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34 



JAMES ARTHUR LECTURE ON 
THE EVOLUTION OF THE HUMAN BRAIN 

1964 



PROBLEMS OUTSTANDING IN THE 
EVOLUTION OF BRAIN FUNCTION 

ROGER W. SPERRY 



THE AMERICAN MUSEUM OF NATURAL HISTORY 
NEW YORK : 1964 



355 













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1869 
THE LIBRARY 



JAMES ARTHUR LECTURE ON 
THE EVOLUTION OF THE HUMAN BRAIN 



JAMES ARTHUR LECTURE ON 
THE EVOLUTION OF THE HUMAN BRAIN 

1964 



PROBLEMS OUTSTANDING IN THE 
EVOLUTION OF BRAIN FUNCTION 



ROGER W. SPERRY 

Hixon Professor of Psychobiology 

California Institute of Technology 

Pasadena, California 



THE AMERICAN MUSEUM OF NATURAL HISTORY 
NEW YORK : 1964 



JAMES ARTHUR LECTURE ON 
THE EVOLUTION OF THE HUMAN BRAIN 

Frederick Tilney, The Brain in Relation to Behavior; March 15, 1932 

C. Judson Herrick, Brains as Instruments of Biological Values; April 6, 1933 

D. M. S. Watson, The Story of Fossil Brains from Fish to Man; April 24, 1934 

C. U. Ariens Kappers, Structural Principles in the Nervous System; The Develop- 
ment of the Forebrain in Animals and Prehistoric Human Races; April 25, 
1935 
Samuel T. Orton, The Language Area of the Human Brain and Some of its Dis- 
orders; May 15, 1936 
R W. Gerard, Dynamic Neural Patterns; April 15, 1937 
Franz Weidenreich, The Phylogenetic Development of the Hominid Brain and its 

Connection with the Transformation of the Skull; May 5, 1938 
G. Kingsley Noble, The Neural Basis of Social Behavior of Vertebrates; May 11, 

1939 
John F. Fulton, A Functional Approach to the Evolution of the Primate Brain; 

May 2, 1940 
Frank A. Beach, Central Nervous Mechanisms Involved in the Reproductive Be- 
havior of Vertebrates; May 8, 1941 
George Pinkley, A History of the Human Brain; May 14, 1942 
James W. Papez, Ancient Landmarks of the Human Brain and Their Origin; 

May 27, 1943 
James Howard McGregor, The Brain of Primates; May 11, 1944 
K. S. Lashley, Neural Correlates of Intellect; April 30, 1945 
Warren S. McCulloch, Finality and Form in Nervous Activity; May 2, 1946 
S. R. Detwiler, Structure-Function Correlations in the Developing Nervous Sys- 
tem as Studied by Experimental Methods; May 8, 1947 
Tilly Edinger, The Evolution of the Brain; May 20, 1948 
Donald O. Hebb, Evolution of Thought and Emotion; April 20, 1949 
Ward Campbell Halstead, Brain and Intelligence; April 26, 1950 
Harry F. Harlow, The Brain and Learned Behavior; May 10, 1951 
Clinton N. Woolsey, Sensory and Motor Systems of the Cerebral Cortex; May 7, 

1952 
Alfred S. Romer, Brain Evolution in the Light of Vertebrate History; May 21, 

1953 
Horace W. Magoun, Regulatory Functions of the Brain Stem; May 5, 1954 
Fred A. Mettler, Culture and the Structural Evolution of the Neural System; 

April 21, 1955 
Pinckney J. Harman, Paleoneurologic, Neoneurologic, and Ontogenetic Aspects 

of Brain Phytogeny; April 26, 1956 
Davenport Hooker, Evidence of Prenatal Function of the Central Nervous System 

in Man; April 25, 1957 
David P. C. Lloyd, The Discrete and the Diffuse in Nervous Action; May 8, 1958 
Charles R. Noback, The Heritage of the Human Brain; May 6, 1959 
Ernst Scharrer, Brain Function and the Evolution of Cerebral Vascularization; 

May 26, 1960 
Paul I. Yakovlev, Brain, Body and Behavior. Stereodynamic Organization of the 
Brain and of the Motility-Experience in Man Envisaged as a Biological 
Action System; May 16, 1961 
H. K. Hartline, Principles of Neural Interaction in the Retina; May 29, 1962 
Harry Grundfest, Specialization and Evolution of Bioelectric Activity; May 28, 

1963 
Roger W. Sperry, Problems Outstanding in the Evolution of Brain Function; 
June 3, 1964 



PROBLEMS OUTSTANDING IN THE 
EVOLUTION OF BRAIN FUNCTION 

Having been for some time one of those "card-carrying 
members" of the American Museum and being indebted to 
the Museum on certain other counts over the years, I much 
appreciate the invitation to give the 1964 James Arthur 
Lecture. I have been forewarned that many in the audience 
will not be particularly carried away by the "latest technical 
advances." I have also been forewarned that another 50 per 
cent are apt to be rather bored by anything else. The motley 
mixture of material with which I have tried to balance the 
diverse interests will, I fear, strain even so broad an encom- 
passing theme as that of evolution. As indicated in the title, 
we shall be concerned more with the functional than with 
the morphological properties of the brain, and more with 
remaining unsolved problems than with the solid progress 
over which we already can beat our chests. 

I wish to skip the beginning steps in the evolution of the 
human brain and pick up the story at about the culmination 
of the latter half of the age of hydrogen gas. In such a way 
we can bypass what is by far the most difficult of all the 
unsolved problems in brain evolution, namely, how, when, 
and where did the hydrogen age and the whole business 
start? This problem we can leave to the proponents of the 
"steady state," the "periodic pulsation," and the "big bang," 
at least until someone comes along with a more credible 
interpretation of the meaning of the red shift. 

We can skip quickly also through those early periods 
when, first, electrons and protons were being used to build 
bigger and better atoms, and then the atoms to make bigger 
and finer molecules, and then these in turn were being com- 
pounded into giant and replicating molecules and self- 



organizing molecular complexes and eventually that elabo- 
rate unit, the living cell. 

We need pause here only to note for future reference that 
evolution keeps complicating the universe by adding new 
phenomena that have new properties and new forces and 
that are regulated by new scientific principles and new 
scientific laws — all for future scientists in their respective 
disciplines to discover and formulate. Note also that the old 
simple laws and primeval forces of the hydrogen age never 
get lost or cancelled in the process of compounding the 
compounds. They do, however, get superseded, over- 
whelmed, and outclassed by the higher-level forces as these 
successively appear at the atomic, the molecular, and the 
cellular and higher levels. 

We can turn now to what is probably the "most unan- 
swered" problem in brain evolution. We encounter it a bit 
later on, presumably after organisms with nerve nets and 
brains have entered the picture. I refer, as you probably 
guess, to the first appearance of that most important of all 
brain properties and certainly the most precious, conscious 
awareness. (I hope that it is safe to assume that, since "mind" 
and "consciousness" have made a comeback in recent years 
and have become respectable terms again in the Boston area, 
it is permissible to mention them here also.) 

In any case, the fossil record notwithstanding, there 
seems to be good reason to regard the evolutionary debut 
of consciousness as very possibly the most critical step in 
the whole of evolution. Before this, the entire cosmic 
process, we are told, was only, as someone has phrased it, 
"a play before empty benches" — colorless and silent at that, 
because, according to our best physics, before brains there 
was no color and no sound in the universe, nor was there 
any flavor or aroma and probably rather little sense and no 
feeling or emotion. 

All of these can now be generated by the surgeon's elec- 



trode tip applied to the proper region of the exposed con- 
scious brain. They can be triggered also, of course, by the 
proper external stimuli, but also, more interestingly, by 
centrally initiated dream states, illusionogenic and hal- 
lucinogenic agents, but always and only within and by a 
brain. There probably is no more important quest in all 
science than the attempt to understand those very particular 
events in evolution by which brains worked out that special 
trick that has enabled them to add to the cosmic scheme of 
things: color, sound, pain, pleasure, and all the other facets 
of mental experience. 

In searching brains for clues to the critical features that 
might be responsible, I have never myself been inclined to 
focus on the electrons, protons, or neutrons of the brain, or 
on its atoms. And, with all due respect to biochemistry and 
the N.R.P., I have not been inclined to look particularly at 
the little molecules of the brain or even at its big macro- 
molecules in this connection. It has always seemed rather 
improbable that even a whole brain cell has what it takes 
to sense, to perceive, to feel, or to think on its own. The 
"search for psyche," in our own case at least, has been di- 
rected mainly at higher-level configurations of the brain, 
such as specialized circuit systems, and not just any juicy 
central nerve network that happens to be complex and 
teeming with electrical excitations. I have been inclined to 
look rather at circuits specifically designed for the express 
job of producing effects like pain, or High C or blue-yellow 
— circuits of the kind that one finds above a high transec- 
tion of the spinal cord but not below, circuits with something 
that may well be present in the tiny pinhead dimensions of 
the midbrain of the color-perceiving goldfish but lacking in 
the massive spinal-cord tissue of the ox, circuits that are 
profoundly affected by certain lesions of the midbrain and 
thalamus but little altered by complete absence of the entire 
human cerebellum. Were it actually to come to laying our 

3 



money on the line, I should probably bet, first choice, on 
still larger cerebral configurations, configurations that in- 
clude the combined effect of both (a) the specialized circuit 
systems such as the foregoing plus (b) a background of 
cerebral activity of the alert, waking type. Take away either 
the specific circuit, or the background, or the orderly activ- 
ity from either one, and the conscious effect is gone. 

In this day of information explosion, these matters are 
not so much of the "ivory tower" as they used to be: To 
the engineer who comes around from Industrial Associates 
with dollars and cents in his eye and company competition 
in his heart the possibility is of more than theoretical inter- 
est that conscious awareness may be something that is not 
necessarily tied to living hardware, that it could prove to be 
an emergent, over-all circuit property that might, in theory, 
be borrowed and, given sufficient acreage, perhaps copied 
some day in order to incorporate pain and pleasure, sensa- 
tions and percepts, into the rapidly evolving circuitry of 
computer intellect. When the aim is to build into your 
circuit systems some kind of negative and positive reinforce- 
ment, then pain and pleasure are about the best kind. And 
eager young theoreticians from the NASA committee or 
from radio astronomy already want a more educated guess 
about the possibility of encountering on other globes other 
minds with perhaps totally different dimensions of conscious 
awareness, and if not, why not? Then there are more immi- 
nent, practical matters such as the need, in view of certain 
other explosions we face, to be able to pinpoint the first 
appearance of consciousness in embryonic development and 
chart its subsequent growth and maturation. 

Unless you are among those who still believe that value 
judgments lie outside the realm of science, you may prob- 
ably agree that a few reliable answers in these general areas 
and their implications could shake considerably the going 
value systems of our whole culture. 



We shift now to certain lesser and subsidiary problems, 
but problems more approachable in research. Unlike the 
situation 25 years ago, most of us today are quite ready to 
talk about the evolution and inheritance not only of brain 
morphology but also of brain function, including general 
behavior and specific behavior traits. Earlier renunciation 
of the whole instinct concept in the animal kingdom gen- 
erally stemmed in large part from our inability to imagine any 
growth mechanisms sufficiently precise and elaborate even 
to begin the fabrication of the complex nerve networks of 
behavior. This outlook was supported in the analytic studies 
of nerve growth all through the 1920's and 1930's which indi- 
cated that nerve fibers grow and connect in a random, dif- 
fuse, and non-selective manner governed almost entirely by 
indifferent, mechanical factors. 

Today the situation is entirely changed. The supposed 
limitations in the machinery of nerve growth are largely 
removed in the new insight that we have obtained in recent 
years into the way in which the complicated nerve-fiber 
circuits of the brain grow, assemble, and organize them- 
selves in a most detailed fashion through the use of intricate 
chemical codes under genetic control (Sperry, 1950a, 
1950b, 1951, 1958, 1961, 1962, 1963). The new outlook 
holds that the cells of the brain are labeled early in develop- 
ment with individual identification tags, chemical in nature, 
whereby the billions of brain cells can thereafter be recog- 
nized and distinguished, one from another. These chemical 
differentials are extended into the fibers of the maturing 
brain cells as these begin to grow outward, in some cases 
over rather long distances, to lay down the complicated 
central communication lines. It appears from our latest evi- 
dence that the growing fibers select and follow specific pre- 
scribed pathways, all well marked by chemical guideposts 
that direct the fiber tips to their proper connection sites. 
After reaching their correct synaptic zones, the fibers then 



link up selectively among the local population with only 
those neurons to which they find themselves specifically 
attracted and constitutionally matched by inherent chemical 
affinities. 

The current scheme now gives us a general working pic- 
ture of how it is possible, in principle at least, for behavioral 
nerve nets of the most complex and precise sorts to be built 
into the brain in advance without benefit of experience. 
Being under genetic control, these growth mechanisms are 
of course inheritable and subject to evolutionary develop- 
ment. The same is true of the differential endogenous 
physiological properties of the individual cell units in these 
networks which, along with the morphological intercon- 
nections, are of critical importance in the shaping of be- 
havior patterns. We have at present only the general outlines 
and general principles of the developmental picture; much 
of the detail has yet to be worked out. Also, the underlying 
chemistry of the demonstrated selectivity in nerve growth, 
as well as the molecular basis of the morphogenetic gradients 
involved, and of all the rest of the chemical "I. D. Card" 
concept remains a wide-open field that so far has been 
virtually untouched. 

In connection with this emphasis on the "inherited" in 
brain organization, one may well question the extent to 
which the observed inbuilt order in the anatomical structure 
necessarily conditions functional performance and behavior. 
Some years ago, when we subscribed to the doctrine of an 
almost omnipotent adaptation capacity in the central ner- 
vous system and to functional equipotentiality of cortical 
areas and to the functional interchangeability among nerve 
connections in general (Sperry, 1958), Karl Lashley sur- 
mised that if it were feasible, a surgical rotation through 
180 degrees of the cortical brain center for vision would 
probably not much disturb visual perception. Rotation of 
the brain center was not feasible, but it was possible to 



rotate the eyes surgically through 180 degrees in a number 
of the lower vertebrates and also to invert the eyeball, by 
transplantation from one to the other orbit, on the up-down 
or on the front-back axis and also to cross-connect the right 
and left eyes to the wrong side of the brain (Sperry, 1950a) . 
All these and different combinations thereof were found 
to produce very profound disturbances of visual perception 
that were correlated directly in each case with the geometry 
of the sensory disarrangement. The animals, after recovery 
from the surgery, responded thereafter as if everything were 
to them upside down and backward, or reversed from left 
to right, and so on. Contrary to earlier suppositions regard- 
ing the dynamics of perception and cortical organization, 
it appeared that visual perception was very closely tied 
indeed to the underlying inherited structure of the neural 
machinery. 

We inferred further from nerve-lesion experiments 
(Sperry, 1950b) on the illusory spinning effects produced 
by these visual inversions that the inbuilt machinery of 
perception must include also certain additional central 
mechanisms by which an animal is able to distinguish those 
sensory changes produced by its own movement from those 
originating outside. The perceptual constancy of an environ- 
ment in which an animal is moving, for example, or of an 
environment that it is exploring by eye, head, or hand move- 
ments, would seem to require that, for every movement 
made, the brain must fire "corollary discharges" into the 
perceptual centers involved. These anticipate the displace- 
ment effect and act as a kind of correction or stabilizing 
factor. These centrally launched discharges must be differ- 
entially gauged for the direction, speed, and distance of 
each move. Along with the dynamic schema for body posi- 
tion which the brain must carry at all times, these postulated 
discharges conditioning perceptual expectancy at every 
move would appear to be a very important feature of the 



unknown brain code for perception. The consistent appear- 
ance of the spontaneous optokinetic reaction of inverted 
vision in fishes, salamanders, and toads would indicate that 
the underlying mechanism is basic and must have evolved 
very early. 

Since the representation of movement at higher cortical 
levels generally seems to be more in terms of the perceptual 
expectancy of the end effect of the movement than in terms 
of the actual motor patterns required to mediate the move- 
ment, the postulated "corollary discharges" of perceptual 
constancy may not involve so much of an additional load, 
in terms of data processing, as might at first appear. 

We are ready now for that old question: How much of 
brain organization and behavior should we blame or credit 
to inheritance and how much to learning and experience? 
As far as we can see now, it seems fair to say that all that 
central nervous organization that is illustrated and described 
in the voluminous textbooks, treatises, and professional 
journals of neuro-anatomy, that is, all the species-constant 
patterning of brain structure, the micro-architecture as well 
as the gross morphology that has so far been demonstrated 
anatomically, seems to be attributable to inheritance. An- 
other way of saying the same thing is that no one has yet 
succeeded in demonstrating anatomically a single fiber or 
fiber connection that could be said with assurance to have 
been implanted by learning. In this same connection, it is 
entirely conceivable (though not particularly indicated) 
that the remodeling effects left in the brain by learning and 
experience do not involve the addition or subtraction of 
any actual fibers or fiber connections but involve only 
physiological, perhaps membrane, changes that effect con- 
ductance or resistance to impulse transmission, or both, all 
within the existing ontogenetically determined networks. 

The foregoing picture leaves plenty of room for learning 
and for the combined effects of learning plus maturation 

8 



during that prolonged period in human childhood when 
these two factors overlap. Nevertheless the present picture 
represents a very considerable shift of opinion over the past 
two decades in the direction of inheritance. 

Some of you may find certain aspects here a bit difficult 
to reconcile with other inferences drawn in recent years 
from a series of sensory deprivation studies on mammals in 
which cats, monkeys, chimpanzees, and other animals have 
been raised in the dark or with translucent eye caps or in 
harnesses or holders of various sorts and in which, as a 
result of the various kinds of deprivation of experience in 
their early development the animals came to show subse- 
quent deficits, moderate to severe, in their perceptual or 
motor capacities. The tendency to interpret these findings, 
along with those from human cataract cases, as evidence 
of the importance of early learning and experience in 
shaping the integrative organization of the brain we have 
long felt to have been overdone (Sperry, 1950a, 1962). 
In nearly all cases the findings could be equally well 
explained on the assumption that the effect of function is 
simply to maintain, or to prevent the loss of, neural organ- 
ization already taken care of by growth. What the results 
have come to show in many of these studies is that certain 
of the newly formed neuronal elements, if abnormally 
deprived of adequate stimulation, undergo an atrophy of 
disuse. In much the same way cells of the skeletal muscles 
differentiate in development to the point at which they are 
contractile and ready to function, but then they too atrophy 
and degenerate if not activated. This basic developmental 
"use-dependent" property in maturing neurons, or even 
some evolutionary derivative of it, applied farther centrally 
beyond the sensory paths amid more diffuse growth pres- 
sures, especially among cortical association units, could, 
however, have true patterning effects and become a definitely 
positive factor in learning and imprinting. 



We have been approaching very closely here the general 
problem of memory. Among brain functions, memory cer- 
tainly rates as one of the prime "problems outstanding." 
Whatever the nature of the neural mechanism underlying 
memory, it seems to have appeared quite early in evolution. 
(Some writers say that even flatworms have memory!) We 
are frequently impressed in our own work with learning 
and memory in cats, and even in fishes, with the fact that 
their simple memories, once implanted, seem to be strong 
and lasting. With respect to memory, then, what separates 
the men from the animals is very likely not so much the 
nature of the neural trace mechanism as the volume and 
the kind of information handled. The problems that relate 
to the translation and coding of mental experience, first 
into the dynamics of the brain process, and then into the 
static, frozen, permanent trace or engram system, pose the 
more formidable aspects of the memory problem. 

Fundamental to these memory questions, as also to the 
problems of perception, volition, learning, motivation, and 
most of the higher activities of the nervous system, is that 
big central unknown that most of us working on the higher 
properties of the brain keep tangling with and coming back 
to. You may find it referred to variously as: the "brain 
code," or the "cerebral correlates of mental experience," or 
the "unknown dynamics of cerebral organization," or the 
"intermediary language of the cerebral hemispheres," or, 
in some contexts, just the "black box." Thus far we lack 
even a reasonable hypothesis regarding the key variables 
in the brain events that correlate with even the simplest of 
mental activities, such as the elementary sensations or the 
simple volitional twitch of one's little finger. 

In our own efforts to help to chip away at this central 
problem of the language of the hemispheres, we have been 
trying for some 10 years first to divide the problem in half by 
splitting the brain down the middle before we start to study 

10 



it. (Many times we wonder if the end effect of this split 
brain approach is not so much to halve our problems as 
it is to double them.) At any rate, the brain-bisection 
studies leave us with a strong suspicion that evolution may 
have saddled us all with a great deal of unnecessary dupli- 
cation, both in structure and in the function of the higher 
brain centers. 

Space in the intracranial regions is tight, and one won- 
ders if this premium item could not have been utilized for 
better things than the kind of right-left duplication that 
now prevails. Evolution, of course, has made notable errors 
in the past, and one suspects that in the elaboration of the 
higher brain centers evolutionary progress is more encum- 
bered than aided by the bilateralized scheme which, of 
course, is very deeply entrenched in the mechanisms of 
development and also in the basic wiring plan of the lower 
nerve centers. 

Do we really need two brain centers, for example, to tell 
us that our blood sugar is down or our blood pressure is 
up, or that we are too hot or too cold, and so on? Is it 
necessary to have a right and also a left brain center to let 
us know that we are sleepy or angry, sad or exuberant, or 
that what we smell is Arpege or what we taste is salty or 
that what we hear is voices, and so on and on and on? 
Surely most of us could manage to get along very well with 
only one cerebral anxiety mechanism, preferably in the 
minor hemisphere. 

Emotion, personality, intellect, and language, among 
other brain business, would seem by nature to be quite 
manageable through a single unified set of brain controls. 
Indeed, the early loss of one entire hemisphere in the cat, 
monkey, and even in man causes amazingly little deficit 
in the higher cerebral activities in general. 

With the existing cerebral system, most memories as well 
have to be laid down twice — one engram for the left 

11 



hemisphere and another engram copy for the right hemi- 
sphere. The amount of information stored in memory in 
a mammalian brain is a remarkable thing in itself; to have 
to double it all for the second hemisphere would seem in 
many ways a bit wasteful. It is doubtful that all this 
redundancy has had any direct survival value (unless evolu- 
tion could have foreseen that neurologists would be opening 
and closing the cranium to produce brain lesions under 
careful aseptic conditions that permit survival). 

In the human brain, of course, we begin to see definite 
evidence of a belated tendency in evolution to try to cir- 
cumvent some of the duplication difficulties. A de-duplica- 
tion trend is seen particularly in the lateralization of speech 
and writing within the single dominant hemisphere in the 
majority of persons. Speech, incidentally, is another essen- 
tially symmetrical activity for which a double right and 
left control is quite unnecessary, even at the lower levels 
of the motor hierarchy. When the brain does try in some 
individuals to set up two central administrations for speech, 
one in each hemisphere, the result tends to make for 
trouble, like stammering and a variety of other language 
difficulties. 

The fact that the corpus callosum interconnecting the 
two cerebral hemispheres is so very large and the functional 
damage produced by its surgical section is so very minor 
in most ordinary activities seems to be explainable in part 
by the fact that the great cerebral commissure is a system 
for cross communication between two entities that to a 
large extent are each completely equipped and functionally 
self-sufficient. The corpus callosum appears late in evolu- 
tion, being essentially a mammalian structure, and its 
development is closely correlated with the evolutionary 
elaboration of the neocortex of the mammalian cerebral 
hemispheres. 

Accordingly it is not surprising that it is in the human 

12 



brain, and particularly in connection with speech, that the 
functional effects produced by surgical disconnection of the 
two cerebral hemispheres become most conspicuous. Dur- 
ing the past two years we have had an opportunity to test 
and to study two patients, formerly unmanageable epilep- 
tics, who have had their right and left hemispheres discon- 
nected by complete section of the corpus callosum, plus 
the anterior commissure, plus the hippocampal commissure, 
plus the massa intermedia, in what is perhaps the most 
radical surgical approach to epilepsy thus far undertaken. 
The surgery was done by Drs. Philip J. Vogel and Joseph 
E. Bogen (see Bogen and Vogel, 1962) of Los Angeles. 1 
It seemed a reasonable hope, in advance, that such surgery 
might help to restrict the seizures to one hemisphere and 
hence to one side of the body, and possibly to the distal 
portions of arm and leg, since voluntary control of both 
sides of the head, neck, and trunk tends to be represented 
in both hemispheres. In our colony of split-brain monkeys 
that have had similar surgery, we not uncommonly see 
epileptic-like seizures, especially during the early weeks 
after brain operations, and these seizures show a definite 
tendency to center in the distal extremities of the arm and 
leg and to be restricted to one side. It also seemed reason- 
able that this surgery might help the patients to retain 
consciousness in one hemisphere during an attack, if not 
throughout, at least during the early stages, and thereby 
give them a chance to do things that might help to break 



1 The surgical treatment of these cases was undertaken at the suggestion of 
Dr. Bogen after extensive consultations on all aspects. The surgery was per- 
formed by Dr. Vogel, assisted by Dr. Bogen and other staff members at the 
Loma Linda Neurosurgical Unit, White Memorial Hospital. Most of the tests 
reported here were planned and administered by Michael S. Gazzaniga of our 
laboratory, with the writer collaborating on a general advisory basis. 

The original work included here was supported by grants from the National 
Institutes of Health (MH-03372, S-F1-MH-18,080) and by the Frank P. Hixon 
Fund of the California Institute of Technology. 

13 



or control the seizures, or at a rninimum to allow time in 
which to undertake protective measures before the second 
side became involved. It was further hoped that such 
surgery might reduce the severity of the attacks by the 
elimination of a very powerful avenue for the right-left 
mutual reinforcement of the seizures during the generalized 
phase, especially during status epilepticus, which was of 
major concern in both the cases cited above. 

Judged from earlier reports of the cutting of the corpus 
callosum and from the behavior of dozens of monkeys that 
we have observed in the laboratory with exactly the same 
surgery (Sperry, 1961, 1964), it seemed unlikely that this 
kind of surgery would produce any severe handicap, or 
surely none so bad as certain other forms of psychosurgery 
that have been used on a much more extensive scale. That 
the surgery might decrease the incidence of the seizures to 
the point of virtually eliminating them (as it seems to have 
done so far in both cases) was unexpected; our fingers 
remain very much crossed on this latter point. 

Everything that we have seen so far indicates that the 
surgery has left each of these people with two separate 
minds, i.e., with two separate spheres of consciousness 
(Gazzaniga, Bogen, and Sperry, 1962, 1963). What is 
experienced in the right hemisphere seems to be entirely 
outside the realm of awareness of the left hemisphere. This 
mental duplicity has been demonstrated in regard to percep- 
tion, cognition, learning, and memory. One of the hemi- 
spheres, the left, dominant, or major hemisphere, has speech 
and is normally talkative and conversant. The other mind 
of the minor hemisphere, however, is mute or dumb, being 
able to express itself only through non-verbal reactions; 
hence mental duplicity in these people following the sur- 
gery, but no double talk. 

Fortunately, from the patients' standpoint, the functional 
separation of the two hemispheres is counteracted by a large 

14 



number of unifying factors that tend to keep the discon- 
nected hemispheres doing very much the same thing from 
one part of the day to the next. Ordinarily, a large common 
denominator of similar activity is going in each. When we 
deliberately induce different activities in right and left hem- 
ispheres in our testing procedures, however, it then appears 
that each hemisphere is quite oblivious to the experiences 
of the other, regardless of whether the going activities 
match or not. 

This is illustrated in many ways: For example, the 
subject may be blindfolded, and a familiar object such as 
a pencil, a cigaret, a comb, or a coin is placed in the left 
hand. Under these conditions, the mute hemisphere con- 
nected to the left hand, feeling the object, perceives and 
appears to know quite well what the object is. It can 
manipulate it correctly; it can demonstrate how the object 
is supposed to be used; and it can remember the object 
and go out and retrieve it with the same hand from among 
an array of other objects. While all this is going on, the 
other hemisphere has no conception of what the object is 
and says so. If pressed for an answer, the speech hemisphere 
can only resort to the wildest of guesses. So the situation 
remains just so long as the blindfold is kept in place and 
other avenues of sensory input from the object to the talk- 
ing hemisphere are blocked. But let the right hand cross 
over and touch the test object in the left hand; or let the 
object itself touch the face or head as in the use of a comb, 
a cigaret, or glasses; or let the object make some give-away 
sound, such as the jingle of a key case, then immediately 
the speech hemisphere produces the correct answer. 

