des  latenccs. 

Un  second  facteur  perturbant  parait  bien  etre  la  presence  des  phases  de 
desorientation,  qui  survicnnent  et  ccssent  dc  maniere  imprevisible.  Ces 
c:tats  critiques  ne  semblent  pas  relever  de  troubles  de  la  fonction  mnesique; 
dans  ce  cas,  en  effet,  on  s'attendrait  a  observer  les  plus  fortes  perturbations 
en  debut  de  seance,  les  performances  s'amcliorant  avec  les  essais  suivants; 


p.    BUSER    ET   A.    ROUGEUL  547 

or,  il  n'en  est  ricu.  Non  plus  que  do  troubles  dc  I'attcntion:  Ic  chat  donue 
dc  uoinbrcux  indices  dc  reaction  a  la  stimulation-signal  et  son  attitude 
traduit  un  coniportcnient  d'intense  recherche,  ce  qui  exclut  entui  totale- 
nient  rhypothese  dun  etat  d'inhibition  interne. 

En  fiiit,  le  tableau,  decrit  de  faqon  analogue  par  Zubek  (1952)  rappcllc 
beaucoup  a  notre  sens  celui  de  I'apraxie-agnosie  chez  rhoinme,  ^  a  la  tois 
par  I'lnipossibilite  d'acconiplir  "sur  ordre'  une  serie  de  inouveinents  inten- 
tionnels  et  par  la  perseveration  caracteristique.  On  relevc  d'ailleurs  dcs 
syniptonics  suggestifs  d'une  agnosie  pure,  telle  par  exeinplc  I'incapacite 
iiiomcntancc  pour  Taninial  de  reconnaitre  la  nourriture  qu'il  vient  dc  se 
procurer  par  niouveiuent  conditionne. 

Finalement,  on  se  heurte,  dans  cette  tentative  pour  identifier  le  syn- 
drome, a  I'existence  c'vidente  dc  deficits  purcment  scnsoricls  du  domaine 
somesthesique,  proprioccptif  ou  tactile,  bicn  que  ces  deficits  ne  paraissent 
pas  cssenticls  puisque  ranimal  est,  on  fa  vu,  theoriquemcnt  capable  d'ap- 
prendrc  et  de  realiser  le  mouvement  scion  des  modalites  normales. 

Si,  dautre  part,  on  sen  tient  aux  donnees  classiqucs  sur  Ics  projections 
somesthesiqucs,  il  est  essentiel  de  noter  que  quatrc  sujets  etaient  porteurs 
de  lesions  interessant  partiellement  tout  au  moins  les  aires  somatiques  I  et 
II  (VA,  UA,  BE,  CU);  tous  se  sont  comportcs  normalement  vis-a-vis  de 
la  tachc  imposce.  Sous  un  autre  angle,  on  ne  pent  d'ailleurs  que  rappeler 
les  donnees  recentes  faisant  etat  de  la  conservation  d'uii  mouvement 
conditionne  apres  deafferentation  de  la  patte  chez  le  chat  (Gorska  et 
Jankowska,  1959;  Jankowska,  1959). 

Ainsi  que  nous  le  rappelions  en  introduction,  la  plupart  des  ablatuins 
eftectuees  sur  les  carnivores  et  interessant  le  cortex  frontal  avaient  surtout 
conduit  a  des  descriptions  du  comportement  spontane  et  ne  permettaient 
gucre  de  prevoir  les  modalites  scion  lesquelles  un  animal  pourrait,  a  un 
signal  donne,  accomplir  un  mouvement  determine  de  caractere  volitionnel. 
Parmi  les  quelques  travaux  qui  cependant  se  rapportent  plus  directcment 
aux  problcmes  d'apprentissage,  certains  ne  concernent  que  la  discrimina- 
tion tactile  apres  ablation  du  cortex  somatique  (Sperry,  1957,  1959), 
tandis  que  d'autres  retiennent  fattention  en  ce  qu'ils  signalent  des  troubles 
plus  generaux  de  I'elaboration  motrice.  C'cst  ainsi  que  Zubek  (1952J 
decrit  des  phases  de  desorientation  chez  des  chats  depourvus  de  cortex 
somatique,  tandis  que  I'ecolc  de  Konorski  (St(j.>pieh  et  St(j^pieh,  195S,  1959; 
St^^pieh,  Stfpieh  et  Konorski,  i960)  dii^erencic  les  repercussions  obtenues 

'  On  est  frappc  en  effct  de  Tanalogic  cntre  les  siy;iics  rencontres  ici  et  les  descriptions  classit^ucs 
en  neurologic  cliniquc;  cf.  en  particulier  Von  Monakow  et  Moiirgue  (iy2S)  ct  cgalcnicnt 
Ajiirriaguerra  ct  Hecaen  (i960). 

NN 


548  BRAIN    MECHANISMS    AND    LEARNING 

(chez  Ic  chicn)  scion  que  I'ablation  intcrcssc  Ic  cortex  proprenicnt  soincs- 
thesique,  on  inotcur,  ou  cntni  prefrontal.  A  cc  titre  d'ailleurs,  Ics  rcsultats 
cites  depasscnt  en  precision  les  notrcs.  Il  est  vrai  que  les  conditions  d'analyse 
n'ont  pas  etc  identiques;  il  serait  en  particulier  malaise  de  saisir  chez  le  chat 
dcs  modifications  fines  dc  la  faculte  de  difterenciation  (entrc  signal  et 
simple  ambiance)  etant  donne  que  celle-ci  n'cst  jamais  parfaite  (ainsi  qu'en 
temoignc  la  courbc  dcs  appuis-errcurs),  au  contrairc  du  chien.  Et  de  fait, 
I'ablation  du  cortex  'prefrontal'  efticace  chez  cc  dernier  s'cst  averee  sans 
repercussion  durable  chez  le  chat  (ablation  du  gyrus  proreus). 

Un  certain  nombre  dc  points  relatifs  a  I'aspect  neurophysiologique  dc 
ces  observations  mcritent  d'autre  part  d'etre  examines.  Nous  etant 
initialemcnt  propose  de  connaitrc  le  role  du  cortex  'moteur',  il  nous 
apparait  maintenant  qu'en  raison  sans  doute  de  la  contiguite  des  aires 
somesthcsiquc  et  motrice  nos  rcsultats  nc  permettent  pas  de  rcsoudre  avec 
securite  la  question  d'un  role  plus  particulier  de  I'un  ou  de  I'autrc  terri- 
toire.  A  vrai  dire,  il  semble,  etant  donne  un  certain  nombre  de  rcsultats 
recents,  que  I'alternative  ne  saurait  etre  posee  dans  le  cadre  des  schcmas 
classiques  opposant  strictcment  dans  leur  topographic  corticale  les  affc- 
rences  somcsthesiques  aux  effcrences  pyramidales.  Tout  porte  a  penser  que 
I'organisation  du  cortex  sensorimotcur  est  plus  complexc. 

D'une  part,  il  apparait  probable  que  chez  Ic  chat  le  cortex  'moteur' 
(gyrus  sigmoide  anterieur  et  partie  anterieurc  du  gyrus  sigmoide  posterieur) 
posscde  des  projections  somcsthesiques  independantes  de  I'aire  proprenicnt 
somatique  (Oswaldo-Cruz  et  Tsouladze,  T957;  Buser  et  Aschcr,  i960),  en 
sorte  que  I'argument,  dcveloppe  ci-dessus,  de  la  non-importance  de  I'aire 
somesthesique  primaire,  ne  saurait  en  toute  objectivite  etre  considcrc 
comme  decidant  de  Tinutilitc  dcs  informations  tactiles  ou  proprioccptives 
dans  I'apprentissage  ou  I'cxecution  du  mouvement  volontaire.  Dc  fa(;"on 
plus  generalc  d'ailleurs,  le  role  'integrateur'  du  cortex  moteur,  pc'risig- 
moidc,  se  degage  d'autre  part  d'expericnces  cftcctuees  —  toujours  sur 
I'animal  aigu  —  illustrant  I'existence,  a  cc  niveau,  de  convergences  de 
projections  scnsorielles  'extra-primaires'  visuellcs,  acoustiques,  en  mcnie 
temps  que  somcsthesiques  (Feng  et  col.,  1956;  Buser  et  Imbcrt,  1959; 
Buser  et  Aschcr,  i960);  a  cet  egard,  il  est  net  que  la  zone  pcrisigmoide 
s'oppose  a  I'aire  dc  projection  purement  somesthesique,  a  locahsation  plus 
posterieure. 

Un  autre  point,  correlatif  du  precedent,  est  celui  de  la  voie  effcrente 
responsablc  dcs  cftets  observes.  On  evoquc  evidemmcnt,  par  habitude 
et  par  tradition,  I'intervention  dc  la  voie  cortico-bulbo-spinale,  'pyrami- 
dale',    d'autant   que   I'experimentation   aiguc   nous   a   appris   (Buser   et 


p.    BUSER    ET   A.    ROUGEUL  549 

Aschcr,  i960)  qu'aux  integrations  scnsoricllcs  rcalisecs  au  niveau  de  la 
zone  pcrisignioidc  correspond  la  niisc  en  jeu  d'une  reponsc  efterente 
reverberee;  I'integration  a  cc  niveau  pourrait  done  bien  se  raniencr  a 
I'c'laboration  d'une  decharge  corticituge,  pyranudale,  vers  Ic  bulbe 
(noyaux  craniens  ou  formation  reticulee  bulbo-pontique)  ou  vers  les 
niotoneurones  spniaux.  Il  est  trappant,  a  ce  titre,  que  les  troubles  observe's 
ici  ne  I'aient  c'te  qu'apres  cluiiination  totale  —  ou  subtotale  dans  Ic  cas  du 
groupe  II  —  du  contour  que  rcxpc'rimcntation  aigue  ou  I'anatoniie 
(Garol,  T942;  Woolsey  et  Chang,  1948;  Lance  ct  Manning,  1954;  Porter, 
1955)5  deliniitent  coninie  aire  de  depart  du  tractus  pyramidal.  Mais,  ici 
encore,  le  role  exclusif  des  pyramides  n'est  pas  dcmontrc'  pour  autant. 
Des  interruptions  du  tractus  pyramidal  (Langworthy,  1928;  Tower,  1935; 
Marshall,  1936;  Liddell  et  Phillips,  1944),  qui  nous  eussent  peut-ctre 
permis  dc  conclure,  n'ont  ete  eftectuees,  chez  le  chronique,  que  dans  des 
buts  distmcts  du  notre.  D'un  autre  cote,  le  tractus  pyramidal  n'cst  mani- 
festement  pas  I'unique  systeme  efferent  issu  de  la  zone  sensorimotrice, 
puisqu'on  connait  I'intervention  des  voies  cortico-reticulaires,  particuliere- 
ment  abondantcs  a  ce  niveau,  dans  le  controlc  retlexe  (Hugelin  et  Bon- 
vallct,  1957)  ou  dans  la  decharge  mt^tricc  (Colle  ct  Massion,  1958;  Aschcr 
et  Gerschenfeld,  i960).  D'autres  observations  devront  toutefois  dire  dans 
ces  conditions  pourquoi  les  voies  corticorc'ticulaires  issues  du  cortex 
moteur  ont,  dans  I'elaboration  motrice,  un  role  plus  decisif  que  celles  qui 
sont  issues  d'autres  territoires  tels  le  cortex  visuel  ou  acoustique.  A  titre 
d'hypothcse,  on  pourrait  suggerer  que  c'est  I'elimination  combinee  des 
voies  pyramidales  et  des  projections  corticoreticulaires  —  extrapyramidalcs 
par  consequent,  et  que  seule  realise  I'ablation  du  cortex  moteur  —  qui 
pourrait  decider  de  la  gravite  des  troubles  ainsi  observe's. 

De  fa(;:on  gcnerale  done,  le  probleme  de  la  participation  du  cortex 
moteur,  nccessairement  devenuc  celle  du  cortex  sensorimoteur,  a  la 
motricitc  volontairc  chez  les  carnivores  ne  parait  pas  admettre  de  solution 
simple.  D'une  part,  il  est  certain  que  ce  niveau  considere  dans  son  en- 
semble joue  un  role  indubitablement  plus  important  que  d'autres  aires 
corticales,  ainsi  qu'en  temoignent  en  particulier  les  experiences  dc  con- 
trole.  D'un  autre  cote,  toutefois,  fobtention  sporadique  de  mouvements 
pratiquement  normaux  pourrait  e'videmment  laisser  conclure  a  son 
'inutilitc',  dans  I'elaboration  du  gestc  conditionnc.  En  somme,  la  question 
ne  saurait  etre  tranchc'e  entre  la  necessite  ou  non  du  niveau  cortico-moteur 
dans  le  conditionnemcnt  c'tudie;  il  parait  bien  davantagc  justitie  de  se 
demander  comment  s'accomplit  I'integration  sensorimotrice  soit  en 
presence,  soit  en  I'absence  de  ce  niveau  cortical,  'absence'  qui  d'aiUeurs, 


550  BRAIN    MECHANISMS    AND    LEARNING 

par  la  niisc  en  jcu  probable  dc  structures  vicariantcs,  laisse  uuc  part 
d'incertitudc  aux  deductions  faites,  point  justement  soulignc  par  Semmcs 
et  Chow  (1955).  A  cet  egard,  nos  observations  paraisscnt  particulierement 
bien  concretiser  la  conception  plus  souple,  souvent  proposcc  d'ailleurs,  d'un 
role  regulateur  du  niveau  cortical,  agissant  sur  des  structures  sous- 
jacentes,  elles-memes  susceptibles  d'etre  Ic  siege  d'unc  elaboration  sensori- 
motrice.  Il  est  cnfni  probable  que  Ics  conclusions  dcduites  ici  ne  le  sont  que 
pour  la  categoire  envisagee  de  conditionnement,  des  taclies  en  particulier 
plus  simples,  tclles  que  le  rcflexe  positif  de  salivation,  ctant,  on  doit  le 
penser,  plus  independantcs  encore  dc  I'ecorce  (Hernandez-Peon  et  col., 
1958),  alors  que  d'autres  plus  complexes,  impliquant  par  cxemple  des 
operations  de  discrimination,  resteront  sans  doute  plus  directement  liees  a 
sa  presence  (voir  par  exemple  Brutkowski,  1957). 

Resume 

Cettc  etude  concerne  les  repercussions  de  I'ablation  du  cortex  sensori- 
moteur  du  chat  sur  I'apprentissage  et  I'execution  du  mouvement  dans  une 
epreuve  de  conditionnement  alimentaire-moteur. 

1.  L'ablation  totale  bilaterale  du  cortex  sensorimoteur  (avec  ou  sans 
persistance  d'uiie  fraction  de  I'aire  somatique  II)  ne  supprimc  pas  entiere- 
ment  la  possibilite,  pour  Taninial,  d'cffectuer  le  geste  conditionne  (appui 
sur  un  levier)  selon  les  modahtes  ct  dans  des  delais  correspondant  a  ccux 
des  animaux  normaux.  Toutefois,  dc  tels  appuis  sont  rarcs,  I'execution  du 
mouvement  se  trouvant  defniitivement  perturbee  a  divers  egards.  On  s'est 
efForce  d'analyser  les  composantes  de  ces  perturbations  dont  n'existe  pas 
I'cquivalent  chez  des  sujets  porteurs  d'ablations  sensorimotrices  partielles, 
ou  de  lesions  etendues  des  zones  prcfrontales,  postericures  ou  laterales  du 
neocortex  et  qui,  a  ce  titre,  constituent  des  controles. 

2.  L'evaluation  statistique  des  latcnces  d'appuis,  efFectuce  pour  chaque 
sujet,  revclc  une  difference  significative  cntre  normaux  (ou  controles)  ct 
operes;  groupees,  pour  les  premiers,  elles  sont  notablement  dispcrsccs  en 
cas  d'elimination  scnsorimotrice.  Ces  latcnces  varient  d'autrc  part  dans 
des  limites  considerables  d'unc  seance  de  travail  a  la  suivante,  fait  egale- 
ment  en  contraste  avec  le  comportement  des  controles.  Par  contrc,  la 
frequence  des  appuis  spontancs  qui  survienncnt  en  debut  d'apprentissage 
est  plus  reduite  apres  ablation. 

3.  Les  modalites  memes  d'execution  du  mouvement  chez  ces  sujets 
sont  profondement  troublces.  On  decrit  deux  groupes  distincts  d'ano- 
malies:  des  phases  d'hyperactivitc  'automatique'  d'une  part,  qui  paraissent 


p.    BUSER   ET    A.    ROUGEUL  55 1 

interfere!'  avec  I'elaboratioii  volitionnelle;  des  periodcs  de  desorientation, 
d'autre  part,  rammal  devenant  transitoirement  incapable  d'execiiter  le 
niouvenient  d'appui. 

La  signification  de  ces  rcsultats  est  discutee,  en  particulier  sous  Tangle 
d'une  confrontation  avec  les  donnees  neurophysiologiques  relatives  a  la 
mise  en  jeu  du  cortex  nioteur,  et  d'un  eventucl  role  de  la  voie  pyramidale 
dans  la  regulation  de  I'activitc  volitionnelle  chcz  le  chat. 

Summary 

A  study  was  performed  on  cats,  of  the  effects  of  removing  sensorimotor 
cortex  (or  other  cortical  areas)  on  learning  and  executing  the  lever-pressing 
movement  to  a  signal  stiniulus,  in  an  instrumental  conditioning  situation 
(alimentary  motor). 

After  total  bilateral  removal  of  sensorimotor  cortex  (leaving  or  not  a 
small  part  of  somatic  II),  normal  scores  (pattern  and  latency  of  gesture) 
may  still  be  obtained,  but  most  of  the  observed  movenients  arc  disturbed 
in  several  ways  which  have  been  analysed. 

Evaluating  latencies  of  pressing  movement  reveals  a  first  group  of 
significant  differences  between  normal  and  sensorimotor  deprived  animals: 
statistical  dispersion  of  latency  values  is  much  larger  in  the  latter  case;  in 
time  also,  individual  delays  for  deprived  animals  appear  mostly  variable  in 
course  of  one  session. 

In  contrast  to  this,  spontaneous  conditioned  movement  appear  less 
frequent  in  ablated  than  in  normal  animals. 

Two  types  of  qualitative  disturbances  of  movements  are  further 
described:  'automatic'  hyperactivity  on  one  side,  which  may  interfere 
with  volitional  elaboration;  desorientation  phases,  on  the  other,  the  animal 
becoming  temporarily  iniable  to  execute  the  correct  secjuence  of  move- 
ments to  obtain  food  —  though  remaining  strongly  motivated  for  food 
reward. 

None  of  the  previously  described  disturbances  are  defmitely  observed, 
following  other  cortical  removals  (visual  area,  temporo-occipital  cortex, 
whole  neocortex  but  sensorimotor  area,  prefrontal  cortex). 

These  results  are  discussed  in  relation  to  neurophysiological  data  on 
afferent  projections  to  and  'integrative'  properties  of  the  motor  (perisig- 
moid)  cortex  in  cat. 

DISCUSSION 

Kc:)NORSKi.  Since  our  laboratory  has  been  concerned  in  recent  years  with  the 
study  oi  the  effects  of  scnsori-motor  lesions  upon  instrumental  conditioned  reflexes 


552 


BRAIN    MECHANISMS    AND    LEARNING 


(CRs)  ill  dogs,  and  our  results  are  in  many  respects  similar  to  those  obtained  by  Dr 
Buser,  it  would  be  relevant  to  summarize  them  at  this  point. 

The  general  method  of  our  experiments  was  such,  that  we  trained  the  animals  to 
perform  a  motor  act  consisting  in  lifting  the  right  foreleg  and  putting  it  on  the 
food-tray  to  given  conditioned  stimuli  (CSs);  each  such  movement  pertormed  to  a 
CS  was  reinforced  by  food.  After  the  motor  CR  was  firmly  established,  particular 
parts  of  the  scnsori-motor  cortex,  or  the  whole  of  it,  were  removed  and  the  effects 
of  these  lesions  examined.  I  shall  speak  here  only  on  the  results  of  bilateral  ablations. 


Fig.  I 
The  dorsal  and  lateral  surface  of  the  cerebral  cortex  of  dog  represented  on  the  plan. 
I,  sensory  cortex;  II,  motor  cortex;  III,  pre-motor  cortex,  a,  sulcus  ansatus;  c,  sulcus 
centralis;  cr,  sulcus  cruciatus;  pr,  sulcus  prcsylvius. 


\n  the  course  of  our  study  it  appeared  to  be  useful  to  divide  the  scnsori-motor 
cortex  into  three  roughly  parallel  belts  (Fig.  i):  i.  'sensory  cortex',  situated  be- 
tween the  line  of  sulcus  ansatus  and  of  sulcus  centralis  and  corresponding  to  the 
zone  described  recently  by  Hamuy,  Broniiley  and  Woolsey;  2.  'motor  cortex', 
situated  between  the  line  of  sulcus  centralis  and  of  sulcus  cruciatus;  3.  'premotor 
cortex',  situated  between  sulcus  cruciatus  and  its  prolongation  and  sulcus  pres)'lvius. 

After  ablation  of  the  first  strip  —  sensory  area  —  the  instrumental  CR  is  lost  for 
several  weeks,  but  the  general  behaviour  of  the  animal  is  quite  adequate,  and  he 
reacts  correctly  to  CSs,  although  he  seems  unable  to  perform  the  trained  movement. 
After  some  time  the  instrumental  reaction  returns  without  additional  training 
(Stepieii  and  Stepieii,  1959). 


p.    BUSER   ET    A.    ROUGEUL  553 

After  ablations  of  the  motor  cortex  —  second  strip  —  the  instrumental  reflex  is 
even  less  impaired  than  in  the  previous  case,  but  the  animals  display  a  striking 
symptom  of  confusing  legs,  i.e.  they  perform  the  trained  movement  either  with 
the  right  or  with  the  left  foreleg.  This  almost  never  occurs  either  before  the  opera- 
tion or  after  any  other  cortical  lesion.  The  animals  also  manifest  hyperkinesis  of 
the  legs  consisting  in  repeatedly  lifting  them  to  various  heights  —  'pedalling 
movements'  —  This  symptom  is  best  seen  when  the  animal  is  lifted  into  the  air 
(Stcpieii,  Stepieii  and  Konorski,  i960). 

While  after  ablations  of  sensory  or  motor  cortex  the  movements  ot  the  animal 
are  more  or  less  awkward  and  ataxic,  after  the  removal  of  the  third  strip  —  pre- 
motor  area  —  they  are  as  skilful  as  before  operation,  but  a  striking  disintegration 
of  instrumental  CRs  takes  place.  The  animal  is  able  to  perform  the  trained  move- 
ment without  any  'teclinical'  difliculty,  but  he  does  not  'know'  when  to  perform  it. 
So  the  movements  appear  very  often  in  the  intervals,  sometimes  with  great 
frequency,  but  they  often  fail  to  appear  to  the  CS  itself.  Instead,  the  animals  display 
either  a  strong  orienting  reaction  towards  the  source  of  the  stimulus,  or  a  strong 
direct  alimentary  reaction  to  the  bowl,  or  both.  During  the  experiment  the 
animal  displays  many  irrelevant  activities,  so  that  his  whole  behaviour  may  be 
qualified  as  'stupid'  (Stepien,  Stepieii  and  Konorski,  i960). 

To  put  it  briefly  one  can  say  that  after  sensory  lesions  the  animal  is  ataxic  and 
paretic  but  his  general  behaviour  is  normal.  After  premotor  lesions,  on  the  con- 
trary, the  animal  is  quite  skilful,  but  his  general  behaviour  is  'senseless'.  Lesions  of 
the  motor  cortex  produce  intermediary  symptoms.  The  ablation  of  the  whole 
sensori-motor  cortex  makes  the  animal  both  strongly  ataxic-paretic  and  'stupid'. 

BusER.  I  was  quite  interested  by  Dr  Konorski's  remarks.  As  far  as  general  be- 
haviour is  concerned  it  is  true  that  cats  and  dogs  behave  in  similar  ways  after  total 
ablation  of  the  whole  sensorimotor  cortex.  But  we  were  not  led  as  yet,  to  con- 
sider that  different  divisions  of  this  frontal  cortex  play  different  roles.  The  reason 
for  these  discrepancies  may  be  due:  (i)  to  phylogeny,  the  premotor  cortex  in  cat 
being  smaller  and  probably  less  important  than  in  dogs.  Actually,  a  cat  deprived  of 
premotor  cortex  almost  behaves  —  in  our  pattern  of  testing  —  as  a  normal  control 
animal;  (2)  to  unequal  capacity  tor  diftercntiation  between  signal  and  environment, 
which  is  normally  very  clear  cut  in  dogs,  and  never  perfect  in  cats;  thus  a  slight 
impairment  in  the  latter  case,  could  be  considered  as  remaining  within  limits  of 
normal  variations. 

Doxyi.  I  would  like  Dr  Buser  to  tell  us  a  little  more  about  these  very  interesting 
units  in  the  sensorimotor  area,  on  which  the  auditory  and  visual  systems  also  seem 
to  converge.  What  are  their  firing  patterns  and  latencies  for  the  various  sensory 
stimuli  ? 

Buser.  hi  preparations  under  chloralosc  and  in  unanaesthetized  but  curarized 
preparations,  exploration  of  the  cat's  motor  cortex  with  macroelectrodes  as  well  as 
microelectrodes  reveals  the  existence  of  sensory  responses  to  somatic  stimulation. 
Average  latencies  are  twice  (or  at  most  three  times)  the  one  on  primary  cortical 
fields;  microelectrode  recordings  further  show  convergencies  of  all  three  modalities 
on  the  same  neurones,  finally,  facilitation  or  occlusion  occur  at  this  level  when  two 
different  sensory  modalities  are  applied  in  combination. 

1  This  and  further  questions  refer  to  a  chapter  on  electrophysiological  recordings,  which 
has  been,  for  the  sake  of  simplicity,  omitted  in  this  paper. 


554  BRAIN    MECHANISMS    AND    LEARNING 

Olds.  Dr  Buser  mentioned  that  he  could  tell  from  the  oscilloscope  tracing  that  a 
response  was  abortive.  I  didn't  sec  quite  which  was  the  characteristics  of  the  tracing 
that  indicated  that  a  response  was  an  abortive  one. 

Buser:  As  recording  evoked  potentials  to  the  signal  stimulus  trom  the  motor 
cortex,  it  appeared  to  us  that  a  normal  lever  pressing  movement  was  preceded  by 
an  electrocortical  activation  as  well  as  by  an  apparent  'suppression'  of  these  frontal 
evoked  responses.  A  further  and  rather  surprising  observation  was  that  inefficient, 
or  'abortive'  movements,  though  being  also  preceded  by  a  slight  desynchroniza- 
tion,  were  not,  in  most  of  the  cases,  accompanied  by  a  suppression  of  motor  evoked 
responses. 

Segundo.  Dr  Buser,  variotis  groups  in  the  Institut  Marey  have  explored  the 
cortical  and  subcortical  distribution  of  sensory  volleys  extensively.  Could  you  give 
us  an  idea  as  to  what  pathways  visual  and  acoustic  impulses  may  follow  to  reach  the 
motor  cortex. 

Buser.  The  precise  route  for  light  and  sound  onto  the  motor  cortex  still  remains 
a  matter  for  discussion. 

We  have,  until  now,  very  little  to  add  to  opinions  expressed  by  others,  suggest- 
ing a  role  of  the  pretectal  area  (Wall  et  ah,  1953)  or  reticular  formation  (Hunter  and 
higvar,  1955).  Nevertheless,  some  of  our  recent  results  seem  to  indicate  that  a  small 
area  in  the  posterior  thalamus  —  close  to  both  suprageniculate  and  magnocellular 
fraction  of  medial  geniculate,  as  well  as  centre  median  could  play  an  important 
role  in  transmission  of  light  impulses  to  the  motor  cortex  (Buser  and  Bruner,  un- 
published). 

JouvET.  Did  you  record  simultaneously  in  the  visual  cortex  and  the  reticular 
formation? 

Buser.  Not  yet. 

Garcia-Austt.  What  differences  exist,  if  any,  between  the  latencies  and  shape  of 
potentials  evoked  by  visual  stimuli  on  the  motor  cortex  on  one  hand  and  on  the 
visual  cortex  on  the  other  >. 

Buser.  In  brief,  evoked  responses  to  light,  recorded  from  the  sensory  motor 
cortex,  in  chronic  animals,  sho\v  following  characteristics:  latency  about  three 
times  that  of  the  primary  response,  longer  duration  and  smooth  contours  (no 
sharp  surface  positive  component);  smaller  amplitude  (one-half  to  one-third). 


NON-SENSORY  EFFECTS  OF  FRONTAL  LESIONS  ON 
DISCRIMINATION  LEARNING  AND  PERFORMANCE 

H.  Enger  Rosvold  and  Mortimer  Mishkin 

In  his  recent  Salmon  Lectures,  Magoun  (1958)  has  described  how  even 
the  Ancients  had  formiUated  theories  of  brain-behaviour  relationships. 
To  them  it  appeared  that  sensory,  associative  and  motor  faculties  were 
served  by  clearly  separated  parts  of  the  brain  each  of  which  was  uniquely 
organized  for  its  specific  function.  Conceptions  of  brain  organization  have 
progressed  through  a  variety  of  formulations,  but  at  each  stage  there  have 
been  those  who  were  ready  to  defend  this  ancient  conception  of  a  cerebral 
localization  of  function.  Thus,  at  widely  separated  times,  Ferrier  (1875), 
Bianchi  {192.2}  and  Jacobsen  (193  s)  have  contended  that  the  most  anterior 
cerebral  structure,  the  prefrontal  lobes,  was  an  'association'  area  con- 
cerned with  complex,  non-sensory  functions  clearly  distinguishable  from 
the  sensory  functions  served  by  posterior  cortex.  Recently,  however, 
studies  such  as  those  of  Woolsey  (1958),  Neff  and  Diamond  (1958), 
Rose  and  Woolsey  (1958)  and  Lilly  (1958)  have  shown  that  the  neural 
representation  of  sensory  functions  encroach  upon  'association'  cortex, 
suggesting  that  the  prefrontal  lobes  may  be  involved  in  sensory  processes 
after  all.  It  is  appropriate,  therefore,  to  take  a  new  look  at  the  behavioural 
evidence  related  to  this  problem. 

For  the  most  part  experimental  studies  concerned  with  frontal  lobe 
function  have  emphasized  the  severe  effects  of  damaging  this  structure  on 
performance  of  delayed-response  tests.  Furthermore,  the  results  have 
clearly  supported  the  view  that  impairment  on  this  type  of  problem  is 
uniquely  associated  with  frontal  as  opposed  to  posterior  cortical  lesions 
(Blum,  Chow  and  Pribram,  1950;  Meyer,  Harlow  and  Settlage,  195 1). 
Finally,  and  most  important  in  connection  with  the  present  problem,  in 
emphasizing  the  specific  nature  of  this  frontal-lobe  deficit,  investigators 
since  Jacobsen  (1935)  have  contrasted  it  sharply  with  the  absence  of 
deficit  on  sensory  discrimination  tasks.  Impairment  on  discrimination  tasks 
has,  instead,  been  reserved  for  the  effects  of  posterior  lesions. 

Unfortunately,  however,  this  enthusiasm  to  dissociate  delayed  response 
and  sensory  discrimination  functions  has  resulted  in  the  neglect  of  impor- 
tant contradictory  evidence.  For  example,  Pribram,  Mishkin,  Rosvold  and 
Kaplan  (1952)  did  not  deal  with  the  fact  shown  in  the  right  of  Fig.  i  that 

555 


556 


BRAIN   MECHANISMS    AND    LEARNING 


their  frontal  animals  were  significantly  inferior  to  normals  in  retention  of 
a  visual  discrimination  habit. ^  They  emphasized,  instead,  that  their  animals 
showed  some  savings  in  relearning  the  habit  (the  left  of  Fig.  i),  and  used 
these  data  to  support  the  thesis  put  forth  earlier  byjacobsen  (1935)  that 
frontal  lesions  leave  discrimination  functions  unimpaired.  In  defending 
Jacobsen's  thesis  they  were  ignoring  not  only  their  own  results,  but  also  a 
nimiber  of  other  reports  in  the  intervening  20  years  which  had  clearly 
implicated  frontal  cortex  in  discrimination  learning  and  retention.  In 

VISUAL    DISCRIMINATION     RETENTION 


300- 


S   150 


PRE        POST 


30 


(T      15 


N—      3 


(PRIBRAM,  ROSVOLD.MISHKIN,  a  KAPLAN,  1952  ) 

Fig.  I 
Effects  of  frontal  lesions  on  visual  discrimination  retention. 


1940,  for  example,  Allen  had  demonstrated  that  dogs  with  pre- 
frontal lobectomies  were  unable  to  learn  to  discriminate  olfactory  stimuli. 
In  1943,  Harlow  and  Dagnon  had  shown  that  monkeys  with 
prefrontal  lobectomies  were  impaired  in  learning  even  simple  discrimina- 
tions in  vision.  And  again  in  1952,  Blum  had  shown  that  prefrontal 
monkeys  were  deficient  in  auditory  discrimination  learning.  Surely,  such 
evidence  demonstrating  impairment  after  frontal  lesions  in  all  sensory 

^  This  and  the  following  figures  arc  derived  from  the  data  appearing  in  the  reports  of  the 
authors  indicated.  In  all  figures,  operated  and  control  groups  of  monkeys  are  denoted  as 
follows:  F  —  Frontal,  N  —  Normal,  P  —  Parietal,  PT  —  Posterior  Temporal,  T  —  Temporal. 
A  number  below  the  bar  graph  denotes  the  number  cif  monkeys  in  the  group. 


H.    ENGER    ROSVOLD    AND    MORTIMER    MISHKIN 


557 


modalities  can  hardly  go  unchallenged  if  the  theory  that  the  frontal  lobes 
are  not  concerned  with  sensory  functions  is  to  be  maintained. 

Until  recently,  however,  even  these  disturbnig  results  could  be  explained 
away.  Few  of  the  early  studies  contained  operated  controls  and  so  it  was 
possible  to  argue  that  a  generalized  impairment  in  all  modalities  simply 
reflected  a  non-specihc  post-operative  disturbance  which  might  be 
expected  to  result  from  any  large  cerebral  lesion.  Contrast  this  with  the 
specific  sensory-perceptual  deficits  which  have  been  demonstrated  after 
selective  ablations  of  the  posterior  'association'  cortex.  For  example,  Pri- 
bram and  Barry  (1956)  and  Wilson  (1957)  comparing  directly  the  effects 


DISCRIMINATION     LEARNING 


N->       4  4  < 

(BRUSH  a  MISHKIN    1959  1 


N  — »       3  2  2 

{WEISKRANT2    &    MiSHKtN     1958) 


N— ►      3  •» 

[ETTLINGER    3    WEGENER  .956) 


Fig.  2 
Effects  of  frontal  lesions  on  visual,  auditory,  and  tactual  discrimination  learning 


oi  intcrotemporal  and  posterior  parietal  lesions  found  a  marked  impair- 
ment in  visual  discrimination  following  the  temporal  but  not  the  parietal 
lesion,  and  simultaneously,  a  marked  impairment  in  tactual  discrimination 
following  the  parietal  but  not  the  temporal  lesion.  In  comparison  with 
these  specific  deficits  it  seemed  reasonable  to  argue,  especially  in  view  of 
the  absence  of  evidence  to  the  contrary,  that  frontal  lesions  were  produc- 
ing only  relatively  minor,  non-specific  impairment,  which  was  unrelated 
to  frontal-lobe  function,  per  se. 

As  shown  in  Fig.  2,  however,  the  contrary  evidence  has  now  been 
obtained.  The  discrimination  impairment  following  frontal  lesions  may 
be  non-specitic  as  regards  sensory  modalities  but  it  is  specific  to  damage  in 
the  frontal  area  and  it  is  certainly  not  minor,  hi  fact,  as  these  studies  by 


558 


BRAIN    MECHANISMS    AND    LEARNING 


Brush  and  Mishkin  (1959),  Wciskrantz  and  Mishkin  (1958)  and  Ettlingcr 
and  Wegener  (1958)  show,  frontal  lesions  may,  on  occasion,  produce 
deficits  in  discrimination  learning  which  are  even  greater  than  those 
produced  by  lesions  of  the  posterior  area  most  closely  associated  with  the 
modality  in  question.  It  can  no  longer  be  argued  that  a  frontal  lesion 
leaves  discrimination  learning  unimpaired. 

What  then  becomes  of  the  notion  that  frontal  cortex  is  unrelated  to 
sensory  discrimination  functions  ?  The  answer  appears  to  be  that  it  is  still 
correct,  for  a  careful  analysis  reveals  that  it  is,  in  fact,  a  non-sensory 

VISUAL   DISCRIMINATION     LEARNING 


UNBAITED 


BAITED 


100- 


IQO-, 


cc  50- 


F-i; 

N 

N-»    4  4  N-^     4 

(BRUSH  a  MISHKIN  1959) 

Fig.  3 
Ertects  of  troiitdl  lesions  on  visual  discrimination  learning 
different  training  procedures. 


kith  two 


deficit  which  underlies  the  frontal  animals'  discrimination  impairment. 
This  conclusion  is  based  on  experiments  showing  that  manipulation  of 
non-sensory  variables  determines  whether  or  not  the  discrimination 
learning  of  frontal  animals  will  be  impaired  . 

In  Fig.  3  for  example,  it  may  be  seen  that  the  identical  animals,  tested 
on  the  same  visual  discriminations,  are  deticient  when  trained  in  one  way 
but  not  in  the  other.  In  both  conditions  there  are  a  scries  of  discriminations 
in  which  two  objects  are  presented  simultaneously  for  a  few  trials  and  the 
monkey  must  learn  which  of  the  pair  is  rewarded.  The  difference  between 
the  procedures  is  that  in  the  'un baited'  ci>iidition  tlie  choice  on  the  first 


H.    ENGER   ROSVOLD    AND    MORTIMER    MISHKIN 


559 


trial  is  never  rewarded,  and  so  on  succeeding  trials  the  animal  must  learn 
to  choose  the  other  cue.  Conversely,  in  the  'baited'  condition  the  choice  on 
the  fnst  trial  is  always  rewarded,  and  so  on  later  trials  the  animal  must 
learn  to  choose  the  same  cue.  It  has  been  demonstrated  that  in  this  situation 
the  monkey's  initial  response  to  each  new  pair  of  objects  is  frequently 
determined  by  its  preference  for  one  object  over  the  other.  Thus,  for  the 
animal,  the  difference  between  the  two  conditions  is  the  difference  be- 
tween overcoming  and  persisting  in  an  initial  preference.  Animals  with 

TACTUAL    DISCRIMINATION    LEARNING 


500- 


250 


EFFORTLESS 


500 


tr  250- 


EFFORTFUL 


(ETTLINGER   S  WEGENER    1958) 


IROSVOLD,  BATTIG,  MISHKIN-UNPUBLISHED) 


Fig.  4 
Effects  of  frontal  lesions  on  tactual  discrimination  learning  with  two 
different  training  procedures. 

frontal  lesions  do  fnid  it  difficult  to  reverse  their  preference,  as  shown  by 
their  poor  performance  in  the  'unbailed'  condition.  They  do  not  have 
difficulty,  however,  in  discriminating  the  objects,  since  their  performance 
in  the  other  condition  equals  that  of  the  normals.  The  evidence  here  is 
clearly  against  ascribing  to  frontal  animals  a  visual  perceptual  loss.^ 

It  is  possible  to  show  that  the  same  pattern  of  results  can  be  obtained  in  a 
tactual  discrimination  by  manipulating  another  non-sensory  variable.  In 
Fig.  4  it  may  be  seen  that  when  frontal  monkeys  are  trained  on  tactual 
discrimination  with  one  procedure,  they  are  impaired;  with  another 

^  It  is  perhaps  worth  indicating  that  such  a  loss  can  be  assigned  to  animals  with  tcniporal 
lesions,  since  they  have  been  found  to  be  equally  impaired  in  both  conditions. 


<,6o 


BRAIN    MECHANISMS    AND    LEARNING 


procedure  they  arc  not.  Here  the  difference  between  the  two  procedures 
is  that  in  the  'effortless'  condition  the  manipulanda  are  easy  to  move, 
whereas  in  the  'effortful'  condition  they  can  be  moved  only  with  great 
difficulty.  Since  visual  cues  are  excluded  the  sensory  information  necessary 
for  making  the  discrimination  in  either  condition  cannot  be  obtained  until 
the  response  is  actually  initiated.  But  once  the  response  has  been  initiated 
the  monkey  has  a  strong  tendency  to  complete  it,  regardless  of  the  dis- 
criminanda.  In  the  'effortless'  condition,  where  it  is  possible  to  complete 

AUDITORY    DISCRIMINATION     LEARNING    and    PERFORMANCE 


100- 


50- 


NO  SHOCK 


SHOCK 


SHOCK  REMOVED 


SHOCK  RETURNED 


(ROSVOLD,  BATTIG,  MISHKIN -UNPUBLISHED  ) 


Fig.  5 


Effects   of  frontal   lesions   on   auditory  discrimination  learning  and  performance 
with  two  different  training  procedures. 

the  response  with  case,  the  frontal  annuals  seem  to  learn  the  discrimination 
relatively  slowly.  In  the  'effortful'  condition,  on  the  other  hand,  where 
completing  the  response  requires  considerable  strength,  frontal  animals 
learn  the  relevant  tactual  discrimination  as  quickly  as  the  controls.^  Thus, 
unless  frontal  monkeys  are  effectively  deterred  from  completing  a  response 
which  they  have  already  initiated,  they  will  do  so  regardless  of  the  dis- 
criminanda,  and  appear  to  have  a  tactual  deficit  when  in  fact  they  do  not. 
A  particularly  dramatic  example  of  the  effect  of  a  non-sensory  variable 
is  shown  in  Fig.  5.  As  with  the  visual  and  tactual  discriminations,  it  may 

^  The  two  graphs  in  this  figure  represent  the  performance  of  animals  from  different  studies. 
Therefore,  the  absolute  levels  of  performance  in  one  study  cannot  be  compared  with  those  in 
the  other.  The  appropriate  comparison  is  each  frontal  group  with  its  own  control. 


H.    ENGER    ROSVOLD    AND    MORTIMER    MISHKIN  561 

be  seen  that  in  auditory  discrimination,  also,  the  frontal  animal  is  deficient 
with  one  training  procedure  but  not  with  another.  The  tn'st  graph 
represents  the  performance  level  achieved  m  the  last  lOO  of  over  2000 
training  trials  in  which  responses  to  the  negative  stimulus  were  deterred 
only  by  the  usual  extinction  procedure.  Up  to  this  point  the  frontal 
animal  appeared  to  be  completely  unable  to  discriminate  the  auditory 
cues.  However,  as  soon  as  responses  to  the  negative  stimulus  were 
severely  punished  by  the  introduction  of  strong  electric  shocks,  this  monkey 
discriminated  very  well  indeed.  Within  100  trials  it  achieved  almost 
perfect  discrnnination,  equalling  the  performance  of  the  normal.  An  even 
more  surprising  result  is  illustrated  in  the  last  two  graphs  of  the  figure. 
The  frontal  animal's  deficit  could  be  turned  on  and  off,  sometimes  even 
within  the  same  testing  session,  by  the  simple  expedient  of  removing  or 
reapplying  the  shock.  Such  an  impairment  can  harcily  be  attributed  to 
sensory  effects  of  the  lesion. 