The same kind of right-left mental separation is seen in 
tests involving vision. Recall that the right half of the visual 
field and the right hand are represented together in the 
left hemisphere and vice versa. Visual stimuli such as pic- 
tures, words, numbers, and geometric forms flashed on a 

15 



screen directly in front of the subject and to the right side 
of a central fixation point are all described and reported 
correctly with no special difficulty. On the other hand 
similar material flashed to the left half of the visual field is 
completely lost to the talking hemisphere. Stimuli flashed 
to one half field seem to have no influence whatever, in 
tests to date, on the perception and interpretation of stimuli 
presented to the other half field. 

Note in passing that these disconnection effects do not 
show up readily in ordinary behavior. They must be demon- 
strated by the flashing of the visual material fast enough so 
that eye movements cannot be used to sneak the answers 
into the wrong hemisphere, or in the testing of right and 
left hands vision must be excluded with a blindfold, audi- 
tory cues eliminated, and the hands kept from crossing, 
and so on. One of the patients, a 30-year old housewife 
with two children, goes to market, runs the house, cooks 
the meals, watches television, and goes out to complete, 
three-hour shows at the drive-in theater, all without com- 
plaining of any particular splitting or doubling in her per- 
ceptual experience. Her family believes that she still does 
not have so much initiative as formerly in her houseclean- 
ing, in which she was meticulous, and that her orientation 
is not so good, for example, she does not find her way back 
to the car at the drive-in theater as readily as she formerly 
could. In the early months after surgery there appeared to 
be definite difficulty with memory. By now, some eight 
months later, there seems to be much improvement in this 
regard, though not complete recovery. Involvement of the 
fornix would have to be ruled out before effects like the 
latter can be ascribed to the commissurotomy. 

In the visual tests again, one finds plenty of evidence that 
the minor, dumb, or mute hemisphere really does perceive 
and comprehend, even though it cannot express verbally 
what it sees and thinks. It can point out with the left hand 

16 



a matching picture from among many others that have been 
flashed to the left field, or it can point to a corresponding 
object that was pictured in the left-field screen. It can also 
pick out the correct written name of an object that it has 
seen flashed on the screen, or vice versa. In other words, 
Gazzaniga's more recent results show that the dumb left 
hemisphere in the second patient is not exactly stupid or 
illiterate; it reads a word such as "cup," "fork," or "apple" 
flashed to the left field and then picks out the corresponding 
object with the left hand. While the left hand and its hemi- 
sphere are thus performing correctly, however, the other 
hemisphere, again, has no idea at all which object or which 
picture or which name is the correct one and makes this 
clear through its verbal as well as other responses. You 
regularly have to convince the talking hemisphere to keep 
quiet and to let the left hand go ahead on its own, in which 
case it will usually pick out the correct answer. 

These minor differences of opinion between the right 
and left hemispheres are seen rather commonly in testing 
situations. For example, the left hand is allowed to feel and 
to manipulate, say, a toothbrush under the table or out of 
sight behind a screen. Then a series of five to 10 cards are 
laid out with names on them such as "ring," "key," "fork." 
When asked, the subject may tell you that what she felt in 
the left hand was a "ring." However, when instructed to 
point with the left hand, the speechless hemisphere delib- 
erately ignores the erroneous opinions of its better half and 
goes ahead independently to point out the correct answer, 
in this case the card with the word "toothbrush." 

As far as we can see, about the only avenue remaining 
for direct communication between mind-right and mind-left 
is that of extrasensory perception. If any two minds should 
be able to tune in on each other, one might expect these two 
to be able to do so, but thus far no evidence of such effects 
is apparent in the test performances. 

17 



The conscious awareness of the minor hemisphere pro- 
duced by this vertical splitting of the brain often seems so 
remote to the conversant hemisphere as to be comparable 
perhaps to that produced by a spinal transection. To go 
back here to some of the issues on which we started, one 
wonders if we can really rule out, as I implied above, the 
alternative contention of those who maintain that spinal 
cords, loaves of bread, and even single molecules have a 
kind of consciousness. Either way, the inferences to be 
drawn regarding the evolution and elaboration of conscious- 
ness for most practical purposes remain much the same. 

We are often asked if each of the disconnected hemi- 
spheres must not also have a will of its own and if the two 
do not then get into conflict with each other. In the first 
half year after surgery, particularly with the first patient, 
we got reports suggesting something of the kind. For ex- 
ample, while the patient was dressing and trying to pull on 
his trousers, the left hand started to work against the right, 
pulling them off again. Or, the left hand, after just helping 
to tie the belt of his robe, went ahead on its own to untie 
the completed knot, whereupon the right hand would have 
to supervene again to get it retied. The patient and his wife 
used to refer to the "sinister left hand" which sometimes 
tried to push the wife away aggressively at the same time 
that the hemisphere of the right hand was trying to get her 
to come and help him with something. These antagonistic 
movements of right and left hands are fairly well restricted 
to situations in which the reactions of left and right hand 
are easily made from the same common supporting posture 
of body and shoulders. Generally speaking, there are so 
many unifying factors in the situation and functional har- 
mony is so strongly built into the undivided brain stem and 
spinal networks, by express design, that one sees little overt 
expression or overflow into action, at least, of conflicting 
will power. 

18 



This matter of having two free wills packed together 
inside the same cranial vault reminds us that, after con- 
sciousness, free will is probably the next most treasured 
property of the human brain. Questions and information 
relating to the evolution of free will have practical impact 
rating right at the top, along with those of consciousness. 
As such it probably deserves at least a closing comment. 
Some maintain that free will is an evolved, emergent prop- 
erty of the brain that appeared between man and the higher 
apes, or, depending on whom you read, maybe somewhere 
after bacteria perhaps, but before houseflies. 

Unlike "mind," "consciousness," and "instinct," "free 
will" has made no comeback in behavioral science in recent 
years. Most behavioral scientists would refuse to list free 
will among our problems outstanding, or at least as an 
unanswered problem. (To agree that behavior is unlawful 
in this respect might put them out of work as scientists, you 
see, and oblige them perhaps to sign up with the astrologers' 
union.) Every advance in the science of behavior, whether 
it has come from the psychiatrist's couch, from microelec- 
trode recording, from brain-splitting, or from the running 
of cannibalistic flatworms, seems only to reinforce that old 
suspicion that free will is just an illusion. The more we 
learn about the brain and behavior, the more deterministic, 
lawful, and causal it appears. 

In other words, behavioral science tells us that there is 
no reason to think that any of us here tonight had any real 
choice to be anywhere else, or even to believe in principle 
that our presence here was not already "in the cards," so 
to speak, five, 10, or 15 years ago. I do not feel comfortable 
with this kind of thinking any more than you do, but so far I 
have not found any satisfactory way around it. Alternatives 
to the rule of causal determinism in behavior proposed so far, 
like the inferred unlawfulness in the dance of subatomic 
particles, seem decidedly more to be deplored as a solution 

19 



than desired. 

The above statements are not to say that, in the practice 
of behavioral sciences, we must regard the brain as just a 
pawn of the physical and chemical forces that play in and 
around it. Far from it. To go back to the beginning of the 
present lecture, recall that a molecule in many respects is 
the master of its inner atoms and electrons. The latter are 
hauled and forced about in chemical interactions by the 
over-all configurational properties of the whole molecule. 
At the same time, if our given molecule is itself part of a 
single-celled organism such as Paramecium, it in turn is 
obliged, with all its parts and its partners, to follow along 
a trail of events in time and space determined largely by 
the extrinsic over-all dynamics of Paramecium caudatum. 
When it comes to brains, remember that the simpler electric, 
atomic, molecular, and cellular forces and laws, though 
still present and operating, have been superseded by the 
configurational forces of higher-level mechanisms. At the 
top, in the human brain, these include the powers of per- 
ception, cognition, reason, judgment, and the like, the op- 
erational, causal effects and forces of which are equally or 
more potent in brain dynamics than are the outclassed inner 
chemical forces. 

You sense the underlying policy here: "If you can't lick 
'em, join 'em," or, as Confucius might say, "If fate inevitable, 
relax and enjoy," or, "There may be worse fates than causal 
determinism." Maybe, after all, it is better to be embedded 
firmly in the causal flow of cosmic forces, as an integral part 
thereof, than to be on the loose and out of contact with these 
forces, "free floating" as it were and with behavioral possi- 
bilities that have no antecedent cause and hence no reason, 
nor any reliability when it comes to future plans, predictions, 
or promises. 

And on this same theme, just one final point : If you were 
assigned the task of trying to design and build the perfect 

20 



free-will model (let us say the perfect, all-wise, decision- 
making machine to top all competitors' decision-making 
machines), consider the possibility that your aim might not 
be so much to free the machinery from causal contact, as the 
opposite, that is, to try to incorporate into your model the 
potential value of universal causal contact; in other words, 
contact with all related information in proper proportion — 
past, present, and future. 

It is clear that the human brain has come a long way in 
evolution in exactly this direction when you consider the 
amount and the kind of causal factors that this multidimen- 
sional intracranial vortex draws into itself, scans, and brings 
to bear on the process of turning out one of its "preordained 
decisions." Potentially included, thanks to memory, are the 
events and collected wisdom of most of a human lifetime. 
We can also include, given a trip to the library, the accumu- 
lated knowledge of all recorded history. And we must add 
to all the foregoing, thanks to reason and logic, much of the 
future forecast and predictive value extractable from all these 
data. Maybe the total falls a bit short of universal causal 
contact; maybe it is not even quite up to the kind of thing 
that evolution has going for itself over on Galaxy Nine; and 
maybe, in spite of all, any decision that comes out is still 
predetermined. Nevertheless it still represents a very long 
jump in the direction of freedom from the primeval slime 
mold, the Jurassic sand dollar, or even the latest 1964-model 
orangutan. 

LITERATURE CITED 

BOGEN, J. E., AND P. J. VOGEL 

1962. Cerebral commissurotomy in man. Bull. Los Angeles Neurol. Soc., 
vol. 27, p. 169. 

Gazzaniga, M. S., J. E. Bogen, and R. W. Sperry 

1962. Some functional effects of sectioning the cerebral commissures in man. 

21 



Proc. Natl. Acad. Sci., vol. 48, pt. 2, p. 1765. 
1963. Laterality effects in somesthesis following cerebral commissurotomy 
in man. Neuropsychologia, vol. 1, p. 209. 

Sperrv, R. W. 

1950a. Mechanisms of neural maturation. In Stevens, S. S. (ed.), Handbook 

of experimental psychology. New York, John Wiley and Sons, p. 236. 
1950b. Neural basis of the spontaneous optokinetic response produced by 

visual inversion. Jour. Comp. Physchol., vol. 43, p. 482. 
1951. Regulative factors in the orderly growth of neural circuits. Growth 

Symp., vol. 10, p. 63. 
1958. Physiological plasticity and brain circuit theory. In Harlow, H. F., and 

C. N. Woolsey (eds.), Biological and biochemical bases of behavior. 

Madison, University of Wisconsin Press. 

1961. Some developments in brain lesion studies of learning. Fed. Proc, 
vol. 20, p. 609. 

1962. How a random array of cells can learn to tell whether a straight line 
is straight — discussion on. In Foerster, H. von, and G. W. Zopf, Jr. 
(eds.), Principles of self-organization. New York, Pergamon Press, 
p. 323. 

1963. Chemoaffinity in the orderly growth of nerve fiber patterns and con- 
nections. Proc. Natl. Acad. Sci., vol. 50, p. 703. 

1964. The great cerebral commissure. Sci. Amer., vol. 210, p. 42. 



22 



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I, 



AMES ARTHUR LECTURE ON 
THE EVOLUTION OF THE HUMAN BRAIN 

1965 



EVOLUTION OF PHYSICAL 
CONTROL OF THE BRAIN 



JOSfi M. R. DELGADO 



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THE AMERICAN MUSEUM OF NATURAL HISTORY 
NEW YORK : 1965 






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JAMES ARTHUR LECTURE ON 
THE EVOLUTION OF THE HUMAN BRAIN 



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EVOLUTION OF PHYSICAL 
CONTROL OF THE BRAIN 



JOSE M. R. DELGADO, M.D. 

A ssociate Professor of Physiology 

Yale University School of Medicine 

New Haven, Connecticut 



THE AMERICAN MUSEUM OF NATURAL HISTORY 
NEW YORK : 1965 



JAMES ARTHUR LECTURE ON 
THE EVOLUTION OF THE HUMAN BRAIN 

Frederick Tilney, The Brain in Relation to Behavior; March 15, 1932 

C. Judson Herrick, Brains as Instruments of Biological Values; April 6, 1933 

D. M. S. Watson, The Story of Fossil Brains from Fish to Man; April 24, 1934 
C. U. Ariens Kappers, Structural Principles in the Nervous System; The Develop- 
ment of the Forehrain in Animals and Prehistoric Human Races; April 25, 
1935 

Samuel T. Orton, The Language Area of the Human Brain and Some of its Dis- 
orders; May 15, 1936 
R. W. Gerard, Dynamic Neural Patterns; April 15, 1937 
Franz Weidenreich, The Phylogenetic Development of the Hominid Brain and its 

Connection with the Transformation of the Skull; May 5, 1938 
G. Kingsley Noble, The Neural Basis of Social Behavior of Vertebrates; May 1 1 , 

1939 
John F. Fulton, A Functional Approach to the Evolution of the Primate Brain; 

May 2, 1940 
Frank A. Beach, Central Nervous Mechanisms Involved in the Reproductive Be- 
havior of Vertebrates; May 8, 1941 
George Pinkley, A History of the Human Brain; May 14, 1942 
James W. Papez, Ancient Landmarks of the Human Brain and Their Origin; 

May 27, 1943 
James Howard McGregor, The Brain of Primates; May 1 1, 1944 
K. S. Lashley, Neural Correlates of Intellect; April 30, 1945 
Warren S. McCulloch, Finality and Form in Nervous Activity; May 2, 1946 
S. R. Detwiler, Structure-Function Correlations in the Developing Nervous Sys- 
tem as Studied by Experimental Methods; May 8, 1947 
Tilly Edinger, The Evolution of the Brain; May 20, 1948 
Donald O. Hebb, Evolution of Thought and Emotion; April 20, 1949 
Ward Campbell Halstead, Brain and Intelligence; April 26, 1950 
Harry F. Harlow, The Brain and Learned Behavior; May 10, 1951 
Clinton N. Woolsey, Sensorv and Motor Systems of the Cerebral Cortex; May 7, 

1952 
Alfred S. Romer, Brain Evolution in the Light of Vertebrate History; May 21, 

1953 
Horace W. Magoun, Regulatory Functions of the Brain Stem; May 5, 1954 
Fred A. Mettler, Culture and the Structural Evolution of the Neural System; 

April 21, 1955 
Pinckney J. Harman, Paleoneurologic, Neoneurologic, and Ontogenetic Aspects 

of Brain Phylogeny; April 26, 1956 
Davenport Hooker, Evidence of Prenatal Function of the Central Nervous System 

in Man; April 25, 1957 
David P. C. Lloyd, The Discrete and the Diffuse in Nervous Action; May 8, 1958 
Charles R. Noback, The Heritage of the Human Brain; May 6, 1959 
Ernst Scharrer, Brain Function and the Evolution of Cerebral Vascularization; 

May 26, 1960 
Paul I. Yakovlev, Brain, Body and Behavior. Stereodynamic Organization of the 
Brain and of the Motility-Experience in Man Envisaged as a Biological 
Action System; May 16, 1961 
H. K. Hartline, Principles of Neural Interaction in the Retina; May 29, 1962 
Harry Grundfest, Specialization and Evolution of Bioelectric Activity; May 28, 

1963 
Roger W. Sperry, Problems Outstanding in the Evolution of Brain Function; 

June 3, 1964 
Jose M. R. Delgado, Evolution of Physical Control of the Brain; May 6, 1965 



EVOLUTION OF PHYSICAL 
CONTROL OF THE BRAIN 

INTRODUCTION 

I would like to express my gratitude for the privilege of 
addressing this distinguished audienee, and also my feeling 
of responsibility in following so many illustrious predeces- 
sors and in honoring the founder of the James Arthur Lec- 
tures on the Evolution of the Human Brain. The topics 
covered by earlier speakers in this series have included be- 
havioral implications derived from cerebral anatomy and 
physiology, neurophysiological problems, comparative 
anatomy, embryology, and fossil skulls. In this year's lec- 
ture, I would like to project cerebral evolution toward the 
future without losing touch with the solid ground of ex- 
perimentation. 

The human brain has evolved with a functional asymmetry 
which may be responsible for some of the conflicts of our 
present age. Apparently it has been easier for man to direct 
his attention outward to the environment than inward to 
deal with the complexity of his own mental structure, and 
easier to understand and manipulate Nature than to control 
his own behavior. In prehistoric times, and even today in 
primitive societies, man was and is at the mercy of the ele- 
ments. When disaster struck, and floods, pestilence, or hun- 
ger desolated the land, the only possible reactions were 
fatalistic resignation, appeal to supernatural powers, or 
despair. Modern civilization has progressed so much in the 
understanding and domination of the physical world, that 
relations between man and Nature have been completely 
transformed. Technology is reshaping the face of the earth, 

1 



but the greatest change has taken place in the human brain 
which is now filled with new formulas, theories, and knowl- 
edge, and empowered with a new attitude of confidence 
toward natural forces which are no longer the masters but 
are becoming the servants of man. The expanding sciences 
have directed most of our present intellectual and economic 
power toward industry, biology, electronics, atomic energy, 
outer space, and similar fields of endeavor, while only a 
minor fraction is devoted to inquiry into the roots of men- 
tal faculties. This unbalanced interest has an explanation. 
When observation and reason were the main tools for the 
acquisition of knowledge, philosophical speculation flour- 
ished. When the discovery of new methods permitted the 
scientific exploration of Nature, the study of subjects beyond 
experimental reach was neglected. Certainly, the disciplines 
of psychology and psychiatry have greatly expanded in our 
century, but a perusal of the literature shows that until one 
or two decades ago, the brain was treated as a "black box" 
which could be reached only through the senses. Psycho- 
logical investigations analyzed correlations between sensory 
input and behavioral output, but it was not possible to ex- 
plore the processes lying in between which were hidden in 
the mystery of brain physiology. 

During the last decade we have reached an historical 
turning point because of the development of methods which 
permit the coordination and synthesis of physical, physio- 
logical, pharmacological, and psychological research. As 
will be explained in the following pages, science has devel- 
oped a new electrical methodology for the study and con- 
trol of cerebral functions in animals and humans. Learning, 
emotions, drives, memory, consciousness, and other phe- 
nomena which in the past belonged only in the realm of 
philosophy are now the subjects of neurophysiological ex- 
perimentation. In the last few years, the scalpel of the brain 

2 



surgeon has modified psychological reactions and a wealth 

of wonder drugs has liberated many patients from mental 
institutions. 

I am not so naive as to think that cerebral research holds 
all the answers to mankind's present problems, but I do 
believe that an understanding of the biological bases of 
social and antisocial behavior and of mental activities, 
which for the first time in history can now be explored in 
the conscious brain, may be of decisive importance in the 
search for intelligent solutions to some of our present anxie- 
ties, frustrations, and conflicts. Also, it is essential to intro- 
duce a balance into the future development of the human 
mind, and I think that we now have the means to investi- 
gate and to influence our own intellect. 

In support of these ideas, I shall present a brief outline 
of the evolution of the physical control of cerebral proc- 
esses, followed by several examples of our incipient control 
of behavioral mechanisms, and I will end with a discussion 
of the principles and implications involved. 

HISTORICAL OUTLINE: THEORETICAL 
AND METHODOLOGICAL EVOLUTION 

Animal Experimentation 

For many centures it was accepted that fluids or "animal 
spirits" were the cause of muscle contraction (Galen, 130 
to ca. 200 a.d.), until the famous controversy between the 
schools of Luigi Galvani (1737-1789) and Alessandro 
Volta (1745-1827) focused the attention of nineteenth- 
century scientists and philosophers on the possible physical 
control of some manifestations of life. Contractions pro- 
duced in a frog nerve-muscle preparation by touching it 
with a bimetallic arc were interpreted by Galvani as proof 
of the existence of animal electricity, while Volta believed 
that the electrical source was in the contact of two dissimilar 



metals. This controversy was resolved when Alexander 
von Humboldt (1769-1859) demonstrated that animal 
electricity and bimetallic electricity were co-existing phe- 
nomena. Leg movements evoked in frogs by the inanimate 
force of electricity proved that muscle contraction could be 
induced independently of the "principle of life" which had 
been considered the essential mover of all biological activi- 
ties. The discovery that living organs could be influenced by 
instrumental manipulations directed by the will of a human 
being brought about a revision of the traditional concepts 
of vitalism which were challenged at that time by Emil 
DuBois-Reymond (1818-1896) and other scientists. The 
romantic mystery of the soul's "animal spirits" which had 
dominated biology for almost 2000 years now gave place 
to more prosaic chemical and physical laws, and even ner- 
vous activity could be investigated experimentally. DuBois- 
Reymond not only discovered many basic neurophysiolog- 
ical principles, including action current, polarization, 
electrogenesis, and propagation of the nerve impulse; he also 
provided the technical means for study of the two most 
fundamental processes of neural activity by inventing the 
galvanometer for the detection of electrical currents and the 
induction coil for faradic excitation of nervous tissue. At 
that time, the possibility of exciting the spinal cord and brain 
stem by other than physiological stimuli was violently de- 
bated, and the excitability of the brain was completely 
denied. Then Fritsch and Hitzig (1870) performed a beau- 
tiful series of experiments, applying galvanic stimulations 
to the exposed cerebral cortex of anesthetized dogs. Excita- 
tions of the posterior part of the brain failed to evoke 
motor effects, but in the anterior region contralateral body 
and limb movements were elicited. Weak currents induced 
discrete contractions localized to specified muscle groups, 
while stronger currents increased the strength and spread 

4 



of the evoked responses; it' the intensity was further aug- 
mented, generalized convulsions appeared. 

The scientific impact of these studies, and also the suc- 
cessful clinical localization of speech functions by Broca 
( 1824-1880), promoted great interest in cerebral mapping, 
based on regional ablation and electrical stimulation studies 
attempting to pin precise functional labels to specific ana- 
tomical structures. Fortunately, there was much less specu- 
lation and much more experimentation in these studies than 
in the discredited phrenology, and, in spite of controversial 
issues, many of the facts discovered in the last century have 
remained important scientific contributions. 

One of the main handicaps in these investigations was 
the need for opening the skull and exposing the brain. 
Operations were usually performed under general anesthesia 
which blocked pain perception but also blocked some of 
the most important functions of the nervous system. Emo- 
tions, consciousness, and intelligence were certainly absent 
in heavily sedated animals or in the isolated nerves of the 
squid, and for many years scientists directed their atten- 
tion to sleeping brains and overlooked the complexity of 
awake minds. Textbooks of cerebral physiology were con- 
cerned with synapses, pathways, reflexes, posture, and 
movement, while mental functions and behavior were con- 
sidered to belong to a different discipline. 

Some pioneer efforts, however, were directed toward 
exploration of the waking brain, and techniques were de- 
vised for the introduction of wires through the skull in order 
to apply electrical currents to the brains of conscious ani- 
mals. In 1898, Ewald had the idea of screwing an ivory 
cone into the skull of an anesthetized dog, and the following 
day, when operative anesthesia had worn off, electrodes 
were inserted into the brain through the ivory piece. A leash 
around the animal's neck contained stimulating wires, and 

5 



a small dry-cell battery carried by the observer served as 
the electrical source. Although the technique and results 
were primitive, a way had been found to investigate the 
brain in awake animals. The technique of intracerebral 
electrodes was dormant for many years until Hess (1932) 
developed his own method to explore the hypothalamus 
and other cerebral areas in unanesthetized cats. In a series 
of brilliant experiments, Hess demonstrated that autonomic 
functions, posture, equilibrium, movement, sleep, and even 
fear and aggressiveness may be influenced by electrical 
stimulation of specific cerebral structures. For the first 
time, it was revealed that psychological manifestations like 
rage do not depend exclusively on sensory inputs and physi- 
ological stimuli, but can be induced by electrical currents 
applied directly to the brain. Although these findings did 
not produce a significant impact on philosophical thinking, 
in retrospect they may be considered as important as the 
nineteenth-century demonstration that the contraction of a 
frog muscle did not depend on circulating spirits and could 
be controlled by physical instrumentation. 

For two decades, the methods of Hess attracted only 
limited interest among biologists, but in the 1950's, there 
was a sudden expansion of the new disciplines of psycho- 
surgery, psychosomatic medicine, psychopharmacology, 
and physiological psychology, and many investigators real- 
ized the great research potential of intracerebral methods 
for the study of behavioral-cerebral correlations in awake 
animals. With this increased interest, a variety of technical 
improvements appeared. Electrodes were no longer intro- 
duced free-hand into the brain, but were inserted with 
geometric precision with the aid of micromanipulators and 
stereotaxic coordinates. Anatomical maps of the depths of 
the brain were compiled for rats, cats, dogs, and monkeys. 
Aseptic precautions and instrumental refinements permitted 

6 



long-term implantation of electrodes, which in some cases 
lasted for several years. The sight of experimental animals 
with sockets on top of their heads was exceptional in 1950 
but had spread to hundreds of laboratories around the 
world by 1960. Electrodes were implanted not only in the 
usual laboratory animals, but also in other species, includ- 
ing crickets, roosters, chimpanzees, dolphins, and brave 
bulls. 

Experiments were generally performed under some re- 
straint. Rats were convenient subjects because of their 
behavioral simplicity, and they were not disturbed by a 
light coil of wires connecting their terminal head sockets 
with the stimulators. In this way, the brain was stimulated 
in fully conscious rats while they pressed levers, ran mazes, 
and maneuvered with considerable freedom, being limited 
only by the length of the leads and the size of the cage. A 
similar set-up was also used successfully with cats, provid- 
ing they were peaceful and tame. These studies were often 
extended for months and were very appropriate for the 
investigation of autonomic, somatic, and behavioral effects 
evoked by electrical stimulation of the brain, and also for 
the analysis of electrical recordings taken during spon- 
taneous or induced activities. The combination of intra- 
cerebral electrodes with other physiological and psycholog- 
ical techniques was very fruitful and showed that animals 
can learn to perform instrumental responses to seek or avoid 
stimulation of determined cerebral structures. Scientific 
exploitation of these techniques continues today with uni- 
versal acceptance, as shown by current scientific literature. 

The use of electrodes in monkeys presented a greater 
challenge because of their destructive skills and restless 
curiosity. A heavy protection of the connecting leads was 
necessary when the animal was observed on a testing table. 
In other cases, the monkey was placed in a special restrain- 

7 



ing chair where it could manipulate levers and feed itself 
without being able to reach the terminal sockets on its 
head. In these situations, conditioning and psychological 
testing were successfully performed, but spontaneous be- 
havior was naturally curtailed. 

The connecting leads trailing behind each animal were 
a serious handicap for behavioral studies and were unsuita- 
ble for use in chronic stimulations or investigations of group 
activities. The obvious solution was to use remote-controlled 
instrumentation, with a receiver carried by the animal and 
activated by induction or by radio. Several stimulators of 
this type have been proposed in the last 30 years (see 
bibliography in Delgado, 1963b), but solutions to many 
of the technical problems involved were not found until 
recently, when the development of transistors and elec- 
tronic miniaturization permitted the construction of small, 
practical, and reliable cerebral radio stimulators (Delgado, 
1963b). After a considerable amount of trial and error, and 
in spite of the primates' genius for destroying any equip- 
ment within reach, monkey-proofing of instruments was 
achieved (figs. 3, 4, 5 ) . The use of radio stimulators allowed 
the excitation of cerebral structures in completely free ani- 
mals engaged in normal activities within an established 
colony and unaware of the scientist's manipulations. In this 
way, the role of specific areas of the brain in social relations 
was investigated. At the same time, blood pressure, body 
temperature, electrical activity of the heart and brain, and 
other physiological variables could be recorded by radio 
telemetry. In addition, individual and social behavior have 
been continuously recorded, day and night, by time-lapse 
photography. Radio techniques represented an important 
step toward physical control of the brain, providing an 
essential tool for behavioral studies, and it may safely be 
predicted that within a few years telestimulation will spread 

8 



to most brain research institutes. We can also expect that 
new developments in micro-electronics, including integrated 
circuits and thin film techniques, will facilitate the eonstruc- 
ton of multi-channel radio-activated stimulators reduced in 
size to a few millimeters. The limits of brain control do not 
seem to depend on electronic technology but on the biolog- 
ical properties of living neurons. 

Among possible physiological handicaps, the presence of 
electrodes and repeated applications of electricity could be 
disrupting factors for the normality of the nerve cells. Inser- 
tion of electrodes into the brain substance is certainly a 
traumatic procedure which destroys neural tissue and pro- 
duces local hemorrhage, followed by inflammation, foreign 
body reaction, and the formation of a glial capsule 0.1- 
0.2 mm. thick around the inserted wires. All of this reac- 
tive process is limited to a very small area measured in 
tenths of millimeters, and there is no evidence of functional 
disturbance in the neighboring neurons. Beyond the elec- 
trode tract, the brain appears histologically normal and 
electrodes seem to be well tolerated, as judged by the 
absence of abnormal electrical activity, by the reliability of 
effects evoked by electrical stimulation, and by the con- 
sistency of thresholds through months of experimentation 
(Delgado, 1955b). The longest reported implantation time 
of electrodes in the brain has been over four years, in a 
rhesus monkey. 

From the functional point of view, two aspects should be 
considered in implantation experiments. The first is related 
to fatigability and the second to lasting functional changes. 
Physiological textbooks state that motor effects produced 
by electrical stimulation of the cerebral cortex fade away 
in a few seconds, and that a rest period of about one minute 
is necessary before the cortex recovers its excitability. If 
this were true throughout the brain, electricity could not 

9 



be effectively used for control of cerebral function. How- 
ever, experimentation has shown that the fatigability of 
some areas is slow or negligible. In monkeys, the putamen 
has been stimulated for more than 30 minutes without 
diminution of the elicited postural changes, and the hy- 
pothalamus has been excited for days without fatigue of 
the evoked pupillary constriction. Red nucleus stimulation 
repeated every minute for 14 days has evoked reliable and 
consistent sequential responses. Thus, while a few areas of 
the brain show quick fatigability, it should be recognized 
that many others can be stimulated effectively for minutes 
or even days. The evoked effects generally have lasted only 
as long as the stimulation, but in some cases enduring after- 
effects have been obtained. In the cat, programmed inter- 
mittent stimulations of the amygdala for one hour daily 
evoked bursts of high-voltage fast activity and other signs 
of increased electrical activity, along with changes in spon- 
taneous behavior which outlasted stimulation periods for 
many hours and occasionally for days. In other studies, ex- 
citation of the basolateral nucleus of the cat's amygdala 
for only 10 seconds inhibited food intake for minutes, and, 
in one case, the inhibitory effect persisted for three days 
(Fonberg and Delgado, 1961 ). These findings together with 
extensive experimentation by many authors have demon- 
strated that intracerebral electrodes are safe and can be 
tolerated for years, providing an effective tool for sending 
and recording electrical impulses to and from the brain 
of unanesthetized animals. 

Electrodes in the Human Brain 

With the background of animal experimentation, it 
was natural that some investigators should contemplate the 
implantation of electrodes inside the human brain. Neuro- 
surgeons had already proved that the central nervous sys- 

10 



teni is not so delicate as most people believe, and during 
therapeutic surgery parts of cerebral tissue had been cut, 
frozen, cauterized, or ablated with negligible adverse effects 
on the patient. Exploratory introduction of needles into 
the cerebral ventricles was a well-known and relatively safe 
clinical procedure, and, as electrodes are smaller in diam- 
eter than these needles, their introduction into the brain 
tissue should be even less traumatic. Implantation of elec- 
trodes inside the human brain offered the opportunity for 
prolonged electrical exploration which could be decisive 
for several diagnostic and therapeutic procedures. For ex- 
ample, when brain surgery and ablation are contemplated 
in patients suffering from epileptic attacks, it is essential 
to identify the focal areas of abnormal electrical activity. 
Electrodes may remain in place for days or weeks, during 
which spontaneous seizures can be recorded and detailed 
exploration repeated as many times as necessary. In other 
cases, intracerebral electrodes have been used to deliver 
intermittent stimulations for periods of days or even months 
(Feindel, 1961; Heath, 1954; King, 1961; Sem-Jacobsen 
et aL, 1956; Walker and Marshall, 1961). Similar pro- 
cedures have also been used in patients with intractable 
pain, anxiety neurosis, and involuntary movement. These 
therapeutic possibilities should be considered rather tenta- 
tive, but accumulated experience has shown that electrodes 
are well tolerated by the human brain for periods of at 
least one year and a half, and that electrical stimulations 
may induce a variety of responses, including changes in 
mental functions, as will be explained later. The prospect 
of leaving wires inside the thinking brain could seem bar- 
baric, uncomfortable, and dangerous, but actually the pa- 
tients who have undergone this experience have had no ill 
effects, and they have not been concerned about the idea 
of being wired or by the existence of leads in their heads. 

11 



In some cases, they enjoyed a normal life as out-patients, 
returning to the clinic for periodic stimulations. Some of the 
women proved the adaptability of the feminine spirit to all 
situations by designing pretty hats to conceal their electrical 
headgear. 

The use of electrodes in the human brain is part of the 
present medical orientation toward activation of physiolog- 
ical mechanisms by electronic instrumentation, which al- 
ready extends to several organs of the body. The clinical 
success of electrical driving of cardiac functions in man 
has been widely acclaimed. In spite of the delicacy and 
continuous mobility of the heart, stainless steel leads have 
been sutured to it, and in cases of block in the cardiac 
conduction system, artificial electronic pacemakers have 
been able to regulate heart rhythm, saving the lives of 
many patients. The bladder has been stimulated by im- 
planted electrodes to induce urination in patients with 
permanent spinal block, and paralyzed limbs have been 
activated by programmed stimulators. A method has re- 
cently been described for placing leads in the auditory 
nerve to circumvent deafness caused by inner ear damage. 
Driving malfunctioning organs is simpler than attempting 
to direct the awake brain where millions of neurons are 
functioning and firing simultaneously for different pur- 
poses, but the expected results in this case are even more 
interesting. Exploring intracerebral physiology, we are 
reaching not only the soma but also for the psyche itself. 
Cerebral functions are usually classified in three groups: 
autonomic, somatic, and psychic, and in the following 
pages I shall discuss present experimental evidence for their 
electrical control. 



12 



I \BLE OF HISIORK \I EVOLUTION 
OK PHYSK \i C'ONFROI OF IHI BRAIN 



Findings 

Frog muscle contracted when stimu- 
lated b\ electricity. Volta. Galvani, 
DuBoa-Reymond; 1780, 1800. 1848 

Electrical stimulation of the brain in 
anesthetized dog evoked localized 
body and limb movements. Fritscfa 
and Hitzig. 1870 

Stimulation of the diencephalon in un- 
anesthetized cats evoked well-or- 
ganized motor effects and emotional 
reactions. Hess. 1932 

In single animals, learning, condition- 
ing, instrumental responses, pain, 
and pleasure have been evoked or 
inhibited by electrical stimulation of 
the brain in rats. cats, and monkeys. 
See bibliography in Sheer. 1961 

In colonies of cats and monke\s. ag- 
gression, dominance, mounting, and 
other social interactions have been 
evoked, modified, or inhibited by 
radio stimulation of specific cerebral 
areas. Delgado. 1955a. 1964 

In patients, brain stimulations during 
surgical interventions or with elec- 
trodes implanted for days or months 
have blocked the thinking process, 
inhibited speech and movement, or 
in other cases have evoked pleasure, 
laughter, friendliness, verbal output, 
hostility, fear, hallucinations, and 
memories. See bibliography in 
Ramev and O'Dohertv. 1960 



Imim k \i IONS 

"Vital spirits" are not essential for bio- 
logical activities. Electrical stimuli 
under man's control can initiate and 
modify vital processes 

The brain is excitable. Electrical stim- 
uli of the cerebral cortex can pro- 
duce movements 

Motor and emotional manifestations 
may be evoked by electrical stimula- 
tion of the brain in awake animals 

Psychological phenomena may be con- 
trolled by electrical stimulation of 
specific areas of the brain 



Social behavior may be controlled by 
radio stimulation of specific areas of 
the brain 



Human mental functions may be in- 
fluenced by electrical stimulation of 
specific areas of the brain 



Summary: Autonomic and somatic functions, individual and social behavior, 
emotional and mental reactions may be evoked, maintained, modified, or 
inhibited, both in animals and in man. by electrical stimulation of specific 
cerebral structures. Physical control of many brain functions is a demon- 
strated fact, but the possibilities and limits of this control are still little known. 



13 



ELECTRICAL CONTROL OF AUTONOMIC FUNCTIONS 

Several areas of the brain play important roles in the 
regulation of visceral activity, and extensive studies have 
shown that electrical stimulation of the hypothalamus and 
other cerebral structures can influence vasomotility, blood 
pressure, heart rate, respiration, thermal regulation, gastric 
secretion, food intake, and many other functions of the 
autonomic system. To illustrate the artificial regulation of 
autonomic reactions by electrical means, I shall discuss 
pupillary motility because its mechanisms are relatively 
simple and easy to control. 

The areas that participate in the regulation of pupil size 
are represented on the surface and in the depth of the brain. 
Cortical zones which have inhibitory effects upon respira- 
tion and upon spontaneous movements also produce pupil- 
lary dilatation (mydriasis). In cats, dogs, and monkeys, 
these areas are situated around the sylvian fissure, orbital 
cortex, temporal tip, cingulate gyrus, insula, rhinal fissure, 
and hippocampal gyrus. In the depth of the brain, pupillary 
dilatation may be evoked by stimulation of the basal telen- 
cephalon, hypothalamus, septum, midline group of thalamic 
nuclei, subthalamus, and a large part of the midbrain 
(Hodes and Magoun, 1942; Kaada, 1951; Showers and 
Crosby, 1958). Pupillary constriction (miosis) has a more 
limited representation, localized mainly around the genu 
of the corpus callosum (Hodes and Magoun, 1942; Kaada, 
1951), thalamus, and hypothalamus (Hess, 1954). Accord- 
ing to the region stimulated, pupillary responses will be 
unilateral or bilateral; if bilateral, each eye may respond 
synergically or antagonically. Most classical studies were 
performed under anesthesia and with the brain exposed, 
but recent investigations have been carried out with the 
use of awake animals equipped with intracerebral electrodes. 

In monkeys (Delgado, 1959), electrical stimulation of 

14 




Fig. 1. The diameter of the pupil may be electrically controlled as if it was 
the diaphragm of a photographic camera. The pictures show normal eyes in a 
monkey and the dilatation and constriction of the right pupil evoked by stimula- 
tion of the hypothalamus. Some of these effects are indefatigable and persist for 
days as long as stimulation is applied. 

15 



the inferior part of the lateral hypothalamus produced 
marked ipsilateral miosis, while stimulation of another 
point situated 6 mm. higher in the same tract evoked ipsi- 
lateral mydriasis (fig. 1). The magnitude of the effect was 
proportional to the electrical intensity employed. Stimula- 
tion of the inferior point with 0.8 milliampere (mA) pro- 
duced slight pupillary constriction which increased progres- 
sively as the intensity was augmented to 1.5 mA. At this 
moment, miosis was maximum, and further increase in 
stimulation did not modify the effect. If the hypothalamic 
stimulation was slowly decreased in strength, the ipsilateral 
pupil gradually returned to its normal size. In these experi- 
ments, pupil diameter could be controlled precisely like 
the diaphragm of a camera, by turning the stimulator dials 
to the left or right. A similar dose-response relation was 
seen in the higher hypothalamic point where stimulation 
produced mydriasis. Implantation of electrodes in points 
with antagonistic pupillary effect made it possible to intro- 
duce an artificial conflict by stimulating both areas simultane- 
ously with separate instruments. Results showed that a 
dynamic equilibrium could be established at different levels 
of simultaneous antagonistic excitation. With 1.6 foot- 
candle units of illumination in the laboratory, the initial 
pupillary diameter of 4 mm. was maintained when the 
hypothalamic points were stimulated together at similarly 
increasing intensities up to 4 mA. At any level in this 
dynamic equilibrium, the pupil constricted if intensity was 
increased in the inferior or decreased in the higher point. 
The reverse was also true, and the pupil dilated if stimula- 
tion decreased in the inferior or increased in the superior 
hypothalamic point. To some extent, the effect of excitation 
of the inferior miotic point could be substituted for a light 
shone in the eye, illustrating the possibility of algebraic 
summation of physiological, sensory, and electrical stimuli 

16 



within the brain. These experiments demonstrated that a 
regulation of an autonomic- function like pupillary size can 
be effectively maintained by direct stimulation of cerebral 
structures. 

For how long would this regulation be effective? Would 
the brain fatigue? To answer these questions, long-term 
experiments were designed. Under continuous hypothalamic 
excitation, mydriasis lasted for about 30-40 minutes, after 
which stimulation was ineffective and the pupil gradually 
returned to its original size, indicating a slow fatigability of 
the effect. In contrast, pupillary miosis was maintained in 
several monkeys for as long as stimulation was applied. 
Each Animal was studied while free in a cage and equipped 
with a portable stimulator connected by subcutaneous 
leads to the inferior hypothalamic point. Under continuous 
24-hour stimulation, the size of the ipsilateral pupil was 
maintained at less than 1 mm. in diameter, while the other 
pupil measured a normal 4 mm. As soon as the stimulation 
was discontinued, a rebound effect appeared and the ipsi- 
lateral pupil dilated to about 6 mm. for several hours, and 
then slowly returned to its normal size. In one monkey, the 
stimulation was applied for as long as three days, during 
which pupil constriction was continuous; with cessation of 
stimulation, a rebound effect appeared which lasted for 
two days. 

In other experiments, when the intensity of hypothalamic 
stimulation was adjusted to produce only a 20-30 per cent 
reduction in pupillary size, the reactivity of both pupils to 
light was preserved, although the stimulated pupil was al- 
ways smaller than the control. These results demonstrated 
that a lasting functional "bias" can be introduced in auto- 
nomic reactions by the artificial means of electrical stimu- 
lation of the brain. The physiological equilibrium was elec- 
trically modified, preserving the responses but changing the 

17 



level of functional adjustment. These results are compar- 
able to the modifications in autonomic reactivity (tuning) 
induced by injection of sympathetic or parasympathetic 
agents (Gellhorn, 1957). 

In summary, autonomic functions can be controlled by 
electrical stimulation of the brain. As an example it has 
been shown that constriction of the pupil evoked by cere- 
bral stimulation is reliable, precise, does not fatigue, can 
interplay with physiological stimuli, and may provide a 
functional "bias" to modify the level of physiological re- 
sponses. 

MOTOR PERFORMANCE UNDER 
ELECTRONIC COMMAND 

The significant nineteenth-century discovery of central 
nervous system excitability was based on the fact that elec- 
trical stimulation of the cerebral cortex produced observable 
motor responses. Since that discovery, many investigations 
have been devoted to the analysis of motor representation 
in different areas of the brain. The evoked effects were 
usually described as stereotyped tetanic contractions, pro- 
ducing clumsy movements of the body and extremities and 
lacking the precision and coordination of spontaneous ac- 
tivities. These results were obtained under anesthesia, but 
it was assumed that because of the complexity of the 
mechanisms involved, artificial stimulation could never 
induce, even in awake animals, responses as skillful and well 
organized as voluntary movements. In spite of this assump- 
tion, when stimulation was applied through intracerebral 
electrodes to completely unrestrained animals, it was evi- 
dent that motor performance under electronic command 
could be as complex and precise as spontaneous behavior. 
Before discussing the reasons for success in the electric 
driving of behavior, I will describe examples of simple 
motor responses, complex behavior, and social interaction. 

18 




- - 

— u 
u c 
u 






I) 3 

i i 

o "a 



a 5 



_ 



c — 



19 



Simple Motor Responses 
In the cat, electrical stimulation of the right sulcus cru- 
ciatus, in the anterior part of the brain, produced flexion 
of the left hind leg (fig. 2) with an amplitude of movement 
proportional to stimulation intensity, provided the experi- 
mental situation was constant. For example, in a cat stand- 
ing on all fours, a five-second stimulation of 1.2 mA (mono- 
polar, cathodal, square waves, 0.5 millisecond of pulse 
duration, 100 cycles per second) evoked a leg flexion barely 
off the ground. When the intensity was increased up to 
1.5 mA, the hind leg rose about 4 centimeters, and when 
1 .8 mA were applied, the flexion of the leg was complete. 
The evoked movement usually began slowly, developed 
smoothly, reached its peak in about two seconds, and lasted 
until the end of the stimulation. This motor performance 
could be repeated as many times as desired, and it was 
accompanied by a postural adjustment of the whole body 
which included a lowering of the head, raising of the pelvis, 
and a slight weight shift to the left in order to maintain 
equilibrium on only three legs. The electrical stimulation 
did not produce any emotional disturbance, and the cat was 
as alert and friendly as usual, rubbing its head against the 
experimenter, seeking to be petted, and purring. However, 
if we tried to prevent the evoked effect by holding the left 
hind leg with our hands, the cat stopped purring, struggled 
to get free, and shook its leg. Apparently the evoked motility 
was not unpleasant, but attempts to prevent it were dis- 
turbing for the animal. The artificial driving of motor ac- 
tivities was accepted in such a natural way by the animal 
that often there was spontaneous initiative to cooperate 
with the electrical command. For example, during a 
moment of precarious balance when all paws were close 
together, stimulation produced first a postural adjustment, 
and the cat spread its forelegs to achieve equilibrium by 

20 



shifting its body weight to the right, and only after this 
delay did the left hind leg begin to flex. It was evident that 
the animal was not in a hurry and was taking its time to 
prepare its position for the indueed movement. Preliminary 
adjustments were not seen if the cat's posture was already 
adequate for the required motor performance. In other 
cases, when the animal was lying down with its hind legs 
already flexed, the stimulation effect was greatly diminished 
and consisted mainly of increased muscular tension. 

In cases of conflict between the free movements of the 
animal and those elicited by the experimenter, the final 
result depended on the relative strength of opposing sig- 
nals. Stimulations of the cruciate sulcus at threshold level 
of 1.2 mA, which produced a small leg flexion, were in- 
effective if applied while the cat was walking. To test 
stronger conflicts, the cat was enticed into jumping off a 
table to reach food placed on the floor, and, while it was 
in the air, the cruciate sulcus was electrically stimulated. 
In this situation, intensities of up to 1.5 mA, which usually 
evoked a clear motor response, were completely ineffective; 
physiological activity seemed to override the artificial ex- 
citation and the cat landed with perfectly coordinated move- 
ments. If the intensity was increased to 2 mA, stimulation 
effects were prepotent over voluntary activities; leg flexion 
started during the jump, coordination was disrupted, and 
the cat landed badly. 

A variety of motor effects have been evoked in different 
species, including cat, dog, bull, and monkey. The animals 
could be induced to move the legs, raise or lower the body, 
open or close the mouth, walk or lie still, turn around, and 
perform a variety of responses with predictable reliability, 
as if they were electronic toys under human control (see 
figs. 1-6). Behavior elicited by electrical stimulation was 
not always comparable to spontaneous activity. In a few 

21 



experiments, movements beyond the animal's voluntary 
control were observed, such as the clockwise rotation of 
the eye. In other cases, abnormal responses, disorganized 
contractions, and loss of equilibrium have also been in- 
duced, depending on the cerebral area and parameters of 
stimulation. 

Complex Behavior 

Normal activities in animals are not confined to simple 
motor responses such as hind-leg flexion but include a suc- 
cession of different acts such as body displacement and 
social interaction. In order to study these complex activi- 
ties, which require a situation as free and normal as pos- 
sible, our experimental design included ( 1 ) the establish- 
ment of a colony with four to six monkeys, (2) the con- 
tinuous recording of spontaneous and evoked behavior by 
time-lapse photography, in order to qualify and quantify 
individual and social actions, and (3) stimulation of the 
animals by remote control. The behavior of a group of 
monkeys is an entertaining spectacle, and a few minutes' 
observation gives the impression that their playing, groom- 
ing, chasing, and comic activities are rather unpredictable. 
Long-term studies, however, have shown that individual 
and social behavior is predictable within a known range of 
variability. The study of group behavior is possible pre- 
cisely because of the recurrence of patterns that can be 
identified. Every day the monkeys will eat, play, groom, 
pick, sit, and perform a series of acts which can be analyzed 
and quantified (Delgado, 1962). After the individual pro- 
files of behavior are established, the responses evoked by 
electrical stimulation of the brain may be precisely evalu- 
ated. 

A typical example of complex behavior was observed 
in a monkey named Ludi while she was forming part of a 

22 




Fig. 3. Yawning evoked in the monkey by radio stimulation of the pars magno 
cellularis of the red nucleus. Observe the spontaneous qualities of the evoked 
effect and also the fact that when the monkey is asleep the response diminishes. 



23 



colony with two other females and two males. Ludi was an 
aggressive female who dominated the whole group and 
exercised the usual prerogatives of being the chief, enjoying 
greater territoriality and more food, and moving freely 
around the colony. After different areas of the brain had 
been studied under restraint, the radio stimulator was 
strapped to Ludi, and excitations of the rostral part of the 
red nucleus were started, with the monkey free in her 
colony. Stimulation produced the following complex se- 
quence of responses (fig. 4): (1) immediate interruption 
of spontaneous activities, (2) change in facial expression, 
(3) head turning to the right, (4) standing on two feet, 
(5) circling to the right, (6) walking on two feet with 
perfect preservation of equilibrium by balancing the arms, 
touching the walls of the cage, or grasping the swings, (7) 
climbing a pole on the back wall of the cage, (8) descend- 
ing to the floor, (9) low tone vocalization, (10) threatening 
attitude directed toward subordinate monkeys, (11) chang- 
ing of attitude and peacefully approaching some other 
members of the colony, and (12) resumption of the activity 
interrupted by the stimulation. The whole sequence was 
repeated again and again, as many times as the red nucleus 
was stimulated. Responses 1 to 8 developed during the five 
seconds of stimulation and were followed, as aftereffects, by 
responses 9 to 12 which lasted from five to 10 seconds. The 
excitations were repeated every minute for one hour, and 
results were highly consistent on different days. The re- 
sponses resembled spontaneous activities, were well organ- 
ized, and always maintained the described sequence. Climb- 
ing followed but never preceded turning of the body; vocal- 
ization followed but never preceded walking on two feet; the 
general pattern was similar in different stimulations, but the 
details of motor performance varied and were adjusted to 
existing circumstances. For example, if the stimulation 

24 




E 5 
< y 



25 



surprised the animal with one arm around the vertical pole 
in the cage, the first part of the evoked response was to 
withdraw the arm in order to make the turn possible. While 
walking on two feet, the monkey was well oriented and was 
able to avoid obstacles in its path and to react according to 
the social situation. In some experiments, three monkeys 
in the colony were simultaneously radio-stimulated in the 
red nucleus, and all three performed the full behavioral 
sequence without interfering with one another. Changes in 
the experimental situation could modify the evoked re- 
sponse, as shown in the case of external threat to the colony. 
Waving the catching net or a pair of leather gloves on one 
side of the home cage induced a precipitous escape of all 
monkeys to the other side. Red-nucleus stimulation applied 
at this moment was ineffective and did not interfere with 
the escape of the animals. In other experiments, after being 
deprived of food for 24 hours, the animals were offered 
bananas and oranges which they grabbed and ate voraci- 
ously. During this time, Ludi's response to radio stimulation 
of the red nucleus was completely absent or was reduced to 
only a short turn. In one long experiment, excitation of the 
red nucleus was repeated every minute, day and night, for 
two weeks, with a total of more than 20,000 stimulations. 
The remarkable reliability of responses was demonstrated 
throughout the whole period, with the following significant 
exception. During the day, monkeys take several naps, and 
during the night they have a long period of sleep which is 
interrupted by several periods of general activity. Time- 
lapse recordings showed that, as the stimulated monkey was 
falling asleep, the evoked responses progressively dimin- 
ished until only a small head movement remained. As soon 
as the stimulated animal awoke, the responses reappeared 
with all of their complexity. This finding indicates that the 
effects evoked by cerebral stimulation are not inflexible and 

26 



rigid, but may adapt to changes in the physiological situa- 
tion. Examples of other patterns of sequential behavior 
have been evoked by excitation of several diencephalic and 
mesencephalic structures (Delgado, 1963a, 1964a, 1964b), 
showing that sequential activities are anatomically repre- 
sented in several parts of the central nervous system. 

SOCIAL INTERACTION 

The social interaction of animals requires continuous 
mutual adaptation, and activities depend on a variety of 
factors, including sensory inputs, problem-solving capacity, 
emotional background, previous experience, conditioning, 
drives, instincts, and intelligent integration of all these 
processes. In spite of the extraordinary complexity of these 
supporting mechanisms, there is experimental evidence that 
electrical stimulation of specific areas of the brain may 
influence social interaction such as contactual relations, 
hierarchical situations, submissive manifestations, sexual 
activity, aggressive behavior, and social fear. By definition, 
this type of research requires at least two animals which can 
interact with each other, but the study of groups is naturally 
preferable. 

In 1928 Hess demonstrated that during electrical stimu- 
lation of the periventricular gray matter, cats responded 
as if threatened by a dog, with dilatation of the pupils, 
flattening of the ears, piloerection, growling, and well- 
directed blows with unsheathed claws. Similar offensive- 
defensive reactions have been described by several authors 
(see bibliography in Delgado, 1964a), but it was debatable 
whether the apparently enraged animal was aware of its 
own behavior and whether the evoked reactions were pur- 
posefully oriented; in other words, if the observed phe- 
nomena were true or false rage. Today it is known that 
both types of rage may be elicited, depending on the loca- 

27 



tion of the stimulated points, and we have conclusive evi- 
dence that, in cats and monkeys, well-organized behavior 
may be evoked by stimulation of the amygdala, postero- 
ventral nucleus of the thalamus, fimbria of the fornix, tectal 
area, central gray, and other cerebral structures. The fact 
that one animal can be electrically driven to fight against 
another has been established (Delgado, 1955a). In this 
experiment, stimulation of the tectal area in a male cat 
evoked the well-known pattern of offensive-defensive reac- 
tions. When this animal was placed on a testing stage in 
the company of a larger cat, they enjoyed friendly relations, 
lying close to each other and purring happily until the 
smaller cat was stimulated in the tectal area. At this mo- 
ment, it started growling, unsheathed its claws, and launched 
a fierce attack against the larger animal which flattened its 
ears, withdrew a few steps, and retaliated with powerful 
blows. The fight continued as long as the stimulation was 
applied. The effect could be repeated, and the stimulated 
cat always took the initiative in spite of the fact that it was 
smaller and was always overpowered in the battle. After 
several stimulations, a state of mistrust was created be- 
tween the two animals, and they watched each other with 
hostility. 

Similar experiments were repeated later in a colony 
formed by six cats. When one of them was radio-stimulated 
in the tectal area, it started prowling around looking for 
fights with the other subordinate animals, but avoiding 
one of them which was the most powerful of the group. It 
was evident that brain stimulation had created a state of 
increased aggressiveness, but it was also clear that the cat 
directed its hostility intelligently, choosing the enemy and 
the moment of attack, changing tactics and adapting its 
motions to the motor reaction of the attacked animal. In 
this case, brain stimulation seemed to determine the affec- 

28 



live state of hostility, but the behavioral performance 

seemed dependent on the individuality of the stimulated 
animal, including its learned skills and previous experi- 
ences. Stimulation that increased aggressiveness was usually 
tested for only five to 10 seconds, but, as it was important 
to determine the fatigability of the effect, a longer experi- 
ment was performed by reducing the intensity to a level 
which did not evoke overt rage. The experimental subject 
was an affectionate cat which usually sought petting and 
purred while it was held in the experimenter's arms. When 
it was introduced into the colony with five other cats, a low- 
intensity radio stimulation of the amygdala was applied 
continuously for two hours during which the animal's be- 
havior was affected. It withdrew to a corner of the cage and 
sat there motionless, uttering barely audible growls from 
time to time. If any other cat approached, the stimulated 
animal started hissing and threatening, and, if the experi- 
menter tried to pet him, the growls increased in intensity 
and the animal often spat and hissed. This hostile attitude 
disappeared as soon as the stimulation was over, and the 
cat became as friendly as before. These experiments demon- 
strated that brain stimulation could modify animals' reac- 
tions toward normal sensory perceptions by a modulating 
of the quality of the responses. The effect was similar to the 
modifications of spontaneous behavior observed in normal 
emotional states. 

Monkeys offer better opportunities than cats for the 
study of social interaction because of their more numerous 
and skillful spontaneous activities. It is well known that 
these animals form autocratic societies, where one estab- 
lishes himself as boss of the group, claiming a large amount 
of the living quarters as his territory, feeding first, and 
being avoided by the others, which usually express their 
submissiveness by typical actions such as grimacing, 

29 



crouching, and presenting. In several of our monkey colo- 
nies, we demonstrated that radio stimulation of the postero- 
ventral nucleus of the thalamus and central gray increased 
the aggressiveness of the stimulated animal and affected 
the social hierarchy. Stimulation of the boss monkey in- 
duced well-directed attacks against the other members of 
the group, which were chased around and occasionally 
bitten, but it was evident that the orientation of the evoked 
response was influenced by previous experiences. During 
stimulation, the boss usually attacked and chased the male 
monkeys which represented a challenge to his authority, 
but he did not threaten the female who was his favorite 
partner. These results confirmed the finding in cat colonies 
that aggressiveness induced by cerebral stimulations was 
not blind and automatic, but selective and intelligently 
directed. 