Let  us  consider  what  the  nature  of  the  non-sensory  deficit  might  be. 
The  general  principle  which  emerges  from  the  evidence  as  it  has  been 
developed  to  this  point  can  be  stated  briefly  as  follows.  The  discrimination 
learning  of  an  animal  with  a  frontal  lesion  is  not  impaired  when  its  initial 
response  tendency  to  the  negative  stimulus  is  weak  or  the  deterrent  to  such 
a  response  is  particularly  strong.  Conversely,  when  a  strong  tendency  to 
respond  to  the  negative  stinuilus  is  coupled  with  only  a  weak  deterrent,  a 
clear-cut  deficit  appears.  If  the  principle  is  correct  it  provides  strong 
support  for  the  view  that  damage  to  the  frontal  lobes  results  in  a  loss  of 
inhibition.  This  conception  of  a  loss  of  inhibition  following  prefrontal 
damage  is  a  recurrent  theme  which  can  be  traced  at  least  as  far  back  as 
Schafer's  (1898)  Textbook  of  Pliysiolo(iy.  Most  recently,  a  sophisticated 
variation  of  this  hypothesis  has  been  proposed  by  Konorski  and  his 
associates  (Brutkowski,  Konorski,  Lawicka,  St^pieh  and  St^^pien,  1956). 

A  particularly  clear  example  of  a  c^cficit  which  might  be  labelled  loss  of 
inhibition  is  shown  in  Fig.  6.  In  this  task,  a  'go-no  go'  discrimination, 
operated  monkeys  and  controls  were  trained  to  displace  a  baited  food-cup 
when  they  heard  one  sound,  but  to  refrain  from  displacing  it  when  they 
heard  another.  If  an  animal  made  an  error  by  responding  to  the  negative 
sound,  or  by  failing  to  respond  to  the  positive  one,  the  same  signal  was 
presented  again  and  again  until  the  animal  did  respond  to  it  correctly.  The 
figure  is  a  plot  of  the  number  of  extra  times  the  negative  stimulus  had  to 
be  presented  minus  the  number  of  extra  positives,  over  blocks  of  200 
trials.  Now,  the  preliminary  training  on  this  task  develops  in  the  animal  a 
strong  tendency  to  respond  on  every  trial.  This  is  indicated  by  the  fact 


562 


BRAIN    MECHANISMS    AND    LEARNING 


that  even  the  normal  animals  initially  make  more  errors  by  responding 
when  they  should  not  respond,  than  by  not  responding  when  they  should. 
The  only  deterrent  to  this  strong  generalized  tendency  to  respond  to  the 
negative  cue  is  the  absence  of  reward.  In  line  with  the  principle  stated 
earlier  the  monkeys  with  frontal  lesions  exhibited  a  marked  impairment 
which,  in  the  early  part  of  training  at  least,  may  justifiably  be  labelled  a 
loss  of  inhibition. 


300-1 


200- 


100- 


LOSS   of    INHIBITION    ? 


4  5  6  7 

200- TRIAL   BLOCKS 


Fig.  rt 
Effect  of  frontal  lesions  on  inhibiting  responses  to  the  negative  stimulus  in  a  'go-no  go' 
situation. 


How  can  such  an  impairment  be  accounted  for  theoretically?  The 
answer,  unfortunately,  is  that  there  are  numerous  possibilities  as  can  be 
seen  in  Fig.  7.  An  inhibitory  defect  can  be  postulated  at  any  point  in  the 
stimulus-response  sequence  and  it  will  still  provide  a  reasonable  explana- 
tion of  the  frontal  animal's  deficiency  on  discrimination  tasks.  For  example, 
if  an  inhibitory  defect  were  present  at  the  response  and  ot  the  chain,  the 
neural  model  could  be  a  loss  of  suppression  of  the  cortical  motor  systems. 
Specifically,  an  hypothesis  could  be  developed  on  the  basis  of  avilable 
ncurophysiological  data  (Mettlcr,  1935;  Freeman  and  Krasno,  1940; 
Dusser  de  Barenne,  Carol  and  McCuUoch,  1942)  that  frontal  cortex, 
acting  through  the  cauciate  nucleus,  normally  exerts  a  suppressive  influence 


H.    ENGER    ROSVOLD    AND    MORTIMER    MISHKIN  563 

on  motor  activity.  The  frontal  animal's  mipairment  in  inhibiting  condi- 
tioned motor  responses  might  then  be  considered  a  symptom  analogous 
to  the  locomotor  hyperactivity  'released'  by  frontal  lobe  damage.  A 
theory  somewhat  similar  to  this  was,  ni  fact,  proposed  some  time  ago  by 
Stanley  and  Jaynes  (1949). 

LOSS  OF  INHIBITION 


Type 

Neural  Mechanism 

Manifestation 

Response 

Cortical  Motor  Systems 

Locomotor  Hyperactivity 

Drive 

Hypothalamic  Drive  Systems 

1 

Appetitive  Hyperactivity 

Stimulus 

Reticular  Activating  Systems 

Hyper  re  Activity 

Fic.  7 
The  behavioural  manifestations  and  neural  mechanisms  associated  with  three  proposed  types 
of  inhibitory  defects. 

Alternatively,  if  an  inhibitory  defect  were  assigned  to  the  motivational 
sphere,  the  neural  mechanism  could  be  a  loss  of  suppression  of  hypothala- 
mic appetitive  systems.  By  combining  the  data  ot  Anand  and  Brobeck 
(1951)  and  Dclagdo  and  Anand  (1953)  demonstrating  hypothalamic 
control  over  food  intake  with  the  results  of  Ward  and  McCulloch  (1947) 
demonstrating  frontal  projections  to  the  hypothalamus,  it  might  be 
proposed  that  frontal  cortex  normally  regulates  alimentary  inhibition. 
Increased  appetite,  another  commonly  reported  symptom  of  frontal 
damage  (Morgan  and  Stellar,  1950),  could  then  provide  the  explanation 
for  the  frontal  animal's  ditikulty  in  inhibiting  a  conditioned  food-getting 
response. 

Finally,  if  an  inhibitory  defect  were  postulated  on  the  sensory  side  it 
could  be  ascribed  perhaps  to  a  loss  of  suppression  of  the  diffuse  activating 
systems.  Magoun  (195S)  has  reviewed  the  evidence  indicating  that  the 
brain  stem  may  inhibit  as  well  as  facilitate  sensory  input  and  the  results  of 
Adey,  Segundo  and  Livingston  (1957)  suggest  that  frontal  cortex  may 
exert  an  important  regulating  influence  on  brain  stem  mechanisms.  If 
frontal  damage  caused  a  loss  of  suppression  of  the  diffuse  sensory  input, 
this  would  account  first  of  all  for  the  common  observation  that  the 
frontal  animal  is  hyper-reactive  to,  anc^  easily  distracted  by  extraneous 
stimuli  (Kcnnard,  Spencer  and  Fountain,  1941;  Malmo,  1942).  That  it 
could  also  account  for  the  frontal  animal's  impairment  on  discrimination 

00 


564  BRAIN   MECHANISMS    AND    LEARNING 

tasks  is  suggested  by  the  fact,  well  known  in  conditioning  experiments, 
that  extraneous  stimuli  tend  to  disinhibit  weakly  inhibited  responses. 

It  must  of  course  be  emphasized  that  no  attempt  has  been  made  here  to 
work  out  these  three  hypothetical  mechanisms  in  any  rigorous  fashion. 
The  point  is  simply  that  on  the  basis  of  available  neurophysiological 
evidence,  together  with  the  abnormal  symptoms  observed  in  the  frontal 
animal's  general  behaviour,  a  reasonably  strong  argument  can  be  deve- 
loped in  favour  of  each  of  them.  It  is  this  very  multiplicity  of  possible 
mechanisms,  however,  which  is  the  chief  source  of  weakness  in  the  theory. 
An  uncritical  application  of  the  general  concept  of  a  loss  of  inhibition, 
without  specifying  the  type,  can  probably  be  used  to  explain  any  complex 
behavioural  effect  of  frontal  lobe  damage.  On  the  other  hand,  when  care 
is  taken  to  specify  which  type  of  inhibitory  defect  is  being  considered  it  is 
found  that  there  is  evidence  from  discrimination  learning  experiments 
that  is  inconsistent  with  each  of  them. 

Consider  first  certain  predictions  which  follow  from  the  hypothesis  that 
frontal  lesions  result  in  a  loss  of  response  inhibition.  Suppose  that  two 
stimuli  A  and  B  arc  presented  at  random  on  separate  trials.  A  signals  food 
on  the  left,  and  B  signals  food  on  the  right.  Since  both  responses  are  some- 
times rewarded,  the  correct  response  of  going  left  to  A  on  any  particular 
trail  necessitates  inhibiting  the  built-in  response  tendency  to  the  right. 
Similarly,  going  right  to  B  involves  inhibiting  a  strong  response-tendency 
to  the  left.  As  noted  by  Stanley  and  Jaynes  (1949)  in  the  development  of 
their  theory,  a  loss  of  response  inhibition  should  lead  to  an  impairment  on 
this  'go  left-go  right'  type  of  descrimination  test;  yet,  in  experiments  of 
this  kind  by  Pribram  and  Mishkin  (1955),  in  vision,  and  by  Battig, 
Rosvold  and  Mishkin  (unpublished),  in  audition,  no  such  impairment  was 
found.  Now  for  an  opposite  example,  that  is,  one  in  which  this  particular 
hypothesis  would  probably  not  predict  impairment.  According  to  our 
interpretation,  a  loss  of  suppression  of  the  somatic  motor  systems  should 
produce  difficulty  in  inhibiting  well-established  locomotor  and  manipula- 
tory acts.  On  the  other  hand,  it  should  not  affect  the  inhibition  of  such 
conditioned  autonomic  reflexes  as  salivation.  However,  in  experiments  by 
Brutkowski  (1957)  in  which  dogs  with  frontal  lesions  were  trained  to 
differentiate  positive  from  negative  conditioned  stimuli,  a  severe  impair- 
ment in  inhibiting  salivation  to  the  negative  stimulus  was  observed. 

It  will  be  recognized  that  the  preceding  illustration,  while  weakening 
the  hypothesis  of  a  loss  of  response  inhibition,  simultaneously  strengthens 
the  hypothesis  of  a  loss  in  the  inhibition  of  appetitive  mechanisms.  Other 
evidence,  however,  raises  dii^iculties  for  this  alternative  conception.  For 


H.    ENGER    ROSVOLD    AND    MORTIMER    MISHKIN 


565 


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Brutkowski    et    ol.    (1956) 
Brutkowski  (19S9) 
Lawicka  (1957) 
Lawicka  (unpublished) 
Chorzyna  (unpublished) 

Brutkowski  and  Auleytner 
(in  preparation) 
Lawicka  (unpublished) 

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566  BRAIN    MECHANISMS    AND    LEARNING 

example,  in  a  'go-iio  go'  discrimination  in  which  an  anmial  is  rewarded 
with  food  for  going  to  one  stimulus,  and  is  also  rewarded  with  food  for 
not  going  to  the  other  stimulus  both  stimuli  should  acquire  positive 
reward  value.  With  these  conditions  of  testing,  loss  of  drive  inhibition 
should  not  affect  performance.  Yet  this  technique  of  symmetrical  reward 
was  the  one  employed  in  Weiskrantz  and  Mishkin's  (1958)  'go-no  go' 
auditory  problem  on  which  frontal  aninials  were  so  severely  impaired. 
Conversely,  the  hypothesis  of  a  loss  of  drive  inhibition  sliould  predict 
impairment  whenever  a  rewarded  stimulus  is  paired  with  one  that  is 
consistently  unrewarded.  Thus,  in  a  visual  discrimination  in  which  both 
the  positive  anci  negative  stimuli  arc  simultaneously  present,  frontal 
animals  should  have  greater  difficulty  than  normals  in  inhibiting  responses 
to  the  unrewarded  cue.  Yet,  it  was  the  fact  that  frontal  animals  were 
unimpaired  on  precisely  this  type  of  discrimination  that  first  gave  rise  to 
the  erroneous  generalization  that  frontal  damage  does  not  affect  per- 
formance on  any  discrimination  task. 

The  final  hypothesis  to  be  considered  is  immune  to  all  the  objections 
that  have  been  raised  so  far  since  it  does  not  yield  predictions  with  respect 
to  different  cue-response-reward  combinations.  Predictions  that  would 
follow  from  a  loss  of  stimulus  inhibition  relate  rather  to  the  potentially 
disruptive  effects  of  extraneous  stimuli.  Thus,  discrimination  impairment 
following  frontal  damage  would  bo  expected  to  be  directly  related  to  the 
amount  of  distraction  in  the  testing  situation.  Unfortunately,  the  literature 
on  discrimination  learning  in  frontal  animals  does  not  provide  us  with  a 
clear-cut  test  of  this  prediction.  Nevertheless,  there  have  been  gross 
differences  betwccii  studies  m  terms  of  such  general  testing  conditions  as 
noisy  v.  silent  apparatus,  noisy  c.  sound-shielded  testing  rooms,  the 
possibility  of  visual  exploration  v.  the  exclusion  of  vision,  etc.  The 
presence  of  certain  distracting  influences  has  been  shown  to  have  a  marked 
ciisrupting  effect  on  frontal  animals'  delayed  response  performance 
(Malmo,  1942;  Lawicka,  1957).  However,  as  far  as  can  be  determined, 
there  is  no  such  relationship  between  the  presence  of  extraneous  stimuli 
and  their  impairment  on  discrimination  tasks. 

We  do  not  wish  to  argue  that  our  analysis  of  the  experimental  evidence 
conclusively  rules  out  all  possibility  of  explaining  the  frontal  animals' 
impairment  on  discrimination  tasks  as  a  loss  of  some  form  of  inhibition. 
Perhaps  further  theorizing  along  such  lines  will  suggest  a  mechanism  that 
will  overcome  the  difficulties  that  have  been  raised.  It  should  be  pointed 
out,  however,  that  these  ditlfculties  may  reflect  the  inadequacy  of  the 
general  hypothesis  of  a  loss  of  inhibition  from  which  the  various  specific 


H.    ENGER    ROSVOLD    AND    MORTIMER    MISHKIN  567 

hypotheses  were  derived.  On  this  basis  it  would  seem  profitable  to  begin 
exploring  other  possibilities  and  not  contme  ourselves  to  the  one  class  of 
theoretical  concepts. 

To  summarize  the  major  points  of  this  analysis:  A  survey  of  the  older 
literature,  reinforced  strongly  by  recent  evidence,  has  shown  that  with 
certain  conditions  of  testing  frontal  lesions  produce  severe  impairment  m 
learning  and  performance  on  discrimination  tasks  in  all  sensory  modalities. 
An  explanation  of  this  deficit  in  terms  of  a  sensory-perceptual  loss  w^as 
rejected  in  favour  of  a  non-sensory  loss  specific  to  frontal  lobe  damage. 
While  much  of  the  evidence  favours  an  interpretation  of  the  impairment 
as  a  loss  of  inhibition,  a  careful  examination  of  three  specific  types  of 
proposed  inhibitory  defects  shows  that  none  of  them  satisfactorily 
accounts  for  all  of  the  data.  In  further  work  directed  towards  the  elucida- 
tion of  the  frontal  animals'  non-sensory  impairment,  an  important  problem 
will  be  to  determine  what  relationship,  it  any,  the  deficit  oi  the  frontal 
animal  on  discrimination  tasks  bears  to  its  deficit  on  delayed-response 
tasks,  the  symptom  which  has  traditionally  guided  theory  and  research 
concerning  frontal  lobe  function. 

GROUP   DISCUSSION 

Disiiiliihifion  of  inhibitory  CRs  after  prefrontal  lesions  in  doos 

KoNORSKi  (written  comment).  Since  our  laboratory  has  been  directly  con- 
cerned with  the  problem  of  the  impairment  of  inhibitory  processes  after  prefrontal 
lesions  for  nearly  10  years,  I  should  like  to  present  very  briefly  our  experimental 
material  dealing  with  this  subject  and,  with  our  results  as  a  basis,  to  comment  on 
some  of  the  statements  put  forward  by  Rosvold  and  Mishkin  in  their  paper. 

Our  work  has  been  performed  on  dogs  in  which  we  established  various  types  of 
excitatory  and  inhibitory  CRs ;  then  we  removed,  to  varying  extents,  the  prefrontal 
areas  (or  as  a  control  some  parts  of  the  parietal  areas)  and  observed  the  changes  in 
CRs  for  a  long  time  after  these  operations.  Inhibitory  CSs  were  either  stimuli 
similar  to  the  positive  CSs  (differentiation)  or  were  compounds  composed  of  a 
positive  CS  preceded  bv  another  stimulus  (so  called  conditioned  inhibition). 
Inhibitory  stimuli  were,  of  course,  not  reinforced  by  any  UCS. 

Prefrontal  lesions  consisted  of  amputation  of  the  frontal  poles  rostral  to  the 
prcsylvian  sulcus;  in  this  way  gyrus  proreus,  gyrus  subproreus  and  the  anterior 
part  of  gyrus  orbitalis,  as  well  as  subjacent  white  matter,  were  removed.  Parietal 
lesions  consisted  of  removal   of  parts  of  gvrus  entolateralis  and  suprasplenialis 

In  Table  I  the  results  obtained  in  these  experiments  are  summarized.  As  seen 
from  this  table,  after  prefrontal  lesions  positive  CRs  are  either  normal  or  enhanced, 
while  inhibitory  CRs  are  disinhibited.  This  holds  true  with  respect  to  both  ali- 
mentar)-  (food  and  water)  and  defensive  (electric  shock  and  acid)  reflexes.  Only  in 


568  BRAIN    MECHANISMS    AND    LEARNING 

one  dot^  ill  which  the  shock  reinforcement  was  weak,  and  in  one  dog  in  which 
avoidance  technique  was  used  (i.e.  the  stimuhis  was  not  apphcd  at  all)  disinhibition 
was  not  observed,  hi  Figs,  i  and  3  the  records  of  some  typical  experiments  are 
presented. 

After  parietal  ablations  no  changes  occurred  in  either  positive  or  inhibitory 
CRs. 


Fig.  1 
The  extent  of  prefrontal  and  parietal  (control)  lesions  in  dogs. 
The  corte.x  is  shown  in  two  dimensions.  By  dense  stippling  the  usual  prefrontal  and  parietal 
ablations  are  shown.   Sparse  stippling  denotes  part  of  the  premotor  area  involved  in  our 
extensive  prefrontal  lesions. 

While  limited  ablations  produce  disinhibition,  the  extensive  ones  produce  in  addition 
hyperactivity. 

When,  after  a  prefrontal  operation,  inhibitory  CSs  are  repeatedly  applied  with- 
out reinforcement,  inhibitory  reflexes  are  gradually  re-established,  hi  some  cases 
restoration  occurs  after  only  a  few  trials,  while  in  others  it  takes  a  long  time,  and 
may  be  incomplete.  This  depends  chiefly  on  the  difficulty  of  the  inhibitory  task  for 
a  given  dog  and,  perhaps,  on  the  extent  of  its  lesion. 

The  impairment  of  inhibitory  CRs  after  prefrontal  lesions  could  be  ascribed,  of 
course,  to  the  animal's  loss  of  discriminatory  ability.  But  the  fact  that  disinhibition 
is,  as  a  rule,  only  partial  (which  is  best  seen  in  salivary  reflexes),  and  especially  the 


H.    ENGER    ROSVOLD    AND    MORTIMER    MISHKIN 


569 


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M,  81  Bi  84 


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H    n 


\s 


,  I  I  I  I  I   I  r  I   I   J  I  t  I  I  I  I  r  I   I  I  I   I  I  I  I  I  I  I  'I  I  I  I  (  I  I  I   I  '  I  I  I  I  I  I  I  I  '  I  I  I  I  I  I  I  ''  t  I  I  r  ■  I 

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Fig.  2 
Kymographic  records  of  parts  of  some  representative  experiments  in  dogs  before  and  after 
successive  operations. 

Each  record  comprises  from  top  to  bottom:  bftmg  the  right  foreleg  and  putting  it  on  the 
food-tray;  conditioned  stinmli;  the  moment  of  food  presentation;  time  (5  sec);  symbols  of 
stimuli:  M,,  Metronome,  Bj,  Bell,  B.^,  differential  Bell,  PM,,  Propeller  }  Metronome  (inhibi- 
tory compound);  a,  fragment  of  the  last  experiment  before  first  frontal  ablation;  b,  fragment 
of  the  first  experiment  after  first  frontal  ablation ;  c,  fragment  of  an  experiment  ih  months 
after  first  frontal  ablation;  d,  fragment  of  an  experiment  after  parietal  ablation;  e,  fragment  of 
an  experiment  shortly  after  second  frontal  ablation;  f  fragment  of  an  experiment  a  month 
after  second  frontal  ablation  (After  Brutkowski  et  al.,  1956). 


570 


BRAIN    MECHANISMS    AND    LEARNING 


fact  that,  according  to  Rosvold  and  Mishkin,  it  is  not  observed  when  the  instru- 
mental reaction  to  the  inhibitory  stimukis  is  punished,  speak  against  this  supposition 
and  support  the  view  that  perhaps  we  have  to  do  here  with  the  impairment  of  the 
inhibitory  processes  themselves.  Therefore,  we  must  consider  the  question  of  what 
sort  of  inhibition  is  affected  by  prefrontal  lesions  and  in  which  way  it  is  affected. 
Here  we  must  inevitably  revert  to  the  classical  Pavlovian  notions  of  external  and 


.before    prefrontal    lobectomy  — 


after  prefrontal   lobectomy  — 


Fig.  s 


Examples  ot  disinhibition  of  salivary  food  conditioned  reflexes  after  prefrontal  ablations. 

Each  graph  represents  the  voluminograph  of  salivation  to  a  positive  conditioned  stimulus 
and  to  an  inhibitory  stimulus  following  it.  Note  that  after  prefrontal  lobectomy  positive 
CRs  are  unchanged,  while  negative  ones  are  more  or  less  disinhibited  (After  Brutkowski, 
1957)- 


internal  inhibition  and  to  the  immense  experimental  evidence  on  which  these 
notions  are  based.  It  is  quite  clear  that  what  is  impaired  after  a  prefrontal  lesion  is 
only  internal  (or  conditioned  in  the  wider  sense  of  the  word)  inhibition,  wliile 
external  (i.e.  antagonistic)  inhibition  is  not  affected  at  all  or  may  even  be  increased 
after  this  lesion. 

For  our  further  analysis  we  shall  accept  here,  as  a  working  hypothesis,  a  concep- 
tion put  forward  some  time  ago  by  Konorski  (1948),  according  to  which  internal 
inhibition  is  based  on  the  formation  of  inhibitory  connections  between  the  central 


H.    ENGER    ROSVOLD    AND    MORTIMER    MISHKIN  57I 

representations  of  the  CS  and  UCS,  alongside  the  excitatory  connections  formed 
earlier  between  these  two  representations.  The  prefrontal  lesion  may  either  destroy 
these  inhibitory  connections  leaving  the  excitatory  connections  unaffected,  or  else 
it  may,  by  some  unspecific  release  mechanism  (reticular  formation?),  increase  the 
excitability  oi  unconditioned  centres  [both  appetitive  and  defensive)  and  in  this 
way  give  predominance  to  excitatory  over  inhibitory  impulses.  Irrespective  of 
which  of  these  two  alternatives  (if  any)  proves  to  be  correct  we  have  here  to  do 
exclusively  with  the  phenomenon  labelled  by  Rosvold  and  Mishkin  as  loss  of  drive 
inhibition:  this  is  obvious  for  those  experiments  in  which  classical  CRs  were  used; 
as  tor  those  experiments  in  which  instrumental  reflexes  were  used  it  could  be 
shown  that  disinhibition  of  instrumental  responses  faithfully  reflected  disinhibition 
of  the  salivary  response,  i.e.  oi  the  ahmentary  drive  (Brutkowski,  1959). 

I  cannot  agree  with  Rosvold  and  Mishkin's  argument  that  the  results  obtained 
by  Weiskrantz  and  Mishkm  (195M)  with  a  'go-no  go'  symmetrical  reward  schedule 
to  two  different  sounds  arc  contradictory  to  the  drive  disinhibition  mechanism. 
These  authors  found  that  after  prefrontal  lesions  a  'no-go'  response  is  disinhibitcd 
in  spite  of  the  tact  that  it  is  rewarded.  But  we  know  from  the  vast  experimental 
evidence  of  the  Pavlov  school,  as  well  as  from  our  own  experimental  data  (Konor- 
ski  and  Szwcjkowska,  1952),  that  even  the  repeated  reinforcement  of  an  inhibitory 
stimulus  may  not  lead  to  its  transformation  into  a  positive  stimulus.  The  stimulus  to 
which  the  animal  was  to  refrain  from  responding  in  order  to  obtain  tood  was 
deeply  extinguished  at  the  beginning  of  trainnig,  since  the  animal  repeatedly 
performed  the  trained  movement  to  it  and  did  not  get  food;  as  a  result  this 
stimulus  probably  could  not  be  tully  established  as  a  positive  CS  when,  after  the 
instrumental  response  to  it  had  been  inhibited,  the  animal  was  reinforced.  Had  the 
authors  measured  salivation,  the}-  could  have  checked  whether  or  not  this  supposi- 
tion is  correct.  According  to  the  view  that  the  prefrontal  lesions  did  produce  drive 
disinhibition  oi  inhibitory  alimentary  reflexes,  the  inhibitory  stimulus  became 
excitatory,  which  was  reflected  in  the  animal's  performing  the  learned  movement 
to  it. 

Similarly,  it  seems  to  me  that  the  argument  ot  the  authors  pointing  out  that 
simultaneous-discrimination  habits  should  be  impaired  by  drive  disinhibition  is 
also  not  correct.  The  animal  is  presented  simultaneously  with  two  objects,  the 
reaction  to  one  of  them  being  constantly  reinforced.  As  a  result  tliis  reaction  be- 
comes much  stronger  than  the  reaction  to  the  other  object  since  the  latter  reaction 
is  inhibited  both  by  drive  and  response  inhibition.  There  is,  therefore,  no  reason 
why  atter  a  prefrontal  lesion  the  first  reaction  should  not  predominate. 

Yet,  we  Imvv  tound  that  after  larger  prefrontal  lesions  which  include  the  pre- 
cruciate  areas  a  new  phenomenon  ensues  which  may  be  defined  as  'motor- 
response  disinhibition'.  After  these  lesions  the  animals  not  only  exhibit  locomotor 
hyperactivity,  but  also,  when  put  into  the  experimental  situation  in  which  a 
definite  instrumental  CR  had  been  established,  they  perform  the  trained  movement 
again  and  again  apparently  without  any  relation  to  the  hunger  drive  (Fig.  2C; 
Konorski,  1957).  It  is  worth  mentioning  that  this  sort  of  disinhibition  is,  like  the 
first  one,  'conditioned'.  In  one  dog,  two  different  instrumental  responses  were 
trained  in  two  different  situations;  after  the  more  extensive  prefrontal  lesion  this 
dog  manifested  hyperactivity  ot  the  motor  reaction  specific  to  the  given  situation 
and  not  to  the  other  one. 


57^ 


BRAIN    MECHANISMS    AND    LEARNING 


A  clear  example  of  locomotor  disinhibition  after  large  prefrontal  lesions  was 
also  found  by  Shumilina  (1949)  in  Anokhin's  laboratory  in  experiments  in  wliich 
the  animal  received  food  at  two  ends  of  the  stand  to  two  different  CSs. 

To  summarize,  we  think  that,  to  use  convenient  expressions  introduced  by 
Rosvold  and  Mishkin,  prefrontal  lesions  may  produce  either  relatively  pure  drive 
disinhibition,  when  the  extent  of  the  lesion  is  limited  to  the  frontal  poles,  or,  in 
addition,  motor-response  disinhibition  when  the  lesion  encroaches  upon  the 
pericruciate  area.  It  remains  to  be  elucidated  whether  or  not  it  would  be  possible 
also  to  obtain  pure  motor-response  disinhibition  (without  drive  disinhibition)  if 
only  the  pericruciate  area  were  to  be  removed. 

As  to  the  mechanism  ot  motor-response  disinhibition  it  should  also  be  considered 
as  some  release  phenomenon,  analogous  to  many  forms  of  hypcrmotility  produced 
by  various  subcortical  lesions. 


ucs 


ucs 


cs» 


^•R     CS» 


a  b 

Fig.  4 
Schemes  of  excitatory  and  inhibitory  connections  involved  in 
type  II  conditioned  reflex-arcs,   a,  positive  conditioned  CR;  b, 
inhibitory  CR.  Continuous  Hncs,  excitatory  connections,  broken 
hues,  inhibitory  connections.  Further  exphinations  in  text. 


According  to  the  vast  experunental  evidence  ot  our  laboratory,  the  'reflex-arc 
of  instrumental  CRs  should  be  considered  as  consisting  of  two  parallel  pathways 
(cf.  Wyrwicka,  1952) :  one  pathway  runs  from  the  central  representation  of  the  CS 
through  the  corresponding  drive  centre  to  the  representation  of  the  instrumental 
reaction  (CS-*UCS->-R);  the  second  pathway  runs  directly  from  the  CS  'centre'  to 
the  motor  'centre'  (CS^R).  When  an  inhibitory  CR  is  established,  inhibitory 
connections  are  formed  between  the  CS  and  UCS  centres  ('drive  inhibition')  and 
between  the  CS  and  R  centres  ('motor-response  inhibition'),  but  not  between  the 
UCS  and  R  centres,  since,  to  positive  CSs,  the  movement  R  is  performed  (Fig.  4). 
When  as  a  result  of  prefrontal  lesions  drive  inhibition  is  impaired,  both  classical 
and  instrumental  inhibitorv  reflexes  are  disinhibited,  as  the  pathway-  CS^-UCS  is 
no  longer  blocked.  If  motor-response  inhibition  is  impaired  the  animal  will  be 
hyperactive  but  drive  inhibition  may  be  left  intact. 


H.    ENGER    ROSVOLD    AND    MORTIMER    MISHKIN  573 

As  to  the  third  possibihty  proposed  by  the  authors  (loss  of  stiniukis  inhibition 
manifested  by  hyperreactivity)  I  would  rather  doubt  whether  it  exists  at  all,  since 
we  have  no  conclusive  evidence  that  prefrontal  animals  arc  more  distracted  by 
extraneous  stimuli  than  are  normal  animals  (cf.  the  experiments  by  Butler  and 
Harlow  (1956)  in  which  no  increased  distractability  was  found,  after  prefrontal 
lesions  in  monkeys).  The  detrimental  effect  of  extraneous  stimuli  in  prefrontal 
animals  in  the  delayed-responsc  test  is  simply  due,  as  we  have  shown,  to  the  fact 
that  these  animals  must  keep  their  bodily  orientation  unchanged  during  the  delay 
in  order  to  perform  the  correct  response.  Since  an  extraneous  stimulus  may  provoke 
a  change  in  orientation  (just  as  it  docs  m  normal  animals),  so  correct  dclayed- 
response  performance  is  impossible  for  prefrontal  annuals,  while  normal  animals, 
not  having  to  maintain  their  orientation  during  the  delay,  are  unaffected. 

RosvOLD  and  Mishkin  (written  rebuttal  submitted  as  afterthought).  In  his 
discussion  of  our  paper,  Konorski  has  presented  evidence  which  seems  to  support 
the  view  that  limited  prefrontal  lesions  produce  what  we  have  referred  to  as  a  loss 
of 'drive  inhibition'.  Let  us  re-examine  the  hypothesis  in  terms  of  this  evidence  first. 

According  to  Konorski,  the  instrumental  response  to  a  negative  (unrewarded) 
stimulus  is  normalh'  inhibited  by  both  drive  and  response  inhibition.  For  con- 
venience we  shall  call  the  sum  of  their  effects  the  (total)  inhibitory  tendency.  Now 
if  a  limited  prefrontal  lesion  impairs  drive  inhibition,  but  leaves  response  inhibition 
intact,  then  the  total  inhibitorv  tendency  should  be  reduced  but  not  eliminated. 
Yet,  in  the  experiments  on  auditory  differentiation,  the  animal's  inhibitory  response 
is  not  simply  weakened  by  the  lesion ;  it  is  transformed  into  an  excitatory  response. 
Thus  it  seems  to  us  that  the  drive  disinhibition  hypothesis  does  not  account  satis- 
factorily even  for  data  that  have  been  presented  to  support  it.  Hut  perhaps  this 
difficulty  can  be  avoided  by  making  some  additional  assumption,  e.g.  that  normally 
the  total  inhibitory  tendency  depends  primarily  on  drive  inhibition,  and  when  this 
is  impaired,  sufficient  drive  excitation  is  released  to  overcome  the  intact,  but 
relatively  weaker,  response  inhibition.  In  this  way,  a  strong  inhibitory  response 
might  be  transformed  by  the  lesion  into,  at  least,  a  weak  excitatory  response.  While 
it  is  hardly  our  wish  to  defend  it,  let  us  for  the  moment  accept  some  such  explana- 
tion of  the  impairment  in  auditory  differentiation  (in  which  stimuli  are  presented 
successively)  and  turn  next  to  the  experiments  on  visual  discrimination  with  simul- 
taneously presented  stimuli. 

In  simultaneous  discrimination,  as  opposed  to  differentiation,  impairment  after 
frontal  damage  has  rarely  been  observed.  Konorski  suggests  a  simple  explanation: 
When  both  positive  and  negative  stimuli  are  simultaneously  present,  the  strong 
excitatory  response  which  was  conditioned  to  the  positive  stimulus  before  opera- 
tion will  still  predominate  after  operation.  This  will  be  true  whether  the  inhibitory 
tendency  to  the  negative  stimulus  is  now  merely  reduced,  or,  according  to  our 
added  assumption,  changed  into  a  weak  excitatory  tendency.  But  while  this 
explanation  will  account  for  the  successful  retention  of  a  simultaneous-discrimina- 
tion habit,  we  do  not  believe  it  will  account  for  successful  post-operative  learning. 
When  a  frontal  animal  is  trained  only  after  operation,  an  impairment  of  drive 
inhibition  should  retard  the  development  of  an  inhibitory  tendency  to  the  negative 
stimulus,  and  thereby  delay  the  appearance  of  a  predominant  response  to  the 
positive  stimulus.  In  short,  discrimination  learning  should  be  impaired.  Numerous 
experiments  have  indicated  that,  contrary  to  such  a  prediction,  the  frontal  animal 


574  BRAIN    MECHANISMS    AND    LEARNING 

learns  even  dirt'icult  visual  discriminations  just  as  rapidly  as  its  unoperatcd  control. 

While,  for  simultaneous  discrimination,  Konorski  has  offered  an  explanation 
which  we  have  argued  applies  to  retention  but  not  to  learning,  he  suggests  an 
explanation  for  the  symmetrically  rewarded  'go-no  go'  discrimination  which 
seems  to  us  to  apply  to  learning  but  not  retention.  His  argument  here  is  as  follows. 
The  stimulus  to  which  the  animal's  response  was  extinguished  (the  'no  go'  stimulus) 
also  inhibited  the  animal's  ahmcntary  drive,  despite  the  fact  that  this  stimulus  was 
associated  with  reward  whenever  the  animal  did  refrain  irom  responding  to  it. 
Since  inhibition  of  drive  normally  aids  in  establishing  an  inhibitory  instrumental 
response,  a  loss  ot  drive  inhibition  should  impair  this  conditioning  process  and  so 
produce  the  reported  impairment  in  discrimination  learnnig.  But  this  does  not 
account  for  the  impairment  found  in  the  animals  that  had  learned  the  task  before 
operation.  Early  in  pre-operative  training  the  'no  go'  stimulus  may  have  indeed 
inhibited  the  alimentary  drive  because  the  animals  responded  to  it  regularly,  and 
so  were  rewarded  only  rarely.  As  training  progressed,  however,  the  animals 
tended  to  respond  to  the  'no  go'  stimulus  less  and  less  frequently,  and  as  a  result 
were  rewarded  more  and  more  often.  Finally,  when  the  animals  learned  to  inhibit 
perfectly,  the  'no  go'  stimulus  was  associated  with  reward  on  every  occasion. 
Surely  at  this  stage  of  the  experiment  the  animals  had  learned  to  'expect'  food  (or, 
in  conditioning  terms,  to  salivate)  at  the  sound  of  the  'no  go'  stimulus.  This  stimulus 
should  no  longer  have  been  inhibiting  the  drive,  in  which  case  a  post-operative 
disinhibition  of  drive  could  not  have  caused  the  loss  in  post-operative  retention. 

Our  re-examination  of  the  evidence  relates  so  far  only  to  the  hypothesis  that 
//'/;//rt'^  prefrontal  lesions  produce  a  loss  of  drive  inhibition.  Konorski  has  suggested, 
however,  that  with  somewhat  more  extensive  lesions,  those  invading  also  the 
pericruciate  area  in  dogs,  a  second  type  of  inhibitory  defect  is  produced,  viz.  loss  of 
response  inhibition.  But  would  this  combination  of  disinhibition  hypotheses  help 
to  explain  results  which  each  hypothesis  taken  singly  docs  not  ?  It  seems  to  us  that 
it  would,  in  fact,  make  it  easier  tor  Konorski  to  account  for  his  own  data  demon- 
strating disinhibition  of  instrumental  (in  addition  to  classical)  inhibitory  reflexes, 
and  also  to  account  for  the  impairment  on  the  symmetrically  rewarded  'go-no  go' 
discrimination,  just  discussed.  At  the  same  time,  however,  we  believe  it  would  not 
explain  away  the  absence  of  impairment  on  simultaneous  discriminations,  nor  on 
the  'go  left-go  right'  successive  discriminations,  which  we  described  in  our  paper. 

Grastyan.  Some  years  ago  Dr  Shuskin  pubhshed  some  work  about  this  investi- 
gation concerning  the  influence  of  extirpation  of  frontal  lobes  on  the  behavioural 
aspect  of  conditioned  dogs.  If  I  am  not  mistaken,  Dr  Shuskin's  data  from  many 
points  of  view  arc  in  accordance  with  the  data  of  Dr  Rosvold. 

RosvoLD.  I  don't  know  these  studies.  I  am  very  happy  to  have  this  reference. 

EsTABLE.  Do  conditioned  reflexes  increase  or  decrease  the  capacity  for  discrimina- 
tion? I  ask  this  question  because  discrimination  is  used  in  a  very  particular  sense.  It  I 
have  ten  objects  one  of  which  is  of  iron  and  a  magnet,  only  the  one  of  iron  is 
attached  by  the  magnet.  This  is  not  because  there  has  been  any  discrimination  but 
simply  because  it  could  not  be  otherwise.  In  the  case  of  animals  with  conditioned 
reflexes,  I  wonder  whether  they  respond  in  a  specific  way  to  a  stimulus  which  they 
have  discriminated  or  whether  they  react  because  they  cannot  do  otherwise.  Does 
discrimination  occur  or  is  it  simply  a  way  of  reacting  = 

Anokhin.  During  a  period  of  years,  from  1935  to  1949,  one  ot  my  associates. 


H.    ENGER    ROSVOLD    AND    MORTIMER    MISHKIN  575 

Dr  Schumilina  performed  a  large  number  ot  ablations  ot  the  trontal  cortex  and 
studied  the  consequence  ot  that  removal  under  specific  experimental  conditions. 
Research  on  the  secretion  and  motor  components  of  the  conditioned  reflex  was 
carried  out  jointly. 

This  work  has  led  us  to  consider  that  it  is  quite  impossible  to  define  the  functions 
of  the  frontal  lobes  on  the  only  basis  of  the  'inhibition'  or  'loss  of  inhibition' 
concept.  Such  functions,  it  appears,  are  considerably  more  complex;  we  have, 
moreover,  gathered  evidence  that  their  interpretation  is  directly  determined  by  the 
specific  tiicthod  clioscn  for  the  control  of  the  test's  resiihs. 

In  other  words,  the  decisive  factor  here  is  the  elaboration  of  an  adequate  test 
method  for  checking  the  experimental  data.  Any  correct  understanding  of  results 
will  depend  upon  that  choice. 

Our  research  has  also  shown  the  fact  that  even  after  extirpation  of  the  frontal 
lobes  normal  internal  inhibition  can  develop ;  this  means  that  this  specific  cortical 
function  has  not  been  impaired  by  the  operation.  However  the  animal  is  no  longer 
capable  of  a  higher  form  of  inhibition  whereby  its  brain  may  store  and  co-ordinate 
harmoniously  a  number  of  factors  of  different  nature  which  have  simultaneously 
acted  upon  its  nervous  system. 

In  particular  the  frontal  lobes  normally  contribute  to  preventing  the  enormous 
amount  of  stimuli  from  the  environment  from  releasing  a  full-scale  digestive  reflex, 
even  when  the  stimulating  action  ot  the  various  test  conditions  is  clearly  apparent. 
But,  at  the  moment  when  the  conditioned  stimulus  starts  acting,  this  hidden 
integration  of  the  different  environmental  stimuli  becomes  eflective  also  and 
spreads  to  the  peripheral  system. 

We  have  also  shown  that  after  removal  of  the  frontal  lobes,  what  happens  is  not 
an  over-all  loss  of  inhibition  ot  anv  stimuli  inhibited  up  to  then,  but  the  release  of 
quite  specific  stimuli.  The  stimuli  pattern  involved  specifically  requires  an  alterna- 
tive motor  discrimination  between  right  and  left  side. 

Extensive  and  valuable  literature  on  the  subject  has  appeared  in  our  country,  and 
I  would  be  glad  to  provide  Dr  Rosvold  with  some  of  our  studies.  I  shall  not  fail  to 
send  them  to  him  upon  returning  home. 

Rosvold.  Dr  Anokhin  refers  to  his  experiment  in  which  in  a  situation  involving 
two  feeding  stands  the  animals  are  disinhibited,  he  interprets  it  as  a  loss  of  afferent 
inhibition  or  suppression  of  stimulus  inhibition.  Dr  Konorski  would  interpret  this 
as  a  loss  of  locomotor  or  response  inhibition.  The  same  experimental  material  can 
apparently  be  interpreted  in  different  ways.  Thus,  the  point  of  our  paper:  there  are 
so  many  varieties  of  the  inhibition  notion  that  it  soon  becomes  impossible  to  set  up 
a  critical  experiment. 

Myers.  Dr  Rosvold  has  been  for  a  long  time  concerned  with  the  comparative 
effects  of  frontal  lesion  in  different  species.  I  wonder  what  he  feels  human  studies 
have  to  contribute  to  our  understanding  of  the  etfects  of  prefrontal  damage? 

Rosvold.  With  respect  to  the  comparative  approach  to  this  problem  we  have 
considerable  evidence  of  progressive  changes  in  effect  from  dog  to  man.  Tliis 
makes  us  wonder  whether  we  are  dealing  with  a  unitary  phenomenon  or  not.  For 
example,  delayed  response  performance  is  invariably  impaired  in  monkeys  after 
prefrontal  lesions,  but  in  chimpanzees  this  is  temporary  even  with  radical  lesions 
and  has  never  been  demonstrated  at  all  in  human.  In  answer  to  Dr  Myers's  question 
I  would  say  that  the  principal  value  of  the  studies  ot  humans  with  injured  frontal 


576  BRAIN    MECHANISMS    AND    LEARNING 

lobes  is  to  emphasize  two  facts  (i)  none  of  our  present  notions  of  frontal  lobe 
function  has  been  demonstrated  to  apply  to  man  m  spite  of  many  attempts  to  do 
so,  and  (2)  the  caution  that  one  should  use  in  generalizing  about  brain  function 
without  reference  to  all  available  evidence,  including  that  obtamed  in  man. 