Rhesus monkeys are destructive and dangerous crea- 
tures which do not hesitate to bite anything within reach, 
including leads, instrumentation, and occasionally the ex- 
perimenter's hands. Would it be possible to tame these 
ferocious animals by means of electrical stimulation? To 
investigate this question, a monkey was strapped to a 
chair where it made faces and threatened the investigator 
until the rostral part of the caudate nucleus was electrically 
stimulated. At this moment, the monkey lost its aggressive 
expression and did not try to grab or bite the experimenter, 
who could safely put a finger into its mouth! As soon as 
stimulation was discontinued, the monkey was as aggres- 
sive as before. Later, similar experiments were repeated 
with the monkeys free inside the colony, and it was evident 
that their autocratic social structure could be manipulated 
by radio stimulation. In one case in which the boss monkey 
was excited in the caudate nucleus with 1.5 mA for five 
seconds every minute, after several minutes the other mon- 

30 




31 



keys started to circulate more freely around the cage, often 
in proximity to the boss, and from time to time they 
crowded him without fear. The intermittent stimulation 
continued for one hour, and during this time the territo- 
riality of the boss dropped to zero, his walking time was 
diminished, and he performed no aggressive acts against 
the other members of the colony. About 12 minutes after 
the stimulation hour ended, the boss had reasserted his 
authority, and his territoriality seemed to be as well estab- 
lished as during the control period. In other experiments, 
monkeys instead of investigators controlled the activation 
of radio stimulation. In this situation, subordinate animals 
learned to press a lever in the cage which triggered stimula- 
tion of the boss monkey in the caudate nucleus, inhibiting 
his aggressive behavior (fig. 5; Delgado, 1963c). Inhibitory 
effects have been demonstrated in several species including 
brave bulls, as shown in figure 6 (Delgado, et at., 1964). 

A different type of effect was demonstrated in another 
monkey colony. Radio stimulation of the nucleus medialis 
dorsalis of the thalamus in a female monkey produced a 
sequential pattern of behavior characterized by a movement 
of the head, walking on all fours, jumping to the back wall 
of the cage for two or three seconds, jumping down to the 
floor, and walking back to the starting point. At this mo- 
ment, she was approached by the boss of the colony and 
she stood on all fours, raised her tail and was grasped and 
mounted by the boss in a manner indistinguishable from 
spontaneous mounting. The entire behavioral sequence was 
repeated once every minute following each stimulation, and 
a total of 8 1 mountings was recorded in a 90-minute period, 
while no other mountings were recorded on the same day. 
As is natural in social interaction, the evoked responses 
affected not only the animal with cerebral electrodes, but 
also other members of the colony. 

32 



il" J ft. ~H I 





..J j | ^ J .:..—-] "• 

"---'of J r '"■-> 



^, ^** 



^•*ffi 




T8fc ' 




Fig. 6. A bull in full charge may be suddenly stopped by radio stimulation of 
the anterior part of the thalamus. 

33 



ANALYSIS OF EVOKED MOTOR BEHAVIOR 

The experimental evidence presented in the previous 
pages clearly demonstrates that electrical stimulation of 
the brain can induce predictable behavioral performance 
similar to spontaneous activities. Understanding the sig- 
nificance of these findings requires analysis of the physio- 
logical mechanisms involved in voluntary movements. A 
simple act such as leg flexion requires the precise and pro- 
gressive contraction of several muscles in which the strength, 
speed, and amplitude of activation of many motor units are 
determined by the processing of messages coming from 
joints and muscle spindles integrated with another vast 
amount of information circulating through the central ner- 
vous system. The complexity of neuronal events is even 
greater during performance of sequential responses, in 
which timing and motor correlations must be adjusted to 
the purpose of the movement and adapted to changes in 
the environment. Mechanisms responsible for the physio- 
logical excitation of spontaneous motility must be highly 
sophisticated. In contrast, electrical stimulation of the brain 
is very simple and depends on primitive techniques that 
apply a train of pulses without modulation, without code, 
without specific meaning, and without feedback to a group 
of neurons which by chance are situated within an arti- 
ficially created field. In view of the complexity of neuronal 
integrations, it is not surprising that a few authors have 
downgraded the significance of stimulation effects. How 
can we explain the contradiction between the crudeness of 
these excitations and the refinement of the responses that 
they can elicit? 

When considering whether a simple electrical stimulus 
could be the cause of the many events of a behavioral re- 
sponse, we could ask whether a finger pushing a button to 
launch a man into orbit is responsible for the complicated 

34 



machinery or for the sequence of operations. Evidently the 
finger, like a simple stimulus, is only the trigger of a pro- 
grammed series of events, and consequently electrical 
charges applied to the brain cannot be accepted as the 
direct cause of leg flexion or aggression. The effect of elec- 
tricity is simply to depolarize some neural membranes and 
to initiate a chain reaction. We must remember that even 
at the neuronal level, electrical excitation is not responsible 
for the many biochemical, enzymatic, thermal, and elec- 
trical processes which accompany the evoked action poten- 
tials. Evoked effects, like other chain reactions, depend 
more on the functional properties of the activated struc- 
tures than on the starter. If electrical stimulation is con- 
sidered as a non-specific trigger, our discussion must be 
focused on what is triggered. Why do movements start, de- 
velop, and end? Which motor mechanisms are involved 
within the brain? These basic neurophysiological questions 
are very difficult to answer because of our limited knowl- 
edge, but at least we now have some new tools to initiate 
their study, and experimental hypotheses to guide future 
research. 

A tentative explanation of some of the mechanisms in- 
volved in motor activities has been proposed in the theory 
of fragmental representation of behavior (Delgado, 1964a) 
which postulates that behavior is organized as fragments 
which have anatomical and functional reality within the 
brain, where they can be the subject of experimental analy- 
sis. The different fragments may be combined in different 
sequences like the notes of a melody, resulting in a suc- 
cession of motor acts which constitute specific behavioral 
categories such as licking, climbing, or walking. The theory 
may perhaps be clarified with one example. If I wish to take 
a cookie from the table, this wish may be considered as a 
force called the starter because it will determine the initia- 

35 



tion of a series of motor acts. The starter includes drives, 
motivations, emotional perceptions, memories, and other 
processes. To take the cookie it is necessary to organize a 
motor plan, a mechanical strategy, and to decide among 
several motor choices, because the cookie may be taken 
with the left or right hand, directly with the mouth, or even 
by using the feet if one has simian skills. Choice, strategies, 
motor planning, and adjustments depend on a set of cerebral 
structures, the organizer, which is different from the set 
employed by the starter, because the desire for cookies may 
exist in hungry people or in completely paralyzed patients, 
and the hands can move and reach the table for many dif- 
ferent reasons even if there are no cookies. Finally, the 
actual contraction of muscles for the performance of the 
selected movement to reach the cookie — for example, using 
the right hand — depends on a cerebral set, the performer, 
different from the previous two, because motor represen- 
tation of hands, mouth, and feet is situated in different 
areas of the brain, and the choice of muscle group to be 
activated is under the supervision of a given organizer. 
Naturally, there is a close correlation among these three basic 
mechanisms, and also between them and other cerebral 
functions. The concept of a brain center as a visible ana- 
tomical locus is unacceptable in modern physiology, but 
the participation of a constellation of neuronal groups (a 
functional set) in a specific act is more in agreement with 
our present knowledge. The functional set may be formed 
by the neurons of nuclei far from one another: for instance, 
in the cerebellum, motor cortex, pallidum, thalamus, and 
red nucleus, forming a circuit in close mutual dependence, 
and responsible for a determined act such as picking up a 
cookie with the right hand. 

If we accept the existence of anatomical representation 
of the three functional sets: starter, organizer, and per- 

36 



former, it is logical that they can be activated by different 
types of triggers, and that the evoked results will be related 
to the previous experiences linked to the set. The same set, 
evoking a similar behavioral response, may be activated by 
physiological stimuli, such as sensory perceptions and idea- 
tions, or by artificial stimuli, such as electrical impulses. 
Depending on the location of contacts, when we stimulate 
the brain through implanted electrodes we can activate the 
starter, the organizer, or the performer of different behav- 
ioral reactions, so that natural and artificial stimuli may 
interplay with one another, as has been experimentally 
demonstrated. 

These theoretical considerations may facilitate the un- 
derstanding of so-called willful, free, or spontaneous ac- 
tivity. Obviously, the will is not responsible for the chem- 
istry of muscle contraction, for the electrical processes of 
neural transmission, or even for the intimate organization 
of movements; these phenomena depend on spindle dis- 
charges, cerebellar activation, synaptic junctions, reciprocal 
inhibitions, and other subconscious mechanisms. Voluntary 
activity is initiated by a physiological trigger which acti- 
vates a chain of preformed mechanisms which exist inde- 
pendently inside the brain. The uniqueness of voluntary 
behavior lies in its wealth of starters, each one of which 
depends on a vast and unknown integration of past experi- 
ences and present receptions. However, the organizers and 
performers are probably activated in a similar manner by 
the will and by electrical means, providing the possibility 
of investigating experimentally some of the basic mecha- 
nisms of spontaneous behavior. 

One limitation of electrical activation of behavior is the 
anatomical variability of the brain. Just as there are ex- 
ternal physical differences between individuals, there are 
variations in the shape and size of our cerebral structures 

37 



which make it impossible to place an electrical contact in 
exactly the same location in different subjects. Another 
important limitation is functional variability. The organi- 
zation of brain physiology depends to a great extent on 
individual experience which determines the establishment 
of many temporary or permanent associations among 
neuronal fields. For example, the sound of a bell is neutral 
for a naive animal, but will induce secretion of saliva if it 
has previously been paired with food, and stimulation of 
the auditory cortex should increase salivary secretion only 
in the conditioned animal. Anatomical and functional 
variabilities are the bases for the differences in individual 
personalities. When we stimulate the motor cortex, we can 
predict the appearance of a movement but not the details 
of its performance, indicating that the effects elicited by 
electrical stimulation of the brain have a statistical but not 
an individual determination. 

ELECTRICAL DRIVING OF 
MENTAL FUNCTIONS IN MAN 

Elemental psychic phenomena such as hunger and fear 
can be analyzed in both animal and man, but processes like 
ideation and imagery that are expressed verbally can be 
studied only in human beings. The most extensive informa- 
tion on this subject has been obtained by Penfield and his 
group (see, for instance, Penfield and Jasper, 1954) dur- 
ing surgical operations for epilepsy, tumors, or other ill- 
nesses. In these procedures, the brain was exposed under 
local anesthesia and stimulated electrically under direct 
visual control. More recently, as explained in a previous 
section, electrodes have been implanted in the brain for 
days or weeks, permitting repeated studies in a relaxed 
atmosphere, with the patient in bed or sitting comfortably 
in a chair. From Penfield's publications and from implanted- 

38 



electrode studies, a considerable amount of information has 
demonstrated that brain stimulation may induce anxiety, 
fear, hostility, pleasure, feelings of loneliness, distortion of 
sensory perception, recollection of the past, hallucinations, 
and other psychic manifestations. From all this material, I 
shall select several representative examples dealing mainly 
with ideation, which is perhaps the most interesting and 
least understood of the mental processes. 

Speech Increase 

Patient A. F. was an 11 -year old boy committed to an 
institution because of his uncontrollable epileptic seizures 
and destructive behavior (see Higgins et ai, 1956). Since 
his response to drugs and treatment was unsatisfactory, 
brain surgery was decided upon. To direct the operation, 
four electrode assemblies were implanted in the temporal 
lobes for six days. During this time, intracerebral activity 
was recorded, and several spontaneous seizures were regis- 
tered. Exploration of the patient included several tape- 
recorded interviews of from one and a half to two hours, 
behavioral observations, and 69 intracerebral stimulations. 
Study of the collected data indicated the existence of a 
focus of abnormality in the left temporal tip, and this area 
was successfully removed. Recovery from surgery was un- 
eventful, and in a few weeks the boy was able to enjoy a 
normal life and return to school. Five years later he was 
still seizure-free. 

In our investigations, the conversations between patient 
and therapist were tape-recorded while the spontaneous 
electrical activity of the brain was also being registered, 
and programmed stimulations were applied to different 
cerebral points. The general procedure was explained to 
the patient, but, to avoid possible psychological influences, 
he was not informed of the exact moment of the stimula- 

39 



tions. To establish behavioral and electrical correlations, 
the recorded interviews were transcribed, divided into peri- 
ods of two minutes, and analyzed by two independent in- 
vestigators who counted the number of words and identified 
and quantified the verbal expressions according to 39 dif- 
ferent categories. Table 1 shows the stimulation effects on 
verbal production. During this interview, the patient was 
quiet and spoke only four to 17 words every two minutes. 
Whenever point RP 1-2 was stimulated, the patient's atti- 
tude changed; he became more animated, and his verbal 
output increased sharply to a mean of 88 words per two- 
minute period. 

TABLE 1 

(From Higgins. Mahl, Delgado, and Hamlin. 1956) 



Stimulations RP 1-2 (N-7) r-Test 

Time interval 2'Postim. 2'Prestim. P-Value 



All Others /-Test 

Stimulations (7V-7) P-Value 
2'Postim. 2'Prestim. 



Mean % friendly remarks 6 53 0.02 17 10 

Mean N words by patient 17 88 <0.01 4 9 0.15 

Mean N words by Int. 43 46 — ' 16 30 >0.30 



"Insignificant by inspection. 

These effects were repeated seven times, and in each 
stimulation the patient appeared to be especially optimistic, 
emphasizing the pleasant side of sensory perceptions and 
the happy aspects of his memories and ideas, with many 
of his comments affectionately directed and personally re- 
lated to the therapist. Verbal expression was spontaneous 
in character, his usual personal style and phraseology were 
preserved, and conversational topics were related to the 
experimental situation without a preferred theme. Table 1 
shows that the evoked increase of words and of friendly 
remarks were highly significant, as evaluated by the /-test, 
and also that the effect was specific because it was not pro- 
duced by stimulation of other cerebral points. 

40 



Si \ial Ideation 

In three different patients, thoughts and expressions with 
sexual eontent were indueed by electrical stimulation of 
the temporal lobe. The first case, S. S., was an intelligent 
and attractive woman. 32 years old, who had suffered from 
uncontrollable epileptic attacks for several years. During 
the interviews she was usually reserved, but the first time 
that point A in the second temporal convulsion was excited 
with 6 volts, she became visibily affected, holding the hands 
of the therapist to express her fondness for him and to 
thank him for all his efforts. Several minutes later, after 
another stimulation of the same point, she started to say 
how much she would like to be cured so that she might 
marry, and other stimulations of point A were also followed 
by flirtatious conversation. The provocative play and ideas 
expressed under stimulation of point A did not appear fol- 
lowing stimulation of other cerebral points and contrasted 
with this woman's usually reserved spontaneous behavior. 

The second patient, V. P., was a woman 36 years old 
who had suffered from epilepsy since childhood. Point C 
in the temporal lobe was excited five times at intervals of 
from five to 10 minutes, and after each stimulation the 
patient's mood became friendlier; she smiled, questioned the 
therapist directly about his nationality, background, and 
friends, and declared that he "was nice," that his country 
(Spain) "must be very beautiful," that "Spaniards are very 
attractive," and she ended with the statement "I would like 
to marry a Spaniard." This particular train of thought and 
manner of speaking seemed completely spontaneous, but it 
appeared only after stimulation of point C in the temporal 
lobe, and no such shift to a flirtatious mood was noted 
in her spontaneous conversations following stimulations of 
other cerebral points. 

The third case of evoked change in sexual ideology was 

41 



a young epileptic boy, A. F., who, following stimulation of 
point LP 5-6 in the left temporal cortex, suddenly began 
to discuss his desire to get married. After subsequent stimu- 
lations of the point, he elaborated on this subject, revealed 
doubts about his sexual identity, and voiced a thinly veiled 
wish to marry the male interviewer. 

Experiential Hallucinations 

Hallucinations evoked by electrical stimulation of the 
brain have been lucidly described by Roberts ( 1961 ), who 
wrote: "It is as though a wire recorder, or a strip of cine- 
matographic film with sound track, had been set in motion 
within the brain. A previous experience — its sights and 
sounds and the thoughts — seems to pass through the mind 
of the patient on the operating table. ... At the same time 
he is conscious of the present. . . . The recollection of the 
experiential sequence stops suddenly when the electric cur- 
rent ceases. But it can again be activated with reapplication 
of the electric current." The hallucination may develop 
during the stimulation, with a normal-like progression of 
movements and sounds, which appear more real and vivid 
than when the events actually happened. It is as if the pa- 
tient had a double life, one in the past recalled by the elec- 
trical stimulation, and another in the present, perceiving all 
the sensory stimulation of the surroundings, but both with 
a similar quality of reality, as if the person had a "double 
consciousness" of subjective sensations. In some cases, com- 
ponents of the hallucination are completely new and do 
not belong to the subject's past experience, but usually, as 
Penfield (1952, 1958, 1960) emphasized, the responses 
are a detailed reenactment of previous experiences, an exact 
"flash-back" activation of memories. 

In one of our patients with intracerebral electrodes, de- 
tailed study of the tape-recorded interviews demonstrated 
that the perceptual content of some experiential responses 

42 



was related to the patient's thoughts at the moment of 
stimulation. For example, when the patient was talking 
about her daughter's desire for a baby sister, a stimulation 
was applied to the temporal lobe and the patient heard a 
female voice saying "I got a baby — sister." Baldwin ( 1960) 
has reported a similar observation in which the content of 
visual hallucinatory responses evoked in a 28-year old man 
varied with the sex and identity of the observer seated be- 
fore him in the operating room. In a previous article (Mahl 
et at., 1964) we have suggested that "The patient's 'mental 
content' at the time of stimulation is a determinant of the 
content of the resulting hallucinatory experiences," and we 
offered the so-called "altered-state hypothesis" in which the 
essential effect of stimulation is to alter the state of con- 
sciousness of the patient in such a way that primary proc- 
ess thinking replaces secondary process thinking. (See 
Freud, 1900.) According to this hypothesis, the electrical 
stimulation of the temporal lobe would not activate memory 
traces in the ganglionic record, as postulated by Penfield, 
but would induce a state of consciousness which would in- 
crease the functional probability of primary processes. 

Pleasure 

The possibility that "pleasure centers" might exist in the 
brain was supported by the extensive work of Olds and his 
collaborators (1954, 1956, 1961), who demonstrated that 
rats prefer to stimulate some points of their brains by press- 
ing a treadle, than to satisfy drives of hunger, thirst, and 
sex. Positive behavioral qualities of cerebral stimulation 
have been confirmed in other species including the cat (Sid- 
man et al., 1955) and the monkey (Bursten and Delgado, 
1958). However, "pleasure" has an experiential factor 
which animals cannot report because they lack verbal com- 
munication. Only studies in humans could reveal whether 

43 



electrical stimulation of the brain is able to induce pleasur- 
able sensations. The study of patients with implanted elec- 
trodes yielded affirmative evidence (Delgado, 1960; Sem- 
Jacobsen and Torkildsen, 1960). In one of our cases, 
stimulation of the temporal lobe evoked "pleasant tingling 
sensations of the body" which were openly declared to be 
very enjoyable. The patient's mood changed from its usual 
peaceful state to one of giggling and laughing. She teased 
the doctor and made fun of the experimental situation with 
humorous comments. 

In another patient, temporal-lobe stimulation evoked 
"statements avowing his pleasure at being 'up here' and 
'subject to us' which were classified as 'passive compliance' ' 
(Higgins et al., 1956). For example, when the patient 
had been silent for five minutes, a point in the temporal 
cortex was stimulated and he immediately exclaimed, "Hey! 
You can keep me longer here when you give me these; I like 
those." and he insisted that the "brain wave" testing made 
him "feel O.K." Similar statements followed stimulation of 
other temporal points, but were never expressed spontane- 
ously in the absence of excitations. The statistical signifi- 
cance of these results was P <0.001. as contrasted by X- 
analysis. 

During increased pleasure, the subjects were oriented 
mainly toward themselves, and they often reported experi- 
encing agreeable physical sensations, while during artifici- 
ally increased speech and changes in sexual ideology they 
expressed friendliness for the nearby people. In both cases, 
there was a shift of emotional mood to a happy interpreta- 
tion of reality, and this experience was interpreted by the 
patient as spontaneous and valid, usually without being 
directly related to the stimulation. A shift from pleasurable 
thinking to friendliness and to sexual ideas has been ob- 
served in some cases. 

44 



CONSFQUFNC ES OF BRAIN CONTROL 

Probably the most significant conclusion derived from 
electrical stimulation of the awake brain is that functions 
traditionally related to the psyche such as friendliness, 
pleasure, and verbal expression can be induced, modified, 
and inhibited by direct stimulation of cerebral structures. 
This discovery may be compared with the revolutionary 
tinding almost two centuries ago that contraction of frog 
muscle may be induced by electricity without need of the 
soul's "animal spirits," because experimental analysis of 
mental functions can now proceed without implicating 
metaphysical entities. Research concerning the electrical 
driving of emotions, anatomical correlates of memory, or 
electrical signals related to learning does not interfere with 
personal ideas about the natural or supernatural destiny of 
man and does not involve theological questions, which 
should be disassociated from neurophysiological inquiry. In 
addition to electrical stimulation, there are now techniques 
for exploration of brain function which include electrical 
recording, chemical stimulation, intracerebral chemistry, 
and electron microscopy. The task that we are facing is the 
correlation of neuro-anatomy and physiology with mental 
functions; the investigation of cerebral areas involved in 
psychic manifestations; the analysis of their electrical and 
chemical background; and the development of methods to 
induce or inhibit specific activities of the mind. 

Already we know that some structures, including the 
hypothalamus, amygdala, central gray, and temporal lobe, 
are involved in emotional phenomena, while other areas, 
such as the parietal cortex, do not seem to participate in 
psychic experience. Brain research has expanded rapidly 
in recent years with the creation of institutes for multi- 
disciplinary studies, but this field should attract even more 
of our intellectual and economic resources. Human behav- 

45 



ior, happiness, good, and evil are, after all, products of 
cerebral physiology. In my opinion, it is necessary to shift 
the center of scientific research from the study and control 
of natural elements to the analysis and patterning of mental 
activities. There is a sense of urgency in this redirection 
because the most important problem of our present age is 
the reorganization of man's social relations. While the mind 
of future generations will be formed by pedagogic, cultural, 
political, and philosophical factors, it is also true that edu- 
cation is based on the transmission of behavioral, emotional, 
and intellectual patterns related to still unknown neuro- 
physiological mechanisms. Investigators will not be able to 
prevent the clash of conflicting desires or ideologies, but 
they can discover the neuronal mechanisms of anger, hate, 
aggressiveness, or territoriality, providing clues for the di- 
rection of emotions and for the education of more sociable 
and less cruel human beings. The precarious race between 
intelligent brains and unchained atoms must be won if the 
human race is going to survive, and learning the biological 
mechanisms of social relations will favor the cerebral 
victory. 

Electrical and chemical analyses of mental functions 
have introduced new facts into the much debated problem 
of mind-brain relations. In the interpretation of data, we 
should remember that spike potentials, neurohumors, and 
synaptic transmitters may represent happiness and sorrow, 
love and hate, war and peace, and in the near future we 
can expect to find answers to classical questions concerning 
psychological aspects of the physical brain. How can elec- 
trical stimulation of the temporal lobe be felt as pleasure, 
music, or fear? Why is a ferocious monkey tamed by apply- 
ing a few volts of electricity to its caudate nucleus? As 
discussed in a previous article (Delgado, 1964b), psycho- 
physical correlations may be related to the two elements 

46 



which transmit information in the nervous system, namely, 
the material carrier and the symbolic meaning. In the re- 
ception of sensory inputs, there is an initial electrical cod' 
ing which is the carrier necessary for neural circulation of 
impulses. When a monkey, a savage, or a civilized man 
looks at a pencil, the received visual stimulus is transformed 
into electrical signals and transmitted through optic path- 
ways to the brain. At the levels of retina and optic nerve, the 
coding of the stimulus depends on the visual input, inde- 
pendent of its possible meaning. Symbolism is created by 
the association within the brain of two or more sensory 
receptions or of present and past experiences, but it does 
not depend on the material structure of the object or on 
the pattern of its electrical coding. For a naive monkey or 
for a savage, the pencil is a neutral object; for a writer, the 
pencil is full of associations, uses, and meaning. Symbolism 
is not intrinsic in the object, nor inborn in the brain: it 
must be learned. The most important symbolic tool of the 
mind, language, is not invented by each individual; it is a 
cultural gift of the species. The symbolic meaning may be 
considered an immaterial element of mental functions in 
the sense that it is related to a spatio-temporal association 
between two or more sensory receptions and not to the 
material structure of the inputs. The elements for symbolic 
recognition already exist in the electrical code of the trans- 
mitted signals; however, they are not determined by the 
pattern of the code but by spatio-temporal relations between 
present and past codes which cannot be deciphered by any 
instrument if the reference point of the past is not known. 
These temporal and spatial relations may be considered 
as material or immaterial, depending on the investigator's 
point of view. Obviously, the relations depend on the mate- 
rial existence of some events, but, at the same time, the 
relations are independent of the material organization of 

47 



each event. It is a question of definition, and, if we explain 
the meaning of our terms, there is no conflict. I think, how- 
ever, that it is more practical to consider symbolism as 
non material in order to emphasize the relativity of its 
existence and the fact that it does not depend on the intrin- 
sic qualities of matter but on the previous history of the 
object and of the observer. In the last analysis, behavior 
could be reduced to movement of atoms, but if we are dis- 
cussing the emotional behavior of the monkey, it would be 
difficult to explain it in terms of orbiting particles, and it is 
far more useful to employ psychological concepts. It should 
be clarified that, in the observer, conscious understanding 
of meaning is probably dependent upon progressive steps 
of electrical subcoding of sensory inputs with the creation 
of new material and symbolic elements related to the activa- 
tion of a new series of chemical and electrical phenomena 
affecting specialized neurons. However, the distinction be- 
tween material carrier and symbolic meaning simplifies the 
interpretation of neurophysiological data, because analysis 
of events in receptors and in transmitting pathways will 
provide information about the carrier but not about sym- 
bols. At the same time, it should be expected that electrical 
stimulation of neuronal groups may activate processes re- 
lated to both material carriers and symbolic meaning. This 
working hypothesis may help in the differentiation between 
cerebral mechanisms responsible for transmitting inputs 
and for cognitive processes of received signals. 

From its beginning, wiring of the human brain aroused 
emotional opposition even among scientists, while similar 
wiring of the heart or of the bladder has been received 
enthusiastically. The difference in attitude was no doubt 
related to a more or less conscious personal fear that our 
identity could be attacked and that our mind could be 
controlled. Personal traits such as friendliness, sexual in- 

48 



clination, or hostility have already been modified during 
cerebral stimulation, and we can foresee other influences 
on emotional tone and behavioral reactions. Eleetrieity is 
only a trigger of pre-existing mechanisms which could not, 
for example, teach a person to speak Spanish, although it 
could arouse memories expressed in Spanish if they were 
already stored in the brain. 

Entering into the field of speculation, I would like to 
comment on one question which has already caused wide- 
spread concern. Would it be feasible to control the behavior 
of a population by electrical stimulation of the brain? From 
the times of slavery and galleys up to the present forced- 
labor camps, man has certainly tried to control the behavior 
of other human beings. In civilized life, the intervention of 
governments in our private biology has become so deeply 
rooted that in general we are not aware of it. Many coun- 
tries, including the United States, do not allow a bride and 
groom to marry until blood has been drawn from their veins 
to prove the absence of syphilis. To cross international 
borders, it is necessary to certify that a scarification has 
been made on the skin and inoculated with smallpox. In 
many cities, the drinking water contains fluoride to 
strengthen our teeth, and table salt is fortified with iodine 
to prevent thyroid misfunction. These intrusions into our 
private blood, teeth, and glands are accepted, practised, 
and enforced. Naturally, they have been legally introduced, 
are useful for the prevention of illness, and do generally 
benefit society and individuals, but they have established a 
precedent of official manipulation of our personal biology, 
introducing the possibility that governments could try to 
control general behavior or to increase the happiness of 
citizens by electrically influencing their brains. Fortunately, 
this prospect is remote, if not impossible, not only for obvi- 
ous ethical reasons, but also because of its impracticability. 

49 



Theoretically it would be possible to regulate aggressive- 
ness, productivity, or sleep by means of electrodes im- 
planted in the brain, but this technique requires specialized 
knowledge, refined skills, and a detailed and complex ex- 
ploration in each individual, because of the existence of 
anatomical and physiological variability. The feasibility of 
mass control of behavior by brain stimulation is very un- 
likely, and the application of intracerebral electrodes in 
man will probably remain highly individualized and re- 
stricted to medical practice. Clinical usefulness of electrode 
implantation in epilepsy and involuntary movements has 
already been proved, and its therapeutical extension to 
behavioral disorders, anxiety, depression, and other illness 
is at present being explored. The increasing capacity to 
understand and manipulate mental functions of patients 
will certainly increase man's ability to influence the be- 
havior of man. 

If we discover the cerebral basis of anxiety, pleasure, 
aggression, and other mental functions, we shall be in a 
much better position to influence their development and 
manifestations through electrical stimulation, drugs, sur- 
gery, and especially by means of more scientifically pro- 
grammed education. 

These possibilities pose tremendous problems. As Skin- 
ner asked recently (1961), "Is the deliberate manipulation 
of a culture a threat to the very essence of man or, at the 
other extreme, an unfathomed source of strength for the 
culture which encourages it?" Scientific discoveries and 
technology cannot be shelved because of real or imaginary 
dangers, and it may certainly be predicted that the evolu- 
tion of physical control of the brain and the acquisition of 
knowledge derived from it will continue at an accelerated 
pace, pointing hopefully toward the development of a more 
intelligent and peaceful mind of the species without loss of 

50 



individual identity, and toward the exploitation of the mosl 
suitable kind oi feedback mechanism: the human brain 

studying the human brain. 

ACKNOWLEDGMENTS 

Part of the researeh mentioned in this paper was sup- 
ported by grants from the United States Public Health 
Service and the Office of Naval Research. Some of the 
studies were conducted during a John Simon Guggenheim 
fellowship. The experimental and editorial collaboration of 
Caroline Delgado is warmly acknowledged. 



51 



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Showers, M. J. C, and E. C. Crosby 

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54 



JAMES ARTHUR LECTURE ON 
THE EVOLUTION OF THE HUMAN BRAIN 

1968 



THREE VIEWS OF THE 
NERVOUS SYSTEM 



KENNETH D. ROEDER 



THE AMERICAN MUSEUM OF NATURAL HISTORY 
NEW YORK : 1968 



JAMES ARTHUR LECTURE ON 
THE EVOLUTION OF THE HUMAN BRAIN 



JAMES ARTHUR LECTURE ON 

THE EVOLUTION OF THE HUMAN BK\I\ 

1 9ft S 



THREE VIEWS OF THE 
NERVOUS SYSTEM 



KENNETH D. ROEDER 

Professor of Physiology 
Department of Biology 

Tufts University 
Medford, Massachusetts 



THE AMERICAN MUSEUM OF NATURAL HISTORY- 
NEW YORK : 1968 









JAMES ARTHUR LECTURE ON 
THE EVOLUTION OF THE HUMAN BRAIN 

l rederick Tilney, The Brain in Relation to Behavior; March 15, 1932 

C. Judson Herrick, Brains as Instruments of Biological Values; April ft. 1933 

D. M. S. Watson. The Story of Fossil Brains from Fish to Man; April 24, 1934 

C. U. Aricns Rappers. Structural Principles in the Nervous System; The Develop- 
ment of the Forebrain in Animals and Prehistoric Human Races; April 25. 
1935 

Samuel T. Orton. The Language Area of the Human Brain and Some of its Dis- 
orders; May 15. 1936 

R. W. Gerard, Dynamic Neural Patterns; April 15, 1937 

Franz Weidenreich, The Phylogenetic Development of the Hominid Brain and its 
Connection with the Transformation of the Skull; May 5, 1938 

G. Kingsley Noble, The Neural Basis of Social Behavior of Vertebrates; May 1 1, 
1939 

John F. Fulton, A Functional Approach to the Evolution of the Primate Brain; 
May 2. 1940 

Frank A. Beach, Central Nervous Mechanisms Involved in the Reproductive Be- 
havior of Vertebrates; May 8, 1941 

George Pinkley, A History of the Human Brain; May 14, 1942 

James W. Papez. Ancient Landmarks of the Human Brain and Their Origin; 
May 27, 1943 

James Howard McGregor, The Brain of Primates; May 1 1, 1944 

K. S. Lashley, Neural Correlates of Intellect; April 30, 1945 

Warren S. McCuIloch, Finality and Form in Nervous Activity; May 2, 1946 

S. R. Detwiler, Structure-Function Correlations in the Developing Nervous Sys- 
tem as Studied by Experimental Methods; May 8, 1947 

Tilly Edinger. The Evolution of the Brain; May 20, 1948 

Donald O. Hebb, Evolution of Thought and Emotion; April 20, 1949 

Ward Campbell Halstead, Brain and Intelligence; April 26, 1950 

Harry F. Harlow, The Brain and Learned Behavior; May 10, 1 95 1 
Clinton N. Woolsey, Sensory and Motor Systems of the Cerebral Cortex; May 7, 
1952 

Alfred S. Romer, Brain Evolution in the Light of Vertebrate History; May 21, 
1953 



Horace W. Magoun, Regulatory Functions of the Brain Stem; May 5, 1954 

Fred A. Mettler, Culture and the Structural Evolution of the Neural System; 
April 21, 1955 

Pinckney J. Harman, Paleoneurologic, Neoneurologic, and Ontogenetic Aspects 
of Brain Phylogeny; April 26, 1956 

Davenport Hooker, Evidence of Prenatal Function of the Central Nervous System 
in Man; April 25, 1957 

David P. C. Lloyd, The Discrete and the Diffuse in Nervous Action; May 8, 1958 

Charles R. Noback, The Heritage of the Human Brain; May 6, 1959 

Ernst Scharrer, Brain Function and the Evolution of Cerebral Vascularization; 
May 26, 1960 

Paul I. Yakovlev, Brain, Body and Behavior. Stereodynamic Organization of the 
Brain and of the Motility -Experience in Man Envisaged as a Biological 
Action System; May 16, 1961 

H. K. Hartline, Principles of Neural Interaction in the Retina; May 29, 1962 

Harry Grundfest, Specialization and Evolution of Bioelectric Activity; May 28, 
1963 

Roger W. Sperry, Problems Outstanding in the Evolution of Brain Function; 
June 3, 1964 

Jose M. R. Delgado, Evolution of Physical Control of the Brain; May 6, 1965 

Seymour S. Kety, Adaptive Functions and the Biochemistry of the Brain; May 19, 
1966 

Dominick P. Purpura, Ontogenesis of Neuronal Organizations in the Mammalian 
Brain; May 25. 1967 

Kenneth D. Roeder, Three Views of the Nervous System; April 2, 1968 



THREE VIEWS OF THE 
NERVOUS SYSTEM 

INTRODUCTION 

The theme of the James Arthur Lecture series is the 
evolution of the human brain. Taken in its broadest func- 
tional sense, this topic is the most baffling that faces 
biology today, for man is trying to understand the instru- 
ment of his own intelligence. Part of the problem is that 
there is at present no hint of a "break-through" — nothing 
equivalent to the elucidation of the DNA structure that led 
to such an upsurge of work on the mechanisms of inheri- 
tance. The only recourse is attacks on the problem from 
many directions, some seemingly oblique and indirect. One 
of these directions seeks to understand how simpler nervous 
systems determine adaptive behavior. 

This may be taken as a formal justification for my 
presence here, although the truth is that I work with insect 
nervous systems because I enjoy it. But one cannot remain 
absorbed in any specialty for thirty years without won- 
dering about its wider implications. Therefore, I welcome 
this chance to discuss the working of the nervous systems 
of insects in relation to the way insects behave, and to 
search for a view of my interest set in a wider framework. 

INSECTS AND VERTEBRATES 

Insects and vertebrates compete ecologically to a degree 
found in no other two classes of land animals. Man, as the 
dominant vertebrate, bears the brunt of this competition. 
There are mutterings in some quarters about the advantage 
to man in the extermination of this or that insect species 



or even of whole insect groups. To my mind it makes better 
biological sense to compare the workings of our competitors 
with our own with the object of outmaneuvering them 
rather than exterminating them. 

Insects and vertebrates represent widely divergent 
branches of the phylogenetic tree. Consequently, they show 
striking contrasts as well as similarities. Because these con- 
trasts and similarities are important to my general theme, 
I shall begin by commenting briefly on examples of each. 

Some of the contrasts are self-evident. Approximately 
one million insect species have been described, and it is 
estimated that millions more await description. Approxi- 
mately thirty thousand vertebrate species have been cata- 
logued. Individuals of the great majority of insect species 
weigh less than one-tenth of an ounce; some vertebrates 
weigh many tons. This is not the place to discuss the archi- 
tectural plan of the insect skeleton and how it has imposed 
a mechanical upper limit on its body size. An important 
corollary of this size limitation, however, is that insect 
nervous systems are correspondingly small, even though 
some of their neurons are as large as or larger than our 
own. It follows that insect nervous systems must contain 
fewer neurons, and that there must be parsimony in the 
way neurons are involved in the multifarious patterns of 
insect behavior. I shall try to illustrate this at a later point. 

Insect and vertebrate similarities are, at first glance, less 
apparent. It is generally true, however, that if one dissects 
different animals and inspects their body mechanisms, the 
similarities become more apparent as the grain of the in- 
spection becomes finer. For instance, at the molecular level 
nearly all living things find a common ground. At a coarser 
level, say, that of the light microscope, it is still much 
easier to determine by inspection what the tissues are for, 
that is, contraction, conduction, or secretion, than it is to 



say whether they belong to an insect or to a vertebrate. 
This is also true when such tissues are functionally exam- 
ined. For instance, insect neurons and vertebrate neurons 
seem to operate on the same general principles. 

THREE VIEWPOINTS 

Comparing the workings of insect and human brains is 
like trying to understand a strange and primitive culture 
from the viewpoint of our own civilization. The outward 
cultural expressions — mores, economics, religion, and 
"foreign policy" — seem to us quite difficult to understand, 
and we can make only blanket generalizations from an 
external study. On learning more about individual mem- 
bers of that culture, we find that they are very like our- 
selves and that they have the same joys, anxieties, and 
motivations. The last and most difficult stage of under- 
standing is to learn how individual members of the citizenry 
relate to their fellows to form the cultural mesh that deter- 
mines the image of the strange land. 

I shall try to present what I know about insect brains 
and behavior from three similar viewpoints. First I shall 
discuss in a general fashion the functions of the insect 
brain in relation to certain behavioral patterns. Next, I 
shall summarize the main attributes of that common 
denominator of all higher nervous systems, the neuron. 
Finally, I shall attempt the most difficult task of all — to 
examine how neurons transpose signals from the outer 
world and interact with other neurons forming the neural 
mesh to generate an adaptive behavioral pattern. 

THE INSECT BRAIN 

For an overview of any nervous system, it is best to 
begin by glancing at its origins. Insect ancestors were 
probably wormlike forms having a series of similar body 

3 



segments (fig. 1A). The activities of each body segment 
were largely autonomous and were controlled by a ganglion 
or, rather, a bilateral ganglion pair. The ganglia were 
serially connected by a pair of longitudinal bundles of 
nerve fibers. These connectives played little part in deter- 
mining the local affairs of the individual segments and 






Fig. 1. A. Nervous system of hypothetical ancestor of segmented worms. 
B. Later stage in the evolution of the arthropod brain. The three anterior ganglia 
have moved to a dorsal position and have become practically fused. C. Nervous 
system of the praying mantis. A relatively unspecialized insect nervous system 
with most of the ventral ganglia distinctly separated. The front pair of legs are 
specialized for grasping prey. 



served mainly to coordinate rapid movements such as 
those needed in evading a predator. The system of the worm 
can be likened to a group of self-sufficient rural communi- 
ties that resort to cooperation only when faced by a general 
threat. 



At least three, and possibly more, of these ganglia lay 
in front of the ventrally placed mouth of the worm. The 
remainder were arrayed behind it and along the ventral 
surface of the segment chain. The mouth moved to the front 
end of this primitive creature (the logical spot for gathering 
food), and the anterior ganglia came to assume a dorsal 
position while fusing to form a brain (fig. IB). As the worm 
became more mobile its "distance"' receptors, vision and 
chemo-reception, clustered at its front end and became 
more complex and discriminating. Neurons subserving 
them multiplied, forming the bulk of the adjacent brain. 

Broadly speaking, the nervous systems of insects still 
follow this plan (fig. 1C). The organs of vision and olfac- 
tion have increased enormously in complexity and diversity, 
and corresponding regions of the brain have enlarged ac- 
cordingly. Similarly, many of the body segments and their 
appendages have diversified for walking, grasping, hopping, 
swimming, flying, egg laying, and copulating. Others have 
atrophied or become fused with their neighbors. The seg- 
mental ganglia, however, still retain much of their primitive 
autonomy in coordinating and regulating the local muscle 
sequences needed for these special action patterns. The 
brain plays no part in determining which, or in what order, 
the muscles of a given segment will contract in performing 
a given action. This is determined by the relevant seg- 
mental ganglion or by the ganglia of a few adjacent seg- 
ments acting in concert, as in the coordination of the three 
pairs of legs during walking. 

CONTROL BY INHIBITION 

At first glance, this arrangement seems to leave the 
brain with no higher function beyond that needed to process 
the information coming from the eyes and antennae. There 
is much evidence, however, that the brain exerts what might 

5 



be called an over-all direction, or command function, in 
determining the particular action pattern or behavior mode 
shown by the whole insect under a particular set of condi- 
tions. This control seems to be exerted primarily through 
selective suppression of certain of the locally organized 
action patterns, the behavioral mode shown at any given 
moment being released from this suppression. This conclu- 
sion is based on experiments such as the following. 

The praying mantis waits in ambush for its food, and 
thus remains motionless most of the time; after removal of 
its brain a mantis walks continuously (Roeder, 1937). 
Most insects exhibit sexual behavior only in the presence 
of appropriate releasing stimuli provided by the opposite 
sex; decapitated male mantids make continuous copulatory 
movements irrespective of the presence of a female 
(Roeder, 1935). Ovipository behavior seems to be similarly 
controlled. The motor patterns responsible for song pro- 
duction in crickets are coordinated by the thoracic ganglia, 
yet song patterns specifically connected with different court- 
ship phases can be released in inappropriate circumstances 
by electrical stimulation of certain regions of the brain 
(Huber, 1960, 1967). Flapping of the wings in flight 
normally ceases as soon as the feet of an insect touch the 
ground. If the insect is, however, decapitated while in flight 
this natural "either or" method of replacing the flight mode 
by the walking mode is often ineffective, the insect continu- 
ing in its attempt to fly even after tarsal contact has been 
made. 

These examples suggest that a considerable proportion 
of the direction from the head ganglia is accomplished by 
proscription, that is, by selective suppression of specific 
activities generated and organized in the ganglia of the 
several body segments. There is further evidence that inhi- 
bition may occur at several levels within the brain. Centers 



in the right and left halves having inhibitory control over 
activities organized at a lower level may also inhibit one 
another ( Roeder, 1937). Although the brain seems to have 
this "either or" control over what the whole insect docs. 
the same principle extends to the local segmental activities 
presided over by the segmental ganglia. This is evident in 
the control of alternate stepping movements of the right 
and left legs of a segment and in the control of grooming 
behavior in locusts (Rowell, 1965). 

THE "ONENESS" OF BEHAVIOR 

One of the most commonplace, but to me most remark- 
able, aspects of the behavior of animals is the "oneness" 
or singularity of their acts. An animal seems able to select 
just one mode of behavior even under such circumstances 
as being exposed to stimuli capable at other times of re- 
leasing a wide variety of behavior patterns. It is easy to 
justify the adaptive value of this unity of response, but, 
regarded mechanistically, it seems surprising that a system 
with so many input channels should so rarely compromise 
between conflicting signals. In essence, this problem is one 
of "attention." which is no less marked in insects than in 
higher animals. It is also present at lower levels of the nerv- 
ous system, for the reflex contraction of one muscle group 
automatically inhibits the contraction of its antagonist 
muscles. 

Do the command functions of the insect brain play a 
part in this "oneness" of behavior? In releasing one be- 
havioral pattern does the brain increase the suppression 
of others? If such is the case one would expect to observe 
conflicting behavior patterns in a brainless insect. 

There is some evidence for this. A praying mantis nor- 
mally remains motionless for hours at a time, waiting in 
ambush at the top of a vertical surface. From this vantage 

7 



point it strikes at passing insects which are grasped in its 
specially modified forelegs. If placed on the ground a mantis 
will usually walk until it encounters a vertical object, such 
as a plant stem. It then climbs to the top of this object and 
remains motionless in the in-ambush posture. After the 
removal of its brain, however, a mantis walks continually, 
persisting in its attempts to travel forward even after reach- 
ing the top of a vertical object. If, during these travels, a 
twig or other small object happens to touch the inner, 
spined surface of its foreleg, the object is grasped firmly 
and persistently. The insect appears to be unable to release 
its grip even though this action may impede further for- 
ward progress. The action of grasping does not, however, 
suppress continuous attempts to walk forward, with the 
result that the insect frequently becomes hopelessly en- 
tangled in twigs and grass stems (Roeder, 1937). It might 
be thought that this abnormal behavior is due to sensory 
deprivation, but it is not produced by removal of the eyes, 
optic ganglia, or antennae. In the intact insect the two 
action patterns (grasping and walking) rarely, if ever, 
occur simultaneously, and their simultaneous appearance 
in the brainless mantis places the insect in a behavioral 
cul-de-sac. This suggests that, when the brain is present, 
either one, or neither, but never both, of these behavioral 
modes is released. 

ENDOGENOUS ACTIVITY 

There is little detailed physiological information as to 
how these segmentally determined activities are organized. 
Nor do we understand the nature of the inhibition that 
patterns them locally and controls them selectively from 
the brain. In some cases inhibition appears to operate by 
raising the threshold of a locally organized reflex response, 
that is, by rendering it less likely to occur. This is seen in 

8 



the grasping reflex of the mantis described above and in 
the grooming reflexes of locusts (Rowell, 1965). In other 
cases the segmental neural systems seem to be intrinsically 
unstable, that is, capable of endogenous generation of be- 
havior patterns. Organized sequences of nerve impulses 
are transmitted to appropriate muscles even after the 
ganglion has been deprived of all sensory input. This has 
been shown to be the case with copulatory movements 
generated by the last abdominal ganglion of the male pray- 
ing mantis (Roeder, Tozian, and Weiant, 1960) and with 
wing flapping in locusts (Wilson, 1961, 1967). 

It has long been known (Adrian, 1931) that insect 
ganglia discharge patterns of impulses for considerable 
periods after they have been isolated from all sensory input. 
Some of this endogenous activity may be abnormal (Rowell, 
1965), that is, caused by the surgical insult and unrelated 
to normal behavior. In the two cases cited above, however, 
endogenous neural activity seems to be the basis for move- 
ments that have significance in the lives of the animals 
concerned. There is, indeed, no satisfactory way to dis- 
tinguish between a reflex response, the threshold of which 
has been reduced to extremely low levels, and a system 
that is endogenous or self -excitatory (Roeder, 1955). 

THE BEHAVIOR OF NEURONS 

So far, I have considered only the external or behavioral 
signs of nervous system function. I have glanced, as it were, 
at the "foreign policy" of the cell community that makes 
up an animal. In the preceding paragraph it was necessary 
to mention neurons and nerve impulses. Neurons are the 
unit components of the nervous system or, if you prefer 
the sociological analogy, members of the community that 
formulate the foreign policy. Somehow, the details of the 
mass transactions between brain and ventral ganglia must 



originate in transactions between neurons. Such transac- 
tions are accomplished mainly through nerve impulses. 

It is perhaps as misleading to generalize about a "neuron" 
as it is to generalize about a "person." The transactions 
of neurons in the central nervous system have been most 
closely scrutinized in studies of vertebrates, particularly 
through the monumental work of Eccles (1953, 1964) 
on the spinal cord of the cat. There is no evidence that 
insect neurons operate on basically different principles, 
so I shall draw largely on this work in making my brief 
generalizations. 

The central nervous system can be regarded as an or- 
ganized mesh of nerve fibers. Extending into this mesh 
are fibers from a multitude of sensory neurons (sense cells) 
that are acted upon by the outer world. Out of the mesh 
extend fibers belonging to motor neurons. These connect 
with effectors — the muscle fibers and gland cells that act 
upon the outer world. The patterning of muscle contrac- 
tions that manifests itself as behavior is determined in part 
by the organization and functional state of neurons forming 
the central mesh and in part by the pattern of input signals 
reaching the central mesh from sensory neurons. 

Those neurons lying entirely within the central mesh 
are called interneurons. They are of many sizes and config- 
urations and have many ways of interacting. I must neglect 
entirely the interactions based on neurosecretion and hor- 
mones, and will limit this discussion to rapid, short-term, 
neuron transactions carried out by means of nerve im- 
pulses. 

A generalized diagram of an insect interneuron is 
shown in figure 2. It receives excitation from impulses 
arriving at close contacts (synapses) after traveling in 
nerve fibers (axons) belonging to other neurons. Nerve 
impulses can be detected as small, transient, electrical 

10 



"spikes" propagating along a nerve fiber. Information is 
contained in the frequency, timing, and pattern with which 

nerve impulses reeur. 




I 



A 







O 

o 

Fig. 2. A generalized diagram of an insect interneuron. At left, four pre- 
synaptic fibers make two inhibitory (open circles) and two excitatory (solid 
circles) contacts with its dendrites. The axon of the interneuron forms excitatory 
synapses with other interneurons (at left). An electrode (arrow) leading to an 
amplifier (A) registers the pattern of spikes discharged by the interneuron. When 
presynaptic impulses arrive at two excitatory and one inhibitory synapse (upper 
trace), the integrated result is an increase above the free-running spike frequency. 
Activity of two inhibitory and one excitatory synapse (lower trace) causes a 
decrease in spike frequency. 



Synaptic contacts are of several kinds and are often 
highly complex, but in the present context their most im- 
portant property is that most of them represent a hiatus 
or hindrance to the process of impulse propagation through 
the mesh. This means that the arrival of an impulse at an 

11 



excitatory synapse does not generate in one-to-one fashion 
another impulse in the downstream neuron. It merely in- 
creases for a few milliseconds the tendency of the recipient 
neuron to fire off an impulse of its own. The excitatory 
state wanes exponentially. This means that impulses arriv- 
ing roughly coincidentally at neighboring synapses formed 
on the same interneuron will summate in promoting the 
firing tendency of the neuron, which may cause it either 
to discharge impulses or, if it is already active, to increase 
its firing rate (fig. 2). In the same way, impulses arriving 
with greater frequency at a given synapse summate in their 
effects on the recipient neuron to a greater degree than if 
they impinge on it at more extended intervals. 

A proportion of the synapses formed on many inter- 
neurons are inhibitory. The arrival of an impulse at an 
inhibitory synapse decreases for a few milliseconds the 
tendency of the recipient neuron to fire off an impulse of 
its own. The collective effects of impulses arriving at several 
inhibitory synapses summate in time and space as do those 
arriving at excitatory synapses, and the effects of both 
types are continuously integrated by the recipient inter- 
neuron. Thus, one must picture an interneuron as being 
exposed to a running barrage of excitatory and inhibitory 
effects, each with a "half-life" of a few milliseconds. Its 
own discharge pattern reflect the running integration of 
this barrage. Elsewhere (Roeder, 1967b) I have compared 
the activity of an interneuron to the actions taken by an 
administrator. He bases his actions on decisions reached by 
integrating the positive and negative opinions of others, 
the most recent opinions being the most influential. Some 
interneurons, like lower-level administrators, merely relay 
forward the impulse pattern reaching their synapses. But 
in the central nervous system these are probably in the 
minority, and in any case their behavior is relatively unin- 

12 



teresting in our efforts to understand the transactions of 
the brain. 

References must be made to other sources (Eccles, I 953, 
1964) for the details of synaptic action, chemical effects, 
types of synapse, and the complex feedback arrangements 
found in neuron populations. The point is that synaptic 
interaction of neurons is the only known way in which 
fast-acting integrations and transformations of the central 
nervous system are carried out. Admittedly, it is hard to 
believe that higher nervous functions, such as learning, 
memory, and abstract thought, are based only on such a 
system. New modes of neuron interaction and special 
properties that emerge from the mesh may be discovered, 
but it must be realized that it would be hard to predict the 
properties of a computer if one were given only the prop- 
erties of a single transistor. 

Next, I shall attempt to describe some of the neuron 
signals and transactions concerned in a relatively simple 
piece of insect behavior. 

MOTHS AND BATS 

It is observed that a certain pattern of stimuli impinging 
on an animal bears a causal relation to action having 
adaptive value. The problem facing the neurophysiologist 
is to untangle the mechanisms transforming stimulus into 
action. Commonly, the problem is formidable at the outset; 
the stimulus pattern may be complex and hence difficult 
to define in physical or chemical terms, and it usually im- 
pinges on the animal via thousands of receptor neurons, 
each having a separate fiber leading to the central nervous 
system. Therefore, many pathways must be monitored 
simultaneously in order to assess fully the incoming sensory 
information. The initial difficulty is often insurmountable, 
but it must be overcome before one can know, in terms 

13 








Fig. 3. A, B. Photographic tracks registered by moths flying free in the field 
at night. The loudspeaker on the mast began emitting a series of ultrasonic pulses 
in simulation of a bat at the instant indicated by the bright spot in A and by the 
arrow in B. The tracks have breaks every 0.25 second. The oscillations on the 
tracks are due to the flapping wings of the moths. A. Diving in response to a 
loud sound. B. Turning-away in response to a faint sound (Roeder, 1962). 
B, C. Electronic registration of the attempts of a captive moth to turn away 
from a loudspeaker emitting a train of faint ultrasonic pulses. Upward deflection 
(top trace) indicates an attempt to make a right turn; downward deflection, an 
attempt to turn left. Middle trace shows wing movemens of moth. Lower trace 
indicates onset of pulse train (10 per second). Vertical grid marks 100-milli- 
second intervals. C. Loudspeaker was in horizontal plane and at 90 degrees to 
body axis of moth on left side. D. Same, loudspeaker on right side. Attempts to 
turn away began about 50 milliseconds after first sound pulse. The moth was a 
female of Leucania commoides (Roeder, 1967 ). 



of nerve impulse patterns, how the outer world is being 
reported to the central nervous system under the given 

14 



circumstances. The example I wish to present overcomes 
this initial difficulty. 

Several species of insectivorous bats of North America 
h\ and teed in darkness. They use a kind of sonar to avoid 
obstacles in their path and to find, track, and capture flying 
insects. The operation of this sonar has been clarified by 
the elegant work of Griffin and his students (1958). A 
cruising bat emits a series of ultrasonic cries and appears 
to be able to estimate the distance and direction of objects 
in its flight path from changes in the echoes returning to 



MM 


R 4 3 

^ r ■ — u Y i 

L 




Sl ^2JR 


wwvwvwwwwwvaai 


5 



Fig. 4. A. Ultrasonic cries recorded from a cruising bat thing in the field. 
Time. 100 cycles per second. B. A Single cry on expanded time base. Time. 
1000 cycles per second. C. Artificial ultrasonic pulse similar to those used in the 
experiments described in the text. Vertical grid. 2-milliseconds per division. 
D. Diagram showing the individually variable parameters of the stimulus: 1, 
frequency: 2. amplitude: 3. pulse duration: 4. pulse repetition rate: 5. pulse 
train length. 



its ears. The range of this sonar system for an object the 
size of a flying moth appears to be less than 10 feet. 

Moths of several families, notably the Noctuidae. have 
auditory organs maximally sensitive to the pitch of bat 
cries. They serve the moth as counter-sonar detectors, and 
they are able to register bat cries at distances of up to 130 

15 



feet (Roeder, 1966a). Moths show two types of reaction 
when they are exposed to real or simulated bat cries (fig. 
3 A, B). If the sounds reach the moths at high intensity, 
as from a nearby bat, the insects show various kinds of 
unpredictable behavior, such as twisting, turning, and 
diving toward the ground. If the sounds are received at 
low intensity, for example, by a moth flying 50 to 100 feet 
distant from a hunting bat, the moth turns and steers a 
course directly away from the source of the ultrasonic 
pulses (Roeder, 1962). 

The survival value of turning-away behavior is fairly 
clear. It carries the slower-flying moth out of the feeding 
area of the bat before its presence has been detected by the 
sonar of the predator. Turning-away behavior has been 
examined more closely (Roeder, 1967a; also fig. 3C, D). 
When a moth is mounted in stationary flight (attached to 
a support) and exposed to faint ultrasonic pulses from a 
loudspeaker placed either to its right or its left, the moth 
begins its attempt to turn away 45 milliseconds after the 
beginning of stimulation. The experiments (fig. 3C, D) 
show that it is able to choose the correct direction (right 
or left) after receiving only the first pulse of the series, and 
that it makes the change in flight direction by partially 
folding its wings on the side of the body away from the 
sound source. 