Hebb.  But  let  us  keep  the  record  clear:  the  effects  of  lobotomy  are  different  from 
those  of  lobectomy  m  man. 


STUDIES  OF  HIPPOCAMPAL  ELECTRICAL  ACTIVITY 
DURING  APPROACH  LEARNING 

W.  R.  Adey 

Attention  has  been  directed,  over  the  past  two  decades,  to  the  role  of  the 
hippocampus  and  adjacent  structures  of  the  temporal  lobe  in  such  func- 
tions as  emotional  arousal  and  memory  (Kluver  and  Bucy,  1939;  Bard  and 
Mountcastle,  1948).  Human  studies  have  supported  the  view  that  inter- 
ference with  anterior  and  deep  temporal  structures,  including  the  amygdala 
and  hippocampus,  may  disrupt  both  these  functions  (Scovillc  and  Milner, 
1957;  Meyer  and  Yates,  1955;  Jasper  and  Rasmussen,  1958).  However,  a 
global  view  of  the  functions  of  these  rhinencephalic  areas  in  the  process  of 
learning  might  suggest  that  they  are  concerned  in  the  execution  of  planned 
behaviour  rather  than,  perhaps,  in  the  specific  aspects  of  memory  or 
emotional  functions  as  such. 

The  latter  point  of  view  provided  a  frame  of  reference  for  the  studies 
reported  here.  Morphological  considerations  prompteci  Elliot  Smith 
(1910)  to  draw  attention  to  the  early  differentiation  of  the  hippocampal 
cortex  in  the  brain  of  all  vertebrates,  and  to  the  concurrent  development  of 
the  fornix  as  one  of  the  earliest  eticrcnt  pathways  from  the  cerebrum.  The 
possible  role  of  these  structures  in  aspects  of  motor  performance  relating 
to  learned  behaviour  appears  to  have  attracted  little  attention  from  sub- 
sequent workers,  although  Pribram  and  Mishkin  (1955)  and  Fuller  cr  al. 
(1957)  have  given  elegant  accounts  of  subtle  changes  in  learned  motor 
performance  resulting  from  interference  with  dicse  deep  temporal 
structures. 

The  experiments  described  here  were  conducted  in  collaboration  with 
Dr  C.  W.  Dunlop,  Dr  E.  Holmes  and  Mr  C.  Hendrix,  and  in  the  latter 
part  of  the  project  wc  were  joined  by  Dr  E.  Grastyan.  We  have  studied 
certain  aspects  of  slow-wave  discharges  in  the  hippocampal  and  adjacent 
deep  temporal  lobe  structures  m  the  cat  in  the  course  of  approach  learning. 
Our  attention  has  been  directed  to  the  possibility  of  inhomogeneities  in 
the  functional  activities  of  different  parts  of  the  hippocampal  arch,  and 
particularly  between  the  dorsal  and  ventral  parts  of  the  arch.  In  cross- 
sections  at  any  one  level,  the  hippocampal  arch  has  been  further  subdivided 
into  regions  CAj,  CA2,  CA3  and  CA4  by  Lorente  de  No  (1934).  Our 
implantations  have  been  carefully  placed  in  regions  CA^,  CA3  and  CA4  in 

577 


578  BRAIN    MECHANISMS    AND    LEARNING 

both  dorsal  and  ventral  parts  of  the  arch,  and  in  the  adjacent  entorhinal 
area  of  the  pyriform  cortex. 

Two  essentially  opposing  hypotheses  have  been  offered  in  explanation 
of  the  major  neural  fluxes  through  the  hippocanipal  arch  (Fig.  i).  These 


MPLANTED         ELECTRODE         PLACEMENTS 


DENTATE 
GRANULE    CELLS 


HIPPOCAMPAL 
PYRAMIDAL 
CELLS  : 


B.     SUGGESTED      PATHWAYS      FROM     PHASE    MEASUREMENTS 


(II   UNTRAINED        ANIMAL 


(2)      TRAINED  ANIMAL 


Fig.  I 

A.  Typical  impLmtcd  electrode  placements  in  the  dorsal  and  ventral  parts  of  the  hippocampal 
arch  (zones  CA.„  CA3,  CA4  dorsally,  and  CA.,  and  CA4  ventrally),  and  m  the  amygdala 
(AMYG)  and  entorhmal  area  (ENT). 

B.  In  the  untrained  animal,  phase  measurements  with  an  electronic  computer  of  the  slow- 
wave  trains  during  approach  performance  are  consistent  with  activity  passing  from  septum 
to  dentate  granule  cells  (DENT.  GR),  thence  to  hippocampal  pyramidal  cells  (HIPP.  PYR), 
and  across  die  subiculum  (SUB)  to  the  entorhinal  area  (ENT).  This  accords  with  pathways 
suggested  by  Elliot  Smith  and  Herrick.  The  ventral  hippocampus  shows  little  correlation  of 
itsslow-wave  activity  with  the  approach  after  the  first  few  trials.  This  arrangement  is  reversed 
in  the  trained  animal,  with  a  phase  sequence  in  the  slow-wave  trains  from  entorhinal  area  to 
hippocampal  pyramids,  thus  following  the  temporo-ammonic  tracts  of  Cajal  to  the  dendritic 
trees  of  the  hippocampal  pyramids.  F,  fornix  and  fimbria. 

classical  accounts  have  been  based  primarily  on  morphological  considera- 
tions. Cajal  (1909)  suggested  that  activity  arising  m  the  entorhinal  area 
traversed  the  hippocampus  by  trans-synaptic  activation  of  the  pyramidal 
cell  layer,  with  an  efferent  flux  into  the  fornix.  Contrary  hypotheses 
advanced  by  Elhot  Smith  (1910)  and  Herrick  (i93  3)  h-ive  proposed  an 


W.    R.    ADEY  579 

anterior  influx  from  the  septum  to  the  dentate  granule  cells,  which  in  turn 
relayed  to  the  hippocampal  pyramidal  cells,  with  subsequent  activation  of 
the  entorhinal  area.  Certainly  the  results  of  acute  electrophysiological 
experiments  have  favoured  the  latter  pathways  as  a  source  of  the  rhythmic 
slow  potentials  recorded  in  the  hippocampus  during  various  t)'pes  of 
arousal  (Green  and  Arduini,  1954;  Green  and  Adey,  1956;  Adcy,  Mcrril- 
lecs  and  Sunderland,  1956;  Adey,  Sunderland  and  Dunlop,  1957;  Adey, 
Dunlop  and  Sunderland,  1958).  It  was  to  test  aspects  of  these  various 
fluxes  through  the  hippocampus  in  a  training  situation  that  our  experiment 
was  designed. 

The  test  situation  involved  training  cats  in  a  T-maze  box,  with  food 
reward  on  the  basis  of  a  visual  cue.  Time-lapse  photographs  were  taken  in 
the  course  of  the  animal's  approach.  Our  attention  was  directed  particu- 
larly to  the  appearance  of  certain  regular  slow- wave  trains  at  5-6  cycles/sec. 
in  the  course  of  the  approach  behaviour.  All  records  were  obtained  with 
implanted  bipolar  electrodes  200  pi  in  diameter  and  spaced  1.5  mm.  be- 
tween recording  tips.  Particular  attention  has  been  given  to  the  use  of 
appropriate  time-constants  in  the  recording  amplifiers,  to  record  the  slow- 
wave  activity  undistorted,  and  to  the  elimination  of  artifacts  from  the 
records  in  freely  moving  animals  (Adey,  Dunlop  and  Hendrix,  1959). 

Li  the  naive  animal,  during  its  first  exposure  to  the  training  situation, 
we  found  a  wide  distribution  of  slow  activity  extending  far  into  the  ventral 
hippocampus,  and  exhibiting  a  wide  spectrum  from  4-7  cycles/sec.  The 
animal  continued  to  show  this  activity  until  one  started  the  training 
procedure,  and  the  slow  activity  then  rapidly  disappeared  from  the 
ventral  hippocampus  in  the  first  few  trials  (Fig.  2). 

After  the  initial  presentations,  regular  rhythmic  slow-wave  trains,  at 
5-6  cycles/sec,  appeared  with  each  approach  performance.  This  activity 
was  limited  to  the  dorsal  hippocampus,  particularly  in  CA4,  and  in  the 
entorhinal  area.  Bursts  of  this  5-6  cycles/sec.  activity  may  appear  in  the 
entorhinal  record  on  as  many  as  three  occasions  in  the  approach  per- 
formance: once,  as  the  animal  approaches  first  the  wrong  side  oi  the  box; 
again,  as  it  turns  back,  and  a  third  time  as  it  finally  turns  to  the  right  side 
of  the  box.  In  the  pre-approach  phase,  there  was  often  much  4  cycles/sec. 
activity.  In  Fig.  3,  the  animal  rapidly  proceeded  first  to  the  wrong  side 
of  the  box.  After  a  significant  interval,  during  which  the  animal  stood 
stiU,  moving  its  head  from  side  to  side,  it  proceeded  to  the  right  side  of 
the  box.  There  was  clearly  an  association  of  the  5-6  cycles/sec.  activity 
with  each  of  the  two  phases  of  motor  activity,  with  very  little  evidence  of 
rhythmic  activity  between  these  two  bursts.  By  contrast,  it  did  not  seem 

pp 


580  BRAIN    MECHANISMS    AND    LEARNING 

correlated  with  those  head  movements  of  the  stationary  animal  which 
constitute  many  aspects  of  an  orienting  reflex. 

Certain  aspects  of  the  hippocampal  slow-wave  activity  have  been 
correlated  with  the  orienting  reflex  of  Pavlovian  physiology  by  Grastyan 
('/  al.  (1959).  It  is  not  proposed  to  enter  here  into  a  discussion  of  definitive 
aspects  of  this  reflex,  although  it  may  be  observed  that  Konorski  (1948) 
has  defined  it  as  the  turning  of  the  head  and  eyes  towards  a  sudden  stimu- 
lus, and  that  such  a  definition  has  no  connotation  of  locomotion  towards 
a  goal.  Our  fmdhigs  in  some  twenty-one  animals  have  consistently 
indicated  a  correlation  of  bursts  at  5-6  cycles/sec.  in  the  dorsal  hippocampus 


NAIVE       ANIMAL  -    FIRST  TRIAL 

RUN  2  -  VENTRAL        HIPPOCAMPAL      SYNCHRONtZATlON  WITH     ENTORHINAL   RECORD 

gg^^l'-'aK'  ADV«.CES|  ^°l1i„JH  ■  .  ="u'if=l 


VENTRAL     HIPPOCAMPAL     SYNCHRONIZATION     DECREASED     BUT    SUSTAINED     IN    ENTORH! 
DOORS    LIGHT  ADVANCES       LOOKS  AT  LIGHT  STEPS  UP 


OreN  )      ON  ,  ,  .  ,    . 

, 1    I  SEC 

Fig.  2 
Records  from  the  left  (LVH)  and  right  ventral  hippocampus  (RVH)  and  cntorhinal  area 
(ENT),  showing  the  rapid  disappearance  of  much  of  the  synchronized  slow-wave  activity  from 
the  ventral  hippocampus  between  the  second  and  twentieth  runs  of  the  first  trial.  At  the  same 
time,  a  sustained  6  cycles/sec.  discharge  is  present  at  the  twentieth  trial  in  the  cntorhinal  record 
in  relation  to  the  approach  performance. 


and  in  the  cntorhinal  area  with  the  motor  performance,  rather  than  with 
simple  aspects  of  orientation.  It  may  be  further  emphasized  that  this 
6  cycles/sec.  activity  was  singularly  unadapting  in  the  course  of  training, 
persisting  unaltered  in  as  many  as  1 200-1 400  trials  in  immature  and  adult 
animals.  Throughout  training  it  remained  maximal  in  the  dorsal  hippo- 
campus and  particularly  in  the  entorhmal  area. 

In  studyuig  the  distribution  of  hippocampal  slow-waves  in  the  young 
animal,  we  have  implanted  a  number  of  young  animals  weighing  about 
1.8  kg.  Their  head  size  approached  that  of  the  adult,  and  it  was  possible 
to  implant  and  record  from  them  for  a  period  of  2  to  3  months  without 
significant  electrode  displacement  from  gro\\th  changes.  Initially,  their 


W.    R.    ADEY  581 

behaviour  was  kittenish,  and  they  were  sexually  immature.  At  this  time 
they  showed  a  great  deal  of  4  cycles/sec.  activity  in  'resting'  records. 
During  the  approach  performance  they  showed  typical  5-6  cycles/sec. 
activity  in  the  ventral  hippocampus  and  in  the  entorhinal  area,  but  there 
was  much  less  of  it  in  the  dorsal  hippocampus  than  in  the  adult  animal.  It 
appeared  characteristic  of  the  immature  animal  that  there  was  a  much 
wider  distribution  of  the  'specific'  5-6  cycles/sec.  activity  in  the  approach 
performance  and  that  it  included  the  ventral  hippocampus.  In  contrast  to 
adult  animals,  these  bursts  appeared  dissociated  in  moment  of  onset  in 
different  hippocampal  leads,  and  in  duration  m  different  leads. 

TONE   OFF  GOES   TO  GOES   TO 

a    DOORS  OPEN  WRONG  SIDE  '      ,    s„ '  RIGHT  SIDE 

I  I  1 

SEPT.  .,----.v^'-A/-'"*«*^^Jvv-~'''''~'^ 

a)(|)(3)®(S)(S)(&(i)     <§>    ®     ®   '^     ©15 
'   '   I    1 


Jili^ 


Fig.  3 
.Simultaneous  EEG  and  tinic-lapsc  photographs  of  animal's  approach  in  T-box.  The  dividing 
partition  appears  at  the  top  of  each  frame.  During  the  approach  to  the  incorrect  side  (frames 
2-5)  there  is  a  burst  of  6  cycles/sec.  activity  in  the  entorhinal  lead  (ENT).  This  disappears  as  the 
animal  stands,  turning  head  from  side  to  side  (frames  6-10)  and  reappears  as  the  animal 
changes  position  to  the  correct  side  of  the  box  (frames  11  and  12).  The  amygdaloid  record 
(AMYG)  shows  40/scc.  activity  typical  of  the  hungry  animal,  which  disappears  momentarily 
on  attainment  of  the  food  reward. 


In  such  immature  animals,  trained  to  a  high  level  of  performance  over  a 
period  of  60-90  days,  it  was  observed  that  much  of  the  random  hippo- 
campal slow  activity  disappeared,  and  that  the  behaviour  became  much 
like  an  adult  cat.  Very  strikingly,  6  cycles/sec.  activity  now  appeared  in 
the  dorsal  hippocampus  during  the  approach  performance,  as  seen  typi- 
cally in  the  adult  animal. 

With  Dr  Holmes,  we  have  also  trained  adult  cats  in  a  delayed  response 
situation,  in  which  a  7  second  delay  preceded  approach  to  a  concealed 
food  reward.  During  the  waiting  period  there  was  much  4  cycles/sec. 


582  BRAIN    MECHANISMS    AND    LEARNING 

entorhinal  activity,  and  during  the  actual  approach  typical  bursts  of  6 
cyclcs/scc.  activity  appeared.  On  extinguishing  the  response,  by  removal  of 
the  reinforcing  food  reward,  all  aspects  of  6  cycles/sec.  activity  disappeared 
during  the  period  when  approach  was  permitted.  Some  4  cycles/sec. 
activity  occurred  during  the  delay  period.  On  retraining,  the  rapid  return 
of  the  extinguished  response  was  accompanied  by  the  reappearance  of 
typical  6  cycles/sec.  activity  in  the  entorhinal  area. 

Now  it  is  obvious  that  the  subjective  and  essentially  empirical  inter- 
pretation of  EEG  records  is  open  to  criticism,  and  is  often  quite  uncon- 
vincing. We  have,  therefore,  endeavoured  to  overcome  some  of  these 
subjective  aspects  of  our  interpretation  by  transferring  these  training 
records  to  IBM  pimchcards.  Although  a  tedious  procedure,  this  per- 
mitted the  computing  of  various  aspects  of  the  4  and  6  cycles/sec.  wave 
trains.  We  have  been  fortunate  in  enjoying  the  use  of  the  1BM-709 
electronic  computer,  installed  at  the  Western  Data  Processing  Center,  at 
the  University  of  California  at  Los  Angeles.  The  records  have  been 
subjected  to  both  auto-  and  cross-correlation  studies.  Each  hippocampal 
lead  can  be  auto-correlated;  that  is,  compared  with  itself,  in  order  to 
determine  aspects  of  inherent  rhythmicity  in  the  slow-wave  bursts,  and  to 
detect  hidden  rhythms.  In  cross-correlation,  or  comparison  of  one  lead 
with  another,  it  is  possible  to  determine  the  phase  relations  between  the 
slow  waves  of  one  hippocampal  lead  and  another. 

It  will  be  seen  from  Fig.  4  that  the  auto-correlation  reveals  a  high  degree 
of  rhythmicity,  essentially  sinusoidal,  in  the  records  from  both  dorsal 
hippocampus  and  the  entorhinal  area,  at  approximately  6  cycles/sec. 

Cross-correlations  of  these  records  have  revealed  striking  and  consistent 
differences  in  the  phase  relationships  noted  in  early  training  when  com- 
pared with  those  from  the  same  animal  in  late  training.  In  early  training, 
the  entorhinal  lead  lags  behind,  by  some  20-30  msec,  the  6  cycles/sec. 
activity  in  both  CA.,  and  CA4  zones  of  the  dorsal  hippocampus.  This  is 
precisely  what  would  be  predicted  from  acute  experiments  involving 
direct  septal  stimulation.  By  contrast,  cross-correlations  in  late  training 
show  clearly  that  the  initial  phase  arrangements  arc  now  reversed.  Now, 
the  entorhinal  area  consistently  leads  the  discharge  in  the  dorsal  hippo- 
campus by  as  much  as  65  msec. 

We  may,  perhaps  without  undue  licence,  extrapolate  these  findings  to 
the  morphological  systems  discussed  in  Fig.  i.  In  the  untrained  animal,  the 
phase  distribution  in  the  6  cycles/sec.  bursts,  associated  with  the  approach 
performance,  is  consistent  with  the  system  of  pathways  proposed  by 
Elliot  Smith  (19T0)  and  Herrick  (1933),  and  as  confirmed  in  our  acute 


W.    R.    ADEY 


583 


AUTOCORRELATIONS 

SAMPLING    RATE       20/SEC. 

CAT    7    -    TRIAL  4    -     ENTQRHINJAL     RECORD 


1-5  SECS 


0-5 


-0-5- 


0-5- 


-  0-5h 


SAMPLING    RATE      40/SEC. 

CAT    7    -     TRIAL    4     -     ENTORHINAL      RECORD 


1-5   SECS 


SAMPLING    RATE         40/SEC. 
GAT   7  -  TRIAL    4    -    DORSAL    HIPPOCAMPAL    RECORD 


Fig.  4 


Auto-correlation  functions  prepared  with  an  IBM-709  electronic  computer,  indicating 
inherently  sinusoidal  nature  of  6  cycles/sec.  bursts  of  hippocampal  and  entorhinal  activity 
during  approach  performance. 


584 


BRAIN    MECHANISMS    AND    LEARNING 


electrophysiological  experiments  (Adcy,  Sunderland  and  Dunlop,  1957; 
Adcy,  Dunlop  and  Sunderland,  1958).  In  the  trained  animal,  the  phase 
ciistribution  is  totally  reversed,  taking  on  an  aspect  consistent  with  path- 
ways suggested  by  Cajal,  running  from  the  entorhinal  area  to  the  dorsal 
hippocampus. 

The  probable  significance  ol  these  fnidings  is  turther  exemplified  by  the 
observations  that  in  animals  in  late  training,  awaiting  the  opportunity  to 
make  an  approach  periormance,  auto-corrclations  showed  considerable 

CROSS-CORRELATIONS  — IN   EARLY  TRAINING 
CAT  7  — TRIAL  4— RUN    14 


40  SAMPLINGS/ SEC.      BANDPASS     I-50C.P.S 

A. 


DORSAL    HIPR     LEADS    q-S-  ENTORHINAL    AREA  LEADS 

(REGION  CA4>  _»i„_35MSEC 


"t 


B. 


TRIAL   4   -  RUN   18 


.  DORSAL    HIPP  LEADS 
(REGION  GA2) 


0-5                ENTORHINAL    AREA   LEADS 
-    20  MSEC  *• 


aA..A/V>A., 


05 
SEC 


-0-5- 

FiG.  5 
Cross-correlation  functions  in  early  training,  prepared  with  an  iBM-709  electronic  computer. 
Here,  records  from  hippocampal  zones  CA.,  and  CA,  consistently  lead  those  from  the  entor- 
hinal area  by  20-35  nisec,  thus  resembling  the  effects  of  septal  stimulation  in  acute  experiments 
(see  text). 


irregularity  in  frequency  ot  the  hippocampal  slow  waves,  with  some 
strong  periodic  activity  at  3-4  cycles/sec.  In  cross-correlations,  phase 
angles  of  this  slower  'resting'  activity  showed  considerable  variation,  but 
were  most  consistently  those  in  which  the  dorsal  hippocampus  led  the 
entorhinal  area.  Examination  ot  this  'resting'  3-4  cycles/sec.  activity  in 
the  trained  animal  thus  showed  a  strong  resemblance  to  the  phase 
relations  of  the  faster  5-6  cycles/sec.  bursts  in  the  approach  performance 
of  the  untrained  animal.  It  is  of  some  interest  that  these  phase  angles  can 
be  apparently  sharply  reversed  in  relation  to  the  performance  of  a  trained 


W.    R.    ADEY  585 

task,  and  just  as  quickly  resume  their  'resting'  character.  It  is  a  matter  for 
regret  that  the  tedium  of  preparation  of  card-punched  data  has  greatly 
limited  the  examination  of  many  closely  related  aspects  of  these  problems. 

DISCUSSION 

Returning  briefly  to  the  general  problem  of  the  functions  of  the  hippo- 
campal  formation,  it  may  be  noted  that  the  hippocampal  cortex  occupies 
a  dorsomedial  position  in  the  hemisphere  of  all  vertebrate  brains,  hi  his 
Arris  and  Gale  lectures  to  the  Royal  College  of  Surgeons  in  London  50 
years  ago,  Elliot  Smith  indicated  that  the  discharge  from  this  hippocampal 
cortex  to  subcortical  structures  through  the  fornix  was  one  of  the  first 
great  efferent  pathways  to  appear  in  the  evolution  of  the  forebrain.  Thus, 
it  would  not  be  surprising  if  the  hippocampus  did,  in  fact,  have  functions 
in  planned  motor  performance,  rather  than,  perhaps,  in  memory  or 
emotional  activity.  We  are  further  encouraged  in  this  point  of  view  by  the 
recent  observation  by  Hess  (1959)  that  damage  to  this  cortex  in  birds  leads 
to  the  permanent  loss  of  imprinting  behaviour. 

Now  it  may  be  asked  what  significance  might  attach  to  such  phase 
shifts  in  intrahippocampal  rhythms  in  the  course  of  the  learning  process. 
Any  answer  must  be  entirely  speculative,  but  perhaps  not  unfruitful, 
particularly  if  we  accept  the  need  to  seek  basically  different  ways  of 
examining  neural  processes  in  the  course  of  learning.  It  may  be  suggested 
that  the  informational  coding  of  some  neural  signals  may  be  on  the  basis 
of  certain  phase-comparator  mechanisms,  which  would  allow  an  exceed- 
ingly subtle  and  finely  graded  scries  of  changes  to  be  each  differen- 
tially integrated  in  determining  the  output  of  either  an  individual  neurone 
or  of  the  more  complex  output  of  a  highly  organized  neural  tissue,  such 
as  the  hippocampus,  or  cortical  structures  generally.  Aspects  of  informa- 
tional coding  on  the  basis  of  such  phase-comparison  techniques  are  well 
known  to  communication  engineers  as,  for  example,  in  the  transmission 
of  chrominance  values  in  colour  television  signals,  and  in  phase  modulation 
of  telemetry  signals. 

Can  any  evidence  be  adduced  to  support  the  existence  of  a  phase- 
comparator  mechanism  in  the  hippocampal  systems  studied  here?  No 
definite  answer  is  possible,  but  if  we  turn  for  a  moment  to  the  anatomical 
organization  of  the  densely  packed  hippocampal  pyramidal  cells,  it  is 
apparent  that  they  receive  afferent  fluxes  from  two  main  sources,  one 
from  the  entorhinal  cortex  via  the  temporo-ammonic  tracts,  and  the 
other  from  septal  areas  (and,  thus,  indirectly  from  the  reticular  thalamic 
areas)  via  the  axons  of  the  dentate  granule  cells.  Both  these  aflcrcnt  paths 


586 


BRAIN    MECHANISMS    AND    LEARNING 


conic  into  intimate  contact  with  the  laniinarly  organized,  closely  grouped 
apical  dendritic  trees  of  the  hippocampal  pyramidal  cells.  The  patterns  oi 
phase  relations  and  the  changes  observed  in  these  patterns  in  training, 
particularly  between  the  entorhinal  area  and  hippocampal  areas  CA.,  and 


CROSS-CORRELATIONS  — IN   LATE  TRAINING 
CAT  7  — TRIAL  20  — RUN    I 


40  SAMPLINGS/SEC. 

„ DORSAL   HIPR 

(REGION    CA4) 


BANDPASS      I 

^  Jrso 


5  C.RS. 
DORSAL    HIPR 
(REGION   CA2) 


LEADS 


♦  'b 


20  MSEC 

ENTORHINAL   AREA   LEADS 


ENTORHINAL 

AREA 

-0-5 

DORSAL    HIPP^      LEADS 
fRFGinW  CA4)                ^ 

*               LEADS 

V\A  / 

^^0  5    V 

SEC  ^ 

-0-5- 

\l 

^           ^^    SEC 

Fig.  6 
Cross-correlation  functions  in  late  training,  from  the  same  animal  as  in  Figs.  4  and  5.  By 
contrast  with  Fig.  5,  the  entorhinal  area  now  leads  hippocampal  region  CA4  by  as  much  as 
65  msec,  and  CA,  by  20-25  msec.  These  findings  are  consistent  with  activity  following  the 
pathways  proposed  by  Cajal  (see  text). 


CA4,  may  be  interpreted  on  the  basis  of  such  a  mechanism.  McLardy 
(1959)  has  recently  proposed  an  elaborate  series  of  intrahippocampal 
connections  which  might  also  subserve  such  functions. 

If,  then,  the  concept  of  phase-comparator  mechanisms  should  be  found 


\V.    R.    ADEY  587 

to  lie  at  the  basis  of  the  neural  process  ot  learning,  rather  than,  perhaps, 
cybernetic  notions  of  reverberant  circuits,  or  even  more  convenient  neural 
models  in  which  every  brain  neurone  is  connected  to  every  other,  we  might 
speculate  about  the  parts  ot  the  neurone  in  which  training  might  produce 
altered  conduction  and  excitability  characteristics,  responsible  in  turn  tor 
altered  patterns  of  phase  relations.  It  is  probably  siguiticant  that  the 
regular  rhythmic  hippocampal  slow  waves  seen  here  in  association  with 
the  motor  pcrtormance  arc  maximally  distributed  in  zone  CA4,  a  region 
particularly  rich  in  both  dendritic  arborizations  and  tnie  presynaptic 
terminals. 

There  is  much  evidence  that  the  rhythmic  hippocampal  slow  waves 
arise  in  this  dendritic  layer,  and  that  this  activity  is  not  associated  with  a 
massive  tu'ing  of  the  cells  themselves  (Green  and  Machiie,  1955).  Such 
waves  have  been  attributed  to  ephaptic  activity  between  adjacent  dendritic 
trees  in  the  production  of  the  cortical  alpha  rhythm  (Li,  McLennan  and 
Jasper,  1952).  These  findings  may  indicate  the  importance  of  neural 
integration  ot  considerable  complexity  occurring  in  dendritic  and 
presynaptic  mechanisms. 

It  is  not  improbable  that  neural  integration  ot  this  type  may  occur  in  the 
vertebrate  central  nervous  system  only  in  the  brain  and  not  in  the  spinal 
cord,  and  that  it  may  be  dependent  on  functional  and  structural  arrange- 
ments of  dendritic  and  associated  presynaptic  structures  not  seen  outside 
the  brain  itselt.  It  should  be  a  continuing  and  salutary  reminder  to  those 
disposed  to  extrapolate  directly  from  spinal  to  cerebral  mechanisms  ni 
processes  of  learning  that,  at  the  physiological  level,  singular  differences 
exist  between  spinal  and  cerebral  synaptic  functions  on  even  such  a  simple 
basis  as  the  activity  of  strychnine.  This  evidence  has  been  reviewed  else- 
where (Adey,  1959). 

At  the  behavie^ural  level,  it  is  a  matter  ot  concern  that  the  brain  ot  many 
invertebrates,  including  arachnids  and  earthworms,  with  a  complexity  far 
less  than  that  of  the  human  spinal  cord  (Adey,  195 1),  can  be  readily 
conditioned,  whereas  conditioning  of  the  human  spinal  cord  has  remained 
at  best  a  most  difficult  procedure.  We  might  inquire  as  to  whether  it  is 
reasonable  to  interpret  all  aspects  of  neuronal  excitability  solely  in  terms 
ot  the  membrane  potential  and  trans-synaptic  events  impinging  on  it.  It  is 
difficult  to  avoid  the  conclusion  that  such  a  point  ot  view  would  reduce 
the  role  of  intracellular  structures  to  that  of  air  in  a  balloon.  An  embracing 
view  of  the  neurone  in  the  learning  process  must  surely  take  account,  not 
only  of  the  cell  membrane,  but  also  of  intra-  and  extracellular  relations, 
particularly  as  the  so-called  'extracellular'  space  has  been  shown  in  both 


588  BRAIN    MECHANISMS    AND    LEARNING 

spinal  cord  (WyckofFand  Young,  1956)  and  brain  (Green  and  Maxwell, 
1959;  Luse,  1959)  to  be  completely  occupied  by  glial  tissue  through  which 
all  ionic  and  respiratory  exchanges  must  occur.  It  is  in  the  investigation  of 
such  factors  as  these  that  the  structural  or  functional  changes  induced  in 
'memory  traces'  may,  perhaps,  be  found  to  lie.  At  least,  such  factors  may 
play  a  significant  role  in  the  genesis  of  the  rhythmic  hippocampal  slow- 
wave  trains  so  closely  related  to  the  learning  process. 

ACKNOWLEDGMENTS 

The  studies  described  here  were  assisted  by  Grants  B-1883,  B-610  and 
B-611  from  the  U.S.  Public  Health  Service. 


ROLE  OF  THE  CEREBRAL  CORTEX  IN  THE  LEARNING 
OF  AN  INSTRUMENTAL  CONDITIONAL  RESPONSE 

T.  Pinto  Hamuy 

Because  of  its  complex  structure  and  the  degree  of  development  it 
reaches  in  the  more  highly  evolved  species,  the  cerebral  cortex  has  been 
thought  in  the  past  to  be  the  seat  of  all  learning.  At  present,  however, 
there  is  a  tendency  to  accept  that  cortical  function  is  not  necessarily 
connected  w^ith  all  levels  of  learning  and  that  as  far  as  learning  processes 
arc  concerned,  cortical  and  subcortical  functions  are  interdependent. 

Pavlov  (1942)  held  that  for  the  learning  of  a  conditioned  response  (CR) 
the  cerebral  cortex  is  essential.  He  assumed  that  the  neuronal  association 
between  conditioned  and  unconditioned  stimuli  developed  intracortically. 

Pavlov's  assumptions  have  been  challenged  by  others.  Thus,  in  de- 
corticated dogs,  Zeliony  and  Kadykov  (1938)  observed  conditioned 
responses  to  visual  and  auditory  stimulation.  Girden  and  his  associates 
(1936)  in  the  same  preparation  obtained  conditioning  with  thermal, 
tactile  and  auditory  stimuli. 

The  results  achieved  by  ablation  of  specific  sensory  areas  corresponding 
to  the  sensory  modality  of  the  conditioned  stimulus  are  still  more  con- 
clusive. Wing  (1947)  found  it  possible  in  dogs  deprived  of  visual  cortex  to 
obtain  a  CR  to  a  luminous  stimulus.  Marquis  and  Hilgard  (1937)  obtained 
in  monkeys  with  a  similar  ablation  a  conditioned  palpebral  occlusion  to  light. 

The  evidence  quoted  above  suggests  that  the  integrity  of  the  cerebral 
cortex  is  not  essential  for  the  acquisition  of  certain  simple  types  of  CR. 
We  assumed  that  the  more  flexible  the  behaviour,  the  more  important 
becomes  the  integrity  oi  the  cerebral  cortex  for  its  performance.  To  test 
this  assumption,  we  decided  to  study  in  decorticated  rats  an  instrumental 
CR  (ICR)  which,  involving  an  alternative,  is  an  experimental  situation  oi 
a  higher  degree  of  complexity  than  that  employed  by  Pavlov.  We  defined 
the  degree  of  complexity  by  the  number  of  alternatives  of  reaction  open  to 
the  animal. 

In  our  experiments,  the  animals  received  an  electric  shock  as  uncondi- 
tioned stimulus  (US).  The  animal  could  avoid  it  by  escaping  to  another 
compartment  of  the  chamber  (Fig.  i).  In  the  classical  Pavlovian  experi- 
mental set-up  for  the  establishment  of  a  CR,  this  stimulus  avoidance 
alternative  is  not  provided. 

589 


590 


BRAIN    MECHANISMS    AND    LEARNING 


A  learning  situation  of  still  higher  complexity  may  be  obtained  through 
two  successive  stages  of  conditioning,  as  follows: 

I.  First  stage  (electric  shock  —  light):  the  shock  was  associated  with  a 
luminous  stimulus  —  CS  —  intended  to  condition  the  animal  to  escape  in 
order  to  avoid  the  shock. 


Fig.  I 
Test  situation. 


2.  Second  stage  (light  —  sound) :  once  the  avoidance  CR  to  light  was 
established,  the  conditioning  to  sound,  by  associating  it  with  the  light, 
would  be  attempted. 

Decorticated  rats  did  not  learn  to  react  to  the  light  signal,  i.e.  they 
failed  to  acquire  an  instrumental  avoidance  conditional  response  (lACR) 
to  this  stimulus  (Pinto-Hamuy,  Santibanez,  Rojas  and  Hoffmann,  1957) 
(Fig.  2).  The  extent  of  the  decortication  in  these  animals  averaged  62  per 
cent  of  the  total  cortex  (Fig.  3). 

The  failure  of  these  rats  to  acquire  this  CR  was  contrary  to  the  results 
obtained  by  other  authors,  as  mentioned  (Girden,  Mettler,  Finch  and 
Culler,  T936;  Zeliony  and  Kadykov,  1938).  We  decided  to  investigate  the 


T.   PINTO    HAMUY 


591 


factors  determining  the  incapacity  observed  in  our  rats.  This  might  depend 
on:  {a)  the  location  and  size  of  the  lesion;  (/))  the  experimental  situation; 
(f)  the  animals'  lack  of  pre-operative  experience.  The  fnst  two  of  these 
factors  {a)  and  {b)  are  closely  related,  since  the  complexity  of  the  problem 
can  determine  the  critical  level  of  intact  cortex  that  the  learning  of  a  given 
habit  requires. 


00- 

A  pre-op.  learning 

▲  post-op.  leorning 

NkA           fN--"5 

80- 

/v 

60- 

40- 

20- 

0  - 

TT    I — 1 — 1 — 1 — 1 — 1 — 1 — 1 — 1 — 1 — 1 — 1 — 1 — r 

—1 — 1 — 1    1     1 — 1 — 1 — 1 — r-" 

10 


15 


TEN    TRIAL    UNITS 


Fig.  2 


Learning  curves  of  a  visual  conditioned  response  (VCR)  correspond- 
ing to  a  group  of  normal  rats  (pre-operative  learning)  and  neo- 
decorticated  rats  (post-operative  learning). 


{a)  We  tried  to  answer  the  first  point  by  training  two  groups  of  animals 
on  the  lACR  to  light  (Pinto-Hamuy,  Rojas  and  Araneda,  1959).  One 
group  had  an  ablation  in  the  rostral  half  of  the  cerebral  cortex  ('anterior 
group')  (Fig.  4);  another  had  an  ablation  of  the  caudal  half  ('posterior 
group')  (Fig.  5). 

Each  group  consisted  of  thirteen  animals;  they  were  operated  on  and 
subsequently  trained.  If  the  integrity  of  the  visual  cortex  were  essential  for 
this  learning,  we  should  expect  the  performance  of  the  'posterior  group' 
to  be  inferior.  If,  however,  quantity  was  the  determining  factor,  both 
groups  should  have  a  similar  level  of  performance.  The  curves  of  the 
average  performance  per  session  for  each  group  are  represented  in  Fig.  6. 
Here  we  can  compare  the  performance  of  both  groups  with  partial  lesions 
with  the  results  obtained  in  fourteen  normal  rats  as  well  as  in  a  group 
of  fourteen  decorticated  animals  (the  term  decorticated  is  used  to  mean  the 
group  with  more  extensive  lesions  (i.e.  62  per  cent)).  It  may  be  noted  that 
both  the  'posterior  group'  in  which  the  visual  area  is  involved  and  the 


592 


BRAIN    MECHANISMS    AND    LEARNING 


Fig.  3 
Diagrams  of  dorsal  and  lateral  views  of  the  rat  brain.  Blackened  areas  in- 
dicate complete  cortical  ablation;  striped  areas,  incomplete  cortical  ablation. 
The  boundaries  corresponding  to  the  cortical  projection  of  the  lateral  geni- 
culate body  are  indicated  by  a  dashed  line. 


T.   PINTO   HAMUY 


593 


Fig.  4 

Cortical  lesions  corresponding  to  the  rats  of  the  'anterior  group'  (see  legend 

Fig-  3). 


594 


BRAIN    MECHANISMS    AND    LEARNING 


group  with  an  anterior  lesion  show  a  marked  deficit.  Differences  from 
the  normal  group  arc  significant  both  for  the  'posterior'  and  the  'anterior 
group'  (p  <  G.ooi). 

The  failure  of  the  'anterior  group'  is  worth  noticing,  as  until  now 


Fig.  5 

Cortical  lesions  corresponding  to  the  rats  of  the  'posterior  t^roup'  (sec  legend 

Fig.  3). 


investigators  have  explored  almost  exclusively  the  effect  of  lesions  in  the 
'cortical  area'  of  the  CS  and  only  rarely  the  ci^cct  of  total  decortication  or 
of  extensive  lesions  of  the  non-visual  cortex. 

The  fact  that  four  out  of  fourteen  rats  in  the  'anterior  group'  learned 
the  CR  might  indicate  that  the  average  percentage  (41  per  cent)  of  ablated 


T.  PINTO   HAMUY 


595 


cortex  was  within  the  range  of  the  critical  amount  necessary  to  provoke 
the  faikire  to  learn. 

The  'posterior  group'  with  a  lower  average  of  ablated  cortex  presents, 
however,  a  clearer  deficit  than  the  'anterior  group'.  Both  groups  differ 
significantly  from  one  another  in  their  performance  (p  <  0.05).  These 
results  would  indicate  that  the  locus  of  lesion  can  also  be  regarded  as  a 
relevant  factor.  In  other  words,  the  involvement  of  the  visual  area  would 
determine  a  greater  incapacity  than  similar  lesions  in  other  areas.  It 
should  be  noted,  however,  that  none  of  these  animals  had  the  visual  area 
totally  ablated.  The  amount  of  visual  cortex  removed  in  the  various  rats 


loo- 
se - 

A 

• 
■ 

A 

norma 
ant   les 
DOSt.  le 
decort 

group 
on  group 
sion  group 
coted  group 

ri' 

^    N 

14 

60- 

/ 

1     ^ 

40- 

1 

A/ 

^ 

-•    N 

13 

20- 

J 

\kk'. 

•^1    N 

-13 

n- 

-¥ 

^ 

^>-A.A,^^^,.-*r.*-« 

— 1 — 1— 1 — 1 — r 

-A    N 
-1 — 1 — 

=  14 

0  5  10  15  20  25 

ten   trial   units 

Fig.  6 
Learning  curves  of  a  VCR  corresponding  to  the  following 
groups  of  rats:  normal,  'anterior',  'posterior'  and  decorticated. 


ranged  from  a  minimum  of  60  per  cent  to  a  maximum  of  92  per  cent. 
On  the  other  hand,  the  performance  of  the  group  combining  both  lesions 
was  inferior  to  that  of  the  group  with  the  posterior  lesion.  It  is  probable, 
therefore,  that  the  whole  of  the  cerebral  cortex  —  both  the  specific  as  well 
as  the  rest  of  it  —  plays  a  role  in  this  type  of  learning.  Summing  up,  both 
factors,  namely  the  extent  of  lesion  and  its  locus,  seem  to  have  an  influence 
in  this  respect. 

The  fact  that  some  animals  of  the  'posterior  group'  with  a  removal  of 
only  23  or  31  per  cent  of  the  total  cortex  and  70  and  78  per  cent  respec- 
tively of  the  visual  cortex  were  unable  to  learn  this  lACR  would  suggest 
that  this  failure  is  not  exclusively  due  to  the  locus  or  extent  of  the  lesion 
but  to  some  characteristic  of  the  experimental  situation  that  requires  a 

QQ 


596  BRAIN    MECHANISMS    AND    LEARNING 

greater  integrity  of  the  cortex.  In  other  words,  we  think  that  with  a 
similar  lesion  other  types  of  avoidance  CR  to  a  light  signal  could  have 
been  established.  The  results  already  mentioned  of  Wing  (1947)  and 
Marquis  and  Hilgard  (1937)  would  favour  this  assumption,  since  they 
show  that  it  is  possible  to  condition  a  local  motor  reaction  to  a  light  signal. 
It  is  also  worth  noticing  that  in  these  experiments  the  animal  had  its  own 
body  as  a  reference  for  the  performance  of  movements,  while  in  our 
experiments  the  movement  of  the  rat  involved  spatial  orientation  to  reach 
the  exit  door  from  any  point  of  the  chamber.  Orbach  (1959)  studied  maze 
learning  in  peripherally  blinded  monkeys  that  had  subsequently  an 
ablation  of  the  occipital  cortex;  he  concluded  that  the  visual  cortex 
probably  did  not  have  a  visual  role  only  but  also  a  function  in  spatial 
orientation.  It  may,  therefore,  be  assumed  that  cortical  integrity  may  not 
be  essential  for  the  association  light-US  (shock  in  our  experiments),  but 
that  it  would  affect  the  integration  of  a  general  motor  response  to  a 
light  signal. 

Lashley's  (1935)  experiments  with  rats  eliminate  the  possibility  that  the 
animals  did  not  detect  the  light  signal.  It  has  been  shown  that  although  the 
visual  area  is  essential  for  the  perception  of  detail  vision,  its  ablation  does 
not  alter  the  formation  of  habits  which  require  discrimination  between 
degrees  of  light.  In  short,  the  most  likely  interpretation  of  our  results 
would  be  that  a  facilitating  cortical' action  is  necessary  to  release  a  general 
response  requiring  spacial  orientation  to  a  light  signal. 