THE ACOUSTIC SIGNAL AND THE EAR OF THE MOTH 

These facts narrow the search for what takes place be- 
tween the arrival of a stimulus and the change in flight 
direction. Two other circumstances give additional en- 
couragement to the search. 

First, the cries made by a bat (fig. 4 A, B) can be dupli- 
cated electronically (fig. 4C) with sufficient accuracy to 
produce turning-away behavior. The artificial signal may 

16 



be said to have five different parameters or dimensions, 
each of which can he \aried independently. It is possible, 
therefore, to determine what aspects of the cries of a bat 
will release and steer the evasive behavior of a moth. The 
five parameters of the stimulus (fig. 4D) are: ( 1 ) the fre- 
quency (pitch) of each sound pulse; (2) the amplitude 
(intensity) of each pulse: (3) the duration of each pulse; 
(4) the interval between pulses (repetition rate); and 
i 5 ) the duration of the whole pulse train. 

The present question is: How are these parameters trans- 
lated or encoded by nerve-impulse patterns coming from 
the ear of the moth and integrated by interneurons in its 
central nervous system? The question may be put slightly 
differently: Which of these parameters is significant in 
determining what the moth finally does? 

The second encouraging circumstance is the extreme 
anatomical simplicity of the ear of a moth, which was 
pointed out more than forty years ago (Eggers. 1925). A 
noctuid moth has only two receptor cells in each ear, com- 
pared with about fifty thousand in each ear of a human 
being. Such a difference is a striking example of the parsi- 
monious distribution of neurons in insect nervous systems 
mentioned above. Practically, it simplifies the task of read- 
ing out and assessing the total information reaching the 
central nervous system of the moth via the channel that 
connects it with the outside world. Electrodes can be placed 
on the acoustic nerve, and the spike patterns delivered by 
these two sense cells are readily interpreted under different 
conditions of stimulation. 

The details of the ear of a moth are shown in figure 5. 
The bipolar sense cells (A, and A 2 ) are connected to the 
eardrum by fine and complex organelles that transduce the 
acoustic energy into a train of nerve impulses. The central 
ends of A, and A 2 extend as two nerve fibers in the tym- 

17 




TYMPANIC 

MEMBRA f IE 



Fig. 5. Diagram of dorsal view of the right tympanic organ of a noctuid 
moth. The tympanic membrane faces obliquely rearward and outward into the 
constriction between thorax and abdomen. The scoloparium is a thin strand of 
tissue attached to the inner surface of the tympanic membrane and suspended 
in the air-filled sac by a ligament (top). The acoustic sense cells, Aj and A 2 , 
lie in the scoloparium. Their distal processes, extending toward the tympanic 
membrane, transform sound energy into a series of nerve impulses, transmitted 
to the central nervous system by the Ai and A» nerve fibers. The B fiber arises 
from a non-acoustic sense cell, serving probably to register mechanical distor- 
tions of the tympanic organ. Courtesy of Scientific American. 

panic nerve connecting with the pterothoracic ganglion. 
This nerve mass, which consists of the second and third 
thoracic ganglia, is the site for the major neuronal trans- 
actions concerned in bat avoidance. 



NEURAL TRANSFORMATIONS AND TRANSACTIONS 

The traffic of nerve impulses flowing from the tympanic 
organ to the central nervous system is detected by an 
electrode placed on the tympanic nerve. The sequence of 
frames (fig. 6) shows how the spike patterns generated by 
the more sensitive sense cell (A,) changes as the intensity 

18 



of a brief, ultrasonic pulse is increased by measured steps. 
As the sound becomes louder, the spike pattern changes in 
several respects: (a) more spikes are generated, that is. 
a longer train is produced, although the duration of the 
stimulus remains constant; (b) the spikes are more closely 
spaced; (c) the latency or interval between the stimulus 




Fig. 6. Spike responses (upper traces) recorded from an electrode on the 
tympanic nerve of the moth, Xylena curvimacula, when pulses of 25 kilohertz 
and 5 milliseconds in duration (middle traces) were directed at the ear. Sound 
intensities are given in decibels above an arbitrary value (0) producing a minimal 
acoustic response. Time marker (lower traces), 1000 cycles per second. 



and the first spike of the series becomes less; and (d) at 
lower intensities only the sense cell A, is stimulated, where- 
as, at sound intensities ten times greater, it is joined by 
responses of the A. sense cell (not shown in fig. 6). 

Stated in another way, a hypothetical homunculus, sta- 
tioned at the central termination of one tympanic nerve 
in the thoracic ganglion, could determine intensity differ- 

19 



ences in the stimulus by four different criteria, not all of 
them equally good. Criterion "a" might be ambiguous in 
pulse duration, a longer pulse being confused with a louder 
pulse. Criterion "b" would give a fairly accurate measure 
of differences in pulse loudness. Criterion "c" would be 
useful to the homunculus only if he could compare signals 
coming from the right and left ears in response to the same 
sound pulse. Criterion "d" would be a rough measure and 
useful only in comparing very large differences in sound 
intensity. Because we are concerned solely with the neu- 
ronal mechanism of turning-away, which occurs at intensi- 
ties capable of exciting only the A, sense cells, criterion 
"d" can be neglected. 

The same experiment, carried out with sound pulses of 
different frequency (parameter 1), gives the same results 
over a wide frequency range, roughly 15 to 100 kilohertz. 
Thus, the moth appears to be tone deaf. The homunculus 
could not measure parameter 1 from the spike signals 
reaching him, although inspection of figure 6 shows that 
the other four parameters of the stimulus are measured in 
the spike pattern generated by the sense cells. 

The next step is to find interneurons influenced by the 
Aj signal and to determine in what ways they further trans- 
form the spike pattern. A metallic microelectrode is low- 
ered into the ganglion and used as an electrical probe. It 
is moved about in search of the A, signal and of events 
showing some causal relation to it. 

From here on the trail becomes confused by a babel of 
spike patterns, mostly of unknown origin and significance. 
The A, pattern is easily recognized (fig. 7A). It reaches 
the ganglion 3 to 5 milliseconds after sound reaches the 
tympanic organ. Downstream from this point in the neu- 
ronal mesh a number of interneurons have been encoun- 
tered whose signals show various types of relation to the 

20 



A, response (Roeder, 1966b). I shall mention only three 
of these, as they hint at ways in which the central nervous 
system may convert stimulation into behavior. 

The pulse-marker neuron is excited by a train of three 








AV a WaVaWaWaVaWA 



Fig. 7. Responses to stimulation of the tympanic organ recorded with micro- 
electrode from sensory and interneurons in the pterothoracic ganglion of noctuid 
moths (Caenurgina erechtea and Heliothis zea). A. Ai spikes recorded from 
neuropile in response to a 5-millisecond ultrasonic pulse (middle trace); time 
( lower trace ). 1000 cycles per second. B. Ai spikes (small downward deflections) 
and single pulse-marker spike (large upward deflection) in response to 5-milli- 
second sound pulse (lower trace). Time, 2 milliseconds per division. C. The 
same, response to a longer (38-millisecond) sound pulse. Time, 5 milliseconds 
per division. D. Single pulse-marker spike recurring in response to each of a 
series of short ultrasonic pulses (lower trace) repeated 40 times a second. 
E. Train-marker response. Spikes are indicated as dots on a raster that should 
be read like consecutive lines on a printed page. Groups of larger dots are Ai 
spikes, and indicate parameters 2-5 of the stimulus. Smaller dots are train-marker 
spikes, recurring at a frequency independent of the pulse repetition rate through- 
out the stimulation period. F. Change in the pattern of spikes in the motor nerve 
supplying a muscle controlling extension of the forewing in response to stimula- 
tion of the tympanic organ (middle trace). Motor response begins about 20 
milliseconds after first sound pulse reaches the ear. Second sound pulse appears 
to have no effect. Time, 100 cycles per second. 



21 



or four A, impulses coming from the ear on the same side 
of the body (fig. 7B). The synaptic effects of the A, im- 
pulses produce sufficient summation to trigger the pulse- 
marker only if they are separated by intervals of 2 
milliseconds or less. Typically, the response of the pulse- 
marker is a single large spike, irrespective of the duration 
of the stimulating sound pulse (parameter 3) and of the 
resulting train of A spikes that impinges upon it. This 
curious behavior of the pulse-marker (one spike per ultra- 
sonic pulse irrespective of its duration) seems to depend 
on a neuronal mechanism that requires 4 or 5 milliseconds 
without synaptic bombardment by A, impulses in order 
that the interneuron be "reset" to respond. This pause does 
not occur when a long and moderately intense pulse reaches 
the ear (fig. 7C). The pulse-marker will, however, generate 
spikes up to 40 times per second if the long pulse is broken 
into short pulses (fig. 7D). This behavior is interesting in 
three respects. 

First, the pulse-marker spike transmitted downstream 
can be said to have discarded parameters 2 and 3 as 
defined by the original ultrasonic stimulus. A homunculus 
observing only the signal generated by one pulse-marker 
could not judge differences either in the intensity or in the 
duration of the original stimulus. He could still determine 
pulse intervals (parameter 4) and the duration of the pulse 
train (parameter 5). 

Second, pulse-markers connected to the right and left 
ears and sending their spikes into a mechanism that com- 
pared relative times of arrival would be capable of steering 
a moth in flight away from a distant sound source, because 
the latency of the pulse-marker spike is long and variable, 
depending as it does on the arrival of three or four A spikes 
at sufficiently short intervals. Therefore the latency is 
inversely related to intensity, and relative intensity (right 
versus left ear) could be determined by marking whether 

22 



the right or the left pulse-marker fired first in response to 
a given pulse. A neuronal mechanism making sueh a com- 
parison has not yet been found. 

Third, the behavior of the pulse-marker shows a striking 
correlation with the behavior of flying moths exposed to 
different ultrasonic pulse patterns (Roeder, 1964, 1967a). 
Long, continuous tones produce only transitory turning- 
away or none at all, whereas pulsed ultrasound causes a 
sustained attempt to turn. 

Among the neurons the signals of which have been 
intercepted, two others seem relevant to the present account. 
The first has been termed the train-marker neuron. 

The train-marker neuron is inactive during silence, but 
begins to discharge a train of spikes at an independent 
frequency throughout the period in which a train of ultra- 
sonic pulses reaches the ear (fig. 7E). The spike repetition 
rate of the train-marker bears no relation to the pulse 
repetition rate of the stimulus. Thus, the homunculus pro- 
vided only with the train-marker signal would be able to 
measure only the duration of a pulse train (parameter 5). 
The other parameters of the stimulus would be lost to him. 

Another interneuron, rarely encountered, appears to add 
the A T signals coming from the right and left ears. It fires 
twice as many spikes when both ears are stimulated as 
when either ear alone is exposed to ultrasonic pulses. 

TURNING-AWAY 

These and other bits of information (Roeder, 1966b, 
1967b) are insufficient for a definition of the neuronal 
mechanism that is responsible for turning-away behavior. 
The reason may be likened to the uncertainty principle in 
physics — the deeper one searches for answers the greater 
is the disturbance created by one's searching methods in the 
beautifully poised living system. But one is heartened by 

23 



the hope that the biological obstacles are mainly technical 
rather than theoretical as in the uncertainty principle 
facing the physicists. 

Many attempts have been made to approach the turning- 
away response from the motor end, but the percentage of 
success has been very small. In a few cases changes in the 
pattern of motor impulses traveling to the wing-folding 
muscles have been registered when the ear had been stimu- 
lated with ultrasonic pulses (fig. 7E). 

Incomplete though they are, the data presented give 



TABLE 1 

Parameters of the Ultrasonic Stimulus Present 

in Various Signal Patterns 



Signal 
Pattern of 



1 2 

Frequency Amplitude 



Duration 



4 

Pulse 

Interval 



5 
Train 
Length 



Stimulus 
Tympanic nerve 
Pulse-marker 
Train-marker 
Turning-away behavior 


X 


X 
X 


X 
X 


X 
X 
X 


X 
X 
X 
X 
X 



" Not present at the pulse repetition rates in bat cries. 



hints as to the kind of processing occurring in the central 
nervous system. The original stimulus had five variable 
parameters. The first of these, frequency (parameter 1), 
is omitted from the tympanic nerve signal. Similar stages 
in which other parameters are discarded are represented by 
the pulse-marker (parameters 2 and 3) and the train- 
marker (parameter 4) interneurons (table 1). It is as if 
each parameter present in the original stimulus is a separate 
key that permits admittance to a specific door but becomes 
useless once the door in question has been passed. 

At this point it seems worthwhile to compare the in- 
formational content regarding the original stimulus that 

24 



is contained in the signal patterns registered at various 
points in the nervous system of the moth with that con- 
tained in its ultimate reaction — the turning-away behavior. 
Such a comparison is summarized in table 1 . A train of 
sound pulses reaching one ear at higher intensity causes a 
steady, sustained attempt to turn away from the stimulus. 
A continuous tone or a single pulse causes only a transitory 
turning attempt. As the table shows, an observer of this 
behavior could infer from it only the direction and the 
pulse-train length of the stimulus; none of the other param- 
eters of the original stimulus would be reflected in the 
response. The neurophysiological experiments summarized 
in table 1 suggest some of the steps in this elimination of 
stimulus parameters as nerve signals propagate through 
the nervous system and eventually shape the reaction of a 
moth to a passing bat. 

CONCLUSION 

The mechanisms whereby nervous systems generate adap- 
tive behavior have been regarded from three different 
viewpoints. The first, which might be called the "center" 
viewpoint, observes changes in behavior following relatively 
massive surgical interference with the sense organs or with 
parts of the central nervous system. It provides only a 
broad picture of the functional topology of the nervous 
system, and leads to concepts of "regions," or "centers," 
interacting with each other. The center viewpoint has been 
of particular heuristic value in anlayzing insect nervous 
systems because insect ganglia show a high degree of ana- 
tomic separation, which is to some extent correlated with 
function. For instance, it suggests that the insect brain 
determines the "oneness," or "singularity," that is so uni- 
versal in animal behavior. Such determination is accom- 
plished under given conditions by the inhibition of all but 

25 



one of the action patterns organized by the segmental 
ganglia. 

At the present time, the center viewpoint seems un- 
related to the much closer and more fine-grained viewpoint 
of modern neurophysiology. Indeed, its conclusions do not 
even require the postulation of neurons, nerve impulses, 
or synapses. When regarded from the viewpoint of neuro- 
physiology, the widely separated phylogenies of insect and 
vertebrate nervous systems find a common base in the 
behavior of single neurons. But when observed only from 
the tip of a mircoelectrode differences between these two 
groups of animals become mainly quantitative. There, the 
second, or neuron, viewpoint also has its limitations. 

The third viewpoint takes the findings of neurophysiol- 
ogy for its basic assumptions. Given the intramural prop- 
erties of neurons, it is concerned with neuron interaction, 
with information transfer in neuron populations, and with 
the way these and other functions could transpose a stimu- 
lus pattern significant in the life of an animal into a re- 
sponse promoting its survival. 

At present, the neuron communities that can be com- 
prehended from this viewpoint are small and simple, several 
orders of magnitude simpler than those that are the concern 
of the center viewpoint. Attempts to describe behavior in 
terms of neuron populations are in their infancy. An infant 
can handle, however, only simple toys, and hence I believe 
that the simpler neuron communities — the nervous systems 
of insects — have much to offer. 



26 



LITERATURE CITED 

Adrian, F. D. 

1930. The activity of the nervous system of the caterpillar. Jour. Physiol., 
vol. 70. pp. 34-35. 

Eccles, J. C. 

1953. The neurophysiologies! basis of mind. Oxford. Clarendon Press, 

314 pp. 
1964. The physiology of synapses. New York, Academic Press, 316 pp. 

Eggers, F. 

1925. Versuche liber das Gehor der Noctuiden. Zeitschr. f. Vergl. Physiol., 
vol. 2. pp. 197-314. 

Griffin, D. R. 

1958. Listening in the dark. New Haven, Yale University Press, 413 pp. 

Hi ber. F. 

1960. Untersuchungen iiber die Funktion des Zentralnervensystems und inbe- 
sondere des Gehirnes bei der Fortbewegung und Lauterzeugung der 
Grillen. Zeitschr. f. Vergl. Physiol., vol. 44, pp. 60-132. 

1967. Central control of movements and behavior of invertebrates. In 
Weirsma, C. A. G. (ed.). Invertebrate nervous systems. Chicago, Uni- 
versity of Chicago Press, 370 pp. 

Roeder, K. D. 

1935. An experimental analysis of the sexual behavior of the praying mantis. 

Biol. Bull., vol. 69, pp. 203-220. 
1937. The control of tonus and locomotor activity in the praying mantis. 

Jour. Exper. Zool., vol. 76, pp. 353-374. 
1955. Spontaneous activity and behavior. Sci. Monthly, vol. 80, pp. 363-370. 
1962. The behaviour of free flying moths in the presence of artificial ultra- 
sonic pulses. Animal Behaviour, vol. 10, pp. 300-304. 
1964. Aspects of the noctuid tympanic nerve response having significance in 

the avoidance of bats. Jour. Insect Physiol., vol. 10. pp. 529-546. 
1966a. Acoustic sensitivity of the noctuid tympanic organ and its range for the 

cries of bats. Ibid., vol. 12, pp. 843-859. 
1966b. Interneurons of the thoracic nerve cord activated by tympanic nerve 

fibers in noctuid moths. Ibid., vol. 12, pp. 1227-1244. 
1967a. Turning tendency of moths exposed to ultrasound while in stationary 

flight. Ibid., vol. 13. pp. 890-923. 
1967b. Nerve cells and insect behavior. Cambridge, Harvard University Press, 

238 pp. 

27 



Roeder, K. D., L. Tozian, AND E. A. Weiant 

1960. Endogenous nerve activity and behaviour in the mantis and cockroach. 
Jour. Insect Physiol., vol. 4, pp. 45-62. 

Rowell, C. H. F. 

1965. The control of reflex responsiveness and the integration of behaviour. 
In Treherne, J. E., and W. L. Beament (eds. ), The physiology of the 
insect central nervous system. New York, Academic Press, 277 pp. 

Wilson, D. M. 

1961. The central nervous control of flight in a locust. Jour. Exp. Biol., vol. 
38, pp. 471-490. 

Wilson, D. M. 

1967. An approach to the problem of control of ryhthmic behavior. In 
Wiersma, C. A. G. (ed.), Invertebrate nervous systems. Chicago, Uni- 
versity of Chicago Press, 370 pp. 



28 



tar 

t 



THIRTY-NINTH 

JAMES ARTHUR LECTURE ON 

THE EVOLUTION OF THE HUMAN BRAIN 

1970 



WHAT MAKES 



MAN HUMAN 



/ 



KARL H. ^PRIBRAM 



THE AMERICAN MUSEUM OF NATURAL HISTORY 
NEW YORK : 1971 



THIRTY-NINTH 

JAMES ARTHUR LECTURE ON 

THE EVOLUTION OF THE HUMAN BRAIN 



THI 



THIRTY-NIN I H 
JAMF.S ARTHUR LECTURE ON 
EVOLUTION OF IMF HUMAN BRAIN 

1970 



WHAT MAKES MAN HUMAN 



KARL H. PRIBRAM 

Professor and Head 

Neuropsychology Laboratories 

Stanford University 



THE AMERICAN MUSEUM OF NATURAL HISTORY 
NEW YORK : 1971 



LIBRARY 

OF THE 



JAMF.S ARTHUR LECTURES ON 
THI EVOLUTION OF THE HUMAN BRAIN 

Frederick Tilney, The Brain in Relation to Behavior; March 15, 1932 

C. Judson Herrick, Brains <m Instruments of Biological Values; April 6, 1933 

D. M. S. Watson, The Story of Fossil Brains from I'isli to Man; April 24, 1934 

C. U. Ariens Kappers, Structural Principles in the Nervous System; The 
Development of the Forehrain in Animals and Prehistoric Human Races; 
April 25, 1935 

Samuel T. Orton, The Language Area of the Human Brain and Some of its 
Disorders; May 15, 1936 

R. W. Gerard. Dynamic Neural Patterns; April 15, 1937 

Franz Weidenreich, The Phylogenetic Development of the Hominid Brain and its 
Connection with the Transformation of the Skull; May 5, 1938 

G. Kingsley Noble, The Neural Basis of Social Behavior of Vertebrates; May 
11, 1939 

John F. Fulton, A Functional Approach to the Evolution of the Primate Brain; 
May 2, 1940 

Frank A. Beach, Central Nervous Mechanisms Involved in the Reproductive 
Behavior of Vertebrates; May 8, 1941 

George Pinkley, A History of the Human Brain; May 14, 1942 

James W. Papez, Ancient Landmarks of the Human Brain and Their Origin; 
May 27, 1943 

James Howard McGregor, The Brain of Primates; May 11, 1944 

K. S. Lashley, Neural Correlates of Intellect; April 30, 1945 

Warren S. McCulloch, Finality and Form in Nervous Activity; May 2, 1946 

S. R. Detwiler, Structure-Function Correlations in the Developing Nervous 
System as Studied by Experimental Methods; May 8, 1947 

Tilly Edinger, The Evolution of the Brain; May 20, 1948 

Donald O. Hebb, Evolution of Thought and Emotion; April 20, 1949 

Ward Campbell Halstead, Brain and Intelligence; April 26, 1950 

Harry F. Harlow, The Brain and Learned Behavior; May 10, 1951 

Clinton N. Woolsey, Sensory and Motor Systems of the Cerebral Cortex; May 
7, 1952 

Alfred S. Romer. Brain Evolution in the Light of Vertebrate History; May 21, 
1953 



Horace W. Magoun, Regulatory Functions of the Brain Stem; May 5, 1954 

*Fred A. Mettler. Culture and the Structural Evolution of the Neural System; 
April 21, 1955 

*Pinckney J. Harman, Paleoneurologic, Neoneurologic, unci Ontogenetic Aspects 
of Brain Phylogeny; April 26, 1956 

* Davenport Hooker, Evidence of Prenatal Function of the Central Nervous 

System in Man; April 25, 1957 

* David P. C. Lloyd, The Discrete and the Diffuse in Nervous Action; May 8, 

1958 

"Charles R. Noback, The Heritage of the Human Brain; May 6, 1959 

*Emst Scharrer, Brain Function and the Evolution of Cerebral Vascularization; 
May 26, 1960 

Paul I. Yakovlev, Brain, Body and Behavior. Stereodynamic Organization of the 
Brain and of the Motility-Experience in Man Envisaged as a Biological 
Action System; May 16. 1961 

H. K. Hartline, Principles of Neural Interaction in the Retina; May 29, 1962 

Harry Grundfest, Specialization and Evolution of Bioelectric Activity; May 28, 
1963 

"Roger W. Sperry, Problems Outstanding in the Evolution of Brain Function; 
June 3, 1964 

"Jose M. R. Delgado, Evolution of Physical Control of the Brain; May 6, 1965 
Seymour S. Kety, Adaptive Functions and the Biochemistry of the Brain; May 
19, 1966 

Dominick P. Purpura, Ontogenesis of Neuronal Organizations in the Mammalian 
Brain; May 25, 1967 

"Kenneth D. Roeder, Three Views of the Nervous System; April 2, 1968 

tPhillip V. Tobias, Some Aspects of the Fossil Evidence on the Evolution of the 
Hominid Brain; April 2, 1969 

"Karl H. Pribram, What Makes Man Human; April 23, 1970 



"Published versions of these lectures can be obtained from The American 
Museum of Natural History, Central Park West at 79th St., New York, 
N. Y. 10024. 

tTo be published for The American Museum of Natural History by the 
Columbia University Press. 



The hippopotamus may well regard man, with his physical weakness, 
emotional unpredictability, and mental confusion as a freak. . . . 

(Heschel, 1965, p. 23) 



CONTENTS 

Introduction 1 

What A Code Is 4 

Brain Function in Awareness 

The Motor Mechanism and Acts 12 

Signs and Symbols: Association or Differentiation? 18 

Propositions and Reasoning: Using Signs Symbolically and 

Symbols Significantly 26 

Conclusion 31 

References Cited 33 



WHAT MAKES MAN HUMAN 

Introduction 



/\ //// MIDDLl li. is THINKERS WERE 
TRYING l<> DISCOVER PROOFS FOR i m 

I Ms i / \< l <>l (.on TOD n ll /■ SEEM l <> 
LOOK FOR PROOF I OR I III t.XISIIXCI: Ol 

M '\ (III s< in i . i< lt , r „ p, 26) 



What makes man human is his brain. This brain is 
obviously different from those of nonhuman primates. It is 
larger (Jerison. 1961), shows hemispheric dominance and 
specialization (Mountcastle, 1962), and is cytoarchitec- 
turally somewhat more generalized (Bailey and von Bonin, 
1951; Lashley and Clark. 1945). But are these the 
essential characteristics that determine the humanness of 
man? This paper cannot give an answer to this question for 
the answer is not known. But the problem can be stated 
more specifically, alternatives spelled out on the basis of 
available research results, and directions given for further 
inquiry. 

My theme will be that the human brain is so constructed 
that man, and only man, feels the thrust to make meaningful 
all his experiences and encounters. Development of this 
theme demands an analysis of the brain mechanisms that 
make meaning — and an attempt to define biologically the 
process of meaning. In this pursuit of meaning a fascinating 
variety of topics comes into focus: the coding and recoding 
operations of the brain; how it engenders and processes 
information and redundancy; and, how it makes possible 
signs and symbols and propositional utterances. Of these, 
current research results indicate that only in the making of 
propositions is man unique — so here perhaps are to be 
found the keynotes that compose the theme. 

1 



My concern with meaning originated in an attempt to 
formulate what ails the current educational process 
(Pribram, 1964, 1969a). Education entails communication 
between generations. As such, educational institutions have 
been set up to transmit information. Our schools have 
rightly been occupied with problems of information storage 
and retrieval: what ought to be taught in what period of 
time and how it is to be demonstrably retrieved. 

But, it seems this is not enough. From those whom we 
try to educate we hear rumblings and even shouts of 
discontent — discontent which arises at least in part from 
our failure to meet an educational need. What might this 
be? Is the mere acquisition of information insufficient? May 
the accumulation of information even be a cause of the 
problem? Is it not imperative to attempt to impart some- 
thing additional, something which makes information 
meaningful? 

Information measurement theory provides an interesting 
starting point for inquiry into this question. In an organism 
endowed with memory the acquisition of information can, 
on occasion, actually lead to an increase in uncertainty. 
Take, for instance, a family. The wife is at home, her 
husband away on a trip, and two children are in college. 
Her husband informs her that he will call on Thursday, her 
birthday. Letters from the children give the additional 
information that they also will call. When the phone rings 
the wife experiences an amount of uncertainty equivalent 
to the amount of information she was given initially. She 
can reduce her uncertainty by obtaining more "informa- 
tion": asking who's calling. But note that though at the 
moment of the call the answer to her question provides 
information, when the extended time period over which 
the entire episode has transpired is considered, the answer 

2 



is a repetition of one of the earlier messages. Thus, over 

time, uncertainty is countered, not by something novel, not 
b\ information, but by redundancy, i.e., by repetition. 

My thesis will be that meaning — the gerund of an old 
English word for intend, give purpose to — is made possible 
by repetition. Let me spell out this thesis, first in general, 
then in brain terms. Repetition comes in many forms. Some 
forms, some patterns of repetition, are more meaningful 
than others. Patterns of repetition are called codes. Codes 
are constructed for a useful purpose. When an organism 
is uncertain he has two alternative strategies to follow: one, 
he can reduce uncertainty by seeking real novelty, i.e., 
information. This, as already noted, will often bring only 
temporary relief because of man's mnemonic capacity. The 
other strategy is to reduce uncertainty by coding — by 
enhancing redundancy, repeating the familiar. This carries 
the penalty of boredom unless the patterns of repetition are 
varied. Varying a code turns out to be a remarkably 
powerful instrument for effectively reducing uncertainty 
because it permits using information in unexpected ways. 

From my own research I have concluded that one of the 
most pervasive — perhaps the most pervasive — of the opera- 
tions of the brain is. when the need is felt, to actively revise 
the patterns of redundancy in which information is encoded 
(Pribram. 1969b). There are several levels of these en- 
coding operations, each useful in its own way. Let me first 
say something about what a code is and then describe the 
types of codes constructed by the brain. 