For  the  deficits  shown  by  the  anterior  group  there  are  two  possible 
reasons:  (a)  that  a  cortical  lesion  of  about  41  per  cent  may  determine  a 
serious  deterioration  of  the  animal's  capacity  to  acquire  an  lACR  to  a 
light  signal,  independent  of  its  location;  (b)  that  within  the  anterior  region 
there  may  be  one  or  more  specific  areas  the  integrity  of  which  is  essential 
for  this  type  of  learning.  The  relevant  areas  may  be:  somatic  area  I  and  II, 
motor  cortex  and  orbito-frontal  cortex.  Lawicka  (1956),  Lawicka  and 
Konorski  (1959),  Brutkowki  (1959),  found  that  pretrontal  lesions  deter- 
mine changes  in  the  behaviour  of  the  animal  in  a  second  order  conditioned 
reflex.  The  first  of  these  authors  reports  that  conditioned  inhibition  dis- 
appears after  this  ablation.  St^pieii  and  St^^picn  (1959)  found  a  temporal 
loss  of  an  instrumental  CR  after  ablation  of  somatic  areas.  These  studies, 
however,  refer  to  changes  observed  on  post-operative  retention.  The 
integrity  of  the  somatic  and  motor  areas  may  be  important  for  the 
integration  of  tactile  and  proprioceptive  cues  utilized  by  the  animal  to 
find  its  way  to  the  door.  The  motor  cortex  may  be  necessary  to  facilitate 
this  general  motor  response. 


T.   PINTO    HAMUY 


597 


(/))  To  enable  us  to  analyse  the  experimental  situation  ironi  the  point 
of  view  of  the  factors  responsible  for  the  failure  of  our  rats  to  acquire 
an  avoidance  CR,  we  kept  all  other  elements  of  the  experiment  constant, 
changing  only  the  CS  (Saavedra,  Garcia,  Oberti  and  Pinto-Hamuy, 
1959).  For  this  purpose  we  used  a  sound  of  2400  c./sec.  as  CS.  A  group  of 
fifteen  rats  with  an  average  of  ablated  cortex  of  62  per  cent  was  trained. 
The  animals  managed  to  learn  even  though  their  performance  was 
inferior  to  that  of  the  normal  control  group  (Fig.  7).  They  achieved  a  pcr- 
tormance  averaging  65  per  cent  of  the  CR  at  the  thirtieth  session  of 
training. 


10  15 

TEN     TRIAL    UNITS 


Fig.  7 
Learning  curves  of  an  auditory  conditioned  reflex  (ACR)  correspond- 
ing to  groups  of  normal  and  ncodecorticated  rats. 


The  performance  app>ears  high  if  we  compare  the  level  reached  by  this 
group  with  the  results  obtained  when  trying  conditioning  by  means  of  a 
light  signal. 

We  wondered  whether  this  could  be  related  to  an  easier  conditioning 
with  auditory  signals.  To  answer  the  question  we  compared  the  learning 
of  CR  of  normal  rats  using  luminous  and  auditory  stimuli  similar  to  those 
employed  in  the  decorticated  animals  (Saavedra,  Garcia,  Oberti  and 
Pinto-Humay,  1959).  There  is  a  difference  which  appears  in  favour  t^f  the 
auditory  group,  this  difference  being,  however,  substantially  less  marked 
than  in  the  decorticated  animals  (Fig.  8).  These  results  agree  with  those 
obtained  by  Chow  ct  al.  (1957)  in  cats  who  established  an  ACR  in  450 
trials  to  light  but  needed  only  150  using  a  tone.  Morrell  and  Jasper  (1956) 
observed  a  similar  order  of  difficulty  for  the  conditioning  of  an  alpha 


598 


BRAIN    MECHANISMS    AND    LEARNING 


flicker  response.  Girden  ct  al.  (1936)  were  able  to  install  ni  a  decorticated 
dog,  CRs  to  thermal,  auditory  and  tactile  stimuli,  but  were  unable  to  do 
so  with  light. 

It  is  possible  that  the  easier  establishment  of  CRs  to  auditory  stimuli  in 
comparison  with  light  signals  is  related  to  the  fact  reported  by  Bernhaut 
er  ^/.  (1953)  that  auditory  stimuh  are  in  general  more  effective  activators  of 
the  reticular  formation  and  thus  of  the  cortical  projection  areas.  On  the 
other  hand,  the  assumed  facihtatory  activity  of  the  cortex  would  be  more 
essential  for  the  establishment  of  a  visual  memory  trace  on  sub-cortical 
structures. 


NORMAL    RATS 


uj  100 


to    80 


o    40 


N  =  I5 


A  visuol    codifioned    reflex 
o   auditory    conditioned    reflex 


-T — I — I — I — r— 

5  10  15  20 

TEN    TRIAL    UNITS 


25 


Fig.  8 
Learning  curves  of  one   ACR   and    a    VCR  in  two   groups  of 
normal  rats. 


The  Study  of  other  possible  variables  depending  on  the  experimental 
situation  are  under  way. 

(f)  Another  point  investigated  was  the  influence  of  preoperative  training 
on  the  capacity  of  decorticated  rats  to  acquire  a  VCR. 

Seven  animals  were  trained  in  this  avoidance  CR  before  decortication. 
Decortication  determined  a  loss  of  the  habit,  which  could  be,  however, 
relearned  up  to  a  certain  level  (Fig.  9).  They  scored  a  level  of  70  per  cent  of 
CR  at  the  twenty-fourth  session,  which  normal  rats  had  already  reached 
at  the  tenth. 

We  were  also  interested  in  finding  out  the  degree  of  specifity  that  this 
previous  experience  required:  that  is,  if  the  training  in  the  pre-operative 
period  should  be  conducted  with  the  same  CS  used  post-operatively.  With 
this  idea  in  mind,  we  trained  eight  animals  to  respond  to  an  auditory 


T.   PINTO    HAMUY 


599 


signal  (unpublished  observations).  Once  the  learning  was  achieved,  they 
were  decorticated  and  subsequently  trained  in  a  CR  to  a  light  signal 


10  15  20 

TEN    TRIAL    UNITS 

Fig.  9 


25 


Pre-  and  post-operative  learning  of  a  VCR  in  a  group  of  seven  rats. 

(Fig.  lo).  In  this  case,  the  experience  oi  the  general  experimental  situation 
was  enough  to  obtain  a  level  markedly  superior  tc^  that  obtained  by  the 
decorticated  rats  without  any  previous  training. 


100- 

•  VCR,  post   op. 
A  VCR,  post  op 

learning    (ACR, 
learning 

pre  op. 

leorninq) 

80- 

60- 

.   ^ 

N-.8 

40- 

/ 

/           ^^ 

w^ 

20- 

y^^ 

0- 

l^-^y^^ 

I    1    I    I 

L  N  •  1 4 
— 1 — |— ' 

10  15 

TEN     TRIAL    UNITS 


20 


Fig.  id 
Learning  curves  of  a  VCR  in  two  groups  of  neodecorticated 
rats.  One  with  preoperative  training  in  an  ACR;  the  other  with 
no  preoperative  training. 

We  believe  that  our  results  and  those  of  other  authors  show  that  it  is 
difficult  to  generalize  about  the  function  of  different  structures  of  the 
central  nervous  system  in  a  specific  type  of  learning. 


600  BRAIN    MECHANISMS    AND    LEARNING 

In  Other  words,  and  in  order  to  draw  conclusions  concerning  the  role 
of  the  cerebral  cortex  in  the  learning  of  conditioned  responses,  the  follow- 
ing factors  must  be  taken  into  consideration: 

I.  The  kind  of  CR  that  is  employed,  whether  a  classical  Pavlovian  or 
instrumental  response. 

3.  The  nature  of  the  conditioned  stimulus. 

3.  The  type  of  motor  response  involved  in  the  experimental  situation. 

4.  The  previous  experience  of  the  animal. 

5.  The  amount  of  cerebral  cortex  remaining  intact,  and 

6.  The  locus  of  the  lesion. 

In  spite  of  these  limitations,  some  of  our  results  may  be  considered 
conclusive  in  the  sense  that:  ((7)  the  specific  cortex  of  the  CS  is  essential  for 
the  acquisition  of  this  visual  habit  (posterior  group);  (h)  a  lesion  of  about 
41  per  cent  (anterior  group)  placed  outside  the  specific  cortex,  may  also 
determine  a  serious  deficit.  Nevertheless  the  'CS  specific  cortex'  would  be 
more  important  in  the  sense  that,  of  two  lesions  of  the  same  size,  the  one 
placed  in  the  visual  cortex  should  cause  the  greater  deficit. 

Neurologically,  the  learning  of  an  lACR  which  implies  a  general 
motor  response,  may  be  regarded  as  sharing  characteristics  with  both 
sensory  discrimination  learning  and  serial  learning.  In  our  experimental 
situation,  as  it  also  occurs  in  discrihiination  learning,  the  specific  cortex  is 
more  important  than  the  rest  of  the  cortex;  on  the  other  hand,  as  in  maze 
learning,  the  participation  of  other  cortical  areas  is  necessary. 

Another  important  possibility  is  that  the  integrity  of  the  cerebral  cortex 
is  perhaps  essential  only  for  the  acquisition  of  a  certain  habit  and  not  when 
preoperative  training  has  taken  place.  We  think  that  the  importance  of  the 
cortex  in  the  learning  of  conditioned  reflexes  has  been  minimized  because 
research  has  been  mainly  concerned,  not  with  acquisition  of  a  habit,  but 
with  postoperative  retention  and  relearning.  Another  source  of  mis- 
interpretations is  the  tendency  to  overlook  the  fact  that  conditioned 
responses  obtained  m  decorticated  dogs  are  deeply  modified  (Girden  et  al, 
1936).  It  seems  that,  in  general,  deficits  are  considered  as  such  only  when 
they  appear  in  their  maximal  expression. 

GROUP   DISCUSSION 

Chow.  I  wanted  to  ask  Dr  Pinto  how  she  interprets  her  results  in  the  light  of 
Lashley's  old  study,  and  his  conclusions  on  the  equipotentiality  ot  the  neocortex  in 
the  rat. 

Pinto-Hamuy.  We  have  come  to  an  intermediate  opinion  regarding  the  impor- 
tance of  the  cortex  in  this  kind  of  learning;  we  consider  its  function  to  some  extent 


T.  PINTO    HAMUY  60I 

as  a  whole,  but  the  specific  cortex  would  also  matter.  One  could  suggest  that  lesions 
placed  outside  the  specific  cortex  have  to  be  of  a  certain  extent  in  order  to  deter- 
mine an  impairment  similar  to  a  smaller  lesion  placed  in  the  specific  cortex. 

RosvOLD.  What  did  the  rats  do  when  they  did  not  movef 

Pinto-Hamuy.  When  the  shock  began  they  ran  to  the  other  compartment.  And 
even  that  sort  of  'unconditioned'  response  needed  a  certain  learning  after  ablation 
of  the  neocortex. 

Hebb.  Do  I  assume  that  the  rats  were  all  reared  in  small  cages?  The  reason  for  my 
asking  is  a  fact  which  has  puzzled  us  very  much ;  if  rats  are  reared  in  a  small  cage, 
lesions  of  the  anterior  part  of  the  brain  will  have  an  equal  effect  with  lesions  in  the 
posterior  part,  in  complex  learning  situations.  If  rats  are  reared  in  a  large  cage  with 
a  number  of  objects,  so  that  they  have  a  naturalistically  normal  experience  during 
growth,  they  show  a  very  different  picture.  The  animals  with  anterior  lesions  now 
show  little  effect.  An  equal  lesion  in  the  posterior  part  of  the  cortex  (it  does  not 
have  to  be  visual  cortex)  will  produce  gross  defects.  Here  is  another  case,  when  we 
are  talking  about  the  mode  of  physiological  organization  of  the  brain,  where  we 
must  take  into  account  (as  a  possible  source  of  variability  between  experiments)  the 
conditions  of  rearing  and  the  past  history  of  the  animal. 

Pinto.  I  do  not  think  our  cages  were  particularly  small;  our  animals  had  space  to 
move  around.  They  measured  45  X  15  X  28.5  centimetres. 

CoviAN.  Have  you  observed  differences  with  just  unilateral  neodecortication? 

Pinto.  We  did  not  study  that  kind  of  preparation  because  we  had  previous 
experience  with  discrimination  learning  following  a  unilateral  lesion;  very  obvious 
changes  were  not  found  in  this  type  of  learning  with  unilateral  lesion. 


SIGNIFICANCE  OF  THE  PHOTIC  STIMULUS 
ON  THE  EVOKED  RESPONSES  IN  MAN 

E.  Garci'a-Austt,  J.  BoGACz  AND  A.  Vanzulli 

INTRODUCTION 

If  the  retina  of  a  normal  man  placed  in  a  dark  and  quiet  room  is  stimu- 
lated with  flashes  ot  constant  intensity  and  frequency,  the  subject  under- 
goes a  series  of  psychological  phenomena.  Of  these  phenomena  the  most 
constant  are  those  pertaining  to  attention.  The  attention  state  follows  a 
defined  time  pattern.  The  first  flashes,  taking  the  subject  by  surprise, 
arouse  his  attention.  Subsequently,  through  monotonous  repetition,  the 
flashes  lose  significance  and  he  becomes  uninterested.  If  under  these  condi- 
tions the  stimulus  is  discontinued  at  regular  intervals  for  a  constant 
period  of  time,  a  new  interest  is  added,  darkness.  The  stimuli  regain 
significance  on  being  preceded  by  a  period  of  darkness  and  once  more  the 
subject  becomes  attentive  to  them,  but  he  again  loses  interest  on  becoming 
habituated  to  the  regular  repetition  of  the  association  of  darkness  and 
flicker.  If  on  this  same  attention  level  a  constant  tone  is  added  at  the  end  of 
the  period  of  darkness,  the  flashes  regain  significance  and  the  same  pheno- 
menon is  repeated. 

Is  there  any  method  of  objectifying  the  neurophysiological  processes 
associated  with  these  modifications  in  attention;  The  study  of  the  evoked 
potentials  contribute  important  elements  t(^  the  elucidation  of  this 
problem.  In  this  connection  Hernandez-Peon  and  Donoso  (1957),  Joiivet 
and  Courjon  (1958)  worked  on  subcortical  recordings  in  man.  Obviously 
this  method  does  not  allow  for  a  systematic  study. 

It  has  been  shown  that  from  scalp  recordings  it  has  been  possible  to 
extract  the  evoked  potentials  by  the  use  of  different  methods,  taking  into 
account  either  the  space  factor  (Grey  Walter,  1954;  Remond  and  Ripoche, 
1958),  or  the  time  factor  (Dawson,  1947;  Calvet,  Cathala,  Hirsch  and 
Scherrer,  1956). 

In  the  present  investigation,  methods  of  temporal  superposition  have 
been  used  to  study  in  man  the  influence  of  the  changes  in  the  significance 
of  the  photic  stimulus  on  the  evoked  response. 

603 


604  BRAIN    MECHANISMS    AND    LEARNING 

VISUAL   EVOKED    RESPONSES 

Dawson  (1947)  was  the  first  author  to  record  through  the  scalp  the 
evoked  responses  to  electrical  stimulation  of  the  peripheral  nerves  in  man. 
He  used  the  superposition  of  fifty  or  more  successive  sweeps  in  a  single 
record,  leading  as  is  customary  the  potentials  on  the  Y  axis  and  the  sweep 
synchronized  with  the  stimulus  on  the  X  axis.  'In  such  a  record  any 
waves  which  follow  the  stimulus  by  a  regular  interval  will  all  occur  at  the 
same  place  on  the  trace;  they  may  thus  be  detected  although  they  are  no 
larger  than  the  deflection  produced  by  the  spontaneous  activity  of  the 
brain  and  scalp  muscles.  As  deflections  due  to  these  causes  are  not  regularly 
related  to  the  stimulus,  they  tend  to  occur  at  a  different  place  on  each 
successive  sweep  and  therefore  appear  oidy  as  a  thickening  of  the  baseline' 
(Dawson,  1947).  Ciganek  (1958  a,  b)  used  this  technique  tor  recording  the 
evoked  potentials  by  photic  stimuli  in  man. 

Calvet,  Cathala,  Hirsch  and  Scherrcr  (1956),  and  Calvet,  Cathala, 
Contamin,  Hirsch  and  Scherrer  (1956)  used  another  technique  of  super- 
position for  recording  in  man  the  evoked  visual,  somato-sensorial  and 
auditory  responses.  They  led  the  cortical  potentials  on  the  Z  axis  thus 
causing  variations  in  the  luminous  intensity  of  the  cathode  ray.  On  the 
X  axis  the  sweep  was  synchronized  with  the  stimulus,  and  on  the  Y  axis 
a  high  frequency  was  fed  to  obtain  a  wide  luminous  strip.  On  a  single 
frame  twenty  to  fifty  successive  sweeps  were  superimposed.  By  this  means 
a  strip  was  obtained  whereon  the  asynchronic  waves  of  the  EEG  were 
superposed,  giving  a  grey  tone,  and  the  evoked  potentials  were  added 
together,  giving  a  clear  contrast  between  light  and  shadow.  The  strip  was 
analysed  after  magnification  by  a  photoelectric  cell,  and  a  linear  record 
thus  obtained. 

In  this  investigation  these  two  techniques  were  employed  to  record  the 
evoked  visual  response  in  forty-three  experiments  carried  out  on  normal 
adults.  Dawson's  technique  (1947)  of  superposition  is  simple,  reliable,  and 
permits  an  adequate  study  of  the  sequence  of  the  potentials.  However,  as 
it  is  purely  a  procedure  of  superposition  without  adding  the  potentials,  its 
amplitude  was  small.  When  working  with  the  stroboscope  at  a  distance 
of  over  3  m.  from  the  retina  the  response  was  not  recorded.  The  technique 
of  superposition  and  addition  of  Calvet  ct  al.  is  more  complicated,  requires 
a  longer  procedure  and  is  less  safe.  A  straight  baseline  cannot  always  be 
obtained  owing  to  differences  in  the  luminous  intensity  of  the  cathode 
rays.  Potentials  are  distorted  by  contrast,  by  the  non-linearity  of  the 
photographic  process  and  by  the  need  to  use  the  photo-electric  cell  wnth 


E.    GARCIA-AUSTT,   J.    BOGACZ    AND    A.    VANZULLI  605 

a  slot  of  a  given  width.  On  the  other  hand  this  method  has  the  advantage 
of  having  a  greater  sensibihty,  for  potentials  are  added,  unlike  the  other 
method  in  which  they  are  superposed  only.  Their  greater  sensibility  made 
it  possible  to  record  evoked  responses  with  the  stroboscope  placed  at  a 
distance  of  over  3  m.  from  the  retina. 

In  all  experiments  the  frequency  of  the  flicker  stimulation  was  of  0.5- 
5/sec.  With  both  techniques,  twenty  to  fifty  sweeps  were  superimposed. 
The  stroboscope  was  situated  at  a  distance  of  3  m.  from  the  eyes,  but  in 
some  experiments  it  was  placed  nearer  to  check  the  eftect  ot  the  distance. 

The  visual  evoked  response  was  recorded  by  these  procedures  in  the 
following  regions:  occipital  (O2  electrode  of  10/20  system),  parietal 
(P4),  central  (C4  and  C6),  frontal  (F4)  and  temporal  (T2  and  T6).  C4,  T2 
and  O2  were  the  positions  most  often  used.  No  response  was  recorded  in 
the  nose  and  frequently  not  in  the  prefrontal  region  (Fp2). 

The  evoked  potential  was  constituted  by  a  succession  of  regular  naono- 
morphous  waves  of  4-5  or  more  hemicycles.  The  usual  sequence  of  polarity 
was  as  follows :  surface-negative,  positive,  negative,  positive  and  negative. 
The  peaks  of  the  three  fu-st  negative  waves  developed  at  80-120,  180-240, 
270-300  msec,  and  the  peaks  of  the  two  first  positive  waves  developed  at 
120-170  and  230-250  msec.  In  most  cases  the  last  waves  were  of  longer 
duration. 

The  latency  of  the  first  negative  wave  was  15-40  msec.  Sometimes  the 
latency  was  higher  —  from  80  to  100  msec,  —  because  the  first  negative 
wave  was  missing.  Its  absence  was  noted  on  various  occasions  when  a 
common  reference  electrode  was  used  on  the  mastoid.  On  the  other  hand 
It  was  never  absent  when  the  nose  was  used  as  a  reference.  The  latency  of 
the  first  negative  wave  was  at  its  minimum  on  O2.  On  C4  and  T2  the 
peak  of  the  first  negative  wave  had  a  delay  of  15-30  msec,  with  respect  to 
O2.  The  duration  of  the  waves  was  longer  on  C4  and  T2  than  on  O2. 

The  amplitude  of  the  response  was  related  to  the  duration  of  the  waves: 
the  longer  the  duration,  the  greater  the  amplitude.  With  Dawson's 
method  the  values  reached  were  between  30-40  microvolts.  The  maximum 
amplitude  of  the  response  was  obtained  on  O2,  the  minimum  on  F4  and 
in  the  mastoid,  when  the  nose  was  the  reference  electrode. 

In  general  a  slight  increase  in  amplitude  was  observed  in  all  regions  with 
eyes  shut,  although  the  superposition  was  better  with  the  eyes  open 
because  the  alpha  rhythm  was  then  eliminated.  All  cases  were  studied  in 
wakefulness.  The  waking  state  was  controlled  by  analysing  the  spon- 
taneous electrical  activity  recorded  by  means  of  an  electroencephalo- 
graph. On  bringing  the  stroboscope  nearer  to  the  retina,  and  thus  increasing 


6o6  BRAIN    MECHANISMS    AND    LEARNING 

the  intensity  of  the  stimukts,  the  amphtude  in  all  the  regions  was  increased. 

The  evoked  response  had  the  same  characteristics  when  it  was  recorded 
in  the  subject  after  an  interval  of  several  days. 

Between  the  evoked  responses  from  the  occipital  region  and  those  from 
other  regions  differences  of  latency,  amplitude,  phase  and  duration  were 
observed.  The  presence  of  a  single  generator  located  in  the  depth  ot  the 
occipital  region  could  explain  the  differences  of  amplitude  and  phase 
owing  to  the  different  distance  and  orientation  of  the  electrodes.  How- 
ever, the  difi^erences  in  latency  and  duration  of  the  response  cannot  be 
satisfactorily  accounted  for  by  the  physical  propagation  of  the  occipital 
response,  because  for  the  frequencies  recorded  the  reactance  of  the  brain 
coverings  is  negligible  (Grey  Walter,  1950).  Furthermore  during  the 
continuous  or  discontinuous  flicker  stimulation,  as  will  be  shown  later  on, 
the  response  of  the  different  regions  may  vary  independently. 

It  is  necessary,  therefore,  to  recognize  that  other  regions  of  the  brain  are 
activated.  The  magnitude  of  the  delay  (15-30  msec.)  existing  between  the 
occipital  potential  and  the  potentials  of  the  other  regions,  leads  to  the  belief 
that  the  latter  must  course  through  pathways  with  more  numerous 
synapses.  The  small  distance  between  the  electrodes  eliminates  the  possi- 
bility that  this  delay  may  be  due  solely  to  axonic  conduction. 

To  sum  up,  the  evoked  visual  response  studied  in  these  experiments  is  a 
rhythmic,  complex  potential,  of  long' latency,  of  diffuse  distribution  over 
the  scalp,  recorded  during  wakefulness  with  the  eyes  open  or  shut. 

Evoked  visual  responses  have  been  the  subject  of  numerous  studies  in 
animals  and  in  man  since  Bartlcy  and  Bishop  (1933)  described  them  for  the 
first  time  in  the  cat,  by  stimulation  of  the  optic  nerve.  Shape  and  topo- 
graphic distribution  vary  considerably  according  to  the  state  of  attentiveness. 

Two  components  of  the  evoked  response  are  distinguished  regardless  of 
whether  the  recording  is  made  in  the  animal  in  the  area  of  primary  pro- 
jection (Gerard,  Marshall  and  Saul,  1936;  Marshall,  Talbot  and  Ades, 
1943;  Chang,  1950)  or  in  man  through  the  scalp  (Ciganek,  1958b):  the 
initial  component  and  the  after-discharge,  hi  both  cases  the  after-discharge 
is  similar.  It  is  not  known  what  relation  may  exist  between  the  initial 
component  recorded  in  the  area  of  specific  projection,  primary  evoked 
potential,  and  the  initial  component  of  the  response  recorded  through  the 
scalp.  Ciganek  (r95Sb)  maintains  that  some  of  the  waves  which  constitute 
the  initial  component  correspond  to  the  primary  evoked  response. 

The  distribution  of  the  evoked  visual  response  is  not  limited  to  the 
striate  area,  but  in  experimental  conditions,  in  the  anaesthetized  animal 
(Gerard,  Marshall  and  Saul,  1936;  Marshall,  Talbot  and  Ades,  1943;  Clare 


E.    GARCIA-AUSTT,   J.    BOGACZ    AND    A.    VANZULLI  607 

and  Bishop,  1954),  in  the  waking  animal  (Buscr  and  Borcnstcin,  1957)  as 
in  man  (Ciganck,  I9s8a),  it  may  be  recorded  at  a  distance. 

The  evoked  visual  response  in  waknig  man  studied  in  this  investigation 
corresponds  in  its  characteristics  and  distribution  to  that  described  by 
Calvet  ct  al.  (1956)  and  by  Ciganek  (1958  a,  b).  The  potential  studied  by 
Walter  and  Grey  Walter  (1949)  is  certainly  the  same  one,  although 
described  in  less  detail.  On  the  other  hand,  other  responses  recorded  in 
wakmg  man  such  as  the  'waking-on-eftect'  (Davis,  1939;  Davis,  Davis 
Loomis,  Harvey  and  Hobart,  1939)  and  the  'pointes  vertex'  (Gastaut, 
1953),  probably  respond  to  dit^^erent  mechanisms  since  they  have  a  different 
distribution. 

It  may  be  presumed  that  diis  diffuse  evoked  visual  response  corresponds 
in  latency,  topography  and  conditions  ot  recording  during  wakefulness  to 
the  'reponse  irradiee'  ot  Buser  and  Borenstein  (1957)  recorded  in  cats. 

EFFECT    OF    CONTINUOUS    FLICKER    STIMULATION 

On  application  oi  a  continuous  flicker  frequency  the  evoked  responses 
underwent  progressive  changes  showing  modifications  in  dieir  amplitude, 
form,  frequency  and  topographic  distribution. 

Aiiiplitiide.  In  subjects  who  had  no  previous  knowledge  of  the  technique 
and  who  were  unaware  of  the  conditions  of  the  test,  the  responses  to  the 
first  flashes  were  invariably  of  greater  amplitude  than  to  succeeding  ones 
(Figs.  I  and  2).  As  time  passed  the  amplitude  was  progressively  reduced. 
This  decrease  was  apparent  after  300-500  flashes  and  was  maintained 
during  the  whole  experiment,  which  comprised  from  2000  tc^  4000 
flashes  in  15-20  minutes. 

Frequently,  after  the  initial  reduction  a  ciiscrete  increase  was  found  in 
the  amplitude  without  obtaining,  however,  the  initial  values  recorded  at 
the  beginning  of  the  experiment.  On  some  occasions  a  repeated  waxing 
and  waning  was  observed,  but  always  maintaining  a  lesser  amplitude  than 
the  original  one. 

The  reduction  of  the  evoked  response  in  man  as  a  consequence  of  the 
repetition  of  the  stimulus  is  similar  to  the  phenomenon  of  habituation 
described  in  the  animal  by  auditory  or  photic  stimulation  (Hernandez- 
Peon,  Jouvet  and  Scherrer,  1957;  Jouvct  and  Hernandez-Peon,  1957; 
Hernandez  Peon,  1958;  Hernandez-Peon,  Guzman-Flores,  Alcaraz  and 
Fernandez-Guardiola,  1958;  Palestini,  Davidovich  and  Hernandez-Peon, 
1959)- 

Hc^wever,  the  time  course  of  habituation  was  considerably  faster  in 


6o8 


BRAIN    MECHANISMS    AND    LEARNING 


man.  Whilst  the  cat  requires  hours  to  become  habituated  to  an  inter- 
mittent photic  stimuhis,  man  did  this  in  a  few  minutes.  It  should  be  borne 
in  mind  ni  this  respect  that  in  man,  as  a  consequence  of  the  liigher  develop- 
ment ot  his  nervous  system,  learning  is  much  faster  than  in  the  carnivores. 
Furthermore,  the  significance  of  a  flash  is  much  greater  to  a  caged  animal 
on  the  defensive  than  to  a  man  who,  although  he  has  no  previous  know- 
ledge of  the  experiment,  knows  what  a  flash  is  and  also  knows  that  he  will 
not  have  to  face  anything  unpleasant  or  dangerous  during  the  experiment. 


f 


t 

IvAA/\AAA 


Fig.  I 


Changes  of  the  visual  evoked  response  by  effect  oj  habituation.  Continuous  flicker 
frequency  2/sec.  Stroboscope  at  3  m.  from  the  retina.  Eyes  open.  Fifty  super- 
imposed sweeps.  Dawson's  technique.  Arrow  indicates  the  stimulus.  Lead 
02-right  mastoid  (10/20  system),  (i)  control  without  stimulation;  (2)  flashes 
1-50,  three  waves  are  observed  surface-negative-positive-negative;  (3)  flashes 
101-150,  the  first  negative  wave  tends  to  disappear  and  the  others  are  re- 
duced in  amplitude;  (4)  flashes  301-350,  the  first  negative  wave  has  dis- 
appeared; (5)  flashes  401-450,  amplitude  even  more  reduced.  Calibrations, 
25/sec.,  50  microvolts. 


To  the  cat,  the  flash  signifies  danger,  to  man  it  is  simply  light.  Conse- 
quently, it  is  possible  that  the  latter  soon  ceases  to  pay  attention  to  it  and 
becomes  habituated. 

Persons  subjected  to  the  action  ot  a  repetitive  photic  stimulus,  on  being 
questioned,  stated  that  after  a  tew  hundred  flashes  their  interest  decreased 
on  realizing  that  the  stimulus  was  monotonously  repeated. 

Some  subjects  with  previous  experience  showed  a  lesser  amplitude  in 
their  response  to  the  first  flashes.  For  example  the  tirst  100-150  flashes 
evoked  responses  of  lesser  amplitude  than  the  150-250  following  ones. 
Subsequently  the  amplitude  was  again  reduced,  the  habituation  which  was 
to  persist  throughout  the  whole  experiment  becoming  apparent.  In  these 
subjects  the  factor  of  initial  surprise  was  lacking,  their  attention  becoming 


E.    GARCIA-AUSTT,   J.    BOGACZ    AND    A.    VANZULLI  609 

more  concentrated  a  few  minutes  after  the  beginning  of  the  experiment 
when  they  were  teehng  more  comfortable. 

Form  afid  frajiiciicy.  During  habituation  the  evoked  potential  had  a 
tendency  to  become  more  complex  and  to  present  a  greater  number  of 
waves  (Fig.  2 A).  The  waves  multiplied  progressively.  This  change  was 
more  noticeable  in  the  fnst  negative  wave  where  a  notch  appeared  which 
as  it  became  deeper  was  transformed  into  a  surface  negative-positive- 
ncgativc  wave.  In  some  cases  all  the  waves  were  multiplied,  the  evoked 


A  B 


^   "^^'^'^-A        /V^/>aA/V.    i-V'^s/^'WA/*^ 


t       ' ■    t  ' '   t 


Fig.  2 
Changes  of  the  visual  evoked  response  by  effect  of  liabituatioii.  Continuous  flicker 
frequency,  Stroboscope  at  3  m.  from  the  retina.  Forty  superimposed  sweeps. 
Technique  of  Calvet  and  co-workers.  Arrows  indicate  the  stimulus.  Lead  02-right 
mastoid.  A,  B,  and  C,  experiments  performed  on  different  subjects.  (1)  at  the 
beginning  of  the  experiment;  (2)  when  habituation  was  achieved.  A,  the  initial 
component  before  habituation  is  constituted  by  three  w-aves  and  after  habituation 
the  amplitude  decreases  and  the  waves  become  more  numerous.  B,  with  eyes 
open,  after  habituation  the  amplitude  is  reduced  and  a  fast  after-discharge  of 
22/scc.  develops.  C.  with  eyes  closed,  after  habituation  the  amplitude  docs  not 
change  and  a  slow  after-discliargc  of  14/sec.  sets  in.  Calibration,  200  msec. 


potential  being  consticuted  by  a  succession  of  6  to  8  cycles  of  low 
amplitude.  Occasionally  the  progressive  reduction  of  the  amplitude 
finally  caused  the  disappearance  of  some  waves,  notably  of  the  first 
negative  wave  which  generally  was  of  lesser  magnitude  than  the  following 
ones  (Fig.  i). 

Provided  the  flicker  stimulation  was  a  low  frequency  (0.5-2  sec.)  and 
that  it  was  prolonged  for  a  lengthy  period,  there  constantly  appeared  in 
succession  to  the  evoked  response  a  regular  rhythm,  present  throughout 
the  whole  extension  of  the  sweep  (which  lasted  up  to  2  seconds  (Fig.  2, 
B  and  C) ) .  This  rhythm  was  of  variable  frequencies  of  two  ranges :( i )  alpha 


6lO  BRAIN    MECHANISMS    AND    LEARNING 

frequency  and  (2)  20-45 /seconds.  The  first  appeared  with  closed  eyes  in  all 
subjects  and/or  with  open  eyes  in  subjects  who  in  these  conditions 
presented  an  alpha  rhythm.  Its  frequency  was  the  same  as  that  of  the 
spontaneous  alpha  rhythm.  The  fast  rhythm  was  present  with  open  eyes  in 
subjects  not  presenting  the  alpha  rhythm  and  it  had  the  same  frequency  as 
that  of  the  spontaneous  rhythm. 

The  slow  after-discharge  of  alpha  frequency  is  similar  to  that  described 
by  Ciganek  (1958b)  who,  however,  noted  it  as  being  inconstant.  This  is 
explained  by  the  fact  that  the  after-discharge  develops  only  in  the  course 
of  habituation  and  this  temporal  evolution  was  not  taken  into  account  by 
this  author.  Hernandez-Peon  (personal  communication)  also  observed  the 
development  of  a  slow  after-discharge  in  the  cat  through  habituation. 

Bremer  and  Bonnet  (1950)  studying  the  response  evoked  by  auditory 
stimulation  in  the  awake  or  anaesthetized  cat  ('encephale  isolc'  preparation) 
described  two  types  of  after-discharge:  the  slow  one  of  8-12  seconds 
observed  during  sleep  and  the  fast  one  which  appeared  in  wakefulness  or 
under  light  ether  anaesthesia.  The  after-discharges  which  appeared  by 
effect  of  habituation  in  man  are  comparable  to  those  described  by  these 
authors.  Their  frequency  varied  with  the  background  rhythm  to  the 
EEG:  the  subjects  showing  a  moderately  synchronized  tracing  (alpha 
rhythm)  presented  a  slow  discharge.  In  other  activated  record  presented  a 
rapid  after-discharge.  In  other  word's,  the  spontaneous  rhythm  tends  to  be 
synchronous  with  the  photic  stimulation  as  a  consequence  of  being 
triggered  by  it. 

Topo(^rapliic  distribution.  In  the  course  of  habituation  the  evoked 
responses  of  O2,  C4,  T2  and  T6  experienced  a  similar  evolution.  How- 
ever, the  evoked  responses  of  the  central  and  temporal  regions  underwent 
greater  reductions  in  amplitude.  In  some  instances  the  central  and  temporal 
responses  disappeared  whilst  the  occipital  response  persisted  (Fig.  3). 
Since  the  amplitude  of  the  evoked  potential  in  the  central  and  temporal 
regions  was  less  than  in  the  occipital  region,  it  might  be  thought  that  a 
reduction  in  the  amplitude  oi^  the  response  would  cause  the  earlier 
disappearance  in  those  regions  where  originally  the  amplitude  had  been 
less.  Nevertheless  a  decrease  in  amplitude  and  even  the  disappearance  of 
the  central  and  or  temporal  responses  was  observed  without  any  change 
appearing  in  the  amplitude  of  the  occipital  potential.  This  fact  indicates 
that  during  habituation  the  evoked  response  undergoes  a  true  reduction  in 
its  topographic  distribution,  and  from  being  diffuse  tends  to  become 
localized  in  the  occipital  region. 

The  fast  or  slow  after-discharges  produced  by  habituation  are  recorded 


E.    GARCIA-AUSTT, 


BOGACZ    AND    A.    VANZULLI 


6ll 


preferably  in  the  occipital  region.  In  other  regions  they  were  recorded 
inconstantly. 

The  lesser  variability  of  the  occipital  response  was  more  clearly  shown 


I 


Fig.  3 


Clmiiges  of  the  visual  evoked  response  by  effect  of  habituation  and  attention.  Continuous  flicker 
frequency  2/sec.  Stroboscope  at  1.5  m.  from  the  retina.  Eyes  open.  Forty  superimposed 
sweeps.  O2  and  C4,  controls,  leads  of  the  10/20  system,  common  reference  in  the  right  mastoid, 
(i)  flashes  1-40,  same  leads,  complex  responses  are  observed  on  O2  and  C4;  (2)  flashes  1081- 
1120,  habituation  of  the  response  on  C4;  on  O2,  no  modifications  are  observed;  (3)  flashes 
1121-1160,  the  subject  counts  number  of  flashes,  the  response  increases  on  C4,  on  O2  no 
changes  (dishabituation  by  attention) ;  (4)  flashes  1 161-2000,  without  counting  flashes,  response 
is  again  reduced  on  C4  as  in  (2),  on  O2  no  changes.  Calibrations,  100  msec,  100  microvolts. 


when  the  intensity  of  the  flash  was  increased  by  bringing  the  stroboscope 
near  the  retina.  In  some  cases  with  the  stroboscope  placed  at  a  distance  of 
1.50  m.  or  less  from  the  retina,  no  changes  were  observed  in  the  amplitude 
of  the  occipital  potential  even  when  the  flicker  stimulation  was  prolonged 

RR 


6l2  BRAIN    MECHANISMS    AND    LEARNING 

for  20  minutes.  On  the  other  hand  the  same  subjects  showed  habituation 
to  this  response  with  the  stroboscope  at  a  distance  of  3  m.  or  more.  This  is 
not  surprising  since  it  is  well  known  that  the  more  intense  the  stimulation, 
the  harder  it  is  to  achieve  habituation.  Even  when,  on  increasing  the 
intensity  oi  die  stimulus  no  decrease  in  amplitude  was  observed  during 
habituation,  a  slow  after-discharge  appeared  in  experiments  with  closed 
eves  (Fig.  2,  C).  It  is  interesting  to  emphasize  this  point  since  it  proves  that 
modifications  in  the  amplitude  and  form  ot  the  response  during  habitua- 
tion may  take  place  independently. 

Summarizing,  the  changes  in  the  evoked  visual  response  observed  dur- 
ing habituation  to  a  continuous  flicker  stimulation  were  as  follows: 
(i)  reduction  of  amplitude,  (2)  multiplication  of  the  waves,  (3)  appearance 
of  a  fast  or  slow  after-discharge  depending  on  the  background  rhythm 
and  (4)  reduction  m  diftiision.  The  changes  observed  during  dishabituation 
provoked  by  attention  or  by  modifications  in  the  quality  of  stimuli,  were 
opposite. 

/ 


Fig.  4 
Change::  of  the  visual  evoked  response  by  effeit  of  attention.  Continuous 
flicker  frequency  0.5/sec.  Stroboscope  at  3  ni.  from  the  retina.  Eyes 
open.  Forty  superimposed  sweeps.  Lead  02-right  mastoid  10/20 
system.  Arrow  indicates  the  stimulus,  (i)  control  without  stimulation; 
(2)  flashes  1-40,  response  formed  by  three  successive  oscillations;  (3) 
flashes  41-80,  throughout  this  period  an  intense  tone  is  associated,  the 
response  tends  to  disappear,  the  first  wave  only  persisting  with  a  very 
low  amplitude;  (4)  flashes  81-120,  in  the  same  conditions  as  in  (2) 
without  the  associated  tone,  the  response  reappears.  Calibration, 
200  msec. 


Habituation  was  a  persistent  phenomenon.  If  after  habituation  had 
become  established  the  stimulus  was  suspended  for  15-30  minutes,  on 
applying  it  again  the  response  maintained  the  same  characteristics.  In 
previously  trained  subjects  fewer  flashes  were  needed  to  establish  habitua- 
tion. Similar  results  have  been  obtained  in  animals  by  Hernandez-Peon, 
Jouvet  and  Scherrer  (1957). 

If  during  the  continuous  flicker  stimulation,  before  habituation  was 
established,  the  attention  of  the  subject  was  withdrawn  from  the  repetitive 


E.    GARCIA-AUSTT,   J.    BOGACZ    AND    A.    VANZULLI  613 

Stimuli  and  focused  on  some  other  interesting  stimulus,  the  amplitude  of 
the  response  decreased.  This  reduction  was  seen  for  example  when  the 
subject  was  performing  a  mental  calculation  or  was  made  to  listen  to  an 
intense  continuous  tone  during  the  flicker  stimulation  (Fig.  4).  Hernandez- 
Peon  et  al.  (1957)  reported  the  same  phenomenon  in  the  optic  pathways  of 
the  cat,  Buser  and  Rougcul  (1956)  found  it  in  the  cerebral  cortex,  and 
Jouvet  and  Courjon  (1958)  studied  it  in  man  by  recording  from  the  optic 
radiations. 

Inversely  it  was  possible  to  provoke  a  state  of  dishabituation  by  increas- 
ing the  attention  directed  to  the  flicker.  For  example,  when  the  subject 
counted  the  flashes  (Fig.  3)  or  simply  checked  a  possible  variation  in  them, 
the  amplitude  of  the  response  increased,  the  after-discharge  disappeared 
the  waves  became  simplified  and  the  response  was  recorded  in  other 
regions  as  well  as  in  the  occipital  region.  In  other  words  the  response 
regained  its  prc-habituation  characteristics. 

When,  alter  habituation,  a  click  or  a  brief  tactile  stimulus  was  associated 
with  each  flash,  dishabituation  was  again  provoked.  If  this  association  was 
prolonged  for  a  time  habituation  again  set  in.  On  suspending  the  associa- 
tion and  continuing  with  the  pure  flicker,  dishabituation  again  took  place. 
That  is  to  say,  that  habituation  was  observed  whenever  the  stimulus, 
either  pure  or  in  its  associated  form,  was  sufficiently  repeated,  and  dis- 
habituation took  place  whenever  the  stimulus  was  modified  by  association 
or  disassociation. 


EFFECT    OF    DISCONTINUOUS    FLICKER    STIMULATION 

When,  having  achieved  habituation  of  the  response  by  continuous 
flicker  stimulation,  the  stimuli  were  interrupted  for  regular  and  constant 
periods,  after  three  to  seven  trials  dishabituation  was  achieved  (Fig.  5).  The 
response  regained  all  its  initial  characteristics.  The  most  remarkable  feature 
was  the  increase  in  amplitude. 

If  a  discontinuous  flicker  stimulation  was  used  initially  without  previous 
habituation  having  been  established,  an  increase  in  amplitude  was  again 
obtained,  but  this  time  of  lesser  magnitude.  In  either  case  if  stimulation  by 
a  discontinuous  flicker  was  continued,  after  ten  to  fifteen  trials  the  response 
became  habituated  (Figs.  5  and  6).  The  general  evolution  of  the  response 
was  not  the  same  in  the  different  regions  explored.  Whilst  in  O2  the 
increase  in  amplitude  was  only  discrete  and  the  response  was  rapidly 
rehabituated,  in  C4  and  T2  the  increase  was  greater  and  more  persistent. 