What A Code Is 



WOXDER, OR RADICAL AMAZEMENT, IS A 
WAY OF GO/.YG BEYOND WHAT IS GIVEN IX 
THIXG AND THOUGHT. REFUSING TO TAKE 
AXYTHIXG FOR GRANTED, TO REGARD ANY- 
THING AS FINAL." (HESCHEL, 1965, pp. 78-79) 



Not so long ago my laboratory came into the proud 
possession of a computer. Very quickly we learned the fun 
of communicating with this mechanical mentor. Our first 
encounter involved twelve rather mysterious switches which 
had to be set up (U) or down(D) in a sequence of patterns, 
each pattern to be deposited in the computer memory before 
resetting the switches. Twenty such instructions or patterns 
constituted what is called the "bootstrap" program. Only 
after this had been entered could we "talk" to the computer 
— and it to us — via an attached teletype. For example: 
DUUUUUDDDDUD 
DDDDDDDDUUDD 
DUUUDDUDUUUD 
DUDDUDDDUUDU 
DDUDDDDUUUUUandsoon. 
Bootstrapping is not necessarily an occasional occurrence. 
Whenever a fairly serious mistake is made — and mistakes 
were made often at the beginning — the computer's control 
operations are disrupted and we must start anew by 
bootstrapping. 

Imagine setting a dozen switches twenty times and 
repeating the process from the beginning every time an 
error is committed. Imagine our annoyance when the 
bootstrap didn't work because perhaps on the nineteenth 
instruction an error was made in setting the eighth switch. 
Obviously, this was no way to proceed. 

4 



Computer programmers had early faced this problem and 

solved it simply. Conceptually, the twelve switches are 

divided into four triads and each combination of up or 

down within each triad is given an Arabic numeral. Thus, 

D D D became 



D 


D 


U 


became 


1 


D 


U 


D 


became 


2 


D 


U 


U 


became 


3 


U 


D 


D 


became 


4 


U 


D 


U 


became 


5 



U U D became 6 

U U U became 7 
Conceptually, switching the first toggle on the right becomes 
a 1 , the next left becomes a 2, the next after this a 4, and 
the next an 8. If more than a triad of switches had been 
necessary, if, for instance, our computer had come with 
sixteen switches, we should have conceptually divided the 
array into quads. Thus the bootstrapping program now 
consisted of a sequence of twenty patterns of four Arabic 
numerals, such as: 

3 7 2 2 

14 

3 4 5 6 

2 2 15 

10 3 7 etc. 
and we were surprised at how quickly those who boot- 
strapped repeatedly, actually came to know the program 
by heart. Certainly fewer errors were made in depositing 
the necessary configurations — the entire process was speed- 
ed and became, in most cases, rapidly routine and habitual. 
Once the computer is bootstrapped it can be talked to 
via a teletype in simple alphabetical terms, for example, 
JMP for jump, CLA for clear the accumulator, TAD for 

5 



add, etc. But each of these mnemonic devices merely stands 
for a configuration of switches. In fact, in the computer 
handbook the arrangement for each mnemonic is given in 
Arabic notation: e.g. CLA = 7200. This in turn is easily 
translated into UUUDUDDDDDDD should we be 
forced to set the switches on the computer by hand because 
the teletype has gone out of commission. 

In the first instance, then, programming is found to be 
the art of devising codes, codes that when hierarchically 
organized facilitate learning, remembering and reasoning. 
The power of the coding process is not to be underestimated. 
Should you doubt this, try next month to check your bank 
statement against your record of expenditures and do it all 
using Roman rather than Arabic numerals. Can you imagine 
working out our national budget in the Roman system? 

Next let me turn to an analysis of the classes of codes 
engendered by the brain. These must account for the exist- 
ence of subjective states such as perceptions and feelings; 
for the achievement of acts in the organism's environment; 
for the construction of signs and symbols by which organ- 
isms communicate with each other; and for the composition 
of propositions, the tools with which man reasons and has 
fashioned his culture. Research on the brain mechanisms 
relevant to each of these classes has in recent years yielded 
some fascinating surprises (Pribram, 1971). Let me share 
some of these surprises with you in the search for meaning 
even if at times the connection between brain, behavior 
and meaning will appear to be remote. My route is a 
deliberate one, however, because for me: "Knowing [about 
meaning has not been] due to coming upon something, 
naming and explaining it. Knowing has been due to some- 
thing forcing itself on [me]."' (Heschel, 1965. p. 109). 



Brain Function in Awareness 



//// EXPERIENCl 01 I MEANING IS AN 

I \/7 nil \< / 01 i 1 1 ii INVOLVEMEN1 ... 
\<>l i\ EXPERIENCl a I PR/1 ill REFER 
I \< l 01 VI i\l\(.. i:i I \u IRING I DIMl S 
sio\ 0P1 \ l(> H I ill \l l\ HI l\(.s 

(HESCHEL, 196$, p. 79) 



During the past decade a series of studies initiated by 
Kamiya (1968) has shown that people can discriminate 
their brain states. These studies use electrical signals to 
indicate brain function and recordable behaviors as meas- 
ures of psychological state. A subject readily acquires the 
ability to discriminate the occasions when his brain is giving 
off alpha rhythms from those when his brain's electrical 
activity is desynchronized. An interesting incidental finding 
in these studies has been the fact that when Zen and Yoga 
procedures accomplish their aims, subjects can attain the 
alpha brain rhythm state at will. Kamiya's training 
procedures can and are being used as a short cut to Nirvana. 

More specific are some recent experiments of Libet 
(1966) that have explored a well-known phenomenon. 
Since the demonstrations in the late 1 800's by Fritsch and 
Hitzig (1870) that electrical stimulation of parts of man's 
brain results in movement, neurosurgeons have explored its 
entire surface to determine what reactions such stimulations 
will produce in their patients. For instance, Foerster (1936) 
mapped regions in the postcentral gyrus which give rise to 
awareness of one or another part of the body. Thus sensa- 
tions of tingling, of positioning, etc. can be produced in the 
absence of any observable changes in the body part experi- 
enced by the patient. Libet has shown that the awareness 
produced by stimulation is not immediate: a minimum of a 
half second and sometimes a period as long as five seconds 

7 



elapses before the patient experiences anything. It appears 
that the electrical stimulation must set up some state in the 
brain tissue and only when that state has been attained does 
the patient experience. 

What do we know about the organization of these brain 
states apparently so necessary to awareness? They display 
some curious properties. One would expect that when the 
brain rhythms which are correlated with the subject's 
report are disrupted, the behavioral functions would also 
be interfered with. This is not the case. Focal epileptic 
discharge in the postcentral gyrus (Stamm and Warren, 
1961 ) and elsewhere, unless it becomes pervasive and takes 
over the function of a large part of the brain, does not 
seriously disrupt awareness. I have densely scattered epi- 
leptic lesions in various areas of the nonhuman primate 
brain in a series of carefully carried out experiments and 
found that despite the electrical disturbance produced, 
problem-solving ability remains unimpaired provided the 
ability had been acquired before electrical seizure discharge 
began (Kraft, Obrist and Pribram, 1960; Stamm and 
Pribram. 1960; Stamm and Pribram, 1961 ). (The acquisi- 
tion of appropriate performances after the discharges be- 
come established is, however, slowed approximately 
fivefold. ) 

In short, the brain state necessary to awareness appears 
to be resistant to being disrupted by local damage provided 
this damage is not overly extensive. An estimate of the 
limits on the extent to which disruption can take place 
without undue influence on the state comes from experi- 
ments involving brain tissue removals. Some 85% (or in 
some experiments even more, Galambos, Norton and 
Frommer, 1967; Chow, 1970) of a neural system can be 
made ineffective without seriously impairing the perform- 

8 



ances dependent on that system ( Lashley. 1950). What 
sort oi state is it that ean function effectively when only 
10 or 15 of it remains and all of what remains need not 
he concentrated in one location? 

The answer is that the effective units of the state must 
be distributed across the tissue involved. Each unit or small 
cluster of units must be capable of performing in lieu of the 
whole. Until very recently it was difficult to conceive of 
such a mechanism. 

But just as information processing by computer is an 
aid in conceptualizing the way in which coding operations 
are hierarchically constructed, so another engineering 
domain helps us to understand the problem of the "dis- 
tributed" state. This domain is called optical information 
processing (van Heerden. 1968) because optical systems 
work this way; or. holography, because each part of a 
recorded state can stand in for the whole (Leith and 
Upatnicks, 1965). 

The essential characteristic of a holographic state is 
the encoding of the relation among recurrences of neigh- 
boring activities. This is known technically as a spatial 
phase relationship. In optics, ordinary pictures encode only 
the intensity of illumination at any location; a hologram 
encodes spatial phase in addition. 

Holograms have many properties of interest to the brain 
scientist. Foremost of these is the fact that information is 
distributed in the holographic record. Thus one can take 
a small part of the hologram and reconstruct from it an 
image in most respects the same as that reconstructed from 
the whole record. Second, a great deal of information can 
be stored in one hologram. Several major companies (IBM, 
RCA ) have been able to encode well over a million bits in 
a square centimeter. Third, an entire image can be recon- 



structed from a hologram when illumination is reflected 
from one feature or part of the scene originally recorded. 
This is the property of associative recall. 

Holograms were first constructed mathematically by 
Dennis Gabor (1949, 1951) and crude reproductions were 
achieved. Later they were improved immensely by illu- 
minating the object with a laser beam. Because of the 
similarity of properties of the optical hologram and the 




MONOCHROMATIC 
POINT LIGHT SOURCE 



OBJECT 



FOCAL PLANE 
WITH FILTER 



IMAGE 



Fig. 1. The information to be stored is originally present on a transparent 
slide in the object plane O. It is illuminated by parallel light from a coherent 
light source L, like a laser beam. Consequently, in the image plane I one will 
see an image of the transparent object, faithful within the limitations of the 
optical system. We now expose a photographic plate, not in I, but in the focal 
plane F, to the light diffracted by the object. This plate, after exposure, is de- 
veloped and a positive is made of it, which is put back in F. This filter, which has 
a transmission in each point proportional to the original light intensity, is called 
a hologram. 



facts about the brain reviewed in the passages above, I 
have suggested that one important encoding process in the 
brain follows the mathematical rules of holography 
(Pribram, 1966). My laboratory is now working on the 
problem of just how the hologram is realized in neural tissue 
(Pribram, 1969a). 

The neural hologram is a state in which information is 
encoded in such a way that images can be constructed. 

10 



Although images are evanescent, they occur. Although they 
cannot be directly communicated, they exist. At least three 
types of images can be discerned subjectively, however, and 
for each a separate neural system has been identified. Images 
constructed by the operations of the classical sensory sys- 
tems refer to events external to the organism (Pribram, 
1966); images constructed by the operations of the limbic 
forebrain monitor the world within (Pribram, 1967a; 
Pribram, 1970); and, images constructed by the brain's 
motor mechanisms structure the achievements an organism 
aims to accomplish (Pribram, et al., 1955-56; Pribram, 
1971). I want now to take a look at these motor mech- 
anisms, for without them behavior could not occur and 
we could never make our images meaningful. 



11 



The Motor Mechanism and Acts 



•THE DEED IS THE DISTILLATION OF THE 
SELF." (HESCHEL, jg^, p. g4) 



Neuroscientists have engaged in a century-long con- 
troversy regarding the functions of the motor cortex of the 
brain. The view common to all protagonists has been that 
this tissue serves much as does a keyboard upon which the 
remainder of the brain — or the mind — constructs the 
melodies to be executed by muscles as behavior (Sherring- 
ton, 1906). What has been controversial is the nature of 
the keyboard. Does it encode, i.e. contain a representation 
of, individual muscles or even parts ( Woolsey, Chang and 
Bard, 1947; Bucy, 1949); or, does the keyboard encode 
movements, spatial and temporal combinations of muscle 
contractions, much as do the more complex controls of an 
organ which encode chords, timbre, etc. (Walshe, 1948; 
Lashley, 1921)? 

Some years ago I set out to see for myself where I stood 
in this controversy. I repeated some of the classical experi- 
ments and performed others. The results were surprising 
and I was unable to understand them fully until very 
recently when additional data from other laboratories 
became available. 

The first surprise came with the discovery that sensory 
nerves from both skin and muscle send signals to the motor 
cortex by pathways no more circuitous than those by which 
such signals reach sensory cortex (Malis, Pribram and 
Kruger, 1953). If the motor cortex were indeed the final 
common path for cerebral activity, a funnel, what business 
has it to be informed so directly from the periphery? The 

12 



problem was compounded by a scries of reports of experi- 
ments analyzing the organization of peripheral motor con- 
trol which appeared about this time (Granit, 1955; Granit 
and Kellerth. 1967; Kuffler and Hunt. 1952). The results 
of these experiments showed that one-third of the fibers 
leaving the spinal cord destined for muscle end in muscle 
receptors and have, under the experimental conditions, no 
immediate influence on muscle contraction. What happens 
when these fibers (called the y system because they are the 
smallest in diameter) are stimulated electrically is that a 




A B 

Fig. 2. A. Cortical response evoked by stimulation of superficial peroneal nerve. 
Upper trace in the postcentral "sensory" cortex; lower trace in the precentral 
"motor" cortex. Time: 10 msec. B. Same as A except that stimulus was applied 
to posterior tibial nerve. Note that the response in the "motor" cortex is prac- 
tically identical to that in the "sensory" area. 




Fig. 3. These responses were obtained 
on sciatic stimulation after complete 
resection of cerebellum plus additional 
resection of cortex of both postcentral 
gyri. Upper trace, postcentral exposed 
decorticated white matter: lower trace, 
precentral cortex. Time: 2 and 10 msec. 
This indicates that the responses shown 
in Fig. 2 do not traverse the sensory 
cortex or the cerebellum on the way 
to the "motor" cortex. 



13 



change is produced in the signals going to the spinal cord 
from the muscle receptors. Until these experiments were 
reported it had been thought that the signals from the 
muscle receptors accurately reflected the states of contrac- 
tion or relaxation of the muscles. Now it became necessary 
to take into account the fact that messages from the central 
nervous system could influence the muscle receptors in- 
dependent of any changes produced in the muscle. 

The results of both these sets of experiments spelled the 
end to a simple stimulus-response model of how the nervous 
system controls behavior (Miller, Galanter and Pribram, 
1960). At the periphery the reflex arc became an untenable 
fiction; at the cortex the keyboard had to give way to some 
more sophisticated conception. 

The second surprise regarding the motor mechanism 
came with the discovery that I could remove huge amounts 
of motor cortex with very little impairment of muscle 
function (Pribram, et al., 1955-56). Neither individual 
muscle contractions nor any particular movements were 
seriously altered by the surgery. Yet something was amiss. 
Certain tasks were performed with less skill despite the fact 
that slow motion cinematography showed the movements 
necessary to perform the task were executed without flaw in 
other situations. My interpretation of this finding was that 
behavioral acts, not muscles or movements, were encoded 
in the motor cortex. An act was defined as an achievement 
in the environment that could be accomplished by a variety 
of movements which became equivalent with respect to the 
achievement. Thus a problem box could be opened by use 
of a right or left hand; amputees have learned to write with 
their toes. Encoded in the motor cortex are the determinants 
of problem solution and of writing — not the particular 
movements involved in the performance. 

14 



What I could not fathom at the time was how the 

determinants of an act could be encoded. Two experiments 
have recent]) helped to clarify my perplexity. One was 
performed by Bernstein ( 1967) in the Soviet Union. Bern- 
stein photographed people clad in black leotards carrying 
out preassigned tasks against black backgrounds. Patches 
of white were attached to the leotards at the locations of 
major joints. Examples of the tasks are hammering a nail 
and running over rough terrain. Cinematography showed 
only the white patches, of course. These described a running 
wave form which could be analyzed mathematically. From 
his analysis Bernstein could predict within 2 mm. where the 
next movement in the action would terminate — where the 
hammer blow would fall, what level the footsteps would 
seek. It became obvious that if Bernstein could make such 
a calculation, the motor cortex could also do it. Interest- 
ingly, the equations Bernstein used were the temporal 
equivalent of those which describe the hologram. 

The second experiment gives a clue as to which deter- 
minants of acts are encoded. Evarts ( 1967) impaled cells 
in the motor cortex of monkeys with fine electrodes and 
recorded the activity of these cells while the monkey pushed 
a lever. Different weights were attached to the lever so 
that greater or lesser force had to be exerted by the monkey 
in order to accomplish the task. Evarts. to his surprise, 
found that the activity of the cortical neurons from which 
he was recording varied not as a function of the length or 
stretch of the muscles used to push the lever but as a 
function of the force needed to perform the task. Apparently 
what is encoded in the motor cortex is a representation of 
the field of forces describing the conditions necessary to 
achieve an action. 



15 



Now the earlier experimental results began to make sense. 
The motor mechanism resembles a set of thermostats rather 
than a keyboard (Merton, 1953). At the periphery the 
receptors are subject to a dual influence: they are sensitive 
to muscle tension, which reflects the force exerted on the 
muscle, and they are sensitive to signals from the central 
nervous system by way of the y fibers. This is much like the 
sensitivity of the thermocouple in a thermostat which is com- 
posed of two pieces of metal separated when cool but which 
make contact with each other by expanding when warmed. 
In addition to the sensitivity to temperature change the size 
of the gap between the pieces of metal can be varied by the 
little wheel at the top of the thermostat — i.e. the device can 
be set to be more or less sensitive to heat. There is by now 
a large body of evidence that the y motor system works by 
setting the muscle receptor's sensitivity to changes in muscle 
tension (Mettler, 1967). There is also a great deal of evi- 
dence that much of the brain's control over muscle function 
is performed by making changes in set, in biasing the y sys- 
tem, and not in making muscles move directly. Note that the 
setting device of the thermostat is calibrated for tempera- 
ture, that it has encoded on it the information necessary 
to control the activity of the furnace to reach the goal set 
for it and that this goal can be met over a wide range of 
changes in the temperature of the environment. Note also 
that the furnace need not display any fixed rhythm of on 
and off — this rhythm will vary with the environmental exi- 
gencies. In the same manner, the brains motor mechanism 
can encode the set points, the information necessary to 
achieve certain acts. The brain need not keep track of the 
rhythms of contraction and relaxation of individual muscles 
necessary to achieve an act any more than the thermostat 
needs to keep track of the turnings on and off of the furnace. 

16 



The encoding problem is immensely simplified — only end 
states need to be specified. As already noted these can he 
computed h\ extrapolation from holographic -like equations 
that summarize the sequence ( repetitions ) of forces ( muscle 
tension states) exerted. 

This is the manner in which the brain achieves acts. But 
we are not yet arrived at meaning. Acts can be stereotyped, 
routine. They can be made necessary by environmental 
change, necessary merely to maintain the organism's equi- 
librium in the face of such changes. No, there is more to 
meaning than just action, as there is more to meaning than 
just imaging. Meaning is derived when acts intend (from the 
Latin intendere, to stretch toward), that is, reach out to. 
thus impaling otherwise evanescent images and keeping 
them from slipping away. The brain makes this possible 
by constructing signs and symbols. 



17 



Signs and Symbols: Association or Differentiation? 



"KNOWLEDGE IS FOSTERED BY CURIOSITY; 
WISDOM IS FOSTERED BY AWE. AWE PRECEDES 
FAITH; IT IS THE ROOT OF FAITH.'' 

(HESCHEL, 1965, p- 89) 



Much of my own research on nonhuman primates has 
been devoted to the problem of how the brain makes pos- 
sible signs and symbols. For many years I questioned 
whether, in fact, nonhuman primates could construct signs 
and symbols but my doubts have now been resolved by work 
with two chimpanzees, one studied by the Gardners ( 1969) 
at the University of Nevada and one by Premack (1970) at 
the University of California at Santa Barbara. The Nevada 
chimpanzee named Washoe ( after the county in which Reno 
is located) has been taught to communicate using a sign 
language devised for the deaf and dumb. Earlier attempts 
to set up a rich communicative system between chimpanzee 
and man had failed. The Gardners felt that this failure was 
due to the limitations of the chimpanzee vocal apparatus 
and therefore decided to use a gestural system instead. The 
system chosen, American Sign Language, has the added 
feature that it is a relatively iconic rather than a phonetic 
system, thus much less complex in its structure than is 
human speech. 

Washoe has learned to use approximately 150 signs. She 
can string two or three signs together but not in any regu- 
larly predictable order. Comparison with deaf human chil- 
dren of comparable age shows marked differences in the 
way in which gestural signs are used — but more of this later. 
The point here is that sign making is possible for the non- 
human primate. 

18 



The Santa Barbara chimpanzee, Sarah, is being trained 
by an entirely different method to an entirely different pur- 
pose. Premack has taken operant conditioning methods and 
applied them to determine just how complex a system of 
tokens can be used to guide Sarah's behavior. Experiments 
performed in the 1930's had already shown that chim- 
panzees will work for tokens — in fact a chimpomat had been 
constructed for use with poker chips. The chimpomat was 
an outgrowth of the delayed response task, the indirect form 
of which uses a temporary token to indicate where a piece 
of food (a reinforcer) is to be found subsequently. The de- 
layed response task had been devised to determine whether 
animals and children could bridge a temporal gap between a 
momentary occurrence and a later response contingent on 
that occurrence. The bridge, which animals and children 
can construct, has been variously conceptualized in terms of 
"ideas." "memory traces," "short term memory organiza- 
tion." etc. Premack's chimpanzee has demonstrated that 
behavior dependent on tokens is not only possible but that 
hierarchical organizations of tokens can be responded to 
appropriately. 

In all of these experiments the crux of the problem is that 
the token does not call forth a uniform response. Depending 
on the situation, that is, the context in which the token 
appears, the token must be apprehended, carried to another 
location, inserted into a machine or given to someone, traded 
for another token or traded in for a reward. Or, as in the 
original delayed response situation, the token stands for a 
reward which is to appear in one location at one time, an- 
other location at another time. 

I shall use the term "symbols" to describe these context 
dependent types of tokens to differentiate them from "signs" 
which refer to events independent of the context in which 

19 



they appear. ( This distinction is consonant with that made 
by Chomsky [1963]. "Formal Properties of Grammars," 
and is used here to indicate that the primordia of the rules 
that govern human language are rooted in what are here 
called "significant'* and '"symbolic" processes.) There is now 
a large body of evidence to show that the cortex lying be- 
tween the classical sensory projection areas in the posterior 
part of the brain is involved in behavior dependent on dis- 
criminating signs and that the frontal cortex lying anterior 
to the motor areas is involved in performances dependent 
on symbolic processes. 

The surprise came when experiments were devised to 
show how these parts of the brain worked in determining 
sign and symbol. The ordinary view is that progressively 
more complex features are extracted or abstracted from in- 
formation relayed to the projection areas: the simpler ex- 
tractions occur in the projection areas per se, more complex 
abstractions demand relays beyond this primary cortex to 
adjacent stations where associations with information from 
additional sources (e.g. the primary projection areas) are 
made available (Hubel and Wiesel, 1965). Unfortunately 
for this view there is a good deal of experimental evidence 
against it. 

Most direct is the fact that if progressive cortico-cortical 
relays are involved in the ability to utilize signs and symbols, 
then removals of these relays should impair the ability. This 
is not the case. The posterior and frontal cortices specifi- 
cally concerned in sign discrimination and in delayed re- 
sponse lie some distance from the primary sensory and 
motor areas. Complete removal of the tissue that separates 
the primary areas from those involved in discrimination and 
delayed response does not permanently impair the perform- 
ance of these tasks (Lashley, 1950; Chow, 1952; Pribram, 

20 









39 



Fig. 4. Diagrammatic reconstruction of the brain after an essentially complete 
lesion of the peristriate cortex. Representative cross sections are shown by num- 
ber indicating placement on brain diagram. The monkey from whom this brain 
was taken retained a visual discrimination habit perfectly. 



21 



Spinelli and Reitz, 1969). Ergo, cortico-cortical "abstrac- 
tive" relays cannot be the mechanism at issue. 

Two possibilities remain to explain the involvement of 
those cortical areas remote from the primary projection 
zones in discrimination and delayed response behavior. In- 
formation may reach these areas by routes independent of 
those that serve the primary projection cortex. This possi- 
bility is being actively explored in several laboratories. In 
the rhesus monkey, however, there is already evidence that 
these independent routes do not play the desired role: de- 
struction of the pathways does not lead to a deficit in the per- 
formance of discriminations or delayed response (Chow, 
1954;Mishkin, 1969). 

The third possibility is one that I have been seriously ex- 
ploring for the past decade and a half (Pribram, 1958a). 
This alternative holds that sign and symbol are constructed 
by a mechanism that originates in the cortex and operates 
on the classical projection systems in some subcortical loca- 
tion. Thus the effects of the functioning of the cortex in- 
volved in signing and symbolizing are conceived to be trans- 
mitted downstream to a locus where they can preprocess 
signals projected to the primary sensory and motor cortex. 

A good deal of evidence has accrued to this third alterna- 
tive. Perhaps most important is the fact that a large portion 
of the pathway relays within the basal ganglia, motor struc- 
tures of the motor mechanism of the brain (Reitz and Pri- 
bram, 1969). Sign and symbol manipulation thus involves 
the same brain structures that are used by the organism in 
the construction of acts. The suggestion that derives from 
these anatomical facts is that signifying and symbolizing 
are acts, albeit acts of a special sort. 

There is, of course, a difference in the neuroanatomy in- 
volved in signifying and that involved in symbolizing. This 

22 









Putamen 
A18 






Fig. 5. Responses evoked by stimulation of the part of the temporal lobe in- 
volved in vision. Note tracts passing through the putamen, one of the major 
motor structures in the brain. Horizontal marks indicate the location of the 
tip of the recording electrode from which the response was photographed. 



23 



difference, as well as the behavioral analysis or the tasks 
involved, tells a good deal of what these behavioral processes 
are all about. The pathways for signifying influence the pri- 
mary sensory systems. Connections have been traced by elec- 
trophysiological techniques as far peripheral as the retina 
(Spinelli, Pribram and Weingarten, 1965; Spinelli and Pri- 
bram, 1966) and the cochlear nucleus (Dewson, Nobel and 
Pribram, 1 966), for instance. The connections important to 
the symbolic process have not as yet been determined as 
fully, but a good deal of the evidence points to involvement 
with the limbic systems structures on the innermost bound- 
ary of the forebrain (Pribram, 1958b) . 

This connection between limbic and frontal lobe func- 
tion demands a word or two. Removal of tissue in these 
systems does not impair sign discrimination but does impair 
performance on such tasks as delayed alternation (Pribram, 
et al., 1952; Pribram, et al., 1966; Pribram, Wilson and 
Connors, 1962), discrimination reversal (Pribram, Douglas 
and Pribram, 1969), shuttle-box-avoidance (Pribram and 
Weiskrantz, 1957) and approach-avoidance, commonly 
called "passive" avoidance (McCleary, 1961). In all of 
these tasks some conflict in response tendencies, conflict 
among sets, is at issue. The appropriate response is context 
(i.e. state) dependent and the context is varied as part of 
the problem presented to the organism. Thus a set of con- 
texts must become internalized (i.e. become brain states) 
before the appropriate response can be made. Building sets 
of contexts depends on a memory mechanism that embodies 
self referral, rehearsal or, technically speaking, the operation 
of sets of recursive functions. (The formal properties of 
memory systems of this type have been described fully by 
Quillian, 1967.) The closed loop connectivity of the limbic 
systems has always been its anatomical hallmark and makes 

24 



an ideal candidate as a mechanism tor context dependency 
( Pribram. 1961 ; Pribram and Kruger, 1954). 

As an aside, it is worth noting that much social-emotional 
behavior is to a very great extent context dependent. This 
suggests that the importance of the limbic formations in 
emotional behavior stems not only from anatomical connec- 
tivity with hypothalamic and mesencephalic structures but 
also from its closed loop, self-referring circuitry. It remains 
to be shown ( although some preliminary evidence is at hand 
| Fox, et al., 1967; Pribram. 1967b]) that the anterior 
frontal cortex functions in a corticofugal relation to limbic 
system signals much as the posterior cortex functions to 
preprocess sensory signals. 

Thus signs and symbols are made by the brain's motor 
mechanism operating on two classes of images — in the case 
of signs those that encode sensory signals and in the case 
of symbols those that monitor various states of the central 
nervous system. Signs are codes invariant in their reference 
to events imaged — their meaning is context free. The mean- 
ing of symbols, on the other hand, is context dependent and 
varies with the momentary state induced in the brain by the 
stimulation. Both signs and symbols convey meaning, make 
possible a temporal extension of otherwise momentary 
occurrences. 

Man shares the meaning conveyed by sign and symbol 
with nonhuman animals. This form of meaning, though per- 
haps more highly developed in man than in other animals, is 
not what makes him peculiarly human. Our search for man's 
unique thrust to make all his experiences and encounters 
meaningful needs to proceed to yet another level of com- 
plexity of encoding: only man makes propositions and rea- 
sons with them. 