6l4  BRAIN    MECHANISMS    AND    LEARNING 

There  were  differences  in  the  temporal  course  ot  changes  in  different 
subjects  (Fig.  7). 

These  modifications  oi  the  evoked  response  caused  by  discontinuity  of 


7   A/V^^^v^^^ 


8 


4    ''■\l\p-''''^''-^         '0 

6  -y^l^p^^y"^-^^      12  AvA/^A/V^ 


t 


t 


Fig.  5 


Changes  of  the  visual  evoked  response  by  effect  of  discoiitiniioiis  flicker  stiiiiiilatioii. 
Stroboscope  at  distance  of  3  in.  from  the  retina.  Eyes  open.  Forty  superimposed 
sweeps.  Flicker  frequency  2/sec.  during  20  seconds,  interrupted  during  20  seconds, 
Lead  C4-right  mastoid,  10/20  system.  Arrows  indicate  the  stimulus,  (i)  control 
without  stimulation;  (2)  after  habituation  to  a  continuous  flicker  frequency, 
after  1200  flashes;  (3)  first  trial  after  darkness-flicker  association,  the  response  is 
comparable  to  the  previous  one;  (4-6)  3rd,  4th  and  5th  trials  respectively,  the 
responses  increase  progressively  (dishabituation,  time  conditioning);  (7-10)  7th, 
15th,  17th  and  lyth  trials  respectively,  the  response  starts  to  decrease  until  in  (10) 
it  attains  amplitude  and  form  comparable  to  those  of  (2)  (rehabituation) ;  (11  and 
12)  2 1st  and  22nd  trials  respectively,  the  rehabituation  is  accentuated  and  an  after- 
discharge  of  20-22/sec.  develops.  Calibration,  100  msec. 


the  flicker  are  an  example  of  electrocortical  time  conditioning  where  the 
period  of  darkness  acts  as  a  conditioned  stimulus  and  the  flicker  as  an 
unconditioned  one. 


E.    GARCIA-AUSTT,   J.    BOGACZ    AND    A.    VANZULLI 


615 


The  interruption  of  the  flicker  by  regular  periods  of  darkness  contri- 
buted a  new  motive  oi'  interest  to  the  flashes.  Persons  subjected  to  these 
tests  stated  that  owing  to  the  monotonous  repetition  ot  the  continuous 
flicker  their  attention  decreased  (habituation).  In  these  circumstances  when 


40  200  560  »0  680  840  lOOOnbflOJOIWHWO  (      5     5     7     9     ^1     15    <5     1 
FLASHE:S(CF5)  TBIAL5(DFS) 

(DFS 


5   ?   7   ; 

TRIALS 
+  TACTIL  STIMULI) 


Fig.  6 
Climiges  of  the  visual  evoked  response  hy  effect  of  continuous  and  discontinuous  flicl<er  stinuilation  and 
through  tactile-flash  association.  Ordinates,  percentage  of  initial  peak  to  peak  amplitude  of  the 
evoked  response.  Abscissas,  times,  represented  by  the  number  of  flashes  during  the  continuous 
flicker  stnnulation  (CFS)  at  a  frequency  of  4/sec.  and  by  trials  carried  out  every  10  seconds  witli 
discontinuous  flicker  stimulation  (DPS)  at  the  same  frequency  for  10  seconds.  Lead  02-right 
mastoid.  Stroboscope  at  a  distance  of  3  m.  from  the  retina.  Eyes  open.  In  the  first  part  of  the 
experiment  with  CFS  an  irregular  reduction  of  the  amplitude  is  observed.  But  if  under  these 
conditions  of  habituation  a  DFS  is  employed  the  amplitude  increases  quickly.  However,  after 
a  few  trials  it  tends  to  decrease  again.  If  under  these  new  conditions  during  the  DFS  every  flash 
is  simultaneously  associated  with  a  brief  tactile  stimulus  (tactile-flash  association)  the  response 
again  increases  in  amplitude  until  the  end  of  the  e.xperiment. 


the  flicker  was  suspended  for  the  first  time  for  a  few  seconds  they  beheved 
the  experiment  to  have  terminated.  However,  after  a  few  trials  associating 
darkness  and  flicker  they  realized  that  after  a  certain  constant  period  of 
darkness  the  flashes  were  always  resumed  and  then  their  attention  to  the 
flashes  increased.  In  other  words  the  interruption  of  the  flicker  gave  new 


6i6 


BRAIN    MECHANISMS    AND    LEARNING 


signihcancc  to  the  stimulus.  If  this  darkness-flicker  association  was  pro- 
longed for  a  time  without  modifications,  they  once  again  lost  interest  in 
the  stimulus,  their  attention  decreasing  accordingly  (rehabituation). 


I    I    I   I    I   I   I   I    I    I   I    I   I    I   I   I    i    I   i    I   I   I 


i       5      5      7      9      11      {?     15     1?     ^?     21     25    25     ??    ?9     ?1 

TRIALS  (DfS) 

Fig.  7 
Cliain;cs  of  the  risiial  evoked  rdipome  by  effect  of  diicoiiliniioiis  flicker  st'uniiLitioii. 
Ordinates,  percentage  of  initial  peak  to  peak  amplitude  of  the  evoked  response. 
Abscissas,  trials  carried  out  every  20  seconds  with  discontinuous  flicker  stimulation 
(DFS)  at  2/scc.  for  20  seconds.  Lead  02-right  mastoid.  Stroboscope  at  a  distance 
of  3  m.  from  the  retina.  Eyes  open.  Two  experiments  carried  out  in  different 
subjects  who  had  had  no  previous  knowledge  of  the  conditions  of  the  test,  are 
plotted.  The  temporal  course  of  changes  in  experiment  number  21  (white  dots) 
is  faster  than  the  one  of  experiment  26  (black  dots).  In  experiment  21  the  ampli- 
tude increases  quickly  and  reaches  its  highest  value  in  the  5th  trial.  After  the 
1 3  th  trial  it  begins  to  decrease  regularly.  In  experiment  26,  the  amplitude  increases 
slowly  and  retains  high  values  until  the  end  of  the  test  at  the  31st  trial. 


INTERACTION    BETWEEN    THE    DISCONTINUOUS    FLICKER    STIMULATION 

AND    A    TONE 

The  association  ot  a  sound  in  the  period  ot  darkness  during  the  discon- 
tinuous flicker  also  provoked  modifications  in  the  response.  When  after 
the  establishment  of  habituation  to  the  discontinuous  flicker  an  intense  and 


E.    GARCIA-AUSTT,    J-    BOGACZ    AND    A.    VANZULLI 


617 


constant  tone  was  emitted  at  the  end  of  the  period  ot  darkness,  tor  example 
durmg  the  last  10  seconds,  the  response  became  dishabituated  after  three 
to  eight  trials  (Fig.  8).  The  nicrease  in  amplitude  was  marked  and  in  some 
cases  surpassed  the  initial  amplitude  prevailing  before  habituation.  This 
phenomenon  was  always  more  marked  and  more  rapid  than  the  dis- 


^   "W^ 


Fig.  8 

Clhviges  ofllie  I'imal  evoked  response  by  effect  of  tone-flicker  ctssociotion. 
Stroboscope  at  3  m.  from  the  retina.  Eyes  open.  Forty  superimposed 
sweeps.  Lead  C4-right  mastoid  10/20  system.  Arrows  indicate  the 
stimulus.  Discontinuous  flicker  frequency  2/sec.  during  20  seconds, 
interrupted  during  20  seconds,  (i)  control  without  stimulation;  (2) 
habituation  to  discontinuous  flicker  frequency  after  twelve  trials 
without  association  with  tone.  A  response  of  low  amplitude  and 
after  discharge  of  i6/sec.  is  observed.  Three  to  eight  successive  trials 
with  tone  (10  seconds)  —  flicker  (20  seconds)  —  darkness  (10  seconds) 
association;  (3)  ist  trial  with  tone-flicker  association,  no  appreciable 
changes  were  noted  in  respect  to  previous  one;  (4)  3rd  trial,  slight 
increase  in  amplitude  of  response;  (5-8)  4th,  7th,  9th,  nth  trials 
respectively,  the  response  continues  increasing  and  is  simplified. 
Calibration,  100  msec. 


liabituation  provoked  by  the  discontinuous  tiicker  stimulation  without 
association  of  sound. 

If  the  trials  with  this  tone-flicker  association  were  prolonged  rehabitua- 
tion  of  the  response  was  obtained.  This  rehabituation  was  more  delayed 
and  inconstant  than  that  in  the  darkness-flicker  association,  requiring 
fifteen  to  twenty  trials  to  appear. 


6i8 


BRAIN    MECHANISMS    AND    LEARNING 


The  presence  ot  the  tone  at  the  beginning  of  the  period  of  darkness, 
i.e.  the  flicker-tone  association,  provoked  modifications  comparable  to 
the  tone-flicker  association,  but  inconstant  and  less  important  (Fig.  9).  In 


/ 


8 


iO 


11 


t 


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Fig.  9 
Chaii^Ci  ot  the  I'Isiuil  evoked  response  by  effecl  of  fliiker-toiie  iissocicUioii.  Stroboscope 
at  3  m.  from  the  retina.  Eyes  open.  Forty  superimposed  sweeps.  Lead  03-right 
mastoid,  10/20  system.  Arrows  indicate  the  stimulus.  Discontinuous  flicker 
frequency  2/sec.  during  20  seconds,  interrupted  during  20  seconds,  (i)  control 
without  stimulation;  (2)  habituation  to  discontinuous  flicker  frequency  after 
ten  trials  without  association  with  tone;  (3-12)  successive  trials  with  flicker 
(20  seconds)  —  tone  (10  seconds)  —  darkness  (10  seconds)  association;  (3)  ist 
trial  with  flicker-tone  association,  no  appreciable  modifications  with  respect 
to  previous  trial  are  noted;  (4)  6th  trial,  the  response  is  considerably  increased; 
(5-7)  7th,  9th  and  loth  trials  respectively,  response  again  decreases;  (8-1 1)  nth, 
i6th,  21  St  and  29th  trials  respectively,  an  increase  takes  place  and  is  maintained; 
(12)  31st  trial,  decreases  again.  Calibration,  200  msec. 


some  experiments  the  central  response  underwent  remarkable  changes 
whereas  the  occipital  one  did  not  show  significant  variations  (Fig.  lo). 

The  dishabituation  obtained  by  the  tone-flicker  or  flicker-tone  associa- 
tions persisted  during  various  trials  when  these  stimuli  were  substituted  by  a 


E.    GARCIA-AUSTT,   J.    BOGACZ    AND    A.    VANZULLI 


619 


discontinuous  flicker  without  tone  association.  But  the  subject  rapidly 
became  rehabituated  it  the  trials  were  repeated  (extinction).  This  rehabitua- 
tion  was  much  more  rapid  than  that  caused  by  persistence  ot  the  initial 
association  (tone-flicker). 


FLASMCS  (CrS)  TRIALS  (DFS)  TRIALS  (DrS  +  TONC) 

Fig.  10 

Clitiin^es  of  the  visual  evoked  response  by  effect  of  coiitiiiuoiis  ami  discontinuous  flicl<er  stinnilation 
and  throngli  tone-flicker  association.  Ordinatcs,  percentage  of  initial  peak  to  peak  amplitude 
of  the  evoked  response.  Abscissas,  time,  represented  by  the  number  of  flashes  during  the 
continuous  flicker  stimulation  (CFS)  at  a  frequency  of  2/sec.  and  by  trials  carried  out  every 
20  seconds  with  discontinuous  flicker  stimulation  (DFS)  at  the  same  frequency  for  20 
seconds.  Stroboscope  at  a  distance  of  1.5  m.  from  the  retina.  Eyes  open.  Black  and  white 
dots,  simultaneous  records  from  the  occipital  and  the  central  regions  respectively.  Dur- 
ing the  CFS  the  response  decreases  in  amplitude  chiefly  in  C4.  During  the  DFS  an  increase 
of  the  amplitude  in  C4  is  observed.  In  O2  the  response  does  not  show  significant  changes. 
When  a  tone  is  emitted  at  the  end  of  the  periods  of  darkness  (tone-flicker  association, 
DFS  +  tone),  the  amplitude  of  the  central  responses  increases  even  more.  The  occipital 
response  undergoes  no  changes. 


In  most,  the  variations  in  the  responses  were  different  in  the  central, 
temporal  and  occipital  regions,  being  more  marked  and  persistent  in  the 
first  two. 

The  changes  in  the  evoked  visual  response  by  the  interaction  of  tone 
and  flicker  constitute  another  example  of  the  electrocortical  conditioning 


620  BRAIN    MFXHANISMS    AND    LEARNING 

in  man.  The  facilitation  of  the  specific  response  to  an  intermittent  sound 
after  conditioning  by  association  with  a  continuous  Hght,  was  observed  in 
the  cat  by  Jouvct  (1956)  and  Jouvet  and  Hernandez-Peon  (1957).  The 
resuks  described  in  different  conditions  of  stimulation  (continuous  light, 
intermittent  sound)  agree  with  the  statement  previously  made,  that  the 
association  of  a  continuous  tone  and  ot  an  intermittent  flight,  facilitated 
the  evoked  response  by  light  in  man,  after  conditioning.  Buser  and 
Rougeul  (1956)  established  that  the  'rcponse  irradiee'  increases  in  ampli- 
tude in  the  course  of  sensorial  conditioning.  It  has  already  been  stated  in 
this  paper  that  it  is  probable  that  this  response  corresponds  to  the  diffuse 
respt^nse  of  the  scalp  record  in  man. 

Dishabituation  by  conditioning  was  described  in  the  cat  by  Hernandez- 
Peon,  Jouvet  and  Scherrer  (1957).  The  auditory  response  was  dishabituated 
on  the  acoustic  stimulus  being  given  a  new  significance  by  association  with 
an  electric  shock  to  the  forepaw  of  the  animal.  Lelord,  Fourmant,  Calvet 
and  Scherrer  (1958)  described  in  man  the  conditioning  of  the  response 
evoked  by  sound  (conditioned  stimulus)  by  association  with  light  (un- 
conditioned stimulus).  After  various  trials  on  successive  days  a  diffuse 
response  was  obtained  by  a  sound  which  before  the  conditioning  evoked 
no  response.  This  is  a  phenomenon  of  delayed  appearance,  differing, 
therefore,  from  the  rapid  changes  of  the  visual  evoked  response  already 
described. 

When  the  visual  stimulus  acted  as  an  unconditioned  stimulus  in  the  tone- 
flicker  association  the  changes  in  the  response  were  greater  than  when  it 
took  the  form  of  a  conditioned  stimulus  in  the  flicker-tone  association.  In 
other  words  the  changes  in  the  vsiual  'unconditioned'  response  were 
greater  than  in  the  visual  'conditioned'  response.  This  fact  agrees  with  the 
view  sustained  by  other  authors  as  Buser  and  Roger  (1957),  'que  c'est  au 
niveau  de  la  zone  corticale  inconditionellc  que  se  concentre  I'essentiel  des 
cvenements  caracteristiques  de  la  liaison  conditionclle'. 

Persons  subjected  to  the  tone-flicker  interaction  stated  that  after  various 
associations  they  became  aware  that  the  tone  was  always  followed  by  a 
series  of  flashes  and  consequently  when  they  started  listening  to  it  they 
were  already  prepared  to  see  the  light,  thus  paying  more  attention  to  it. 
On  the  other  hand,  the  flicker-tone  association  had  the  same  effects  on 
attention  to  sound,  the  effects  on  attention  to  light  being  variable. 

CONCLUDING    REMARKS 

The  amplitude,  form  and  distribution  of  the  scalp  visual  evoked  re- 
sponse in  man  depend  on  the  significance  of  the  photic  stimuli. 


E.    GARCIA-AUSTT,   J.    BOGACZ    AND    A.    VANZULLI  621 

When  the  stiniuhis  is  significant  and  therefore  attention  is  paid  to  it,  the 
response  is  relatively  simple  and  widespread.  When  on  the  other 
hand,  the  stimulus  is  not  significant  and  no  great  attention  is  paid  to  it, 
the  response  is  reduced,  complex  and  localized.  It  is  interesting  to  point 
out  that  during  the  state  of  attention  not  only  has  the  evoked  potential  a 
greater  amplitude  but  also  a  much  larger  area  of  the  brain  receives  the 
'information'. 

These  changes  in  the  response  are  closely  related  to  the  state  ot  sensorial 
receptivity  of  the  subject,  i.e.  the  "attention  level'  towards  the  stimulus. 

Between  these  two  phenomena,  the  electrical  and  the  psychological, 
there  may  exist:  (i)  a  cause  and  effect  relation,  (2)  a  common  cause. 
Although  the  first  possibility  cannot  be  discarded,  it  is  probable  that  both 
are  the  consequence  of  processes  taking  place  in  the  subcortical  systems  ot 
unspecific  projection  (Jouvet  and  Hernandez-Peon,  1957;  Buser  and 
Roger,  1957;  Hernandez-Peon,  Brust-Carmona,  Eckhaus,  Lopez- 
Mendoza  and  Alcocer-Cuaron,  1958;  Gastaut,  1958). 

Directing,  blocking  and  switching  of  the  sensorial  messages  would 
appear  to  take  place  on  the  level  of  the  reticular  formation  and  or  thalamic 
reticular  system.  As  a  consequence  oi  the  analysis  and  integration  taking 
place  in  these  structures,  the  cerebral  cortex  would  receive  information  of 
correct  magnitude  and  proper  distribution  for  immediate  needs.  The 
modifications  of  the  'level'  and  'focus'  of  attention  would  be  the  con- 
sequence of  this  selective  activity. 

Whatever  the  explanation  is,  the  electrical  changes  and  the  variatii^ns  of 
attention  run  side  by  side.  Therefore,  the  electrical  changes  provide  an 
idea  and  may  even  go  as  far  as  to  constitute  a  measure  of  the  concomitant 
psychological  phenomena.  If  this  should  be  so,  with  the  equipment  avail- 
able in  every  neurophysiological  laboratory  and  with  a  simple  and  rapid 
technique  it  would  be  possible  to  obtain  an  objective  appreciation  of  the 
time  pattern  of  attention,  habituation  and  other  forms  of  learning  in  man. 


GROUP   DISCUSSION 

JouvET.  In  connection  with  the  significance  ot  the  amplitude  ot  the  evoked 
responses  in  man,  I  would  like  to  show  you  some  recordings  made  during  stereo- 
taxic surgery  on  the  thalamus.  In  three  patients  suffering  from  intractable  pain 
before  the  thalamotomy,  we  recorded  from  the  V.P.L.  with  a  depth  electrode 
somestiietic  potentials  evoked  by  mechanical  stimulation  of  the  skin  (usually  the 
contralateral  forearm).  When  the  patients,  who  were  conscious,  were  paying 
attention  to  the  stimuli,  the  evoked  responses  had  a  much  higher  amplitude  than 
when  the  patients  were  not  (mental  calculation,  auditory  attention  ...  )  In  some 
cases,  the  evoked  responses  could  disappear  almost  completely. 


622  BRAIN    MECHANISMS    AND    LEARNING 

Naquet.  I  think  wc  must  be  very  careful  about  the  site  where  the  stimulation 
of  the  reticular  formation  is  effective.  In  this  respect,  I  would  like  to  mention  some 
experiments  performed  by  Dumont,  Paillas  and  Hugehn  (1959),  and  by  Hugelin, 
Dumont  and  Paillas  (1959),  on  the  auditory  pathways.  These  authors  demonstrated 
that  if  an  inhibition  of  evoked  response  recorded  at  the  level  of  nucleus  cochlearis 
exists  in  the  animal  'encephale  isole',  this  inhibition  is  not  a  consequence  of  a  direct 
action  at  the  level  of  the  first  relay,  but  the  result  of  muscle  contraction  of  the 
middle  ear,  induced  by  this  stimulation.  Finally,  they  show  that  if  those  auditory 
muscles  are  either  cut  off,  or  curarized,  the  response  at  the  level  of  nucleus  coch- 
learis remains  constant  in  amplitude,  but  at  the  level  of  the  auditory  cortex  it  is 
variable  according  to  the  state  of  synchronization  or  desynchronization  of  the 
cortex.  For  these  authors,  this  last  finding  would  be  due  to  a  purely  cortical 
phenomenon;  in  our  laboratory,  with  Drs  Regis,  Fernandez-Guardiola  and 
Fischer-Williams :  if  you  put  a  cat  under  flaxedil,  its  pupils  change  with  blood 
pressure  and  with  the  state  of  synchronization  and  desynchronization  of  the  cortex 
-  as  was  shown  by  Bonvallet,  Dell  and  Hiekel  (i954)-  When  the  cortex  presented 
some  spindles,  the  pupils  narrowed  and  the  response  in  the  optic  tract  or  in  corpus 
geniculatum  laterale  diminished  in  amplitude,  simultaneously,  at  the  level  of  the 
cortex,  the  response  was  enhanced  and  the  negative  waves  became  more  ample  and 
large  and  could  be  followed  by  a  true  slow  after-discharge,  having  sometimes  the 
aspect  of  spindles.  When  the  cortex  was  desynchronized  (activated  cortex),  the 
pupils  were  wide  and  the  response  in  optic  tract  or  corpus  geniculatum  laterale 
increased  in  amplitude.  Simultaneously,  on  the  cortex,  the  amplitude  of  the 
response  diminished  and  its  morphology  was  altered.  The  positive  phase  remained 
unchanged  and  decreased  discreetly  in  amplitude.  The  slow  negative  wave  was 
nearly  totally  disappearing.  After  atropine  application,  pupils  being  in  constant 
mydriasis  had  no  reaction;  there  is  no  relation  between  their  diameter  and  the 
state  of  relative  synchronization  and  desynchronization  of  the  cortex.  Evoked 
potentials  are  very  large  at  the  level  of  optic  tract  and  corpus  geniculatum  laterale 
and  do  not  vary,  whatever  the  cortical  clectrographic  activity.  At  the  level  of  the 
cortex,  the  response  followed  the  same  variations  as  before  application  of 
atropine. 

These  data,  as  well  as  the  results  of  Hugehn  and  co-workers,  tend  to  prove  that  a 
control  of  specific  afFerences  exists  after  the  thalamic  relay  (as  was  suggested  by 
King  et  ai,  1956)  and  may  play  a  more  important  role  than  in  the  first  relay. 

JouvET.  Investigations  in  man  must  be  made  with  careful  controls  —  with 
atropinizcd  eyes  and  recording  of  eye  movement  because  even  a  slight  movement 
will  interfere  with  the  evoked  potential  at  the  cortical  level. 

It  is  necessary  to  put  some  atropine  in  the  eyes  and  at  least  record  movements  of 
the  eyes  and  eyelids  by  the  electrogram  of  the  blink  and  by  the  slow  potential  of 
the  eyes.  This  is  absolutely  necessary  because  with  a  flash  that  is  more  than  twenty 
centimetres  from  the  eyeballs  even  a  very  slight  eye  movement  would  give  a 
reduction  of  the  visual  evoked  potentials. 

Berger.  What  effect  does  the  frequency  of  the  stimulus  have?  Regarding 
habituation,  we  have  made  experiments  on  what  we  have  called  fatigue.  We 
exposed  the  eye  to  flashes  when  we  thought  that  attention  was  continually  fixed  on 
the  same  subject.  Depending  on  the  area  of  the  retina  which  was  stimulated,  the 
general  fusion  frequency  decreased  significantly  during  a  period  of  between  20  and 


E.    GARCIA-AUSTT,   J.    BOGACZ    AND    A.    VANZULLI  623 

40  minutes  of  exposure.  I  would  like  to  know  the  relation  between  what  you  call 
habituation  and  fatigue. 

Garcia-Austt.  As  to  Dr  Jouvet's  remarks  I  must  say  that  all  subjects  were  given 
careful  instructions  beforehand,  so  that,  throughout  the  experiment,  they  kept 
looking  at  the  stroboscope.  It  is  very  unlikely  that  the  diameter  of  the  pupil  should 
play  an  important  role  as  the  eyes  were  fixed  on  the  stroboscope,  stimulation  was 
alwavs  rhythmic  and  at  constant  frequency  throughout  the  experiment.  Conse- 
quently illumination  remained  unchanged.  The  flash  intensity  was  supra-maximal 
for  any  given  pupillary  diameter. 

In  answer  to  Dr  Berger's  questions,  we  worked  with  frequencies  of  0.5-5/sec. 
which  are  very  far  from  the  fusion  frequency.  Between  this  range  we  did  not  fmd 
variations  in  the  initial  component  of  the  evoked  response.  However,  the  after- 
discharge  was  not  observed  at  4-5  sec.  Of  course,  it  is  not  a  question  of  fatigue.  It 
should  be  mentioned  that  through  association  with  other  stimuli,  a  response  may 
be  habituated  or  dishabituated  and  this  occurs  without  any  interruption  or  changes 
in  the  flicker  frequency. 


CONDITIONNEMENT  DE  DECHARGES  HYPER- 

SYNCHRONES  EPILEPTIQUES  CHEZ  L'HOMME 

ET  L'ANIMAL 

R.  Naquet 

Le  mccauismc  reflcxo-couditiounc  cic  ccrtaincs  epilepsies  a  ete  suppose 
des  la  connaissance  dcs  travaux  de  Pavlov.  Du  point  de  vue  experimental, 
Kreindler  (1955)  conditionne  a  tni  stimulus  prealablement  indifferent 
(son,  odcur  ou  condition  generale  de  I'cxpericncc)  des  crises  gcneralisees 
ou  particllcs,  inconditionnellement  provoquecs  par  une  injection  con\-ul- 
sivante,  ou  par  une  stimulation  electrique  corticale. 

Morrell  et  Naquet  (1956)  et  Morrell  (1957)  ont  etudie  I'evolution  d'un 
conditionnement  son-lumiere  (son  neutre  associe  a  une  stimulation 
linnineuse  nitermittcnte  (SLI)  chez  Tammal  (chat  et  singe),  apres  creation 
de  lesions  epileptogencs  corticales  par  injection  de  creme  d'alumine. 
Lorsque  la  lesion  occupait  la  partie  postericure  du  gyrus  lateralis  (chat)  ou 
la  region  occipitale  (singe),  le  stimulus  lumincux  inconditiomiel  faisait 
apparaitre  des  decharges  hypersynchrc^nes  gc'neralisees,  qui  avaient  une 
frequence  indcpendante  de  celle  du  stimulus  inconditionnel  et  qui  pou- 
vaient  se  poursuivre  apres  sa  cessation  sous  la  iorme  d'une  'post-dc'charge'. 
Ces  decharges  etaient  generalisees  d'emblee,  ou  dcbutaicnt  au  niveau  du 
cortex  lese,  elles  etaient  favorisees  par  I'etat  de  synchronisation  du  trace  et 
etaient  bloquces  par  tout  stimulus  d'evcil. 

Au  cours  des  experiences  de  conditionnement,  ils  ont  constate  que  le 
blocage  conditiomie  [ocncrallzcd  conditional  activation  pattern  and  localized 
coiditional  activation  pattern)  etait  plus  difficilement  obtenu  du  cote  de  la 
lesion,  et  que  Ics  decharges  repctitives  [conditional  rcpctitipe  responses) 
apparaissaient  de  fa^on  plus  nette  de  ce  meme  cote  et  surtout  que  la 
decharge  Iiypersynchrone  gcncralisee(|)(7r('.vp/;((;/  hypcrsynchronons  response) 
pouvait  cgalement  survenir  pendant  le  stimulus  conditic^nnel  ou  en 
I'abscnce  du  stimulus  inconditionnel. 

Naquet  et  Morrell  (1956)  chez  I'animal  normal  (chat)  commc  chez  celui 
porteur  d'une  lesion  occupant  le  gyrus  lateralis  ont  egalement  note  que 
I'injection  progressive  de  cardiazol  pouvait  faciliter  I'apparition  et  le 
'conditionnement'  de  decharges  hypersynchrones  analogues:  en  efFet,  la 
stimulation  lumineuse  intermittente  provoque  sous  I'cftet  du  cardiazol  des 

625 


626  BRAIN    MECHANISMS    AND    LEARNING 

decharges  hypersynchrones  qui  rcvctcnt  I'aspcct  dc  vcritablcs  poiiitc- 
ondes  generalises  auto-entretenus.  Au  cours  dcs  experiences  de  condition- 
nement,  si  Ton  utilise  la  S.L.I,  comme  stimulus  inconditionnel,  ces 
decharges  de  pointe-ondcs  peuvcnt  apparaitrc  pendant  le  stimulus  condi- 
tionncl  et  prendre  la  place  du  blocage  generalise  ou  local  qui  les  precedait. 
Leur  apparition  pendant  I'application  depend  naturellement  du  niveau 
d'lmprcgnation  cardiazoliquc.  Pour  un  niveau  trop  elcve,  la  rcponse  n'est 
pas  difFerenciable  et  apparait  pour  un  stimulus  de  toute  autre  nature,  et  il 
n'est  plus  alors  question  de  parler  dereponseconditionnt'e.  Qu'ils'agissede 
lesions  occipitales  ou  d'injection  de  cardiazol,  les  auteurs  arrivaicnt,  des 
1956,  a  la  conclusion  qu'il  y  avait  une  certaine  opposition  entre  les  phcno- 
menes  de  blocage  conditionne  et  I'apparition  conditionnelle  de  ces 
decharges  hypersynchrones,  celles-ci  n'etant  possible  que  pendant  une 
depression  du  'systeme  d'eveil' 

Chez  I'Homme,  Gastaut,  Regis,  Dongier  et  Roger  (1956)  publiaient 
deux  observations  de  malades  porteurs  d'une  epilepsie  generahsce  de 
type  'Petit  Mai'  photosensible  caracterisee  du  point  de  vue  EEGraphique 
par  des  decharges  de  pointe-ondes  apparaissant  spontancment  et  favorisees 
par  la  S.L.I.  Au  cours  d'experiences  reflexo-conditionnees  ou  un  stimulus 
conditionnel  etait  representc  par  un  bruit  continu  et  un  stimulus  incondi- 
tionnel par  une  lumiere  mtermittente  capable  d'engendrer  des  paroxysmes 
de  pointc-onde,  Ic  stimulus  conditionnel  pouvait  faire  apparaitre  des 
decharges  de  pointe-ondes  generalisces  au  bout  de  la  20eme  presentation 
de  la  lumiere,  alors  que  le  blocage  conditionne  etait  apparu  dcs  les  pre- 
mieres. 

Plus  rccemment,  Stevens  (1959)  a  rapporte  les  resultats  obtenus  au  cours 
d'experiences  de  conditionnement  analogues  chez  quatre  sujcts  prcsentant 
des  decharges  hypersynchrones  de  pointe-ondes  provoquecs  par  une 
lumiere  intermittente :  Aprcs  10  a  15  presentations  du  stimulus  condi- 
tionnel (son)  couple  avec  le  stimulus  inconditionnel  (S.L.I.)  un  stimulus 
nouveau  (son  different)  etait  prcsentc'  sans  lumiere.  Chez  aucun  de  ces 
sujets  I'auteur  n'a  pu  mettre  en  evidence  de  conditionnement  des  decharges 
de  pointe-ondes;  ces  decharges,  en  revanche,  survenaient  plus  frequem- 
ment  pendant  le  stimulus  non  renforce.  L'auteur  conclut  que  les  rcponses 
a  type  de  pointe-ondes  ne  pouvaient  etrc  conditionnees,  mais  que  la 
diffcrenciation,  I'extinction  et  les  phenomenes  de  trace,  augmentaient  leur 
frequence:  conditions  que  Pavlov  designait  comme  favorisant  I'inhibition 
interne  ou  conditionnee,  laquelle  permettrait  I'apparition  des  crises. 

Dans  le  Laboratoire  de  Neurobiologie  de  Marseille  (Professeur  Gastaut) 
une  etude  similaire  etait  entreprise  par  Naquet,  Infante  et  Fernandez- 


R.    NAQUET  627 

Guardiola.  Cette  etude  est  basec  sur  vingt  quatre  sujcts  epilcptiques  ou 
non,  d'ages  variant  entre  dix  et  cinquante  ans.  Tous  prcsentaient  en  com- 
niun  des  decharges  de  pointe-ondes  gencralisees  induites  par  la  S.L.I,  ayant 
unc  frequence  propre,  indcpendante  de  celle  de  la  S.L.I,  et  cessant  avec 
elle  ou  pouvant  se  prolonger  plus  ou  nioins  longtemps  aprcs  elle  (une  a 
plusieurs  secondes).^ 

Parmi  eux,  douze  sujets  presentaicnt  en  outre  des  decharges  de  pointe- 
ondes  identiques,  au  repos  ou  pendant  I'epreuve  de  I'hyperpnce,  indepen- 
dantcs  de  la  S.L.I,  alors  que  les  douze  autrcs  n'en  presentaicnt,  exclusive- 
ment,  que  pendant  la  S.L.I.  Enhn,  quinze  sujets  presentaicnt  un  trcs 
important  entrainemcnt  a  la  S.L.I.,  six  un  discrct,  et  trois  pratiquement  pas. 

Toutes  ces  experiences  ont  etc  realisccs  de  la  fa (^-on  suivante:  le  stimulus 
inconditionnel  ctait  reprcsente  par  une  S.L.I,  d'une  duree  de  deux  secondcs 
environ  utilisee  avec  une  frequence  capable  d'induire  une  decharge  de 
pointe-ondes  localisee  dans  les  rc'gions  posterieurcs  ou  generalisee.  Cette 
stimulation  ctait  repetee  toutes  les  vingt  secondcs,  le  temps  etant  done 
utilise  commc  stimulus  conditionnel.  La  S.L.I,  a  etc  presentee  au  moins 
20  fois  et  parfois  jusqu'a  100  fois  chez  chaque  sujct.  Les  stimulations 
rcpetees  a  intervalles  rapproches  etant  destinees  a  favoriser  la  developpe- 
ment  de  I'inhibition  interne. 


RESULTATS 

Au  cours  de  ce  travail  ont  etc  etudiees  les  modifications  de  I'activite  de 
fond,  cellcs  de  la  reponse  inconditionnelle  et  celles  de  la  rcponse  condi- 
tionnelle. 

(A)  Modifications  a  I'activite  dc  fond. 

Chez  la  plupart  des  sujets,  le  rythme  alpha  se  renforce  progressivement 
et  s'il  existe  des  frequences  lentes  dans  le  trace  dc  repos,  elles  se  developpent. 

Les  decharges  spontanees  de  pointe-ondes,  si  elles  sont  presentes  ante- 
rieuremcnt  voient  leur  nombre  augmenter,  leur  duree  s'allonger. 

Ces  modifications  qui  s'installcnt  progressivement  sont  parfois  brutale- 
ment  remplacces  par  une  acceleration  de  frequence  des  rythmes  chez  des 
sujets  qui  se  lassent  de  I'experience  ou  qui  sont  genes  par  des  conditions 
exterieures  (inhibition  externe). 

(B)  Les  modifications  de  la  reponse  au  stimulus  inconditionnel. 
I.  L'entrainement  a  la  S.L.I. 

L'entrainement  est  d'autant  plus  ample  que  les  rythmes  de  fond  du 

^  Ces  decharges  s'accompagiiaient  soit  d'uiie  absence  Petit  Mai  typique,  soit  d'une  niyo- 
clonie;  elles  pouvaient  etre  infracliniques. 

SS 


628  BRAIN    MECHANISMS    AND    LEARNING 

sujet  sont  mieux  synchronises,  il  tend  done  a  augmenter  d'amplitude  et  a 
irradier  en  dehors  de  la  region  posterieure,  au  cours  de  I'evolution  de 
I'experience. 

FS-R      vwvsi.VtMwn/^v-  A^>v^VVll/v^^'i''.VViM^iv-. 
SI S12 

praOTTi 


■-•-'^^^h'^if^}^y'f^i\'>/l\jif{'^y^^ 


,-  ^ 


%'V^'^^"V|*'  V( 


-.^V*- — VA-*-'»A'V/ 


_S31 

Fig.  I 

Modifications  de  la  decharge  de  pointe-ondes  induite  par 
Ic  stimulus  inconditionnel  (stimulation  lumineuse  inter- 
mittcntc)  au  cours  d'une  experience  de  conditionnement. 

Calibration:  amplitude  lOO  microvolts;  vitesse  I  cm. 
5  par  seconde.  Enregistrement  bipolaire.  FS :  frontale 
superieure;  R:  rolandique;  P:  parietale;  O:  occipitale; 
VA:  vertex  anterieur;  VM:  vertex  inoycn;  S:  signal. 

La  premiere  presentation  de  la  lumiere  (S.i)  ne  provoque 
pas  de  decharge  de  pointe-ondes.  Pour  le  douzieme  essai 
(S.I 2)  la  decharge  apparait  quelques  secondes  apres  la  pre- 
sentation de  la  lumiere.  Pour  le  jieme  assai  (S.31)  la  de- 
charge  de  pointe-ondes  apparait  encore  plus  tot. 


2.  La  decharge  de  pointe-ondc  gc'nerahsee. 

La  decharge  de  pointe-onde  apparait  phis  precocement  par  rapport  au 
debut  de  I'apphcation  du  stiniuhis  inconditiomiel  au  fur  et  a  mesure  que 
I'experience  se  deroulc.  Lorsque  la  decharge  de  pointe-ondes  ne  sicgeait  au 


R.    NAQUET 


629 


debut  que  dans  Ics  regions  postericurcs  clle  tend  a  se  generaliser.  Elle  est  de 
plus  longue  durcc,  c'est-a-dire  que  lorsque  la  dccharge  est  auto-entretenue, 
elle  se  continue  plus  longtemps  apres  la  cessation  de  la  S.L.I.  (Fig.  i). 


pp.  PS    ^^    ^v_J^*l^       ^---v-       — -j|>|^^' 
FS-R 


— m 


A        y,.',~^-tr'^if-'f^\/-yl^ 


«/^^^|l![^jVv-<^V/»rv«-v,^ 


Willliiiiiiiiuililillll 

S.1. 


llliiiiiH|i|ll 


fjMj\rJ — ^^'■^r'^'V^^'>Jl^^ 


S.3. 


.^.tr^^ ^fL^^^-^n^vH^Av^        .-^..^^r^^^-^^ffy^y--^^^T^^ 


Fig.  2A 
Provocation  d'une  dccharge  critique  focalisee  aii  cours  d'une  experience  de  conditioniienient, 
chez  un  siijet  de  i  5  ans  prcsentant  une  epilepsie  de  type  myocloniqiie. 

Calibration:  amplitude  100  microvolts;  vitesse  I  cm.  5  par  seconde.  Enregistrement  bi- 
polaire.  TM:  temporale  moyenne;  TP;  temporale  posterieure;  FP;  frontale  polaire;  FS: 
frontalc  superieure ;  R :  rolandique ;  P :  parietale ;  O :  occipitale ;  S :  signal.  Les  5  premieres  lignes 
du  trace  correspondent  a  I'hemisphere  droit,  et  les  5  dernieres  a  I'hemisphcre  gauche. 

La  premiere  presentation  de  la  lumiere  (S.i)  provoque  une  decharge  de  poiiite-oiides 
generahsee  qui  apparait  avec  un  certain  retard.  La  troisicme  presentation  de  la  lumiere  (S.3) 
provoque  I'apparition  d'une  dccharge  de  pointe-ondes  generalisee  apparaissant  mimediatement 
apres  I'application  du  stimulus  lumineu.x. 

Noter  que  dans  les  deux  cas  la  decharge  de  pointe-ondes  n'est  suivic  d'aucun  phenomcne 
paroxystique  focalise. 


Quoiqu'il  n'existe  pas  de  rapport  exact,  cntre  la  decharge  de  pointe- 
ondes  et  I'etat  de  synchronisation  ou  de  desynchronisation  du  trace,  il  est 
possible  d'atfirmer  que  les  pointe-ondes  tendcnt  a  diniinuer  lorsque  le 
sujet  devient  anxieux  et  gene  et  que  la  frequence  de  son  trace  s'accelere. 


630  BRAIN    MECHANISMS    AND    LEARNING 

3.  L'apparitioii  dc  crises  focalisees. 

Dans  ncuf  cas  sur  vingt  quatrc,  dcs  dcchargcs  dc  pointcs  rythniiques  out 
apparu.  Dans  un  cas  il  s'agissait  d'unc  crise  gcncralisce  d'cniblee  suivaiit 
une  longuc  dcchargc  dc  pointc-c^ndcs  cgalcmcnt  gcncralisce  dcclcnchce 
par  la  trcnte  septicme  presentation  dc  la  luniicre.  Cette  crise  electro- 


S.7 


vJ 


Fig.  2B  (suite  du  2A) 
La  septicme  presentation  dc  la  luniiere  (S.7)  provoquc  une  decharge  de 
polypointe-ondcs  gcncralisce  acconipagnee  de  myoclonics.  Elle  est  suivie 
aprcs  I'arret  dc  la  S.L.I,  d'une  dcchargc  dc  pointcs  rythniiques  rapides 
occupant  la  region  temporo-occipitale  de  Themisphcre  gauche. 

Pendant  ce  temps  le  sujct  presente  quelques  phosphcnes  et  dcvie  les 
ycux  a  droite. 


graphique  s'accompagnait  du  point  de  vue  cliniquc  d'unc  crise  Grand  Mai 
typique. 

Chez  huit  sujcts,  il  s'agissait  de  dcchargcs  critiques  de  pointcs  rythnii- 
ques survenant  soit  une  fois,  soit  plusieurs  foisQusqu'a  huit  a  dix  au  cours 
d'une  memc  seance)  soit  sur  un  hemisphere,  soit  sur  les  deux,  soit  tantot 


R.    NAQUET  631 

sur  I'un,  tantot  sur  I'autrc.  Ccs  dcchargcs  ctaient  focalisccs  ct  occupaient 
en  general  le  carrefour  dcs  regions  teniporale  posterieure,  parietale  et 
occipitale  (Fig.  2  A  et  B).  Elles  pouvaient  rester  localisees  a  cette  region  ou 
irradier  progressivement  en  avant  et  se  generaliser.  Elles  pouvaient  etre 
parfaitement  infracliniques  ou  s'accompagner  de  phcnomcnes  visuels 
(phosphcnes  ou  hemianopsie)  meme  chez  les  sujets  qui  n'avaient  jamais 
prcscntc  dc  crises  de  cette  sorte  auparavant.  Lorsqu'elles  irradiaient  en 
avant,  le  sujet  prcsentait  des  heniiclonics  suivies  ou  non  d'unc  crise 
gencralisee.  Ces  crises  apparaissaient  rarement  dcs  I'application  dcs  premiers 
stimuli  mais  plutot,  aprcs  plusicurs  presentations  dc  la  lumicre  (a  partir  dc 
la  8cme  ou  locmc),  lorsque  les  dccharges  dc  pointe-ondes  augmentaient 
d'amplitudc,  ainsi  que  rentraincment  a  la  lumicre  et  que  I'cnsemble  du 
trace  tendait  a  se  ralentir.  Elles  ne  sont  survcnues  que  chez  les  sujets  qui 
presentaient  un  trcs  important  cntraincmcnt  a  la  lumicre  (ncuf  sur  quinze), 
jamais  chez  les  autres;  elles  sont  apparucs,  qu'il  cxiste  dcs  pointe-ondes 
spontancs  et  provoques  par  la  lumicre,  ou  seulcmcnt  provoqucs  par  la 
lumicre. 

(C)  Les  modifications  dc  la  rcponsc  au  stimulus  conditionncl. 

1.  Pendant  les  deux  secondes  qui  precedent  I'application  du  stimulus 
inconditiomiel,  trcs  rapidcmcnt,  (cntrc  la  3cmc  ct  la  6cmc  presentation  dc 
la  lumicre)  chez  tons  les  sujets,  il  a  etc  possible  dc  notcr  unc  dcsynchronisa- 
tion  gencralisee  dcs  traces  {hloca(^c  avidirioiiuc  i^aicralisc)  (Fig.  3B),  avec 
disparition  dcs  ondcs  Icntcs  ct  blocagc  dune  dccharge  dc  pointe-ondes,  si 
elle  existait  spontancment.  Cc  phcnomcnc  plus  ou  moins  durable,  varie 
selon  le  moment  dc  Fcxpcricncc,  c'cst-a-dire  qu'il  pcut  disparaitre  aprcs 
deux  ou  trois  combinaisons  pour  rcapparaitrc  aprcs  unc  quinzainc  de 
combinaisons,  disparaitre  a  nouveau  ct  rcapparaitrc.  Dans  six  cas  sur  vingt 
quatrc,  unc  dcsynchronisation  uniqucmcnt  limitcc  a  la  region  occipitale 
[hloan^c  coiiditioiiiic  I'Kalisc)  a  pu  ctrc  atiu-mcc  dc  fa(;on  indiscutable 
(Fig.'3C). 

Dans  seize  cas  sur  vingt  quatrc,  un  renforccment  du  rythmc  alpha  ou 
I'apparition  d'ondcs  Icntcs  soit  gcncralisccs,  soit  plutot  localisees  a  la  sculc 
region  occipitale  a  etc  nettcment  constate.  En  general,  cc  phcnomcne 
apparait  aprcs  dc  nombrcuscs  presentations  dc  la  lumicre  (a  partir  de 
quinze  environ)  lorsque  tout  phcnomcne  d'activation  a  disparu,  mais  il 
n'existe  pas  de  regie  absolue.  Par  cxemplc  chez  un  mcmc  sujet  unc  dcsyn- 
chronisation gencralisee  est  toujours  possible  vers  la  trcnticme  presentation 
dc  la  lumicre,  alors  qu'une  dcsynchronisation  localisec  ctait  constatee  a  la 
locme,  et  des  ondcs  lentes  a  la  i2cme. 

2.  Dans  aucun  cas,  il  n'a  ete  possible  d'enrcgistrer  pendant  le  stimulus 


632  BRAIN    MECHANISMS    AND    LEARNING 


B 


C 


D 


1' '  1 1 


/IVNiWiW 


i,^j^' 


S16 


S20 


Fig.  3 
Modifications  dcs  traces  dans  I'espace  de  temps  qui  precede  ini- 
nicdiatenicnt  ['application  du  stimulus  inconditionnel,  chez  un 
sujet  dc  20  ans  presentant  unc  epilcpsie  de  type  'Petit  Mai  absence' 
spontance  et  favorisee  par  la  lumierc. 

Calibration:  amplitude  100  microvolts,  vitesse  i  cm.  5  par 
seconde.  Enregistrement  bipolairc.  R:  rolandique;  P:  parictale;  O: 
occipitale;  S:  signal.  La  S.L.I,  est  representee  par  un  trait  noir 
continu. 

(A)  Lors  du  premier  essai  (S.i)  la  S.L.I,  provoquc  une  dccharge 
de  pointe-ondcs  generalisee  visible  sur  les  deux  canaux  choisis 
pour  la  figure. 

(B)  Pour  le  ycme  essai  (S.9)  un  aplatissement  generalise  dcs  traces 
apparait  avant  la  presentation  de  la  S.L.I. 

(C)  Pour  le  i6eme  essai  (S.16)  I'aplatissement  du  trace  est  simple- 
ment  localise  a  la  region  la  plus  posterieure  du  scalp. 
Noter  que  les  rythmes  de  fond  sc  sont  amplifies  dans  I'inter- 
valle  des  stimulations. 

(D)  Pour  le  2oeme  essai  (S.20)  apparait  une  decharge  hypersyn- 
chrone  juste  avant  I'application  dc  la  S.L.I. 

Noter  que  les  rythmes  de  fond  sont  toujours  plus  amples 
qu'au  debut  de  rexpcricnce  et  qu'ils  se  sont  ralentis  par  rapport 
a  ccux  notes  en  C. 


R.    NAQUET  633 

conditiomiel,  rentraiiiement  dc  la  rcponse  occipitalc  [repetitive  response) 
induite  par  le  stimulus  inconditionnel. 

3.  Dans  sept  cas  sur  vingt  quatre  sujets  utilises,  des  dccharges  dc  pointe- 
ondes  ont  ete  enregistrees  pendant  les  deux  secondes  qui  prcccdaient 
I'application  du  stimulus  inconditionnel  (Figs.  4  et  5).  Il  est  a  noter,  que  ces 
sept  sujets  prcsentaient  dans  leurs  traces  de  repos  des  dccharges  analogues 


S27    iiiiitijilffi 


S28 


- S-^-liiil ■— 


Fig.  4 
Apparition  de  dccharges  de  pointe-ondcs  generalisces  iinmcdiatemcnt  avant  Tapplication  du 
stimulus  inconditionnel.  Continuation  dc  I'expcrience  notee  sur  la  figure  3. 

Calibration:  amplitude  100  microvolts,  vitesse  I  cm.  5  par  seconde.  Enregistrement  bi- 
polaire.  FS:  frontale  supcrieure;  R:  rolandique;  P:  parietalc;  O;  occipitalc;  VA:  vertex  an- 
tcrieur;  VM:  vertex  moyen;  S:  signal. 

Pour  la  27eme  presentation  de  la  lumierc  (S.27)  il  n'existe  pratiqucment  pas  de  modifica- 
tions electrographiques  dans  les  secondes  qui  precedent. 

Les  28eme-30cme  et  33eme  presentations  de  la  S.L.I.  (S.28,  S.30,  S.33)  sont  prccedces  deux 
secondes  avant  d'une  decharge  dc  pointe-ondes  gcneralisee. 


et  qu'elles  ne  sont  jamais  apparucs  chez  ceux  qui  n'en  avaicnt  qu'a  la 
S.L.I.  Lorsque  ces  dccharges  apparaisscnt,  il  est  possible  de  les  voir  se 
rcpcter  pendant  plusieurs  stimulations  successives,  alors  qu'elles  n'existent 
pas  dans  leur  intervallc.  Ellcs  ne  surviennent  cependant  qu'aprcs  de 
nonibreuses  presentations  de  la  lumicre,  en  general,  a  partir  dc  la  quin- 
zicme;  elles  disparaissent  lorsque  le  trace  s'accclere  sous  I'influence  d'une 
inhibition  externe. 


634  BRAIN    MECHANISMS    AND    LEARNING 


SI     

S19    

S32 


S33 


Fig.  5 
Apparition  d'unc  dccharge  dc  pointc-ondcs  ininicdiatcmcnt  avant  I'appli- 
cation  du  stimulus  inconditionncl  chez  un  sujct  dc  14  ans  atteint  d'absence 
de  type  Petit  Mai,  survenant  spontaneinent  ct  provoquee  par  la  S.L.I. 

Calibration:  amplitude  100  microvolts,  vitesse  i  cm.  5  par  secondc. 
Enregistrcment  bipolaire.  P :  parietale ;  O :  occipitalc ;  V  A :  vertex  anterieur ; 
VM:  vertex  moyen;  S:  signal. 

(A)  La  premiere  presentation  de  la  lumicrc  (S.i)  provoquc  unc  breve 
dccharge  de  pointe-ondes  predominant  autour  du  vertex. 

(B)  La  iQcme  presentation  (S.19)  provoquc  unc  dccharge  de  pointe-ondes 
generalisee  auto-entretenue,  ne  cessant  pas  avec  la  stimulation 
lumineuse.  Noter  qu'elle  est  immediatement  precedee  d'une  bouffee 
d'ondes  lentes  predominant  dans  la  region  postcrieure. 

(C)  2  secondcs  avant  la  32eme  presentation  (S.32)  apparait  unc  dccharge 
dc  pointe-ondes  generalisee  analogue  a  celle  rcncontree  parfois 
spontancment,  parfois  provoquee  par  la  S.L.I.  Le  stimulus  incondi- 
tionncl (S.L.I.)  n'est  pas  presente  au  sujet. 

(D)  A  la  stimulation  suivante  le  trace  est  a  nouveau  rapide,  ct  la  33eme 
presentation  (S.33)  ne  provoquc  aucun  phcnomene  paroxystiquc. 


R.    NAQUET  635 

CONCLUSIONS 

Ces  rcsultats  perincttent  dc  tircr  Ics  conclusions  suivantes: 

(a)  La  repetition  du  stimulus  inconditionncl  augmente  les  reponses 
cvoquccs  par  la  S.L.I,  en  meme  temps  qu'elle  favorisc  I'apparition  des 
decharges  hypersynchrones  paroxystiques  a  type  de  pointc-ondcs  et  celle 
de  crises  focalisees. 

Ces  resultats  sont  dus  trcs  probablemcnt  au  fait  que  la  technique  expcri- 
mcntale  utilisce  facilitc  le  dcveloppcmcnt  d'une  inhibition  interne  de 
repetition  ou  habituation  dcja  visible  sur  les  traces  de  repos.  En  eftet  tout 
phcnomcne  qui  tend  a  augmenter  la  synchronisation  physiologique  des 
traces  augmente  I'amplitudc  des  potentiels  cvoques  corticaux  induits  par 
une  stimulation  lumineuse  intermittente  (Naquct  et  Pruvot,  1956)  ct 
favorisc  I'apparition  des  decharges  de  pointe-ondcs  generalisees  alors  que 
toutc  activation  corticale  aura  tendance  a  les  bloqucr,  comme  cela  est 
admis  depuis  plusicurs  annees  chez  I'Homme  et  a  etc  demontrc  experi- 
mentalement  chez  rAnimal  (Naquet,  Drossopoulo  et  Salamon,  1956). 

Si  les  decharges  critiques  f(U~ahsees  peuvent  apparaitrc  en  dehors  de 
toute  experience  de  conditionncmcnt  (Naquet,  Fcgerstcn,  Bert  et  Carcas- 
sonne-Mottcz,  1959),  et  sont  dues  a  I'arrivee  d'aiferenccs  spccihqucs  dans 
unc  aire  occipitale  hypercxcitable,  toute  condition  qui  permettra  I'aug- 
mcntation  d'amplitude  des  potentiels  cvoques  accroitra  les  possibilites  de 
dcclenchement  d'une  crise  par  une  S.L.L 

Ces  conditions  semblent  etrc  reunies  dans  cette  serie  experimentalc  chez 
les  sujets  qui  presentaient  spontanement  une  rcponse  cxagcrce  a  la  lumiere 
ct  chez  Icsquels  le  systemc  d'evcil  est  mis  au  repos  par  la  repetition  rap- 
prochee  de  la  S.L.L  II  est  done  necessaire  de  faire  jouer  dans  le  dcclenche- 
ment de  crises  focalisees  induitcs  par  des  afterenccs  visuellcs  chez  I'Homme 
(veritable  "cpilepsie  de  Clementi")  un  role  predominant  aux  afterenccs 
specifiques,  sans  negliger  cependant  I'etat  des  systcmes  non  spccifiques. 

(/;)  Au  cours  de  ces  experiences,  les  phenomenes  dc  blocage  generahse  et 
localise  mis  en  evidence  chez  ranimal  (Morrell  et  Jasper,  1956;  Morrell, 
Naquet  et  Gastaut,  1957),  et  chez  I'Homme  (Gastaut  et  col.,  1957)  ont 
etc  confirmcs.  Seule  la  sequence  etablie  par  Morrell  et  Jasper  (1956)  chez 
I'animal  n'a  pas  toujours  etc  retrouvee.  Il  n'a  pas  etc  possible  de  mettre  en 
evidence  de  conditionnement  d'une  reponse  repetitive,  seulcs  des  ondes 
lentes,  localisees  ou  diffuses  ont  pu  ctrc  niises  en  evidence  dans  rintervalle 
qui  precede  le  stimulus  inconditionncl.  Ccci  tendrait  a  infirmer  les  travaux 
de  Morrell,  Naquet,  Gastaut  (1957)  et  a  confirmer  les  travaux  de  Jouvet, 


636  BRAIN    MECHANISMS    AND    LEARNING 

Bcnoit  ct  Courjoii  (1957)  chez  ranimal,  ct  ccux  dc  Gastaut  et  col.  (1957) 
ainsi  que  ccux  dc  Stevens  (1959)  chez  rHommc. 

[c)  Toutes  les  fois  qu'unc  rcponse  a  type  de  pointe-ondes  depend 
exclusivcment  de  I'arrivee  d'un  stimulus  lumineux  intermittent  il  n'a 
jamais  etc  possible  dc  la  faire  apparaitre  pendant  le  stimulus  conditionncl. 

En  revanche,  les  dccharges  de  pointe-ondes  spontances,  c'est-a-dire 
ccllcs  qui  existent  en  dehors  d'unc  stimulation  lumincuse  intcrmittente,  et 
ne  sont  que  facilitces  par  cllc,  tendent  a  apparaitre  pendant  Ic  stimulus 
conditionncl.  Mais  a  I'invcrsc  dcs  phcnomcnes  dc  blocagc  qui  surviennent 
trcs  rapidcmcnt,  ces  dccharges  n'apparaissent  qu'aprcs  un  ccrtani  nombre 
de  presentations,  lorsque  les  processus  d'inhibition  se  sont  dcvcloppcs;  en 
dehors  de  I'inhibition  interne  dc  repetition  dcja  signalcc,  le  fait  que  cctte 
inhibition  soit  beaucoup  plus  importante  pendant  le  stimulus  conditionncl 
pose  Ic  problcme  de  la  creation  d'unc  inhibition  conditionncc. 

Comme  cc  conditionnemcnt  n'apparait  que  pour  des  dccharges  existant 
au  repos  on  pent  exclurc  qu'il  a  etc  possible  dc  conditionner  des  dccharges 
de  pointe-ondes  induites  par  la  S.L.I,  mais  que  Ton  a  simplcment  facilite 
I'apparition  de  certaincs  dccharges  prc-existantes.  Le  tcrme  d'epilcpsie 
reflcxo-conditiomicc  post-affercntielle  nc  pcut  done  s'appliqucr  aux 
phcnomcnes  que  nous  avons  obtenus. 

Enfm  la  facilitation  dcs  dccharges  pendant  le  stimulus  conditionnc,  chez 
les  sujets  qui  en  prcscntaient  spontinemcnt,  nous  scmblc  egalcment  la 
consequence  d'un  phenomcne  dc  synchronisation  a  point  de  depart  cortical 
localise  (region  occipitale)  ou  sous-corticale  (thalamus  ou  formation  reti- 
culee  mcsenccphalique).  Les  phcnomcnes  de  blocagc  conditionnc  em- 
pcchent  en  revanche  I'apparition  de  ces  dccharges  dc  pointe-ondes, 
comme  tons  les  phcnomcnes  d'activation  precedemment  dccrits. 

Ces  faits  autorisent  done  a  parlcr  plutot  (en  cc  qui  con^crnc  les  rcsultats 
expcrimentaux  prcsentcs)  dc  conditionnemcnt  d'un  ctat  favorisant 
I'apparition  d'unc  dcchargc  cpilcptique  que  dc  parlcr  dc  conditionnemcnt 
dc  cctte  mcme  dcchargc. 

SUMMARY 

The  first  chapter  is  concerned  with  the  analysis  of  material  published  in 
recent  years  on  the  use  of  reflexo-conditioncd  techniques  (tone  and  light) 
in  the  triggering  of  discharges  of  an  epileptic  form  in  man  and  animals. 

The  second  chapter  is  devoted  to  an  analysis  of  the  results  obtained 
recently  w^ith  these  techniques,  in  the  Laboratoire  de  Neurobiologic  of 
Marseille,  on  subjects  presenting  generalized  spike-and-wave  discharges 
induced  by  intermittent  photic  stimuli  (I.P.S.). 


R.    NAQUET  637 

(a)  Repetitive  unconditioned  stimulation  increases  the  responses  evoked 
by  I.P.S.  at  the  same  time  as  it  favours  the  appearance  of  paroxystic 
hypersynchronous  discharges  of  spike-and-wave  form,  as  well  as  focalized 
seizures  in  the  occipital  region. 

(/))  In  the  course  of  these  expcrunents,  generalized  and  localized 
phenomena  of  blockage  have  been  confirmed.  The  conditioning  of  a 
repetitive  response  could  not  be  evidenced,  localized  or  diffuse  slov\f 
waves  were  found  in  the  intervals  preceding  the  unconditional  stimulus. 

(c)  Every  time  that  a  spontaneous  spike-and-wave  discharge  depended 
exclusively  on  the  I.P.S.,  it  was  never  possible  to  provoke  it  during  a 
conditional  stimulus.  On  the  contrary,  the  spontaneous  spike-and-wave 
discharges  existing  outside  the  I.P.S.  and  which  are  not  facilitated  by  it, 
tend  to  appear  during  the  conditional  stimulus.  But  conversely  to  these 
phenomena  of  blockage,  which  happen  very  quickly,  these  discharges 
appear  only  after  a  certain  number  of  presentations. 

In  the  last  chapter,  the  author  discusses  all  these  phenomena  and 
particularly  the  conditioning  of  the  spike-and-wave  discharges. 

Conclusion:  As  this  conditioning  appears  only  in  discharges  existing  at 
rest,  it  is  possible  to  exclude  that  with  these  techniques  one  could  condi- 
tion spike-and-wave  discharges  induced  by  I.P.S.  One  can  simply  facilitate 
the  appearance  of  some  pre-existing  discharges.  Therefore,  the  term 
'reflexo-conditional,  post-afferential  epilepsy'  cannot  be  applied  to 
phenomena  as  described  above,  because  it  seems  that  it  concerns  mainly 
the  conditioning  of  a  state  which  favours  the  appearance  of  epileptic 
ciischargcs,  and  not  the  conditioning  of  this  discharge. 


GROUP   DISCUSSION 

Magoun.  Dr  Naquel's  presentation  emphasizes  the  role  ot  conditional  processes 
in  the  prevention  and  facilitation  ot  cortical  seizures.  There  is  a  recent  paper  on  this 
subject  by  EfFren,  in  which  the  patient  had  an  uncinate  seizure  which  commenced 
with  an  olfactory  aura.  When  a  strong  odour  was  presented  to  the  patient  each  time 
she  felt  the  aura,  further  progress  of  the  seizure  was  blocked.  Atter  a  surticient 
number  of  such  progress,  the  patient  was  able  to  block  the  progress  of  an  incipient 
seizure  simply  by  thinking  about  this  strong  odour.  One  might  interpret  this  as  a 
conditioned  blockade  or  inhibition  of  an  incipient  seizure.  —  I  wonder  whether 
your  being  able  to  manipulate  these  seizures  with  conditioning  methods  might  be 
used  therapeutically  in  selected  cases. 

Naquet.  My  idea  was  indeed  to  show  a  means  for  preventing  the  appearance  of 
diffuse  or  focalized  epileptic  discharges,  or  on  the  contrary  to  facilitate  them.  It 
seems,  that,  when  a  conditioning  experiment  is  performed,  and  that  a  fit  accom- 
panied   by   generalized   spike-and-wave   discharges  is  concerned,   the  positive 


638  BRAIN    MECHANISMS    AND    LEARNING 

phenomena  are  accompanied  by  dcsynchronization  of  records  which  prevent  the 
appearance  of  discharges.  When  a  phenomenon  of  inhibition  appears  (induced  by 
habituation  or  by  a  conditioning  process),  a  synchronization  may  favour  spike-and- 
wave  discharges. 

It  is  then  possible  by  this  technique  to  prevent  or  facihtate  critical  discharges.  But 
as  we  see,  these  different  states  of  synchronization  and  dcsynchronization  of  the 
record  are  variable  and  do  not  depend  on  the  conditioning  alone.  Therefore,  it 
seems  difficult  to  me  to  apply,  actually,  this  technique  to  therapeutics,  at  least  in 
cases  which  arc  not  preceded  by  an  aura,  and  of  which  the  onset  is  unknown  to  the 
patient. 

Segundo.  Do  you  think  that  conditioned  facilitation  ot  seizures  would  act  only 
to  a  certain  extent  and  within  certain  limits  of  discharges  'intensity'  as  is  known  to 
be  the  case  with  central  brain  stem  influence  upon  cortical  strychnine  spikes; 
(Arduini  and  Lairy-Bounes,  1952). 

Naquet.  I  think  so  —  I  demonstrated  with  Drossopoulos  and  Salamon  (1956) 
the  following  phenomenon:  after  intravenous  injection  of  Metrazol  or  Megiinide 
in  a  cat,  generalized  spike-and-wave  discharges  are  produced.  According  to  the 
dose  of  convulsivant  injected,  it  is  possible  to  obtain  different  effects  after  electrical 
stimulation  of  the  reticular  formation  or  sciatic  nerve :  (a)  with  feeble  doses,  the 
stimulation  of  the  reticular  formation  is  able  to  stop  the  generalized  discharges, 
which  appear  spontaneously  or  after  sensory  stimulations;  (/>)  with  greater  doses, 
the  stimulation  threshold  necessary  to  stop  them  increases,  and  just  before  the 
appearance  of  generalized  seizure,  the  reticular  formation  stimulation  becomes 
unable  to  stop  them,  and  only  a  mere  modification  of  the  shape  of  the  discharge  is 
obtained. 

Chow.  How  can  this  conditioning  of  repetitive  discharge  be  explained  on  a 
neuronal  basis;  We  found  that  in  cats  with  lesions  of  the  anterior  part  of  the  thala- 
mus, the  conditioned  repetitive  discharge  is  very  easily  established.  If  you  destroy- 
some  areas  of  the  cortex  and  if  the  lesion  is  big  enough,  you  cannot  establish 
conditioned  repetitive  discharge. 

Naquet.  It  is  difficult  to  reach  any  conclusion  on  the  significance  of  the  condi- 
tioned repetitive  discharge.  Perhaps  we  are  facilitating  the  appearance  of  some 
rhythnis  existing  before  on  the  cortex.  I  do  not  know  what  the  mechanism  is,  but 
I  agree  with  you  as  to  the  possibility  of  the  cortical  origin  of  these  rhythmical 
phenomena.  For  example,  when  repetitive  responses  appear  at  the  level  of  the 
cortex  in  animals  it  may  mean  that  the  experimenter  has  used  frequencies,  ordin- 
arily found  at  the  level  of  the  cortex  and  that  he  has  obtained  conditions  which 
facilitate  those  frequencies  more  than  others.  It  is  interesting  to  note  that  it  concerns 
mostly  some  slow  frequencies  similar  to  focalized  true  spindles,  and  able  afterwards 
to  become  generalized.  This  fact  results  from  experiments  we  made  with  Morrell, 
after  having  provoked  cortical  irritative  lesions,  as  well  as  from  recent  experiments 
on  the  recruiting  response  just  realized  together  with  Fischer-Williams  and  Fernan- 
dez-Guardiola  on  anoxia. 

Morrell.  This  repetitive  response  is  especially  apparent  when  there  is  evidence 
of  a  decrease  of  reticular  discharge  to  the  cortex,  i.e.  when  it  is  synchronized  rather 
than  desynchronized.  This  represents  then  a  hypersynchronous  activity  in  cortical 
cells  rather  than  in  deeper  structures.  We  have  done  experiments  with  unilateral 
epileptogenic  lesions.  In  those  experiments  under  electro-cortical  conditioning  we 


R.    NAQUET  639 

often  found  repetitive  discharges  on  the  side  of  the  lesion  and  at  the  same  time  dc- 
synchronization  on  the  opposite  side. 

Garcia-Austt.  In  my  experience  the  possibihty  of  modifying  the  seizure  takes 
place  within  a  certain  range  of  intensity,  judged  by  the  frequency  of  the  spikes  and 
tlie  amplitude.  If  the  spikes  are  not  too  frequent,  central  brain  stem  excitation  may 
block  them,  but  if  the  seizure  has  a  certain  degree  of  intensity  then  you  cannot 
block  it  by  reticular  stimulation.  I  would  like  to  ask  whether  you  tried  to  develop 
an  inhibitory  stimulus  and  if  this  stimulus  was  capable  ot  inhibiting  the  discharge. 

Naquet.  In  the  cat  we  were  able  to  block  the  discharge  by  some  negative  tone. 
I  did  not  try  it  on  man. 

Garcia-Austt.  Another  point  is  that  the  patient  learned  to  produce  seizure 
discharge,  a  phenomenon  of  which  he  was  not  conscious.  Now,  it  is  hard  to  con- 
ceive learning  without  a  certain  degree  of  consciousness.  How  would  you  interpret 
this  contradiction  if  there  is  not  an  intermediate  mechanism  that  could  be  activated 
by  the  flicker? 

Naquet.  The  patients  are  not  unconscious  when  we  use  light  and  during  the 
spike-and-waves  discharge.  They  may  have  the  discharge  without  any  impairment 
of  consciousness.  Regarding  the  development  of  inhibition,  our  experiments  with 
lesions  in  cats  and  some  results  we  have  in  man  with  this  type  of  experiment,  may 
prove  that  inhibition  may  start  in  the  cortex  rather  than  in  some  other  subcortical 
structure. 


GENERAL  DISCUSSION 

INTRODUCTION    OF   THE    FIRST    TOPIC:    INBORN    AND    REFLEX    BEHAVIOUR 

Hebb.  I  should  like  to  make  two  comments  on  your  first  group  ot  topics. 

The  hrst  is  that,  to  the  best  of  my  understanding,  our  agreement  on  the  question 
of  the  congenital  or  the  instinctive  is  very  good.  There  are  difficulties  of  termino- 
logy and  probably  still  imperfect  communication  but  so  far  as  I  can  understand, 
wc  have  not  been  saying  different  things.  There  is  not  a  head-on  conflict. 

The  second  poiiit  concerns  the  distinction  that  Lashley  made  in  1938  between 
reflex  and  instinct.  I  think  it  is  most  important  to  recognize  that  instinctive  be- 
haviour is  not  a  complication  of  reflexes  only.  Reflexive  behaviour  depends  on 
specific  receptors  and  effectors,  whereas  instinctive  behaviour  is  something  which 
is  not  definable  in  such  terms.  It  is  not  itself  to  be  described  as  a  series  of  reflexes 
alone. 

Thorpe.  May  I  say  that  I  entirely  agree  with  what  Dr  Hebb  has  just  said.  I 
think  that  this  meeting  has  not  revealed  any  major  disagreement  about  concepts  so 
I  don't  think  much  would  be  gained  by  attempting  a  general  discussion  of  innate 
behaviour  now.  But  there  are  aspects  oi  innate  patterns  which  arc  relevant  to  our 
present  meeting,  and  one  that  interests  me  very  much  is  the  origin  of  patterns  of 
nervous  discharge,  i.e.  the  ncurophysiological  aspect  of  innate  behaviour. 

But  first  I  would  like  to  refer  again  to  a  general  point  which  I  made  earlier  in 
this  meeting,  and  that  is  that  the  best  way  to  decide  whether  we  are  concerned  with 
instinctive  patterns  of  behaviour  or  with  learned  ones  is  to  consider  the  origin  of 
complexity.  Where  does  the  complexity  of  the  behaviour  come  from?  If  we  can 
see  the  necessary  complexity  of  the  input  from  the  environment  then  we  are 
provisionally  justified  in  assuming  that  it  has  been  learned.  If  there  is  complexity 
in  the  behaviour  pattern  which  is  not  seen  in  the  immediate,  or  indeed  the  whole, 
previous  experience  of  the  individual  animal  —  then  we  have  to  assume  that  this 
complexity  comes  from  somewhere  else,  and  it  can  only  have  come  from  the 
inborn  organization  of  the  animal.  That  seems  to  me  to  be  a  valuable  method  of 
deciding  whether  we  are  talking  about  something  which  has  been  learned,  or 
something  that  is  instinctive. 

Fessard.  I  also  think  this  an  essential  distinction  but  not  an  easy  one  to  be  made 
in  practice.  A  reflex  is  an  operation  in  which  we  can  clearly  define  a  stimulus  S  and 
a  response  R,  the  response  thus  appearing  as  a  function  of  the  stimulus.  But  of 
course,  it  is  also  a  function  of  some  unknown  internal  factors  which  we  could  call 
X  for  instance,  and  the  question  of  what  is  a  reflex  and  what  is  not  depends  on  the 
importance  of  X. 

Even  in  the  simplest  reflex  there  are  determining  factors  which  come  from  the 
organism  and  which  are  inborn  or  instinctive.  On  the  other  hand,  in  what  we  call 

641 


642  BRAIN    MECHANISMS    AND    LEARNING 

instinctive  response,  there  are  at  every  instant  internal  stimuli  which  have  a  reflexo- 
genic  power.  The  distinction  between  inborn  patterns  of  X  factors  and  actual 
internal  stimuli  X  is  not  so  easy  to  make  and  there  are  many  controversies  about 
this  point.  I  don't  mean,  however,  that  we  should  not  make  some  distinction  be- 
tween reflex  and  instinct. 

Anokhin.  I  agree  with  Dr  Thorpe:  the  complexity  of  the  inborn  nervous 
structures  is  the  basis  for  inborn  behaviour.  We  have  devoted  our  research  pre- 
cisely to  the  mechanisms  whereby  this  complexity  emerges.  A  study  ot  the  develop- 
ing structures  of  the  nervous  system  of  the  embryo  has  shown  that  they  mature  and 
establish  between  themselves  synaptic  connections  in  a  highly  selective  way  and 
fully  in  conformity  with  the  type  of  behavioural  act  which  is  essential  to  the 
newborn  of  a  given  species,  and  at  the  time  when  it  is  necessary. 

Thus,  tor  instance,  the  descending  tract  of  fibres,  arising  from  the  tegmentum  of 
the  human  foetus,  when  there  are  not  yet  any  other  descending  tracts,  reaches 
the  8th  cervical  segment  and  establishes  there  synaptic  connections  with  precisely 
the  motor  neurones  of  the  anterior  horns,  which  innervate  the  deep  flexors  of  the 
fingers  of  the  hand.  In  turn,  the  nerves  originating  from  the  cervical  cord  of  the 
shoulder,  innervating  the  flexors  of  the  fingers,  are  m^•elinized  earlier  than 
the  other  nerves  of  the  same  level.  All  these  phenomena  contribute  to  the  rapid 
emergence  of  the  grasping  reflex  in  the  human  foetus  which  is  the  first  definite 
behavioural  act  in  the  4th  month  ot  its  prenatal  development.  Such  heterochrony 
is  even  more  clearly  observed  in  the  growth  ot  structures  and  m  the  emergence  of 
functions  in  birds  of  ditfercnt  oecologies. 

Whereas  in  the  chick  hatching  out  of  the  egg  there  is  an  accelerated  differentia- 
tion of  the  motor  elements  of  the  lumbar  region  of  the  spinal  chord,  in  the  rook 
this  accelerated  differentiation  of  the  neurones  affects  first  the  segments  of  the 
shoulder  cervical  region.  Thus  the  accelerated  maturation  of  the  nervous  structures 
progresses  in  exact  correspondence  with  the  functions  which  are  the  first  ones  to  be 
essential  in  relation  to  the  characteristics  of  the  oecology  of  that  animal.  This  can 
also  be  seen,  for  instance,  in  the  fact  that  in  the  organs  of  Corti  of  the  foetus  of  the 
rook  there  develop  precisely  those  receptor  elements  which  correspond  to  the  cry 
of  the  adult  bird:  'Kr  ...  r  ...  r  ...  a  ...  '  (this  can  be  observed  through  a  special 
acoustic  analysis).  This  accelerated,  selective,  oecology-conditioned  development 
of  the  nervous  structures,  has  been  named  by  us  systcnio-oeiicsis  since  specific 
functional  systems  of  the  organism  develop  progressively  and  in  a  selective  way. 

It  is  obvious  that  all  these  reactions  are  truly  inborn  since,  admittedly,  the  new- 
born has  not  yet  had  time  for  any  learning. 

EiBL.  RoEDER  (1955)  pointed  out  that  there  is  no  basic  difference  between  instinc- 
tive and  reflex  behaviour  as  far  as  the  neural  elements  underlying  such  behaviour 
are  concerned.  Different  thresholds  of  neurones  seem  to  make  up  the  main  differ- 
ence, which  is  a  gradual  one.  In  the  stable  neurones  the  excitability  remains  at  a 
constant  resting  threshold.  It  needs  a  stimulus  to  bring  the  excitability  to  the  level 
of  discharge.  After  discharge  the  excitability  falls  to  zero,  then  rises  gradually  again 


GENERAL    DISCUSSION  643 

bricriv  passing  the  resting  threshold.  Atter  this  phase  ot  higher  irritabiht\-  it  tails 
back  to  the  normal  resting  threshold,  hi  the  unstable  neurones  the  excitability,  and 
with  it  the  readiness  to  response,  builds  up  until  the  thresholci  of  release  is  reached 
bv  itseh  and  a  spontaneous  discharge  can  take  place.  Between  these  two  extremes 
all  gradients  can  be  found.  If  for  example  the  resting  and  the  response  thresholds 
become  approximated  one  stimulus  can  lead  to  a  self-perpetuating  sequence  of 
discharges,  as  the  curve  ot  excitability  will  repeatedly  reach  the  releasing  threshold. 
Reflex  behaviour  alwa)s  needs  an  input  tor  discharge  and  is  therefore  more  strictly 
under  atf'erent  control  than  the  more  spontaneous  instinctive  acts,  which  can  go  oft 
in  a  vacuum.  But  normally  thev,  too,  are  released  by  certain  key  stimuli. 

Anokhin.  When  we  speak  ot  inborn  behaviour,  we  should  bear  m  mind  that  all 
our  considerations  can  apply  only  to  the  very  tirst  acts  ot  the  newborn,  since  the 
first  behavioural  acts  enrich  the  inborn  tunctional  s}stems  by  new  afferent  stimuli 
trom  the  environment,  hi  practice  we  never  get  'inborn  behaviour'  in  its  pure  torm 
after  2  or  3  days  following  the  birth  of  an  animal,  although  the  end  nucleus  of  the 
reaction  was  included  in  the  embr)-ogenesis  on  the  basis  ot  the  heterochronic 
growth  ot  the  nervous  structures. 

This  rule  applies  to  such  specific  human  behaviour  as  for  instance  the  human 
mimic  reactions.  As  our  research  has  shown,  as  early  as  on  the  5th  or  6th  month  oi 
its  prenatal  lite,  the  human  toetus  is  able  to  react  to  external  stimuli  by  quite 
diverse  mimetic  reactions. 

The  emotional  quality  ot  these  reactions  is  so  well  determined  that  there  can  be 
no  doubt  in  the  observer's  mind:  'this  is  unpleasant!',  'it  hurts!' 

Fessard.  I  think  the  use,  or  for  some  the  abuse,  of  this  expression  'inborn 
behaviour'  is  also  a  question  of  doctrinal  position.  Our  colleagues  from  Eastern 
countries  have  the  view  some  of  us  find  too  extreme  that  animal  behaviour  is 
entirely  determined  bv  the  stimuli  —  either  external  or  internal  —  present  at  every 
moment.  Most  of  us  prefer  making  a  sharp  distinction  between  what  comes  trom 
the  outside  world  and  what  depends  upon  a  set  oi  internal  incitations  organized 
according  to  an  inborn,  and,  so  to  speak,  ever  present  pattern  ot  dynamic  possibili- 
ties, to  which  correspond  certain  structures  within  the  central  nervous  s}-stem. 

Anokhin.  In  connection  with  the  remarks  made  by  Dr  Eibl  and  with  the 
morphological  assumptions  on  inborn  behaviour,  I  should  like  to  stress  one  physio- 
logical teature  in  the  heterochrony  and  s-\-stematic  maturation  of  the  nervous 
structures  in  embryogenesis.  We  have  been  able  to  note  the  tollowing  rules:  the 
tunctional  system,  which  trom  the  morphological  point  of  view  has  been  formed 
earlier  than  the  other  system,  has  a  rather  low  threshold  of  excitability  and  there- 
fore acts  as  the  dominant  function  at  that  given  stage  of  development.  This  means 
that  any  internal  or  external  stimulus,  however  small,  will  indeed  first  ot  all 
stimulate  into  action  the  dominant  tunctional  system. 

In  this  way  the  physiological  predominance  ot  the  functional  systems  which  has 
matured  earlier  than  others  is  one  of  the  decisive  factors  brniging  about  a  high 
adjustment  and  adequate  timing  ot  inborn  behaviour. 

TT 


644  BRAIN    MECHANISMS    AND    LEARNING 

Thus,  for  instance,  in  the  rook  at  the  hatching  stage  any  external  stinuihis 
strengthens  and  speeds  up  the  act  of  pecking.  Whilst  in  the  young  bird  which  has 
already  freed  itself  from  the  egg  the  same  stimulus  initiates  the  feeding  reaction  bv 
the  opening  of  the  beak. 

In  this  way  the  heredity-fixing,  heterochrony  growth  of  the  nervous  structures 
and  the  oecological  factors  of  a  given  animal  determine  the  perfection  and  accuracy 
ot  its  inborn  behaviour. 

Thorpe.  Obviously  an  animal  is  continually  dependent  on  a  groat  many  things 
in  the  environment  (the  oxygen  supply,  for  instance),  and  if  this  is  changed  the 
whole  behaviour  pattern  may  go  wrong.  But  I  think  we  can  rule  out  that  kind  of 
environmental  factor  as  an  adequate  'explanation'  for  the  complexity  of  instinctive 
behaviour.  I  do  think,  however,  that  you  have  touched  upon  an  important  point 
in  distinguishing  behaviour  arising  from  stimuli  from  within  the  nervous  system, 
without  being  dependent  on  interoceptors,  from  behaviour  which  is  dependent  on 
interoceptors.  Take  behaviour  which  is  emitted  at  regular  intervals  (a  24-hour 
rhythm,  for  instance).  It  seems  to  have  been  shown  that  such  rhythms  can  arise  in 
a  single  cell.  A  probable  instance  is  provided  by  the  cardiac  ganglion  of  the  lobster. 
This  seems  to  be  an  important  example  of  behaviour  which  is  dependent  neither 
upon  interoceptors  nor  exteroceptors. 

On  the  other  hand,  a  great  many  instinctive  behaviour  patterns  are  undoubtedly 
dependent  on  interoceptors.  I  think  ethologists  were  to  blame  at  one  stage 
for  using  the  word  'endogenous'  very  loosely,  sometimes  meaning  'within  the 
animal'  and  sometimes  'within  the  CNS',  and  that  gave  rise  to  much  misunder- 
standing. 

A  further  point:  I  think  the  distinction  between  instinct  and  reflex  referred  to  is 
an  important  one.  I  think  it  is  perfectly  possible  to  define  reflexes  in  such  a  way  as 
to  include  all  behaviour.  But  it  we  do  that  we  have  abandoned  a  very  useful  term 
which  is  most  valuable  for  denoting  the  'partial  reflexes'  of  physiology.  If  we 
expand  the  term  'reflex'  to  include  everything  then  we  tend  to  speak  so  loosely 
that  we  get  involved  in  much  sterile  argument  about  definition. 

Fessard.  I  think  so  too,  in  view  of  the  importance  we  should  give  to  the  notion 
of  'trigger'.  If  the  trigger  is  under  close  control  of  the  environmental  factors  so 
that  yoti  can  make  a  correspondence  between  the  responses  and  the  variations  in 
the  environment,  then  you  can  speak  of  a  reHex  or  of  a  succession  of  reflexes.  But  if 
the  trigger  is  not  under  external  control  and  you  cannot  therefore  anticipate  what 
the  reaction  will  be  like  then  we  may  consider  the  reaction  to  be  instinctive. 

Gerard.  X  incorporates  into  itself  that  part  of  the  experience  of  the  organism 
which  has  been  fixed,  and  therefore  the  reaction  of  the  system  is  different  at  each 
time  from  what  it  was  before.  To  some  extent,  then,  any  line  of  division  is  mean- 
ingless: we  have  a  spectrum,  not  a  series  of  black  and  white  divisions.  We  would 
all  agree  that  the  inborn,  congenital,  and  reflex  mechanism,  and  I  would  think  a 
good  many  of  the  others  also,  are  set  by  the  original  growth  —  of  something  — 
and  learning  leaves  behind  a  change  in  the  permanent  structural  substrate,  which 


GENERAL    DISCUSSION  645 

determines  particular  responses  ot  that  system  to  given  stimuli  at  any  time.  From 
that  point  of  view,  it  seems  useful  to  consider  whether  instinct  is  or  is  not  a  reflex. 
1  don't  recall  the  criteria  Lashley  used,  but  let  me  suggest  an  operational  approach 
to  this. 

If  we  hnd  that  the  behaviour  ot  essentially  all  normal  members  of  an  adequate 
sample  of  some  species  is  the  same  to  the  same  external  situation,  then  we  can  say 
tliat  the  experience  of  individuals  has  been  sufficiently  unitorm  to  insure  a  constant 
response,  for  all  individuals.  I  have  not  been  specific  about  this  experience  tor  it 
includes  everything  that  happened  from  the  time  the  egg  was  fertilized.  Normally, 
the  experience  of  the  2-cell  and  the  S-cell  and  the  32-cell  stages  ot  the  embryo  are 
enormouslv  constant  from  one  individual  to  another,  so  the  behaviour  that  develops 
is  constant,  and  we  can  sately  call  all  this,  inborn  constancy. 

On  this  kind  oi  criterion,  is  instinct  or  instinctive  behaviour  less  determined,  less 
reflex,  if  depending  on  inborn  patterns  than  is  what  we  call  a  spinal  reflex;  If  it  is  as 
constant,  then  it  might  be  perfectly  valid  to  think  ot  it  as  a  reflex.  My  picture  is 
that  the  emotional  patterns  elicited  from  hypothalamic  animals,  and  the  like,  are 
just  about  as  stereotyped  and  universal  as  the  flexor  or  other  reflexes  elicited  from 
the  spinal  cord. 

Magoun.  I  was  happy  to  hear  Dr  Fessard  introduce  an  acknowledgement  to 
philosophy  in  this  discussion  and  would  suggest  that  we  could  go  back  to  John 
Locke  who  proposed  that  the  mind,  as  this  field  was  called  in  the  eighteenth 
century,  was  a  total  blank,  and  that  its  concept  were  derived  entirely  trom  sensa- 
tion. But  he  differentiated  the  content  and  responsiveness  derived  directly  trom 
sensation  trom  that  derived  indirectly  from  reflection  which,  I  think,  is  to  say  that 
sensation  and  reflection  can  be  equated  with  \our  5  and  A',  since  reflection  to 
Locke  was  the  reactivation  ot  previous  sensation.  In  elaborating  those  arguments,  it 
is  of  some  relevance  to  consider  the  attempt  to  detine  the  problem  in  philosophical 
terms  at  least  a  century  betore  it  began  to  be  studied  with  pliysiological 
techniques. 

Fessard.  I  am  surprised  to  see  that  in  the  course  ot  our  debate  no  mention  has 
been  made  ot  'trial  and  error'  learning. 

Thorpe.  I  like  to  think  ot  'trial  and  error'  learning  as  comprising  both  classical 
and  operant  (or  instrumental  or  action)  conditioning,  whichever  term  you  preter 
to  use.  It  is  the  two  together  that  \ou  almost  always  see  co-operating  in  the  natural 
learning  process  of  a  normal  animal.  For  convenience  they  are  isolated  in  laboratory 
experiments  but  they  are  hardl\-  ever  tound  isolated  in  nature.  I  think  'trial  and 
error  learning'  is  an  invaluable  term  to  include  the  two  combined  and  I  have 
indicated  elsewhere  (Thorpe,  1956,  Table  II,  page  So)  how  I  think  this  combination 
should  be  understood. 

Anokhin.  I  should  like  to  sa\-  that  when  we  compare  inborn  to  learned  be- 
haviour, we  should  bear  in  mind  a  universal  rule  ot  behaviour,  which  connects 
both  inborn  and  learned  behaviour:  the  rule  of  evaluation  oi  the  results  of  an  act 
done  with  the  help  ot  the  reverse  afferent  impulses  received  by  the  brain  at  the  end 


646  BRAIN    MECHANISMS    AND    LEARNING 

of  each  act.  It  is  only  by  this  rule  that  the  individual  stages  and  links  of  instinctive 
behaviour  can  be  constructed  into  an  orderly  chain  of  acts,  leading  to  the  final 
adjustment  effect  for  a  given  animal. 

The  point  is  simply  that  for  learned  behaviour  the  system  ot  evaluation  ot  the 
results  of  an  act  done  (on  which  I  reported  at  this  symposium)  —  the  acceptor  ot 
action  is  established  as  a  result  of  individual  experience.  Conversely,  in  the  case  ot 
instinctive  behaviour,  it  has  been  established  as  a  result  of  a  long  philogenetic 
experience  and  has  been  fixed  by  heredity  at  the  time  oi  the  birth  of  the 
animal. 

At  the  present  moment  our  theory  is  confirmed  by  new  facts  and  we  believe 
that  it  is  indeed  the  most  acceptable  one  to  account  for  the  mechanism  ot  the 
adaptive  character  of  inborn  behaviour. 

INTRODUCTION  OF  THE  SECOND  TOPIC  —  SPONTANEOUS  BEHAVIOUR   PATTERNS 

Thorpe.  The  physiological  origin  of  patterned  nervous  discharges  is,  as  I  have 
already  indicated,  a  problem  which  is  fundamental  to  the  study  of  behaviour.  I 
gave  the  example  of  a  single  cell  acting  as  a  pace-maker.  I  mentioned  the  possibility 
of  that  being  so  in  the  cardiac  ganglion  of  the  lobster  and  there  are  a  number  ot 
other  instances  where  a  single  cell  seems  to  be  producing  a  rhythmic  discharge 
which  controls  an  important  and  complex  piece  of  behaviour.  So  there,  presum- 
ably, the  whole  mechanism  for  a  patterned  discharge  is  contained  in  a  single  cell.  I 
would  like  to  ask,  then,  what  you  regard  as  the  normal  condition  for  a  nerve  cell  ? 

Do  you  think  of  the  'standard  nerve  e'en'  as  tending  to  random  discharge  when 
it  is  not  controlled;  but  subject  at  times  to  control  by  a  mechanism  which  can 
cither  completely  inhibit  it  or  else  can  control  it  so  as  to  produce  a  temporal  pattern 
of  discharge?  That  seems  to  me  to  be  the  really  fundamental  aspect  of  this  problem. 
But  in  addition  to  that  I  should  be  extremely  interested  to  hear  the  views  of  the 
various  members  of  this  symposium  on  the  extent  to  which  intracranial  receptors 
(and  other  internal  receptors)  govern  the  discharge  of  nerve  cells,  hi  a  slab  ot 
isolated  cortex  must  the  lack  of  discharge  be  regarded  as  the  normal  state  or  as  a 
special  case  of  inhibition?  There  are  many  other  similar  problems  but  I  hope  I 
have  said  enough  to  indicate  to  you  the  kind  of  tiling  that  strikes  me  as  so  particu- 
larlv  important.  I  hope  I  have  made  myself  clear,  if  not  I  can  perhaps  add  a  word  or 
two  in  the  discussion  later. 

MORRELL.  I  would  like  to  raise  two  questions  with  respect  to  the  subject  ot 
spontaneous  behaviour  patterns.  I  think  one  of  the  most  striking  examples  of  built- 
in  behaviour  patterns  is  that  disclosed  by  the  work  of  Olds  in  the  self-stimulation 
experiments,  hi  those  studies  it  would  appear  that  it  is  the  precise  anatomical 
localization  o(  the  stimulating  electrode  which  determines  whether  the  stimulated 
point  will  be  rewarding  or  'punishing'.  One  wonders  whether  these  same  ana- 
tomical sites  have  the  same  positive  or  negative  significance  m  the  newborn 
animal  as  thev  do  in  the  adult.  It  might  be  interesting  to  see  whether  life  experience 


GENERAL    DISCUSSION  647 

plays  some  role  in  determining  whether  given  anatomical  regions  become  posi- 
tively or  negatively  rewarding.  My  second  question  has  to  do  with  an  observation 
that  has  been  made  repeatedly  tor  many  years  in  psychological  studies  of  learning. 
Most  of  us  have  observed  that  learning  curves  do  not  really  flatten  out  aiter  the 
initial  phase  ot  acquisition  but  actually  continue  to  demonstrate  a  considerable 
amount  of  oscillation.  In  our  experience  this  is  true  oi  habituation  as  well  as  ot 
positive  learning.  One  wonders  whether  at  least  some  portion  of  this  oscillation  is 
not  attributable  to  inborn  excitability  cycles  which  might  determine  the  degree  oi 
responsiveness  possible  at  any  given  moment  in  time.  Biological  rhythms  of  this 
sort  may  have  a  wide  variation  in  frequency  ranging  from  months  or  days  (circa- 
dian  rhythms)  to  cycles  of  very  much  shorter  duration.  Both  Dr  Hernandez-Peon 
and  I  have  been  impressed  with  such  oscillatory  systems  in  our  studies  of  habitua- 
tion. 

Hebb.  It  seems  to  me  that  the  meaning  ot  the  selt-stiimilation  data  is  exactly 
opposed  to  that  ot  spontaneous  behaviour.  The  seeking  tor  stinnilation  in  these 
experiments  is  initiated  by  stimulation  itselt,  as  the  learning  process  goes  on.  The 
nervous  system  acts  in  such  a  way  as  to  produce  an  equivalent  of  external  stimula- 
tion: the  action  being  by  way  of  behaviour,  bv  bar  pressing. 

Olds.  I  am  not  sure  that  I  would  come  to  exactly  the  same  conclusion  as  l)r 
Hebb.  I  think  particularly  relevant  here  is  the  case  where  we  were  reinforcing  unit 
discharges  rather  than  reinforcing  the  overt  response.  In  either  case,  though,  let  me 
point  out,  that  the  response  had  to  be  omitted  first,  in  order  to  be  reinforced.  We 
really  have  in  a  sense  two  problems  here  ot  the  spontaneous  or  the  innate,  first  that 
the  original  response  has  to  be  in  the  repertory  and  has  to  occur  by  chance  or 
'reflex'  before  it  can  be  reinforced;  second  that  in  the  structure  ot  our  organism 
there  has  to  be  a  hypothalamic  mechanism  or  a  system  ot  hypothalamic  mechan- 
isms which,  when  stimulated,  will  either  cause  the  previous  behaviour  to  be 
repeated  or,  in  one  way  or  another,  cause  the  animal  to  come  back  for  more.  That 
is  to  say  two  things  have  to  be  here  prior  to  learning:  one  is  the  spontaneous 
response  and  the  second  is  the  h\pothalamic  reinforcement  mechanism  whatever 
we  postulate  it  to  be. 

One  of  the  other  points  that  I  would  like  to  put  on  record:  The  hypothalamic 
reinforcement  system  appears  to  be  an  innately  diflerentiated  mechanism;  i.e. 
anatomically  divided  into  functional  groups.  As  an  example  I  would  cite  the 
precise  anatomical  determination  ot  self-stimulation  rates.  We  are  sure,  in  the  rat, 
that  by  fir  the  greater  part  ot  the  variance  in  self-stimulation  rate  is  accounted  for 
by  the  placement  of  the  electrodes. 

Let  me  now  go  on  with  the  concept  of  reinforcement  here.  The  behaviour  occurs 
spontaneously  and  there  excitation  in  the  hypothalamus  occurs;  at  this  point 
something  has  to  happen  to  the  previous  behaviour,  or  shall  we  say  to  the  structure 
in  the  organisms  which  somehow  produces  that  behaviour  or  elicits  that  behaviour 
—  it  must  somehow  become  stronger,  more  frequent  or  what  have  you.  I  am  greatlv 
tempted,  and  perhaps  it  is  solely  a  matter  oi  preference  from  these  recent  studies  on 


648  BRAIN    MECHANISMS    AND    LEARNING 

the  rcinforccnicnt  ot  smglc-unit  discharges,  and  from  the  apparent  phenomenon 
that  we  sometimes  ehcit  the  unit  discharge,  say  by  the  pressure  ot  introduction  of 
the  wire,  and  then  reinforce  it,  to  hope,  I  will  not  say  to  suppose,  only  to  guess  that 
the  unit  itself,  the  spontaneous  unit  discharge,  is  something  which  can  be  rein- 
forced. That  is,  that  there  is  a  spontaneous  discharge  pattern  which  has  a  certain 
probabilistic  rate  and  that  this  can  be  augmented  by  stimulating  the  hypothalamus 
after  the  response  has  occurred  in  a  fashion  that  you  would  not  get  it  you  stmiu- 
lated  the  hypothalamus  at  some  different  time. 

Anokhin.  In  connection  with  the  problem  of  the  so-called  'spontaneous  be- 
haviour', I  should  like  to  draw  the  attention  to  those  forms  of  behaviour  which 
depend  on  the  presence  of  nervous  cells  with  a  specialized  metabolism.  At  the 
present  time  it  can  be  agreed  that  certain  cells  of  the  hypothalamus  and  ot  the 
midbrain  have  a  metabolic  process  which  trom  the  chemical  point  ot  view  is  quite 
accurate  and  specific,  hideed,  the  slightest  departure  from  this  specitic  metabolism 
leads  to  the  release  of  a  'trigger'  and  to  the  outburst  of  nervous  impulses  which  are 
already  spreading  within  the  limits  of  given  functional  systems.  It  will  suttice  to 
mention  the  cells  of  the  respirator)-  centre  or  the  receptor  formations  of  the  sino- 
carotid  region,  which  tire  as  a  result  ot  a  slight  increase  ot  CO.,  in  the  blood. 

Even  more  surprising  is  that  nervous  mechanism  which  is  'tuned'  to  the  level  ot 
the  osmotic  pressure  ot  the  blood. 

As  it  has  been  shown,  one  finds  in  the  hypothalamus  nervous  cells  which  by  all 
their  construction  are  adjusted  to  perceive  the  slightest  changes  in  the  osmotic 
pressure  of  the  blood.  Special  vesicles,  representing  part  of  these  nervous  cells, 
react  to  the  variations  of  the  osmotic  pressure  oi  the  blood  by  diminishing  or 
expanding  their  volume;  these  variations  in  volume  bring  about  an  emergence 
and  dissemination  ot  nervous  impulses.  We  know  that  these  impulses  often  belong 
to  one  or  two  cells  and  can  have  a  rather  widespread  inffuence  leadhig  for  instance 
to  a  feeling  of  thirst  and  to  setting  in  action  important  mechanisms  of  the  body, 
which  lead  to  t]uenching  this  thirst.  These  cells,  which  are  rather  few  in  number, 
act  as  'servo-mechanisms'  in  the  true  sense  of  the  word,  transmitting  small  energetic 
variations  in  the  effort  oi  the  whole  organism  with  all  its  muscular  power. 

Numerous  behavioural  acts  are  constructed  according  to  this  pattern,  i.e.  b) 
setting  in  action  nervous  elements  having  a  rather  specialized  metabolism.  Un- 
fortunatelv  we,  as  neurophvsiologists,  do  not  pay  sufficient  attention  to  this 
chemical  specialization  in  the  metabolic  process  ot  individual  nervous  cells, 
whereas  many  torms  ot  the  so-called  'spontaneous  behaviour'  are  connected  to  this 
characteristic  ot  the  neuro-humoral  transmitting  mechanisms. 

Hebb.  I  will  speak  directly  to  the  point  o(  self-stimulation.  I  think  we  have  a 
tendency  to  assume  that  selt-stimulation  is  the  same  as  excitation.  I  noticed  that  the 
two  words  are  used  synonymously  ver\-  otten.  And  this  is  relevant  to  the  third 
point,  as  a  matter  of  fact,  in  asking  about  the  spontaneous  discharge,  and  whether 
the  cell  is  inhibited  or  excited  in  many  of  these  conditions  of  learning.  You  will 
remember  perhaps  that  in  reply  to  an  earlier  question  Dr  Olds  said  that  he  thought 


GENERAL    DISCUSSION  649 

that  self-Stimulation,  at  least  in  learning,  must  be  a  jamming  of  the  normal  activi- 
ties. Now  I  would  think  that  at  the  present  time  we  are  not  certain  what  action  on 
nerve  units  our  svstem  of  self-stimulation  has.  One  thing  is  to  define  the  stimulation 
from  the  point  of  view  of  behaviour  because  it  results  in  a  behaviour,  but  I  think  it 
is  important  for  us  to  realize  that  this  behaviour  might  be  the  result  of  jamming 
one  mechanism  and  releasing  another.  And  it  is  very  clear  to  us,  and  we  can  give 
several  examples  in  which  stimulation  sometimes  elicits  that  kind  of  behaviour, 
sometimes  it  prevents  this  kind  of  behaviour.  And  I  think  we  can  frequently  get  oft 
the  track  bv  assuming  immediately  that  selt-stimulation,  or  any  other  sort  of 
stimulation,  is  necessarily  excitation.  It  might  be  excitation  in  behavioural  terms 
but  in  neural  terms  it  might  be  inhibition  or  jamming. 

Olds.  We  are  surprised  how  often  cortical  units  that  we  try  to  reinforce  appear 
to  be  inhibited  by  stimulation  of  the  very  hypothalamic  areas  which  cause  self- 
stimulation.  We  are  sure  from  proximal  recording  m  the  hypothalamus  that 
hypothalamic  units,  have,  of  course,  their  tiring  rate  augmented.  That  is,  we  can 
elicit  proximal  hvpothalamic  units,  which  is  not  surprising,  nevertheless  we  are 
probablv  disrupting  patterns.  My  own  conception  oi  the  disruption  experiments  is 
precisely  that  while  the  stimulation  of  these  hypothalamic  mechanisms  to  excessive 
discharge  causes  repetition  of  the  preceding  behaviour  and  I  think  leads  to  organiza- 
tion of  positive  reinforcement  mechanisms,  at  the  same  time  it  causes  disruption 
of  the  spontaneous  patterns  which  are  there,  and  I  think  thereby  confusion  ensues 
whenever  acuity  in  a  learning  situation  is  required.  This  is  of  course  theoretical. 

Myers:  I  should  like  to  respond  to  Dr  Morrell's  earlier  comments  regarding 
oscillation  in  learned  behaviour.  Dr  Morrell  described  a  kind  of  instability  or 
variation  in  the  level  of  sustained  performance  in  some  ot  his  animals.  We  have 
found  both  stability  and  lack  of  stability  in  our  own  learning  experiments  with  cats 
and  I  think  we  can  specify  to  a  certain  extent  the  situations  in  which  each  may  occur. 
When  a  learned  response  seems  'easy'  for  an  animal  —  and  'easy'  may  be  defined 
either  in  terms  of  total  number  of  trials  required  to  learn  or  in  terms  ot  the  objective 
degree  of  difference  between  two  patterns  to  be  discriminated  —  then  remarkable 
stability  of  performance  usually  obtains.  This  stability  manitests  itself  not  only  in 
constant  high  level  performance  from  day  to  day  but  also,  as  Dr  Konorski  has 
described,  in  high  level  performance  on  resetting  alter  long,  practice-free  intervals 
of  up  to  a  year  or  more.  Instability  of  performance  occurs,  on  the  other  hand,  when 
the  dirtkulty  of  the  response  approaches  the  limit  of  the  animal's  capacity  to 
attend  to  the  differences  in  the  stimuli.  Brain-operated  animals  may  exhibit  insta- 
bility in  performance  on  'easv'  discriminations  implying  that  an  'easy'  discrimination 
may  become  'difficult'  tor  them. 

Chow.  The  most  fundamental  problem  is  the  first  point  that  Dr  Thorpe  made. 
This  problem  of  self-stimulation,  learning  and  behavioural  oscillation  is  to  me  an 
irrelevancy.  The  most  fundamental  point  is  how  a  single  nerve  cell  in  its  environ- 
ment which  is  probably  relatively  stable  gets  this  oscillation.  At  the  cellular  or 
molecular  level  vou  must  think  ot  a  mechanism  to  account  tor  it.  A  build-up  and 


650  BRAIN    MECHANISMS    AND    LEARNING 

discharge  and  so  on.  I  do  not  know  enough  about  it  to  suggest  an  explanation  but 
I  think  this  is  really  the  problem. 

Hernandez-Peon.  In  reply  to  Dr  Thorpe's  question  as  to  whether  or  not 
sensory  receptors  govern  the  discharge  of  nerve  cells  in  the  central  nervous  system 
I  woulci  like  to  point  out  that  in  the  adult  brain  there  is  a  considerable  amount  of 
tonic  inhibition  acting  upon  the  spontaneous  activity  of  nerve  cells  in  the  central 
nervous  svstem.  In  this  respect,  recent  experiments  of  Soderberg  and  Arden  showed 
that  in  rabbits  a  lesion  ot  the  optic  tract  enhanced  the  electrical  activity  of  the 
lateral  geniculate  body.  Brain  stem  lesions  also  increased  tlais  activity.  These  results 
indicate  that  there  is  certain  degree  of  ascending  inhibition  coming  from  the 
retina  and  tonic  inhibition  from  the  brain  stem,  both  acting  upon  the  lateral 
geniculate  body. 

Gerard.  The  major  advance  in  neurophysiology  in  this  century  was  the  recogni- 
tion that  we  did  not  have,  either  in  nerve  or  neurone  or  whole  nervous  system,  an 
inert  passive  instrument  waiting  for  something  to  arouse  it.  There  is  continuing 
activity.  This  ultimately  reduces  to  processes  at  the  molecular  level  —  wliich  is 
metabolism  —  and  it  is  well  recognized  in  physical  chemistry  that  regular  rhytlunic 
changes  result  only  from  continuous  processes.  Comparably,  only  a  constant  wind 
produces  a  regularly  flapping  flag.  I  think  the  really  basic  questions  are  at  this  level. 
There  is  a  constant  active  metabolism  and  trom  this  rhythms  develop.  It  is  perhaps 
only  secondary,  although  ot  the  greatest  interest,  as  to  whether  these  rhythms  are 
primarily  within  a  single  cell  —  self-stimulated  if  you  want  to  put  it  that  way  — 
whether  there  are  microcircuits,  or  whether  there  are  macrocircuits.  As  a  matter  of 
fact,  the  rhythms  we  found  long  ago  in  the  olfictory  bulb  were  recently  shown  by 
a  couple  of  my  students  to  depend  in  part  at  least  on  microcircuits  between  mitral 
and  granule  cells  —  in  the  olfictory  cortex. 

The  patterns  of  behaviour  must  always  involve  patterns  of  structure  and  patterns 
of  time.  Certain  cells  are  connected  with  certain  other  cells  by  definite  paths ;  and 
these  connections  arc  either  inborn  or  formed  as  a  result  of  learning.  And  there  are 
also  patterns  in  time,  which  mav  be  continuous  activities  or  may  vary  with  the 
physiological  properties  ot  the  responding  units  —  double  tiring,  summation,  etc. 
So  that  I  would  say  we  cannot  now  give  an  explicit  answer  but  we  can  indicate 
the  factors  that  enter  into  the  answer. 

Thorpe.  The  answers  which  have  been  given  have  carried  us  much  turther 
towards  an  explanation.  I  have  learnt  much  from  them.  I  think  that  consideration 
of  the  actual  physical  or  biochemical  mechanism  inside  a  cell  which  can  be  giving 
rise  to  rhythmic  behaviour  is  of  extreme  interest  and  I  wish  we  had  time  to  discuss 
it  much  further.  Perhaps,  however,  it  is  rather  too  much  off  the  main  line  of 
interest  at  the  moment.  But  I  am  very  gratetul  to  the  members  of  the  symposium 
for  the  comments  thev  have  made.  To  close  the  discussion  with  one  tiiial  sugges- 
tion it  seems  to  me  that  the  sort  of  rhythmic  mechanism  which  appears  to  be  acting 
within  a  single  cell  might  also  be  the  kind  of  mechanism  which  is  acting  between 
cells  —  to  inhibit  or  control  or  establish  a  rhvthm. 


GENERAL    DISCUSSION  65  I 

THIRD  topic:  location  of  plastic  change 

KoNORSKi.  To  open  the  discussion  on  this  topic  I  would  hkc  to  emphasize  the 
radical  change  in  our  views,  concerning  the  location  ot  plastic  changes,  which 
took  place  in  the  last  decade  or  two.  At  the  end  of  the  nineteenth  and  in  the  first 
half  of  the  present  centurv  the  view  was  held  that  the  abilit\'  to  form  new  inter- 
neural  connections  is  a  characteristic  of  only  higher  parts  of  the  nervous  system, 
and  in  higher  animals  chieHy,  or  even  exclusively,  of  the  cerebral  cortex.  The 
lower  parts  ot  the  nervous  system  were  supposed  to  be  endowed  with  inborn 
connections  only,  i.e.  connections  developed  durmg  ontogeny  independently  of 
the  animal's  experience.  The  chief  protagonist  of  this  view  was  Pavlov,  who  main- 
tained that  the  functional  specificity  of  the  cerebral  cortex  lies  in  the  formation  of 
acquired  connections;  i.e.  that  the  cerebral  cortex  may  be  considered  as  an  organ  of 
conditioning.  According  to  Pavlov,  the  decorticate  animal  retains  the  whole 
repertory  of  inborn,  or  unconditioned  reHexes  (including  instincts)  but  is  not  able 
to  form  conditioned  connections  on  their  basis. 

However  attractive  this  view,  it  proved  with  the  lapse  of  time  more  and  more 
inadequate.  On  one  hand  it  was  shown  that  manv  innate  activities  (unconditioned 
rertexes)  depend  on  the  cerebral  cortex.  To  give  some  examples:  according  to  the 
well-known  studies  ot  Bard  and  Brooks  placing  and  hoppmg  reflexes  depend  on 
the  sensory-motor  cortex,  maternal  behaviour,  as  shown  by  Beach,  depends  on  the 
medial  parts  of  the  cerebral  cortex,  and  so  on.  A  great  body  ot  evidence  showing 
the  role  of  the  cerebral  cortex  in  the  course  ot  unconditioned  reflexes  was  recently 
given  by  Dr  Asratyan. 

On  the  other  hand  we  have  now  a  rapidly  increasing  amount  of  evidence  to 
show  that  lower  parts  of  the  nervous  axis  are  also  apt  either  to  form  new  inter- 
neural  connections,  or  to  ameliorate  the  existing  ones,  according  to  new  'experi- 
ences' (i.e.  combinations  ot  stimuli).  Much  evidence  of  that  kind  was  presented  at 
the  present  symposium  b\-  Or  Eccles  and  Dr  Hernandez-Peon. 

Therefore,  it  seems  that  the  time  is  ripe  to  abandon  the  old  view  and  to  accept  a 
new  one,  according  to  which  the  ditFerence  between  the  lower  and  the  higher 
parts  ot  the  nervous  s)stem  is  not  that  the  first  of  them  control  inborn  activities  and 
the  second  acquired  activities,  but  that  the  higher  the  centres,  the  greater  is  the 
complexity  of  activities  controlled  by  them.  And  so  those  forms  of  plastic  changes 
which  correspond  to  the  level  of  functional  complexity  proper  to  the  sp)inal  cord 
can  occur  at  the  spinal  level,  as  shown  in  l^r  Hernandez-Peon's  experiments  on 
habituation  to  somatic  stimulations  or  in  l^r  Eccles's  experiments  on  the  increase  of 
spinal  reflexes  by  use.  Some  simple  tonus  ot  conditioning  and  even  diftcrentiations 
can  be  established  111  decorticate  animals  according  to  the  structural  complexity  of 
the  centres  involved.  But  those  learning  processes,  as  well  as  unconditioned 
reflexes,  which  require  for  their  occurrence  a  complex  analysis  of  external  stimuli, 
such  as  patterned  vision  or  sound  patterns,  are  mediated  by  particular  areas  of  the 
cerebral  cortex.  The  examples  ot  such  learning  processes  were  given  at  this 
symposium  in  the  papers  of  Dr  Myers,  Dr  Chow  and  my  own. 


652  BRAIN    MECHANISMS    AND    LEARNING 

Galambos.  I  would  like  to  extend  Dr  Konorski's  remarks  on  brain  'levels' 
where  the  neuronal  events  responsible  for  behavioural  acts  are  oganized.  We  tend 
to  conceive  these  levels  as  'higher'  and  'lower'  cortical  and  subcortical.  What  goes 
on  in  the  cortex  is  supposed  to  be  both  different  from  and  superimposed  upon  what 
transpires  lower  down;  a  kind  of  neuronal  packing  order  exists,  with  cerebral 
cortex  on  top.  Several  workers  have  recently  been  stressing  a  contrary  view  which 
this  symposium  has  not  yet  considered.  According  to  it  the  neuronal  organization 
responsible  for  certain  behavioural  responses  is  essentially  longitudinal,  running 
from  front  to  back  in  the  brain.  The  vomiting  act,  for  instance,  can  be  aroused  by 
shocks  to  localized  areas  of  paleocortex,  hypothalamus  and  medulla,  and  while 
performance  differs  somewhat  depending  on  which  site  is  stimulated,  the  same 
result,  evacuation  of  the  stomach,  is  achieved  by  all  three.  In  some  manner,  there- 
fore, the  neural  organizations  responsible  for  the  response  are  equal  at  several 
different  'levels'.  No  clear  pecking  order  is  discernible.  Whatever  the  'liigher'  level 
imposes  upon  the  'lower'  one  is  uniniportant  compared  to  the  fact  that  all  are 
involved  in  producing  the  act. 

The  idea  ot  searching  tor  the  plastic  changes  of  learning  in  the  longitudinal  as 
well  as  in  the  highest  transverse  (i.e.  cerebral  cortical)  dimension  of  the  brain  is,  as 
Dr  Konorski  points  out,  an  important  new  direction  in  which  research  efforts  are 
tending.  It  can  in  fact  be  argued  from  the  accumulating  evidence  for  widespread 
involvement  of  cortical  and  subcortical  structures  during  learning  that  an  under- 
standing ot  the  succession  of  events  transpiring  in  cells  organized  in  the  rostro- 
caudal  dimension  of  the  brain  is  actually  what  holds  the  key  to  the  neural  basis  ot 
learning.  Cerebral  cortex  probably  participates  merely  as  a  link  in  the  chain  of 
events.  Since  animals  without  cerebral  cortex  obviously  create  the  plastic  brain 
changes  required  for  learning  we  must  conclude  that  what  cortex  does  so  supremely 
well  can  be  accomplished  by  non-cortical  brain  tissue  also.  Despite  the  reasons  for 
denying  an  exclusive  or  unique  role  to  the  cortex  in  learning  no  reasonable  objec- 
tion whatever  can  be  raised  against  the  stand  that  knowledge  of  the  cortical  changes 
that  do  occur  in  learning  would  be  valuable  to  have.  That  plastic  events  occur  only 
there  and  that  these  are  the  most  'important'  ones  to  study  if  we  wish  to  compre- 
hend the  processes  at  work  are,  however,  two  ideas  open  to  much  question. 

Anokhin.  I  am  very  much  interested  in  the  role  played  in  the  process  of  learning 
by  the  different  structures  of  the  brain,  the  cortex  and  the  subcortical  formations. 
At  the  present  time  one  can  hardly  maintain  that  the  process  ot  learning  is  the 
exclusive  prerogative  of  anv  one  nervous  structure,  the  cortex  or  subcortex. 

The  principle  of  the  dynamic  activation  ot  nervous  activit\-  has  shown  that  all 
these  component  parts  of  the  brain  functioning  at  a  given  moment  are  jointly 
involved  in  this  dynamic  activation. 

The  main  thing,  however,  is  that  each  ot  these  parts  brings  its  own  specific 
contribution  to  the  process  ot  learning,  i.e.  to  the  activity  of  the  whole  brain. 
This  is  why  experiments  made  by  extirpating  different  sections  of  the  brain  give 
contradictory  results,  which  we  cannot  understand  so  far. 


GENERAL   DISCUSSION  653 

One  can  only  safely  atiirni  that  the  function  of  the  cortex  of  the  brain  is  to  carry 
out  the  analysis  and  synthesis  of  the  complicated  and  always  diverse  information 
entering  through  extcro-receptors  and  intcro-receptors.  It  should  be  remembered 
that  this  information  enters  through  the  sensory  organs  almost  always  in  a  com- 
plicated form  —  to  use  the  language  of  cybernetics :  in  'codified'  form. 

The  deciphering  of  this  code,  the  distribution  of  its  components  to  different 
structures,  the  comparison  of  this  information  with  the  previous  experience  of  the 
nervous  system  and,  lastly,  as  a  result  of  all  this,  the  most  important  process  of 
afferent  synthesis  which  I  discussed  in  my  report  —  such  are  the  different  processes 
which  may  take  place  in  the  cortex,  preceding  any  learning,  i.e.  preceding  the 
creation  of  the  elementary  conditioned  reflex. 

We  know  now,  however,  that  none  of  these  processes  of  the  cortex  can  take 
place  without  the  constantly  activating  action  of  the  reticular  formation  of  the 
brain  stem  and  of  the  hypothalamus.  This  very  fact  emphasizes  that  the  whole 
brain  is  an  organic  unit  when  it  carries  out  a  behavioural  act,  however  elementary 
this  act  may  be. 

AsRATYAN.  It  seems  to  me  that  what  I  want  to  say  is  connected  to  a  great  extent 
with  a  problem  discussed. 

First  of  all  I  should  like  to  say  somethmg  in  connection  with  the  problem  of  the 
role  of  brain  cortex  in  nervous  activity.  Recently  we  have  tried  out  some  investiga- 
tions in  which  we  studied  different  inborn  reflexes  and  different  neural  and  humoral 
regulations  of  the  functions  of  the  organism  in  chronic  experiments,  before  and 
after  extirpation  of  the  brain  cortex  in  the  animals.  In  most  cases  we  extirpated  the 
entire  cortex  of  the  brain.  But  in  cases  when  we  studied  the  reflexes  of  paired 
organs  (such  as  salivary  glands,  extremities,  etc.)  only  cortex  of  one  hemisphere 
was  removed.  In  the  latter  experiments  the  undamaged  side  served  as  a  control  for 
the  damaged  one.  All  inborn  reflexes,  i.e.  unconditioned,  motor  and  vegetative, 
were  changed  to  a  great  extent  both  in  their  quality  and  stabilit)-.  Many  properties 
of  these  reflexes,  once  changed  remained  so.  We  consider  it  as  a  proof  that  cortex 
takes  part  in  the  accomplishment  of  inborn  nervous  activity,  not  only  in  com- 
plicated activity  but  also  in  simple  reflexes.  It  should  be  noted  that  decortication 
brings  also  changes  in  the  humoral  regulations  oi  the  functions  of  the  organism. 
We  had  about  forty  decorticate  dogs  and  several  rabbits,  the  same  result  was 
obtained  in  all  of  them. 

Further  I  would  like  to  say  a  few  words  on  the  influence  of  constant  environ- 
mental factors  on  the  higher  nervous  activity.  There  is  sufficient  factual  and  theore- 
tical material  for  the  hypothesis  that  this  influence  may  be  represented  as  a  tonic 
conditioned  reflex.  Reflexes  of  this  type  are  elaborated  in  response  to  such  con- 
stantly acting  factors  as  the  time  of  experimentation,  the  experimenter,  the  room 
and  place  of  experiments,  some  details  in  the  physical  arrangement  of  the  apparatus, 
etc.  It  is  well  known  that  there  are  two  types  of  inborn  reflex  activity:  tonic  and 
phasic.  We  have  concrete  facts  which  allow  us  to  divide  conditioned  reflex  activity 
also  into  tonic  conditioned  reflexes  and  phasic  conditioned  reflexes.  Such  tonic 


654  BRAIN    MECHANISMS    AND    LEARNING 

conditioned  reflexes  play  a  very  great  role  in  higher  nervous  activity  because  they 
constitute  a  background  for  the  phasic  conditioned  reflex  activity  and  provide  for 
it  a  functionally  steady  basis.  In  other  words,  I  imagine  the  relations  betw^een  these 
two  types  of  conditioned  reflexes  similar  to  those  well-known  relations  which 
exist  between  tonic  and  phasic  unconditioned  reflexes  and  which  were  so  excel- 
lently investigated  by  Sherrington,  Magnus  and  others. 

Hernandez-Peon.  I  agree  completely  with  the  view  expressed  by  Dr  Konorski 
who  points  out  very  clearly  that  all  the  levels  of  the  central  nervous  system  parti- 
cipate in  learning  and,  of  course,  each  level  participates  in  different  tvpcs  of 
learning.  I  should  like  also  to  add  to  this  general  discussion  that  in  the  absence, 
however,  of  certain  parts  of  the  brain  some  other  part  may  take  over  the  function 
of  the  absent  part.  This  phenomenon  has  been  known  for  a  long  time  and  has  been 
called  'neural  equivalence'.  Therefore,  in  designing  experiments  for  testing  the 
function  of  a  given  part  of  the  brain  we  must  consider  scparatclv  the  immediate 
and  the  late  effects  of  the  lesion. 

Segundo.  The  hypothesis  can  be  advanced  th.it  a  degree  of  freedom  exists 
which  enables  different  individuals  or  even  the  same  individual  under  different 
circumstances  to  learn  one  specific  task  utilizing  different  regions  or  systems  in  the 
brain.  No  direct  proof  of  this  is  as  yet  available  but  such  a  possibility  would  agree 
with  the  following  observations,  (i)  Interference  (by  destruction  or  excitation)  with 
a  given  neural  structure  may  affect  learned  behaviour  in  different  or  even  contradic- 
tory manners.  At  the  level  of  the  caudate  nucleus  for  instance,  lesions  abolished  a 
conditioned  response  in  certain  preparations  but  did  not  affect  it  in  others  (Galeano, 
Roig,  Segundo  and  Sommcr-Smith,  in  preparation)  and  stimulation  effects  were 
conflicting  (Olds,  this  volume).  Tliis  could  indicate  that,  in  different  preparations, 
the  same  structure  participated  differently  in  production  of  the  same  reaction,  (ii)  In 
many  instances,  cerebral  mutilation  has  provoked  loss  of  a  learned  ability  that  was 
re-established  by  subsequent  training.  Participation  of  the  destroyed  structure 
obviously  was  necessary  initialK'  but,  since  re-learning  was  possible,  the  same 
necessary  role  must  have  been  assumed  by  a  different  nucleus. 

Thorpe.  I  agree  with  what  Dr  Segundo  has  just  said.  It  seems  that  an  animal  can 
learn  the  same  thing  simultaneously  in  two  or  more  different  structures  in  the 
central  nervous  svstem.  In  this  connection,  the  case  of  the  animals  reared  under 
imperfect  conditions  and  so  not  of  normal  health,  is  of  special  interest.  Sometimes 
such  animals  cannot  pertorm  certain  activities  normalh^  regarded  as  'instinctive' 
without  practice  or  experience,  but  can  nevertheless  learn  them  very  rapidly.  It 
may  be  that  the  process  which  results  in  the  completion  of  the  innate  behaviour 
pattern  by  learning  takes  place  in  the  same  locus,  but  I  think  it  is  very  likely  that  it 
takes  place  in  a  different  locus  and  that  would  perhaps  be  a  similar  instance  to  that 
Dr  Segundo  had  in  mind:  the  same  pattern  being  acquired  by  two  different 
nervous  structures. 

Myers.  An  oft-mentioned  argument  should  perhaps  be  added  here  to  supple- 
ment Dr  Segundo's  and  Dr  Thorpe's  discussion.  Behavioural  test  situations  given 


GENERAL    DISCUSSION  655 

the  same  name  may  yet  differ  in  details  to  the  extent  that  divergent  results  are 
obtained  with  animals  having  presumably  identical  brain  lesions.  Dr  Rosvold  has 
already  given  us  an  interesting  example  of  such  a  situation  in  which  the  amount  of 
energy  an  animal  must  exert  in  responding  may  determine  whether  or  not  a 
dehcit  is  seen.  Other  important  variables  are  the  degree  oi  dehnition  ot  tigure  from 
ground;  whether  stnnuli  are  presented  simultaneously  or  successively;  the  nature 
and  amount  of  punishment  given  for  incorrect  response  and  the  like,  hi  a  word 
investigators  working  with  learning  in  relation  to  brain  lesions  must  be  acutely 
aware  of  the  behavioural  variables  in  their  experiments  and  must  exercise  them- 
selves excessively  to  maintain  consistency  in  these  details  throughout  an  experi- 
mental series,  and,  finally  must  give  good  enough  account  ot  these  variables  that 
others  may  determine  precisely  what  had  been  done. 

FOURTH  topic:  NATURE  OF  THE  CHANGE 

EccLES.  As  an  investigator  of  the  properties  ot  nerve  cells  and  neural  pathways  in 
the  central  nervous  system,  I  have  been  particularly  interested  in  the  various 
theoretical  accounts  of  the  neural  changes  that  are  responsible  for  conditioned 
reflexes.  There  have  been  many  attempts  to  explain  learning  and  conditioning  by 
the  growth  and  development  ot  synapses,  as  tor  example  by  Tanzi  in  1893;  by 
Cajal  in  1911,  and  by  Hebb  in  1949;  but  no  model  has  been  presented  that  con- 
forms with  known  neurophysiological  properties  of  neurones,  and  at  the  same 
time  accounts  tor  the  simplest  phenomena  of  learning,  i.e.  conditioned  reflexes  ot 
the  Pavlovian  type.  Some  years  ago  in  m\-  book  The  Ncuropliysiolo{;ical  Basis  of 
A4iiid,  I  discussed  critically  two  types  oi  these  postulated  changes  and  presented  in 
outline  a  new  hypothesis  that  at  least  had  the  merit  ot  being  based  on  properties  ot 
the  nervous  system  that  had  been  experimentally  demonstrated.  So  far  as  I  know 
this  hypothesis  has  aroused  ver)-  little  interest  either  from  psychologists  or  from 
investigators  of  conditioned  reflexes,  so  I  welcome  this  opportunity  to  present  it  to 
you  in  the  hope  that  there  will  be  some  critical  discussion. 

Fig.  I A  shows  diagrammatically  an  explanation  of  conditioning  that  has  been 
developed  by  Konorski  and  Gastaut.  The  conditioned  and  unconditioned  stimuli 
(CS  and  US)  activate  respectively  the  emitting  centre  (EC)  and  the  receiving  centre 
(RC).  They  postulated  that  the  potential  connections  between  these  two  centres 
(dotted  lines)  are  transformed  into  'actual  excitatory  connections'  when  excitation 
in  the  tirst  centre  coincides  in  time  with  a  rise  in  excitation  in  the  second  centre. 
This  change  in  connections  between  the  centres  was  envisaged  as  being  due  to  a 
growth  and  multiplication  ot  synaptic  connections,  but  unfortunately  there  is  no 
experimental  evidence  that  activation  of  a  nerve  centre  (RC)  could  cause  the 
development  of  connections  onto  it  from  an  adjacent  activated  centre  (EC)  or  even 
an  increased  eflicacy  of  connections  already  in  existence.  An  alternative  postulate  is 
illustrated  in  Fig.  iB,  which  shows  simply  that  the  CS  and  US  lines  are  assumed  to 
converge  on  the  same  neurones,  activation  bv  the  US  in  close  temporal  contiguity 


656  BRAIN    MECHANISMS    AND    LEARNING 

with  CS  excitation  being  assumed  to  cause  a  general  increase  in  excitability  of  the 
neurones,  which  consequently  can  eventually  be  excited  to  discharge  by  the  CS 
alone,  whereas  initially  CS  was  ineffective.  Again  there  is  no  experimental  evidence 


CS 


U^^,0 .R 


B 


us O *R 


Fig.  I 
Diagrams  illustrating  attempts  to  explain  conditioned  reflexes 
by  plastic  changes  in  synaptic  connections.  Full  description  in 
the  text.  CS  and  US  show  input  into  central  nervous  system  of 
conditioned  and  unconditioned  stimuli  respectively.  In  A  the 
arrows  indicate  nervous  pathways,  while  B  is  a  redrawing  of  a 
highly  simplified  model  in  which  Shimbel  shows  converging 
synaptic  connections  of  the  CS  and  US  lines,  hi  C  nervous 
pathways  are  drawn  as  broad  bands  along  which  conduction 
occurs  as  described  in  the  text,  particularly  in  the  neuronal 
network,  NN.  The  interruptions  in  the  bands  indicate  synaptic 
relays.  Nerve  centres  containing  large  populations  of  neurones 
are  indicated  by  circles,  while  the  neuronal  network,  NN, 
would  be  an  extremely  complex  neuronal  system;  for  example, 
an  area  or  areas  of  the  cerebral  cortex  (Eccles,  1953,  reproduced 
by  permission  of  the  publishers). 


for  this  non-specific  increase  in  neuronal  excitability,  hicreascd  activation  ot 
neurones  changes  only  the  synapses  actually  activated,  i.e.  it  appears  to  be  pre- 
synaptic or  synaptic  not  post-synaptic.  Moreover,  it  gives  rise  to  a  serious  problem 
in  attempting  to  extract  from  such  a  system  an  adec|uate  degree  of  specificity  when 


GENERAL    DISCUSSION  657 

the  lowering  ot  threshold  is  non-specihc  tor  all  synapses  on  a  neurone.  This  is  the 
problem  of  redundant  conditioning,  as  it  is  appropriately  called  by  Shimbel. 

The  hypothesis  that  I  proposed  in  1952  was  built  upon  properties  ot  neuronal 
networks  that  derived  troni  the  convergence  of  synaptic  excitatory  action  on 
neurones  and  also  upon  the  postulate  that  synaptic  use  resulted  in  an  enduring  trace 
ot  increased  etiicacy.  At  that  time  there  was  little  direct  evidence  for  this  latter 
postulate,  but  very  convincing  experimental  evidence  has  now  been  obtained  in 
mv  laboratory,  and  presented  earlier  in  this  symposium.  The  essential  tcatures  ot 
the  hypothesis  are  displayed  in  this  diagram  (Fig.  iC),  but  it  is  important  to  realize 
that  the  actual  neural  events  occur  in  the  neuronal  networks  of  the  diagram  which 
are  shown  as  black  boxes  but  are  of  unimaginable  complexity.  Hence  it  is  import- 
ant to  make  brief  reference  to  the  properties  that  these  networks  are  believed  to 
have. 

hi  order  to  generate  the  discharge  ot  an  impulse  trom  a  neurone  it  is  usually 
necessary  that  there  be  convergence  onto  it  of  several  excitatory  nerve  impulses 
within  a  few  milliseconds.  Thus  eiiective  neuronal  action  does  not  occur  for  a 
serial  one  to  one  arrangement  of  neurones.  Rather  the  propagation  in  a  neuronal 
network  resembles  an  advancing  front  of  traliic  with  many  cells  activated  in 
parallel  at  each  synaptic  linkage  in  the  chain.  With  such  an  arrangement  it  can  be 
showni  that  two  completely  different  inputs  into  a  neuronal  network  can  involve 
many  neurones  in  common  and  yet  emerge  as  completely  ditFerent  outputs,  i.e. 
the  same  neurones  can  participate  in  countless  specific  patterns  of  activity.  A  further 
feature  is  that  closed  loops  of  activated  neurones  are  possible  in  which  impulses 
circulate  again  and  again  over  approximately  the  same  neuronal  pathway  being 
thus  responsible  for  the  reverberatory  activity  that  has  otten  been  postulated. 

In  the  diagram  (Fig.  iC)  there  is  firstly  the  unconditioned  retlex  pathway  US- 
RC-Rjust  as  in  A,  but  this  pathway  is  assumed  also  to  branch  so  that  it  converges 
on  to  the  same  complex  centre  of  neurones  as  does  the  conditioned  stimulus,  CS. 
hi  this  convergence  centre  (CC)  it  is  postulated  that  two  changes  are  brought  about : 
there  is  synaptic  facilitation  so  that  man)  more  neurones  and  neuronal  pathways 
are  excited  to  discharge  impulses  than  would  be  by  either  CS  or  US  alone;  and 
there  is  increased  etiicacy  of  synaptic  knobs  on  account  of  the  excess  use,  those 
specially  activated  as  a  consequence  ot  the  summation  of  CS  and  US  being 
particularly  important.  As  a  consequence  ot  these  two  factors  there  will  be  a 
specific  pattern  of  activation  of  CC  as  shown  diagrammatically  b\'  the  hatched 
pathway  and  this  will  be  further  elaborated  in  the  neuronal  network  NN  that 
leads  to  the  etFerent  pathway,  RC  to  R.  Since  the  spatio-temporal  pattern  oi 
neuronal  activation  in  CC  is  dependent  in  part  on  US,  it  would  be  expected  that, 
as  shown  in  the  diagram,  it  would  in  part  achieve  ctierent  expression  in  the  same 
RC  as  occurs  tor  the  unconditioned  reticx  evoked  by  US.  It  is  evident  that,  if  the 
discharges  of  impulses  into  NN  are  set  up  by  CS  and  US  in  close  temporal  sequence 
and  with  an  adequate  number  of  repetitions,  the  increase  in  synaptic  etiicacy  in  the 
hatched  zone  both  in  the  convergence  centre  (CC)  and  in  the  neuronal  network 


658  BRAIN    MECHANISMS    AND    LEARNING 

(NN)  will  cause  impulses  from  CS  alone  to  be  effective  m  evoking  a  pattern  of 
impulses  in  NN  that  leads  to  the  response  R,  i.e.  a  conditioned  reflex  has  been 
established.  Of  course  the  distinction  between  CC  and  NN  in  the  diagram  is 
arbitrary.  It  is  done  merely  to  separate  the  predominantly  afferent  function  of  CC 
and  the  more  integrative  and  efferent  function  ot  NN,  where  we  can  think  of  the 
eventual  response  as  being  synthesized.  There  is  no  more  time  for  elaboration  ot 
the  postulate  so  that  it  can  be  made  to  account  for  many  of  the  phenomena  of 
conditioning.  Possibly  this  will  be  possible  when  attempting  to  answer  criticisms. 

Gerard.  Before  we  consider  Dr  Eccles's  model  let  me  put  before  yoti  the  one 
by  Beurle  to  which  I  have  referred  several  times.  The  two  are  basically  alike: 
Beurle's  is  worked  out  in  rather  more  detail.  (For  a  fuller  exposition,  and  the 
physiological  evidence  bearing  on  the  model,  see  my  summary  chapter  in  the 
Handbook  of  NctiropliysioU\^y).  Beurle  assumes  a  population  of  neurones,  randomly 
placed  in  a  layer  (such  as  the  cortex)  and  randomly  connected  with  each  other, 
except  for  a  progressive  falling  oft  of  connections  with  distance  of  separation.  Each 
neurone  receives  impulses  from  many  and  passes  on  impulses  to  many.  Several 
incoming  impulses  are  needed  to  fire  a  cell :  thresholds  at  specific  synapses  tend  to 
tall  slowly  with  repeated  activation:  and  thresholds  may  be  temporarily  and 
reversibly  raised  or  lowered  by  the  action  of  inhibitory  or  facilitatory  elements. 

A  wave  of  activity,  entering  such  a  cell  mass,  does  not  engage  all  cells  in  its  path; 
but  it  does  tend  to  engage  a  progressively  large  fraction  until  all  cells  are  active,  or 
a  smaller  fraction  until  the  wave  dies  out,  unless  there  is  regulation  by  a  negative 
feedback  loop.  With  this,  a  wave  ot  constant  intensity  can  travel  through  the  mass, 
the  fraction  of  cells  engaged  in  any  vollime  depending  on  the  past  history  of  the 
system  and  on  the  current  action  of  positive  and  negative  feedback  systems. 
Moreover,  two  or  more  individually  characteristic  waves  may  pass  through  the 
same  neurone  mass,  each  engaging  its  own  special  group  of  neurones.  Two  such 
waves  might,  therefore,  travel  simultaneously  through  the  neurone  pool,  cross  one 
another,  reflect  upon  each  other  or  from  some  other  discontinuity  in  the  mass, 
and  facilitate  one  another  at  the  trajectory  of  crossing  wave  fronts. 

hidccd,  because  of  the  more  than  linear  building  up  oi  excitation  with  the 
number  of  active  neurones,  the  locus  ot  intercepting  waves  can  serve  as  a  source  of 
new  waves,  reflecting  back  through  the  cell  mass  along  the  route  of  either  of  the 
incoming  waves.  With  sufllcient  threshold  lowering  by  repeated  activity,  the 
characteristic  waves  can  originate  at  such  loci  even  without  specific  incoming 
stimulation.  Here  is  the  beginning  ot  a  neural  mechanism  tor  memory  association, 
recall  and  even  imagination.  If  recurrent  connections  carried  messages  back  from 
the  output  of  the  mass  to  the  input  region,  internal  testing  of  alternate  behaviours, 
rather  than  external  testing,  becomes  possible,  and  the  model  accounts  for  reason 
based  on  imagination  and  memory,  and  is  able  to  choose  the  'good'  response  for 
its  first  act. 

All  the  assumptions  here  are  based  on  legitimate  neurophysiological  knowledge; 
even  the  existence  of  a  feedback  loop  (through  the  diftiise  neural  system  of  retictilar 


GENERAL    DISCUSSION  659 

formation  and  related  structures)  which  tacihtatcs  responses  to  'important'  inputs 
and  which  favours  and  fixes  'good'  outputs. 

In  contrast  to  most  models  that  have  been  offered,  which  are  either  empirically 
descriptive  of  observed  neural  behaviour  or  are  mathematically  rigorous  but  little 
related  to  real  nervous  systems,  this  model  is  based  on  neurophysiologically  valid 
assumptions  and  leads  to  mathematically  rigorous  consequences,  some  not  easily 
anticipated,  which  are  congruent  with  many  tacts  of  the  complex  behaviour  of 
mammals  and  man. 

Doty.  All  these  schemes  ignore  the  most  ditiicult  and  probably  the  most  impor- 
tant element  of  the  problem :  the  temporal  order.  Instead,  their  main  reliance  is 
placed  upon  the  convergence  of  excitations  from  multiple  sources  upon  a  common 
network.  This  is  a  safe  and  reasonable  assumption  since  such  convergence  is  well 
known  for  many  regions  of  the  nervous  system  (e.g.  mesencephalic  reticular 
formation,  Amassian  and  DeVito,  1954;  amygciala,  Machne  and  Segundo,  1956; 
basal  ganglia,  Segundo  and  Machne,  1956;  somatosensory  cortex,  Ricci,  Doane 
and  Jasper,  1957).  Dr  Buser  has  just  given  us  another  excellent  example  for  the 
cortical  level.  Victor  Wilson's  demonstration  (1955)  that  post-tetanic  potentiation 
in  one  multisynaptic  spinal  cord  system  is  available  through  non-tetanized  afferents 
assures  us  these  convergent  networks  exist  at  a  functional  level.  Yet  real  as  they  are, 
these  effects  give  no  adequate  basis  for  explaining  the  formation  of  conditioned 
reflexes.  The  temporal  order  of  these  effects  is  exactly  the  opposite  of  those  in 
conditioning.  In  all  multi-syiiaptic  convergence  systems  it  is  the  antecedent  excita- 
tion which  alters  the  response  to  a  subsequent  event.  In  forming  conditioned 
reflexes  on  the  other  hand,  the  antecedent  excitation  (the  CS)  has  essentially  no 
effect  upon  the  response  to  the  subsequent  stimulation  (the  US);  rather  it  is  the 
effect  produced  by  the  antecedent  excitation  which  becomes  altered.  One  might 
call  this  the  'temporal  paradox'  of  conditioning. 

It  is  true  that  Dr  Asratyan  has  just  shown  us  that  a  linkage  exists  in  a  conditioned 
reflex  situation  whereby  the  subsequent  stimulation  can  elicit  the  effects  of  the 
antecedent,  a  'backward'  linkage  in  terms  usually  employed  for  conditioned 
reflexes.  Perhaps  the  foregoing  'convergence  theories'  explain  this  phenomenon. 
These  effects,  however,  are  feeble  and  normally  overwhelmed  completely  by  the 
appearance  of  the  conditioned  reflex.  Dr  Asratyan  showed  equally  well  the  prime 
importance  of  the  temporal  factor  in  forming  conditioned  reflexes,  indeed,  a 
previously  formed  CR  was  lost  when  the  CS  and  US  were  given  simtiltaneously. 
Dr  Giurgea  and  I  have  also  added  here  to  an  extensive  literature  on  the  temporal 
aspects  of  conditioning.  Randomized  or  reversed  temporal  relations  in  the  pairing 
of  cortical  stimulations  did  not  produce  conditioned  reflexes,  whereas  the  same 
stimuli  present  in  the  usual  order  did  so.  Appropriate  temporal  ordering  is  absolu- 
tely essential  to  conditioning.  Thus  one  can  speculate  about  converging  and  'grow- 
ing' pathways  indefinitely,  and  with  a  certain  shadow  of  truth;  but  until  the 
reason  for  this  'paradoxical'  temporal  relation  is  clear,  we  will  not  understand  the 
processes  of  conditioning  or  learning. 

UU 


660  BRAIN    MECHANISMS    AND    LEARNING 

Anokhin.  I  should  like  to  add  something  to  the  remarks  made  by  Dr  Konorski. 

It  is  true  that  Pavlov  believed  that  the  role  ot  the  cortex  of  the  brain  is  a  decisive 
one  in  the  creation  of  a  conditioned  reflex.  However,  his  views  were  not  absolutely 
categorical  on  this  point.  He  recognized  clearly  that  under  certain  circumstances 
the  conditioning  may  be  carried  out  bv  the  subcortical  system  also. 

hi  normal  conditions,  however,  when  the  animal  has  a  normal  cortex,  condition- 
ing is  always  carried  out  under  the  decisive  influence  of  the  cortex. 

hi  fact,  even  in  those  cases  when  one  can  note  elcctrophysiologicallv  a  condi- 
tioned reaction  in  the  subcortical  system  also,  this  reaction  is  not  initiated  there,  but 
has  been  tormcd  in  the  very  preliminary  stage  ot  the  orientating-experimental 
reaction  under  the  direct  control  of  the  cortex. 

Segundo.  I  feel  that  the  essence  of  theories  put  forward  by  Dr  Eccles  and  Dr 
Clerard  is  that  the  passage  of  a  wave  leaves  the  pathway  more  permeable.  1  would 
like  to  ask  whether  these  schemes  would  be  adaptable  to  habituation,  a  process 
which  apparently  involves  the  closure  ot  permeable  pathways?  And  if  so,  how? 

Fessard.  I  would  like  to  add  some  comments  in  line  with  what  has  been  said  on 
the  use  of  models  for  the  understanding  of  learning  mechanisms.  I  think  that 
recourse  to  models  —  either  mathematical  or  physical  —  is  useful,  given  the  fact 
that  the  multitude  of  elements  and  extreme  complexity  ot  their  interconnections 
leave  no  hope  that  we  can  ever  know  every  detail  of  a  neuronal  field  and  its 
functional  properties.  Models  help  to  schematize  the  main  dynamic  features  of  a 
field  but  may  also  be  misleading.  This  is  the  case,  I  believe,  of  models  which 
exhibit  a  complicated  and  diversified  circuitry  as  in  a  radio  set:  such  'machines' 
may  imitate  the  different  modalities  of  conditioning,  they  may  'learn'  but  they  are 
of  little  help  to  give  us  a  better  understanding  of  how  the  CNS  actuallv  works 
during  learning  operations.  This  is  why  probabilistic  theories  applied  to  more  or 
less  ciiftuse  neuronal  networks  are  to  be  preferred,  hi  this  respect,  the  mathematical 
model  by  13eurle,  as  recalled  by  I3)r  Gerard,  is  certainly  a  remarkable  and  liighK 
suggestive  one. 

I  also  think  that  some  useful  qualitative  and  unsophisticated  evidence  must  be 
ascertained  before  any  mathematical  treatment  is  attempted,  when  one  considers 
the  most  fimiliar  connectivity  patterns,  especially  those  exhibited  by  the  wideK- 
distributed  network-like  structures  This  is  quite  apparent  when  we  consider  the 
illuminating  diagram  I3)r  Eccles  has  just  presented  to  us.  I  made  use  of  similar 
notions  in  a  report  with  Dr  Gastaut  (Symposium  on  'Conditionnement  et  Appren- 
tissage,  Strasbourg,  1956;  Presses  Univ.  France,  195H,  p.  216)  where  wc  had  first 
gathered  all  the  experimental  evidence  then  available  which  appeared  to  show  the 
important  role  played  by  subcortical  polyneuronic  nuclei  —  namely,  mesencephalic 
reticular  formation  and  so-called  'diffuse  thalamic  system'  —  in  the  formation  of 
new  conditioned  reflexes.  This  justifies  our  belief  that  some  speculation  should  be 
made  on  the  general  properties  of  neuronal  networks.  By  their  very  nature  the)' 
are  sites  of  election  for  convergences  and  interactions  of  heterosensory  signals.  Our 
schema  differs  from  the  one  of  Eccles  onh'  in  that  he  makes  a  difference  between  a 


GENERAL    DISCUSSION  66  I 

coiivcrs^cncc  centre  (CC)  and  a  neuronal  network  (NN)  whereas  we  think  that 
convers;ences  and  associative  interactions  can  take  place  within  the  same  neuronal 
assemblies  as  those  present  in  the  brani  stem  and  non-specific  diencephalic  nuclei. 

hi  mv  opinion,  the  weakness  ot  all  models  so  far  proposed  is  that  they  usually 
neglect  the  states  of  autogenic  repetitive  firing  which  are  so  common  in  the  nerve 
cells  of  cerebral  structures  in  waking  animals.  This  I  tried  to  point  out  in  m\- 
paper.  Utihzation  of  this  general  property  would  probably  lead  to  a  better  under- 
standing of  the  formation  of  new  associative  links  as  giving  their  functional  role  to 
the  plastic  effects  which  are  the  consequence  of  repetitive  bombardments.  In  that 
respect,  I  do  not  believe  that  closed-loop  circulations  of  impulses  can  be  the  onh', 
not  even  the  main  cause  of  prolonged  firings.  Whatever  the  case,  it  is  difficult  to 
believe  that  the  process  of  reverberation,  when  it  operates  through  multiple, 
intricate,  micro-loops  and  zig-zag  recurrent  pathways  as  are  present  in  neuronal 
networks,  can  have  another  net  result  than  that  ot  deteriorating  the  informative 
content  of  sensory  messages,  in  one  word  of  increasing  'noise'  in  the  communica- 
tion of  signals  within  the  brain.  Shall  we  assume  that  learning  mechanisms  might 
depend  on  such  a  process? 

Another  essential  mechanism  to  which  sufficient  credit  has  not  been  given  in 
models  is  that  o(  inhibition. 

In  answer  to  Dr  Segundo's  remark,  one  can  say  that  it  would  not  be  difficult  to 
introduce  inhibitory  functions  into  the  models  just  alluded  to.  Habituation,  extinc- 
tion, differentiation,  inasmuch  as  they  involve  inhibitory  actions  could  thus  receive 
a  good  svmbolic  representation.  May  I  mention  in  addition  that  plastic  changes  like 
post-tetanic  potentiation  apply  to  inhibitor)-  synapses  as  well  as  to  excitatory  ones. 

Finally,  I  must  confess  that  I  have  also  been  puzzled  by  the  question  raised  by 
Dr  Doty  and  which  he  calls  the  'temporal  paradox  of  conditioning'. 

Could  it  not  be  that  the  conditional  message  being  weak  and  ineffectual  meanders 
through  neuronal  networks,  thereby  losing  time,  so  that  finally  it  reaches  the 
associative  synaptic  fields  at  the  moment  when  they  receive  the  unconditional 
signal? 

Hebb.  The  difficulty  with  these  schemes  is  that  they  arc  quite  unrealistic,  because 
they  depend  on  a  gross  selection  of  data.  There  are  so  many  facts  of  behaviour,  so 
much  psychological  research  that  they  do  not  comprehend,  that  they  cannot  be 
taken  seriously  —  at  least  until  they  show  how  the)'  are  going  to  handle  some  of  the 
main  facts  which  have  accumulated  in  the  criticism  ot  exactly  such  theories  as 
these.  Here  is  a  hastily  compiled  list  ot  the  sort  ot  thing  they  need  to  take  into 
account : 

There  is  the  whole  effect  of  early  experience,  as  modifying  the  adult  capacity  to 
associate  stimulus  with  response.  I  don't  need  to  go  into  the  question  of  whether 
Riesen's  chimpanzees  reared  in  darkness  were  able  to  see,  organically;  the  chim- 
panzee reared  in  unpatterned  light  was  equally  incapable  in  his  visual  learning. 

There  is  the  factor  ot  attention.  I  may  remind  you  again  of  Lashley's  experiment 
in  which  there  was  a  failure  of  learning  to  discriminate  patterns  in  200  trials  — 


662  BRAIN    MECHANISMS    AND    LEARNING 

three  times  as  many  as  would  be  needed  in  other  circmnstanccs  —  because,  prior  to 
that  experience,  he  had  arranged  things  so  as  to  direct  the  animal's  attention  to  the 
size  of  the  diagrams  only;  the  necessary  sensory  stimulation  occurred,  but  the 
central  factor  of  attending  was  absent.  Attention  is  fundamental;  where  does  it  fit 
in  such  theories  as  the  ones  we  are  discussing  now; 

There  are  the  phenomena  of  visual  transfer  and  patterning.  These  theories  talk 
as  though  the  stimulus  input  from  one  object  went  to  one  part  of  the  brain,  from 
another  to  another  part:  a  spatial  separation  is  assumed  for  different  stimulus 
objects.  But  inevitably  there  is  overlap  of  excitations  and  the  differentiation  be- 
tween objects  is  a  matter  of  patterning,  not  the  gross  locus  of  stimulation  or 
central  conduction. 

When  theories  can  deal  with  that  kind  ot  problem  they  will  be  getting  closer  to 
the  realities  of  behaviour.  There  are  the  problems  ot  time  relations  in  serial  order, 
and  the  fact  that  most  learning  is  not  a  one-shot  output  with  a  single  input;  charac- 
teristically it  is  serialized,  each  reaction  producing  further  stimulation,  with  further 
reaction,  and  so  on.  As  Lashley  showed  in  his  Hixon  symposium  paper,  the  time 
properties  of  conduction,  and  reaction  time,  are  such  as  to  prevent  us  from  treating 
serialized  behaviour  as  simply  a  series  of  conditioned  reffexes;  there  is  an  intra- 
cerebral serialization  as  well.  This  aspect  of  the  problem  is  directly  related  to  the 
question  of  ideation,  as  demonstrated  experimentally  by  Broadbent's  holding 
phenomenon. 

These  conditioned-reflex  theories  assume  a  one-way,  through  transmission  m 
CNS,  with  the  exception  that  as  I  understand  Dr  Gerard,  Beurle's  theory  postulates 
a  reverberatory  process  going  on  until  a  'satisfactory  outlet'  is  achieved,  at  which 
point  it  would  stop.  What  stops  it,  in  physiological  terms?  The  whole  question  ot 
reinforcement  is  raised  here,  and  this  is  a  difficult  question  indeed.  There  is  the  fact, 
for  example,  that  frequent  repetition  of  a  response  may  decrease,  instead  of  increase, 
the  probability  that  that  response  will  be  made  again  (and  this  without  overt  punish- 
ment of  any  kind).  The  phenomena  oi  memory  and  forgetting  and  the  facts  to 
which  I  referred  briefly  in  earlier  discussion  (i.e.  the  conditions  in  which  visual 
learning  is  or  is  not  retained),  all  these  and  other  tactual  data  have  to  be  taken 
account  of  When  there  is  so  much  selection,  in  the  phenomena  on  which  a  theory 
of  learning  is  based,  it  cannot  be  taken  seriously. 

EccLES.  I  am  very  grateful  for  these  criticisms,  because  they  give  me  a  chance  to 
show  that  the  hypothesis  is  much  more  adaptable  than  would  appear  at  first  sight. 
The  full  potentialities  of  the  hypothesis  are  not  revealed  by  the  simplified  account 
I  gave.  For  example,  the  neuronal  networks  CC  and  NN  would  be  very  widely 
dispersed  over  the  cortex  and  involve  millions  of  neurones,  as  would  necessarily  be 
the  case  if  convergence  is  to  occur  between  different  sensory  modalities  and  to  be 
so  highly  specific,  as  for  example  occurs  with  conditioning  for  an  ellipse  and  not  for 
a  circle.  Multiple  representation  of  the  neuronal  networks  is  also  not  excluded, 
hence  conditioned  reflexes  could  survive  extensive  cerebral  lesions  and  ablations. 
In  fact  the  hypothesis  will  encompass  any  sensory  experience  that  can  be  analysed 


GENERAL    DISCUSSION  663 

bv  the  central  nervous  system.  Presumably  such  analysis  has  to  be  attributed  to  the 
operation  of  spatio-temporal  patterns  of  neuronal  activit)-. 

I  a^ree  that  the  phenomena  of  attention  and  of  the  orienting  reflex  are  of  great 
importance  in  a  fullv  developed  theory  of  conditioning.  I  would  suggest  that 
cortical  inhibition  is  somehow  involved  in  suppressing  much  of  the  developing 
neural  activitv  that  would  otherwise  arise  from  the  sensory  input  and  that  is  being 
rejected.  Already  there  are  many  instances  of  inhibition  operating  on  the  earliest 
synaptic  relays  on  sensory  pathways.  The  orienting  reflex  can  be  regarded  as 
operating  to  increase  the  level  of  excitability  in  the  convergence  centre,  which 
consequently  functions  more  effectively  and  nitensely. 

Related  considerations  help  to  answer  Dr  Doty's  criticism.  The  temporal  sequence 
for  effective  conditioning  can  be  accounted  for  by  postulating  that  CS  has  to 
develop  its  specific  spatio-temporal  pattern  of  activity  in  CC,  possibly  of  rcverbera- 
torv  character,  before  the  application  of  the  dominant  US.  It  is  helped  to  do  this 
bv  the  background  excitation  added  by  the  orienting  reflex.  But  for  this  temporal 
sequence,  the  US  would  dominate  the  neuronal  activity  of  CC  and  NN  to  the 
exclusion  of  CS,  and  as  a  consequence  there  would  not  be  the  development  of  the 
specific  patterns  of  mcreased  synaptic  efficacy  that  arise  b\-  the  conjoint  CS  and  US 
input.  I  think  Dr  Lashlcv  in  the  Hixon  Svmposium  greatl\-  underestimated  the 
time  that  could  be  occupied  in  developing  specific  patterns  of  neuronal  activit}-  in 
the  unimaginably  complicated  networks  of  the  cerebral  cortex.  The  events  in- 
volved are  of  a  different  order  of  complexity  compared  to  physiological  reflex 
phenomena. 

I  haven't  yet  answered  all  of  the  specific  criticisms,  but  perhaps  I  have  indicated 
the  way  in  which  necessary  development  of  the  hypothesis  can  occur.  We  would 
all  agree  that  conditioning  must  be  explained  in  terms  of  neural  changes  and  that 
immensely  complex  neural  pathways  are  concerned.  The  hypothesis  that  I  have 
proposed  merely  attempts  to  show  how  the  physiological  properties  that  have  been 
experimentally  demonstrated  for  the  synapse  can  account  for  conditioning,  given 
the  complexity  of  pathways  that  forms  the  basis  of  all  our  thinking  about  higher 
nervous  activities. 

Anokhin.  I  should  like  to  remark  that  there  are  two  tundamentalK'  distinct 
phenomena,  which  are  usually  confused  w'hen  discussing  the  problem  of  the 
formation  of  conditioned-reflex  connections. 

The  first  phenomenon  is  the  property  of  the  nervous  tissue  to  retain  a  succession 
of  any  stimuli  provided  they  be  above  threshold.  This  is  a  characteristic  of  the 
nervous  matter,  it  occurs  irrespective  of  which  stimulus  follows  which,  whatever 
their  order  and  even  irrespective  of  w^iether  or  not  these  stimuli  contribute  some- 
thing significant  to  the  life  of  the  organism,  in  the  wide  biological  sense. 

The  second  phenomenon  is  the  genuine  conditioned  reflex,  i.e.  a  constant 
succession  of  stimuli  ending  b}'  some  purposeful  adjusting  effect  for  the  organism, 
i.e.  a  succession  of  stimuli  consolidated  by  a  final  emotional  effect,  the  uncondi- 
tioned stimulus. 


664  BRAIN    MECHANISMS    AND    LEARNING 

An  example  of  the  phenomenon  of  the  first  type  may  be  the  well-known  EEG 
'conditioned  reflex',  when  using  in  a  constant  succession  the  'sound-light'  stnnuli. 

An  example  of  the  second  type  can  be  the  generalized  desynchronization  of  the 
electric  activity  of  the  cortex  which  is  linked  to  a  stimulation  of  all  the  vegetative 
organs  and  which  occurs  in  the  case  of  a  biological  reinforcement,  i.e.  which  ends 
by  an  emotional  discharge. 

Taking  all  this  into  account,  one  should,  in  my  view,  first  consider  by  which 
mechanisms  emotional  discharges  do  contribute  to  the  selective  consolidation  of 
fully  determined  synaptic  connections,  corresponding  to  the  succession  precisely 
of  those  stimuli  which  led  to  this  emotional  discharge. 

I  believe  that  the  solution  to  the  problem  of  the  conditioned  reflex  requires  first 
of  all  the  characteristics  of  the  biological  condition  for  the  closing  of  the  circuit 
itself  and  only  this  aspect  will  enable  us  to  succeed. 

Without  it  any  synaptic  combination  of  hypotheses  for  explaining  the  condi- 
tioned reflex  cannot  lead  us  to  a  solution  of  this  difficult  problem. 

Gerard.  Dr  Eccles  has  taken  up  the  several  points  raised,  and  my  answers  are 
much  the  same  as  his.  Certainly  time  sequences  are  involved  in  behaviour,  but  it 
does  not  really  work  backward  in  conditioning,  and  the  modifications  in  neurones 
and  synapses  are  quite  explicitly  able  to  account  for  conditioned  responses. 

Turning  from  Dr  Doty's  question  to  Dr  Segundo's,  the  issue  is  now  a  reversal 
in  reinforcement  rather  than  in  time.  Habituation  could  be  easil)-  understood  in 
two  ways,  facilitation  of  inhibitory  pathways  with  a  feedback  action,  or  effective 
channelization  of  impulses  into  appropriate  outputs,  with  the  corresponding 
diminution  of  irradiation  to  non-efiectivc  units.  This  parallels  the  recent  evidence 
regarding  learning;  widespread  cortical  activity  occurs  while  a  correct  response  is 
being  learned,  this  mostly  disappears  as  highly  channelized  activity  develops  with  a 
learned  response,  but  reappears  when  tlie  problem  is  changed  or  an  error  is  made 
in  the  response. 

Dr  Hebb's  many  points,  far  from  posing  difficulties  for  the  model,  are  among  the 
very  things  that  it  effectively  does  explain.  The  Broadbent  phenomenon  and  model 
fit  excellently  with  that  of  Beurle ;  the  Lashlcy  experiment  fits  with  the  feedback 
mechanisms  indicated  and  so  for  the  other  specific  points  raised.  As  I  see  it,  the 
neurophysiological  mechanisms  now  available  for  interpreting  behaviour  can 
account,  in  principle,  for  everything  except  the  basic  value  hierarchy  of  the  indivi- 
dual, wliich  things  matter  to  it;  and  this  I  suspect  is  largely  the  residue  of  earlier 
experience,  with  its  reinforcements  and  punishments.  I  can  only  refer  l^r  Hebb  to 
the  chapter  already  mentioned  for  a  fuller  discussion  of  these  problems. 


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INDEX 


INDEX 


Acceptor  apparatus  ot  reflex  action,  203 
Adaptability,  22 

Afferent  influences  on  reflex  action,  191 
synthesis  ot  conditioneci  reflex.   197,   19S. 

202 
Alimentary  conditioning,  403,  404 

instrumental,  527-54 
Amygdala,  effect  of  stimulation.  300 

influence  on  fixation.  2S 
Angiogliocytcs,  310 
Animorgs,  21 

Anoxia,  effect  ot  fixation  ot  experience.  29 
Aphasia,  13 
Approach   learning,   hippocamp.il   electrical 

activity  during,  577-8<S 
Arousal  reaction,  habituation.  45'''.  473 
Auditory    discrimination    during    learning, 

effects  ot  frontal  lesions,  557,  560 

Barbiturates,  efl'ect  on  learning.  29.  32 
Behaviour,  21 

effects  of  tones  reinforced  by  cess.itmn  ot 

painful  stimuli,  265-91 
electrical  correlates,  243 
instinctive,  641 

neurohumoral  factors  in  control,  293-30(S 
patterns,  innate,  66 

unlearned,  interactions  with  ie.irmng  in 
maininals.  53-73 
primitive,  3 
reflex,  641 
spontaneous,  646 
Birds,  imprinting  m,  7(S-<Si 
learning  in,  75-93 
vocalization,  81-90 
Brain  change  in  learning,  2^},  235 

electrical  stimulation,  conditiitned  reflexes 
established  by,  133-51 
effect  on  learning,  157,  172 
single-unit  response,  172 
function,  evolutionary  concepts,  1-20 
functional  regression,  5,  13 
gnostic  intercommunication  between  cere- 
bral hemispheres,  485 
lesions,  effect  on  memory,  1 22 
phylogenetic  development,  2 
Bulbo-pontine    reticular    torination.    tuiic- 
tioiis,  413-31 

Cerebellum,  electrical  stimulation,  133 
Cerebral  cortex,  evoked  potentials,  changes 
bv     previous     reticular     stimulation. 

433-44 
response  to  previous  reticular  stimula- 
tion, 433-44 


!id:- 


e  ot 
■6c  o 
atiis. 


role  111  learning  iif  instrumental  co 

tioning  response,  589-600 
sensorimotor,     effect    of    ablation 
learning,  527-54 
Concentration  lack,  38 
Conditional  response,  instrumental,  r   . 
cerebral  cortex  in  learning  of  589 
Conditioned     reaction     effector     .ipp.u 

formation,  2 1 1 
Conditioning,  alimentary,  40:5,  404 
instrumental,  527-54 
functional   role   of  subcortical    structures. 
402-12 
Connections,    conditioned,    elaboration    and 

torination  of  their  properties,  95-1  n 
C^orpus  callosuin  and  visual  gnosis,  481-505 

Darwin  and  concepts  of  brain  tunction.  1-20 
Deprivation  and  learning  111  in.unmals.  55.  65 
Dentate     gyrus,     single-unit     rc-ponse     to 

electrical  stimulation.  175 
Digit  tests  of  memory,  41,  4C1 
Discrimination    learning    and    perforni.iiKe. 

non-sensory  eflx-cts  of  trom.il  lesions 

-S  5  5-76 

Earthworm,  le.ninng  m.  ^8 

Effector  apparatus  of  reflex  action.  21  1 

Ego, 14 

Electroencephaloi;ram.  effects  of  kaniiii"  on 

effects  ot  tones  reinforced  bv  cessation  of 

painful  stiimiii.  265-(;i 
in  study  of  conditioned  reffex.  190 
Endocrine  factors  in  control  of  animal  be- 
haviour, 293-308 
Hnvironment,     influence     on      conditioned 

reflex  connections,  304 
Epileptic    discharges,     reflex     conditioning, 

625-39 
Excitation,    electrical,    conditioned    reflexes 

established  by,  13^-51 
Experience,  fixation  of",  21-35 
effects  of  drugs.  29 

Eimbria.    smgle-unit    response    to    electrical 

stimulation.  175,  183 
Fixation  of  experience,  21-^5 
Flexor  response,  conditioned,  404,  40s 
Flicker  stimulation,  continuous,  significance 

on  evoked  responses,  607 
discontinuous,    significance   on    evoked 

responses,  613 
For';etting,  28 


699 


700 


INDEX 


iutcrtcrcucc-stmiulation,  154,  165 
mechanism,  changing  concepts,  231-41 
conditioning  in,  carhcst  manifestations, 
243-63 
negative,  neurciphysiological  mechanisms, 

44.S-79 
neuronal  organization,  231,  232 
rate,  38,  39 

reinforcement-interference  test,  167 
relation  to  deep  forebrain  structures,  28 

to  sensorimotor  cortex,  527-54 
self-stinuilation  experiments,  154 
visual,    relation    of  temporal    neocortex, 
507-25 
Locomotor  disinhibition  attcr  trt>ntal  lesions, 
571 

Manimillo-thalamic    tract,     single-unit    re- 
sponse to  electrical  stimulation,   175, 
181 
Mesencephalic  lesions,  effects  on  conditioned 

alimentary  and  tlexor  responses,  405 
Memory,  delayed  response,  46 
recent,  115-32 

delayed  responses,  116 
effect  of  frontal  lesions,  123 
localization,  122 
physiological  mechanism,  120 
relation  to  stable  memory,  127 
tests  for  various  stimuli,  118 
trace  conditioned  reflexes,  115 
reverberating  circuits,  localization,  122 
stable,  relation  tt)  recent  memory,  127 
tests,  41,  I  iS 
trace,  40 

establishment,  41 

effect  of  gnostic  intercommunication, 
489 
Meprobamate,  effect  on  learning,  29,  Ji 
Microvesicles,  321,  322 

Midpontinc  pretrigeminal  preparation,  413 
Mitochondria,  319 
Motoneurones,  activation,  337 

synaptic  action,  356 
Motor  cortex,  electrical  stimulation,  135 

Neocortex,  learning  changes  in,  2}} 

temporal,  relation  to  visual  discrimination 
learning,  507-25 
Nervous  system,  central,  excess  activity,  37 
Nest  building,  53-8 

hormonal  control,  58,  72 
Neurohumoral  factors  in  control  of  animal 
behaviour,  293-308 
during  electrographic  after-discharges.  520        Neuromuscular  junctions,  330 
in  birds,  earlyperiod,  75-93  Neuronal  doctrine  of  structure  ot  ner\iius 

in  mammals,  interactions  with  unlearned  system,  309 

behaviour  patterns,  53-73  Neurones,  26 

instrumental,    hypothalamic    relationship,  and  learning,  38 

,<3  and  recent  memorv,  121 


Freud  on  evolution  of  cerebral  function,  3, 
4.  -V  t2 

frontal  lobes,  lesions,  non-sensory  effects  on 
discrimination     learning      and      per- 
formance, 555-76 
relation  to  afferent  stimulation  ot  con- 
ditioned reflex,  194 

Golgi  type  11  neu^one^.  32N 
CInosis,    visual,    and    the    corpus    callosuni, 
481-505 

Habituation,   functional   role   of  subcortical 
structures,  393-412 
111  niKlpontiiie  preparation,  419 
tactile,  397 
vestibular,  394 
Hippocampus,     cicctrual     activity     during 
approach  learning,  577-88 
inhibitory  t'unction  in  orientation  reflex, 

250  CI  5C.;. 
stimulation,  eflect  on  learning,  183 
Histok)gical      bases      of     neurophysiology, 

309-34 
Hornional  factors  in  control  ot  animal  be- 
haviour, 293-308 
Hypothalamus,   effect  of  electrical  stimul.i- 
tion  on  learning,  162 
electrical  stimulation,  133 
relation    to    mechanisms    of  instrumental 
learning,  153 

Id.  3,  14 

imprinting  in  birds.  78-81 
Injury  feigning,  <>" 
Insects,  learning  in,  48,  49 
Instincts.  4,  5 

instrumental  learning,  relation  of  hypothal- 
amus. 153 

Jackson  on  evolution  of  cerebral  function.  3, 
4,  5 

Laycock  on  evolutiini  of  cerebral  tunction, 

4-  5 
Learned  effects  produced  by  tone  stimulus, 

267 
Learning,  22 

approach,  hippocampal  electrical  activity 

during,  577-88 
brain  change  in,  233,  235 
cerebral  localization,  27,  154,  161 
cumulative,  41,  42 
distinctive  features  in  higher  aninuils,  37-5 1 


INDEX 


701 


Neurones — iwiiii. 

autoactive,  358 

bombardment,     continuous,     effects     on 
synaptic  organization,  375-92 

contacts,  311-16 

functional  specificity.  319 

nutrition,  310 
Neurophysiology,  histological  bases,  309-34 
Neurosis,  humoral  factors  in  development, 

295,  306 
Neurosomes,  319 

Operant-behaviour  analysis,  172 

Optic    chiasma,    section,    effect    on    visual 

gnosis,  482 
Orientating  reaction,  habituation,  463,  473 
Orientation  reflex,  243,  244,  245,  248,  250 

inhibition,  250 
Orienting-investigatory  reaction,  196 
Orgs,  21 

Palaeocortical     systems,     interference     and 

learning  in,  153-87 
Parasynapses,  326 
Pavlov  on  evolution  of  cerebral  function,  3, 

9-1^ 

Pecking  reaction  in  the  towl,  65 

Perikaryon,  326 

Personality,  14 

Phenobarbital,  effect  on  fixation  of  experi- 
ence, 29 

Photic  stimulation,  cortical  response,  425 
stimulus,  significance  on  evoked  responses 
in  man,  603-23 

Plastic  change,  location,  651 
phenomena,  functions,  413-31 

Polecat,  killing  technique,  59 

Post-activation,     facilitation,     as    factor    in 
establishment  of  conditioned  reflexes, 

353-73 
Postcruciate  gyrus,  electrical  stimulation,  137 
Potentiation,  post-tetanic,  353-73 
Prefrontal  lobes,  relation  to  recent  memory, 

123 
Prey  killing,  59 
Purkinje  neurones,  329 
Pyriform  cortex,  effect  of  stimulation.  300 

Rats,  retrieval  of  young  in.  53.  58,  59 
Recall    rei,.'"ioii  to  deep  torchrain  structures, 

28 
Reflex  action,  mechanism,  189 
Reflexes,  conditioned,  3,  10 

acceptor  apparatus,  203 

afferent  synthesis,  197,  198,  202 

alimentary,  403,  404 

cardiovascular  components,  211,  213 

dynamic  pattern,  192 

effect  of  environment,  304 

effect  of  sensorimotor  lesions,  527-54 


effector  apparatus,  formation  of,  211 
elaboration  and  formation  of  properties, 

95-113 

established  by  coupling  electrical  excita- 
tion of  two  cortical  areas,  133-51 

functional  role  ot  subcortical  structures. 

393-41 -i 
instrumental,  role  of  cerebral  cortex  in 

learning  of,  589-600 
local  motor-defensive,  217 
motor,  217 

motor  component,  211 
physiological  architecture,  189-229 
respiratory  component,  211,  212 
return  afferentation  of  results,  221 
role  of  stimuli.  95 

sccreto-motor  method  of  study,  187 
secretory  component,  21 1 
shortened,  234 

trace,  relation  to  recent  memory,  115 
vegetative  components,  213,  216 
monosynaptic,  effects  of  disuse,  338 
post-tetamc  potentiation.  353-73 
unconditioned,  3 
Reflexo-conditioned  techniques,  625 
Reinforcement   of  conditioned   reflex,    236, 

239 
Reinforcement-interference  test,  167 
Rcserpinc,  effect  on  learning,  29 
Response,  conditioned,  133 
delayed,  46 

relation  to  recent  memory,  116 
evoked,   significance   of  photic  stimulus, 
603-23 
Retention  of  learning  during  elcctrographic 

after-discharges,  520 
Reticular  formation,  influence  upon  cortical 

evoked  potentials,  433-44 
Retina,  neurohistology,  329,  330 
Retinopetal  fibres,  330 
Reverberating  circuits  responsible  for  recent 

memory,  localization,  122 
Reverberation,  3 1 

Rhincncephalon,  single-unit  response  to  elec- 
trical stimulation,  177 
Ribonucleic  acid  changes  in  cells  subjected  to 

synaptic  bombardment,  389 
Rodents,  nest  building,  53-8 

Scchenov  on  evolution  tif  cerebral  function, 

II,  12 
Sensory  deafferentatioii.  midpontine.  416 
Sexual  selection,  17 
Signal  responses   265 
Sleep   inhibitory  systems  acting  during,  446, 

470 
neurophysiological  mechanisms,  445-79 
Sleep-wakefulness  rhythm,  413 
Spencer  on  evolution  of  cerebral  function, 

4,  i,  6,  7,  8 


702 


INDEX 


Startle  response,  245,  246,  247,  248,  249 
Stimulus,  conditional,  133 

indifferent,  96 

role  in  conditioned  reflex,  95 

subcutaneous,  behavioural  effects,  268 

unconditioned,  102 
Stimulus-response  connection,  37 
Superego,  3,  15 
Synapse,  activation,  335,  336 

axo-axonic,  317 

axokaryolemmal,  331 

definition  of,  324 

dendro-dendritic,  315,  326,  327 

dendro-somatic,  315,  326,  327 

dendro-somato-dendritic,  315,  326 

mode  of  action,  335 

organization,  lasting  changes  produced  by 
continuous  neuronal  bombardment, 
375-92 

somato-somatic,  317,  326 

trophic  function,  331 
Synaptic  function,  effects  of  disuse,  338 
effects  of  excessive  use,  344 
effects  of  use  and  disuse,  335-52 

relations  in  memorization,  44,  46,  48 

spectrum,  329 


Tactile  habituation,  397,  400 

Tactual    discrimination   learning,    effects   of 

frontal  lesions,,  557,  559 
Telcncephalic  inhibitory  system,  466,  475 
Time  sense,  122 

Tone  reinforcement,  behavioural  and  EEG 
effects,  265,  267,  273 
stimulus,  effect  of  frequency  changes,  281 
localization  specificity,  282 
Trace  conditioned  reflexes,  relation  to  recent 
memory,  115 
systems,  40 

Vestibular   habituation   in   decorticated   and 

decerebrated  cats,  394 
Visual   discrimination  learning,   relation   of 
temporal  neocortex,  507-25 
retention,  effects  of  frontal  lesions,  556 
gnosis  and  the  corpus  callosum,  481-505 
Vocalization  in  birds,  81-90 

Wakefulness  and  cortical  desynchronization, 
417 

Young,  retrieval  in  rats,  53,  58,  59