25 



Propositions and Reasoning: Using Signs Symbolically and 
Symbols Significantly 



"MAN MAY, INDEED, BE CHARACTERIZED AS 
A SUBJECT IN QUEST OF A PREDICATE, AS A 
BEING IN QUEST OF A MEANING OF LIFE, OF 
ALL LIFE, NOT ONLY OF PARTICULAR AC- 
TIONS OR SINGLE EPISODES WHICH HAPPEN 
NOW AND THEN." (HESCHEL, JQ65, p. 54) 



A proposition is a sentence. It is made up of nouns and a 
predicate. Nouns are derived from signs; nouns can be con- 
ceived as signs used in sentences. Verbs are not so easy to 
characterize. Most verbs are also derived from signs; verbs 
indicate actions instead of things. Adjectives and adverbs 
also display this property of signification. Thus cow, green, 
grass, run, chew, stand, trough, drink, water, are all signs 
depicting events and occurrences. Only when used in sen- 
tences do these signs become nouns, verbs, adjectives and 
adverbs. What then makes a sentence? 

Sentences are codes constructed by the mechanism of 
predication. My hypothesis is that predication is a symbolic 
process, i.e. it places linguistic signs into a context dependent 
frame. Predication depends on the verb "is" in its various 
grammatical constructions and according to my hypothesis 
all basic sentences are explicitly or implicitly of the form 
"X is Y." 

As a corollary, predication is conceived to be a statement 
of belief. (See Ayer, 1946, pp. 7-15 and 91-93, for similar 
views.) The maker of a proposition is communicating his 
belief with regard to a relationship among signs. Thus nega- 
tion, qualification and the like are part of predication. The 
sentence "the boy runs" is therefore a shorthand statement 
of the sentence "the boy is running" and indicates certainty 

26 



OH the part of the speaker. "I believe the boy is running"; 
"I think the boy is running"; "the boy may or may not run*' 
are all qualifiers on the certainty with whieh the proposition 
is held. It is this process of making statements of certainty 
of belief that is unique to man and provides the thrust to- 
ward making experiences and encounters meaningful. 

Propositions power meaning by introducing flexibility 
into the relationship among signs. A new level of coding 
emerges, the best formal example of which is the alphabet. 
Each letter is a linguistic sign, a context-free indicator that 
can be used as such — for instance, in organizing a diction- 
ary. The symbolic use of the alphabet, on the other hand, 
provides an infinite richness of meaning through combina- 
tions of the self-same letters where context dependent rela- 
tionships now become paramount. Thus "tap" and "pat" 
have different meanings. 

Man not only uses linguistic signs symbolically, he uses 
linguistic symbols significantly. This he does when he rea- 
sons. He takes a context dependent linguistic symbol and for 
the duration of a particular purpose assigns to it a context- 
free meaning. This is accomplished by making explicit a set 
of rules governing the relationship among linguistic symbols 
"for the duration." The set of rules is. of course, a set of 
propositions. Algebra is probably the most familiar formal 
example of reasoning. 

The point at issue is that though animals make signs and 
symbols, only man appears to use linguistic signs symboli- 
cally in making propositions and linguistic symbols signi- 
ficantly in reasoning. What then is different about man's 
brain that makes possible a reciprocal interaction between 
sign and symbol? 

The common answer to this question is that man's brain 
is characterized by its massive cortico-cortical connectivity 

27 



(Geschwind, 1965). This connectivity is conceived to be 
quantitatively, not qualitatively, different from that of non- 
human brains. But as we have already seen, the postulated 
transcortical relay mechanism of sign and symbol construc- 
tion does not come off well when examined in the light of 
experimental evidence obtained with nonhuman primates. 
Instead, signs and symbols are found to be made by virtue 
of a mechanism that involves cortico-sw/?cortical connec- 
tions that relay in structures hitherto conceived to be motor 
in function. Thus if man's special capability is due to his 
brain's cortico-cortical connectivity, this difference is quali- 
tative not just quantitative. 

The issue is an important one. If, in fact, the cortico- 
cortical connectivity of man's brain proves to be the source 
of his power of propositional language and reasoning, we 
have an answer to the question of what makes man human. 
A great deal is being made today of this cortico-cortical con- 
nectivity in terms of the "disconnection" syndromes that 
result in a variety of aphasias and agnosias. But data from 
the clinic are not always easy to evaluate and misinterpreta- 
tion due to unqualified preconceptions can readily occur. 

I have some misgivings about the validity of the common 
view that cortico-cortical connections are responsible for 
man's human capabilities. I cannot now fully spell out these 
misgivings because they are intuitive and constitute the ques- 
tions directing my research plans for the immediate future. 
But a few points can be made. Obviously the roots of the 
misgivings lie in my experience with nonhuman brains. 
Initially the cortico-cortical hypothesis seemed self-evident. 
Only when experimental result after experimental result dis- 
confirmed the hypothesis was I driven to search elsewhere 
to make sense of the data. However, this is not all. The 
cortico-cortical connection hypothesis implies that informa- 

28 



tion is transmitted ru the connections. The largest bundle of 
connecting fibers, and one that has grown considerably in 
size w hen man is compared to monkey, is the corpus callosum 
which connects the two hemispheres. Yet this increase in the 
connectivity between hemispheres in man has led to hemi- 
spheric specialization, each hemisphere serving widely differ- 
ent functions. The connections seem to make it possible for 
the hemispheres to go their separate ways to a large extent 
rather than to duplicate each other as they do in nonhuman 
mammals (Pribram. 1962: Young, 1962). 

Objections to this view of the functions of the corpus 
callosum immediately come to mind as a result of Sperry's 
( 1964 ) fascinating split-brain patients. Sperry demonstrates 
that each hemisphere can be shown to control awareness in- 
dependent of the other hemisphere once the callosum is cut. 
He infers from this that separate consciousnesses, separate 
minds, exist in one head in these patients. The assumption 
underlying this inference is that ordinarily consciousness is 
of a piece and that we are always single-minded. I challenge 
this assumption. Single-mindedness is an achievement that 
often demands considerable effort whether one is studying, 
listening during a conversation, or driving an automobile. 
Sperry's patients are not unique in being of two minds on 
occasion. 

Other evidence that gives rise to my misgivings with the 
connectionist hypothesis comes from unilateral brain abla- 
tions that produce symptoms which are alleviated by further 
brain ablation. Thus unilateral ablations of the frontal eye- 
fields in monkey and man result in a temporary disregard 
of stimuli in the contralateral visual field ( Kennard. 1939: 
Pribram. 1955 ). Such disregard does not occur if the lesion 
is bilateralized. Also, unilateral occipital lobectomy in the 
cat results in a homonymous hemianopia which is relieved 

29 



when the ipsilateral optic colliculus is removed (Sprague, 
1966). 

These are but straws in the wind but they prevent me 
from obtaining too easy and early a closure on the problem 
of what makes man human. In order that the issue can be 
faced squarely, however, I must offer an alternative to the 
cortico-cortical connection hypothesis. My alternative is 
that man makes meaning through signs, symbols, proposi- 
tions and reasoning by way of corticofugal-subcortical con- 
nections that importantly involve the motor mechanisms of 
the brain. I propose that man's thrust toward meaning de- 
rives from the fact that his brain's motor mechanisms are 
better developed than those of animals. These motor mech- 
anisms are not to be conceived, as we have seen, merely as 
movers of muscles. The brain's motor mechanisms are de- 
vices that set the sensitivity of receptors and afferent chan- 
nels, not just of muscle receptors but those of all receptors 
(including eye and ear) as well. Changes in setpoint regu- 
late awareness and behavior. The changes and their results 
can relatively simply be encoded in brain tissue and thus 
serve as guides subsequently. 



30 



Conclusion 



THINKING 1^ 1 11 l\t. I\l> VO THOUGH! /^ 
BRED IS IN ISOLATED till l\ I III BRAIN. 

(HESi in i /„„-,. p. si, 



The implications for education of this propensity of the 
brain for encoding and recoding its sensitivities are obvious. 
In order to make information meaningful we must allow 
pupils to encode in terms of their own sensitivities which 
are not necessarily ours. They must be given the opportunity 
to repeat the information given in such a way that it be- 
:omes encoded in a context which makes meaning for them. 
They must be encouraged to remake what we give them in 
their own image. 

This is not as difficult as it sounds. As already noted, even 
young children who are deaf use signs differently from the 
way Washoe the chimpanzee uses signs. Human children 
spontaneously make propositions, their language is produc- 
tive (Jakobsen. 1966). All neural tissue is spontaneously 
active, nerve cells beat out electrical signals on their own 
throughout life, much as does the tissue of the heart. In man 
this spontaneity becomes organized early on so that he pro- 
duces propositions, makes sentences. And then he begins to 
play with these sentences, recoding them into different forms 
and reasoning with them. Each new batch of teenagers 
attests to the human proclivity for productively recoding 
what is given. Why not utilize this marvelous capacity to 
advantage in our educational effort? 

To summarize briefly: man's brain is different in that it 
makes imperative the productive use of linguistic signs 
symbolically and linguistic symbols significantly. The flexi- 
bility derived from this difference is immense. Given the 

31 



power of this flexibility man codes and recodes for fun and 
profit. Every artistic endeavor, every working accomplish- 
ment depends for its effectiveness not only on the informa- 
tion conveyed by the theme but on the variations on that 
theme. Human encounter is sustained not just by an ex- 
change of information but by an infinite variety in familiar 
communication. Animals use signs and symbols only in 
special circumstances; man productively propositions all his 
encounters and he reasons about all his experiences. Thus 
man and only man shows this thrust to make meaningful 
his experiences and encounters: he intends, he holds on to 
his images. 

But this is not all. By means of the motor mechanisms of 
his brain man hopefully and continuously sets and resets 
his sensitivities so that his images can become actualized in 
his environment both by virtue of his own behavior and that 
of socially contiguous others. Man's culture expresses these 
hopes, this active thrust toward meaning. For to be human 
is to be incapable of stagnation; to be human is to produc- 
tively reset, reorganize, recode. and thus to give additional 
meaning to what is. In short, "to be human is to be a prob- 
lem." (Heschel, 1965, p. 105). 



32 



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1969. The nature of non-limbic learning. Jour. Comp. Physiol. Psychol., 
vol. 69, pp. 765-772. 

Pribram, K. H., and L. Kruger 

1954. Functions of the "olfactory brain." Ann. N. Y. Acad. Sci., vol. 58, 
pp. 109-138. 

Pribram, K. H., L. Kruger, R. Robinson, and A. Berman 

1955- The effects of precentral lesions on the behavior of monkeys. Yale 
1956. Jour. Biol. & Med., pp. 428-443. 

Pribram, K. H., H. Lim, R. Poppen, and M. H. Bagshaw 

1966. Limbic lesions and the temporal structure of redundancy. Jour. Comp. 
Physiol. Psychol., vol. 61, pp. 368-373. 

Pribram, K. H., M. Mishkin, H: E. Rosvold, and S. J. Kaplan 

1952. Effects on delayed-response performance of lesions of dorsolateral 
and ventromedial frontal cortex of baboons. Jour. Comp. Physiol. 
Psychol., vol. 45, pp. 565-575. 

Pribram, K. H., D. N. Spinelli, and S. L. Reitz 

1969. The effects of radical disconnexion of occipital and temporal cortex 
on visual behaviour of monkeys. Brain, vol. 92, pp. 301-312. 



36 



PRIBRAM, k, H . \M> I \\ I IskKVS 1/ 

1957. A comparison of the effects ol medial and lateral cerebral resections 
on conditioned avoidance behavior of monkevs. Jour. Comp. Physiol. 
Psycbol., vol. 50, pp. 74-80. 

Pribkwi. k H w \ Wilson, and J. Connors 

1 1 h>2. I he effects v\ lesions of the medial forehram on alternation behavior 
of rhesus monkeys. Exp. Neurol., vol. 6. pp. 36-47. 

<)i ii l i w \! k 

1^67. Word concepts: a theoiv simulation of some basic semantic capabili- 
ties. Behav. Sci.. vol. 12, pp. 410-^30. 

Rtn/. S. I . ind K. H. Pribram 

1969. Some subcortical connections of the inferotemporal gvnu of monkey. 
E\p. Neurol., vol. 25. pp. 632-645. 

Shi RRINCTON, C. 

1906. The integrative action of the nervous svstem. Reprint. New Ha\en, 
Yale University Press. 1947. 

Sl'IKKV R. W. 

1964. Problems outstanding in the evolution of brain function. James Arthur 
lecture on the evolution of the human brain. New York. The American 
Museum of Natural History. 

SiMM i 1 1. 1) . \ . \M) K. H. Pribram 

1966. Changes in visual recovery functions produced by temporal lobe 
stimulation in monkeys. EEG Clin. Neurophysiol.. vol. 20, pp. 44—49. 

Spinllli, D. N.. K. H. Pribram, and M. Weingarten 

1965. Centrifugal optic nerve responses evoked by auditory and somatic 
stimulation. Exp. Neurol., vol. 12. pp. 303-319. 

Sprague, J. M. 

1966. Interaction of cortex and superior colliculus in mediation of visually 
guided behavior in the cat. Science, vol. 153. pp. 1544-1547. 

Stamm. J. S.. and K. H. Pribram 

1960. Effects of epileptogenic lesions in frontal cortex on learning and 
retention in monkeys. Jour. Neurophysiol.. vol. 23. pp. 552-563. 

1961. Effects of epileptogenic lesions in inferotemporal cortex on learning 
and retention in monkevs. Jour. Comp. Physiol. Psvchol.. vol. 54, 
pp. 614-618. 

Stamm. J. S.. and A. Warren 

1961. Learning and retention by monkeys with epileptogenic implants in 
posterior parietal cortex. Epilepsia, vol. q. pp. 229-242. 

van Heerden. P. J. 

1968. The foundation of empirical knowledge. The Netherlands, Uitgeverij 
W istik-Wassenaar. 

Walshe, F. M. R. 

1948. Critical studies in neurology. Baltimore. The Williams and Wilkins Co. 

Woolsey. C. N.. H. T. Chang, and P. Bard 

1947. Distribution of cortical potentials evoked by electrical stimulation of 
dorsal roots in Macaca mulatto. Fed. Proc. vol. 6. p. 230. 

37 



Young. J. Z. 

1962. Why do we have two brains? //; Mountcastle, V. B. (ed.). Inter- 
hemispheric relations and cerebral dominance. Baltimore, The Johns 
Hopkins Press, pp. 7-24. 



Many important aspects of the problem of the brain's coding processes are 
dealt with here altogether too briefly. But the present paper will serve as a 
prolegomenon to a more comprehensive study which will appear under the title 
Languages of the Brain: Experimental Paradoxes and Principles in Neuropsy- 
chology, to be published by Prentice-Hall in 1971. 



38 



W-J - * V ■- • ^ 



FORTY-THIRD 

JAMES ARTHUR LECTURE ON 

THE EVOLUTION OF THE HUMAN BRAIN 

19 73 



THE ROLE OF HUMAN SOCIAL BEHAVIOR 
IN THE EVOLUTION OF THE BRAIN 



RALPH L.jHOLLOWAY 



THE AMERICAN MUSEUM OF NATURAL HISTORY 
NEW YORK : 1975 



FORTY-THIRD 

JAMES ARTHUR LECTURE ON 

THE EVOLUTION OF THE HUMAN BRAIN 



THE 



FORTY-THIRD 
JAMES ARTHUR LECTURE ON 
EVOLUTION OF THE HUMAN BRAIN 

1 '> 7 3 



THE ROLE OF HUMAN SOCIAL BEHAVIOR 
IN THE EVOLUTION OF THE BRAIN 



RALPH L. HOLLOWAY 

Professor of Anthropology, Department of Anthropology 
Columbia University, New York 



THE AMERICAN MUSEUM OF NATURAL HISTORY 
NEW YORK : 1975 



LIBRARY 



OF THE 

micoiriu iiiiccm 



JAMES ARTHUR LECTURES ON 
THE EVOLUTION OF THE HUMAN BRAIN 



Frederick Tilney, The Brain in Relation to Behavior; March 15, 1932 

C. Judson Merrick, Brains as Instruments of Biological Values; April 6, 1933 

D. M. S. Watson, The Story of Fossil Brains from Fish to Man; April 24, 1934 

C. U. Ariens Kappers, Structural Principles in the Nervous System; The Develop- 
ment of the Forebrain in Animals and Prehistoric Human Races; April 25, 1935 

Samuel T. Orton, The Language Area of the Human Brain and Some of its 
Disorders; May 15, 1936 

R. W. Gerard, Dynamic Neural Patterns; April 15, 1937 

Franz Weidenreich, The Phylogenetic Development of the Hominid Brain and its 
Connection with the Transformation of the Skull; May 5, 1938 

G. Kingsley Noble, The Neural Basis of Social Behavior of Vertebrates; May 11, 
1939 

John F. Fulton, A Functional Approach to the Evolution of the Primate Brain; May 
2, 1940 

Frank A. Beach, Central Nervous Mechanisms Involved in the Reproductive 
Behavior of Vertebrates; May 8, 1941 

George Pinkley, A History of the Human Brain; May 14, 1942 

James W. Papez, Ancient Landmarks of the Human Brain and Their Origin; May 27, 
1943 

James Howard McGregor, The Brain of Primates; May 11, 1944 

K. S. Lashley, Neural Correlates of Intellect; April 30, 1945 

Warren S. McCulloch, Finality and Form in Nervous Activity; May 2, 1946 

S. R. Detwiler, Structure-Function Correlations in the Developing Nervous System 
as Studied by Experimental Methods; May 8, 1947 

Tilly Edinger, The Evolution of the Brain; May 20, 1948 

Donald O. Hebb, Evolution of Thought and Emotion; April 20, 1949 

Ward Campbell Halstead, Brain and Intelligence; April 26, 1950 

Harry F. Harlow, The Brain and Learned Behavior; May 10, 1951 

Clinton N. Woolsey, Sensory and Motor Systems of the Cerebral Cortex; May 7, 
1952 

Alfred S. Romer, Brain Evolution in the Light of Vertebrate History; May 21, 1953 

Horace W. Magoun, Regulatory Functions of the Brain Stem; May 5, 1954 



*Fred A. Mettler, Culture and the Structural Evolution of the Neural System; April 
21, 1955 

*Pinckney J. Harman, Pale one urologic, Neoneurologic, and Ontogenetic Aspects of 
Brain Phytogeny; April 26, 1956 

*Davenport Hooker, Evidence of Prenatal Function of the Central Nervous System in 
Man; April 25, 1957 

*David P. C. Lloyd, The Discrete and the Diffuse in Nervous Action; May 8, 1958 

*Charles R. Noback, Tfie Heritage of the Human Brain; May 6, 1959 

*Ernst Scharrer, Brain Function and the Evolution of Cerebral Vascularization; May 
26, 1960 

Paul I. Yakovlev, Brain, Body and Behavior. Stereodynamic Organization of the 
Brain and of the Motility -Experience in Man Envisaged as a Biological Action 
System; May 16, 1961 

H. K. Hartline, Principles of Neural Interaction in the Retina; May 29, 1962 

Harry Grundfest, Specialization and Evolution of Bioelectric Activity; May 28, 1963 

*Roger W. Sperry, Problems Outstanding in the Evolution of Brain Function; June 3, 
1964 

*Jose M. R. Delgado, Evolution of Physical Control of the Brain; May 6, 1965 

Seymour S. Kety, Adaptive Functions and the Biochemistry of the Brain; May 19, 
1966 

Dominick P. Purpura, Ontogenesis of Neuronal Organizations in the Mammalian 
Brain; May 25, 1967 

*Kenneth D. Roeder, Three Views of the Nervous System; April 2, 1968 

f Phillip V. Tobias, Some Aspects of the Fossil Evidence on the Evolution of the 
Hominid Brain; April 2, 1969 

*Karl H. Pribram, What Makes Man Human; April 23, 1970 

Walle J. H. Nauta, A New View of the Evolution of the Cerebral Cortex of 
Mammals; May 5, 1971 

David H. Hubel, Organization of the Monkey Visual Cortex; May 11, 1972 

Janos Szentagothai, The World of Nerve Nets; January 16, 1973 

* Ralph L. Holloway, The Role of Human Social Behavior in the Evolution of the 
Brain; May 1, 1973 

*Elliot S. Valenstein, Persistent Problems in the Physical Control of the Brain; May 
16, 1974 



*Published versions of these lectures can be obtained from The American Museum of 
Natural History, Central Park West at 79th St., New York, N.Y. 10024. 

fPublished version: The Brain in Hominid Evolution, New York: Columbia 
University Press, 1971. 



THE ROLE OF HUMAN SOCIAL BEHAVIOR 
IN THE EVOLUTION OF THE BRAIN 

INTRODUCTION 

The presentation of this lecture has particular significance for 
me because only slightly more than 11 or 12 years ago as a 
graduate student of human evolution I discovered with great 
excitement the existence of the James Arthur lectures; these 
surely decided my fate, at least in part. 

I wish to discuss some of the brain endocasts of our earliest 
fossil hominid ancestors and to show that the human brain has 
been around for quite a long time, perhaps three million 
years — or longer. This is somewhat of an about-face for me, for 
when I wrote my dissertation about 10 years ago, I regarded 
endocasts as so much rock or plaster, with little, if any, 
potential of offering evidence on the evolution of the hominid 
brain. I believe I have mellowed. Today endocasts are the 
subject of my major research effort. 

My questions about the human brain are: What lines of 
evidence can we use to learn about it; how did it evolve to its 
present state; can we find something in its evolution relevant for 
today's societal existence? 

Before I discuss these questions in detail, I wish to briefly 
consider my basic conclusions: 

1 . The usual orthodox version of hominid evolution places the 
evolution of the brain as a terminal phase, one that occurs 
after all other parts of the body, such as the hands, the trunk, 
the teeth, and the locomotory anatomy for bipedalism have 
evolved. This view is very oversimplified, if not downright 
incorrect, and approximates truth only if we are willing to 
equate brain evolution with brain enlargement. Indeed, the 
evidence shows that brain modification to a human pattern 
occurred early in human evolution, at least three million 
years ago. 

1 



2. Both brain endocasts and bodily skeletal parts suggest that 
brain :body relationships remained fairly constant during 
most of human evolution, indicating an important set of 
selection pressures for body-size increase. This evidence also 
suggests that brain encephalization, as measured by Stephan's 
(1972) "progression indices" (related to a "basal insectivore" 
line), was already within the human range in the early fossil 
hominids. The mediating factor for increase must have been 
an endocrine-target tissue adjustment resulting in selection 
for increased delays of maturation, or prolonged growth and 
dependency times, important factors in any consideration of 
social behavior. 

3. The humanly organized brain and resultant human cultural 
behavior have been interacting in a positive feedback manner 
during most of human evolution (Holloway, 1967). This 
feedback interaction is probably over, and unless some new 
radical genetic change occurs to interrupt man's present 
growth pattern, or a new social order that practices some 
form of genetic surgery comes into existence, I do not believe 
the human brain will show any further significant evolution 
in terms of size increase. 

4. Brain endocasts have enormous value in the study of human 
evolution that extends far beyond brain-behavior correla- 
tions. They can give us information about variation, popula- 
tion statistics, and brain :body ratios, and therefore have 
importance in relating early hominid populations to ecologi- 
cal parameters such as biomass and growth and development. 

5. Finally, we must realize that human behavior is not a recent 
achievement — our social behavior, our sociality has long evo- 
lutionary roots that cannot be abridged simply by cultural fiat. 

Abbreviations used in the text and figures are: 

ER, East Lake Rudolf 

HE, Indonesian Homo erectus 

MLD, Makapansgat, S. Africa 

OH, Olduvai Gorge 

OMO, Omo Valley, Ethiopia 

SK, Swartkrans 

STS, Sterkfontein 



LINES OF EVIDENCE 
DIRECT 

It lias long been appreciated that the only direct evidence for 
the study of brain evolution comes from the endocasts of our 
fossil ancestors (Edinger, 1929, 1949, 1964; Holloway, 1964, 
1966a; Radinsky, 1967, 1970). Whether they are natural 
endocasts of the South African australopithecines (e.g., Taung, 
STS 60, Type 3, and SK 1585) or prepared in the laboratory 
from latex, plaster of Paris, and plasticine, they give only the 
most limited information about neural structure and no direct 
information about behavior. An endocast is simply a mold of 
the inside bony table of the cranium. Between the bone and the 
underlying brain there are three meningeal tissues of varying 
thickness, as well as a variably distributed amount of cerebro- 
spinal fluid. The thick dura mater, the arachnoid space, the 
investing thin layer of pia mater, and the cerebrospinal fluid all 
"conspire" to eradicate the sulcal and gyral configurations 
imprinted by the surface of the cerebral cortex into the bony 
layer of the cranium. This "conspiracy" varies in different 
orders of animals; it is most severe, unfortunately, in the living 
and fossil species of apes and man. The reasons for this and the 
reasons for variation with age are not totally understood, but 
they are probably linked to differential growth rates of the 
brain and the overlying cranial bones in different regions (e.g., 
Hirschler, 1942; Keith, 1931). 

Endocasts can be obtained from fossil cranial fragments in 
two ways. Natural endocasts occur when the skull is filled by 
fine sediments drifting through the cranial foramina, particu- 
larly the foramen magnum. The sediments may be compacted 
and solidified by percolating mineral solutions, resulting, in 
time, in a solid mass of sedimentary rock inside the skull. The 
skull bones may eventually erode away leaving the endocast 
intact. Usually the skull is preserved around the endocast, as is 
sometimes the case with the South African australopithecines, 
such as the Taung specimen, STS 60, Type 3, and the more 



recent SK 1585 (figs. 1-8). In SK 1585 I deliberately removed 
the already eroded bones to disclose the fine-grained natural 
endocast (see Holloway, 1972a for details). 

Endocasts may also be made by applying liquid rubber latex 
to the inner cranial surface of a skull. This method has been 
used for most of the endocasts, including all the rest of the 
hominids from East Africa, Asia, and Europe. Successive layers 
are built up until a reasonable thickness, perhaps an eighth of an 
inch, is reached. The latex is cured by heat and then collapsed 
from the skull, either before or after stabilizing the dimensions 
with plaster. The external details of the cerebral cortex, as 
transmitted through the dura mater, will be reproduced on the 
surface of the latex. If the inner bony table is eroded before the 
endocasts are made, the details will obviously be missing. 



"V; 




Ti — G — I 



FIG. 1. Lateral view of Taung infant endocast and face positioned together. 
Arrow points to lambdoid suture, which is probably the most anterior extent of 
lunate sulcus. Scale equals 3 cm. 




h 



FIG. 2. Lateral view of Taung infant endocast. Arrow points to third inferior 
frontal convolution. Small portion of frontal lobe remains embedded in facial 
fragment. Scale equals 3 cm. 



INDIRECT 



Brains influence behavior, and occasionally the results of 
behavior become, so to speak, fossilized. Fortunately, the 
paleoanthropologist has lines of evidence for the evolution of 
the brain other than brains or endocasts. There are two sources 
of indirect evidence: (1) cultural products of brain and social 
behavioral activity, e.g., stone tools, shelters, animal remains at 
ancient butchering sites; and (2) skeletal components of the 
masticatory and locomotor systems. No indirect evidence can 
yet be used to demonstrate any specific changes in the brain 
observable at the surface. It is, however, indicative of different 
behavioral capabilities, which require, after all, neural com- 




FIG. 3. Occipital view of Taung infant endocast. Lambdoid suture is distinct. 
Notice gyral curvature (shown by dotted line and arrow) immediately superior and 
anterior to lambdoid suture, indicating that more forward placement of lunate sulcus 
would not be possible. Scale equals 3 cm. 



plexes to effect them. In other words, it supports the idea of 
brain reorganization. 

The first line of indirect evidence applies, as far as we know, 
only to hominids. There is no evidence from the fossil record of 
the cultural behavioral effects in other lines of primates. The 
second line of indirect evidence, that is, musculoskeletal, is far 
more general and applies to all lines of animals, most particu- 
larly to the mammals. But what we see in the hominid fossils is 
rather specific, at least when compared with other fossil 
primates, or extant ones, for that matter. The earliest hominids 
show definite changes in masticatory apparatus — in the teeth, 
jaws, and areas of muscle attachment for the temporalis and 




FIG. 4. Lateral view of plaster replica of SK 1585, endocast from Swartkrans, 
South Africa. A small portion of frontal lobe is missing. Lambdoid suture obscures 
posterior limit of lunate sulcus. (See Holloway, 1972a.) Scale equals 3 cm. 



masseter in particular. We find changes in the molars as far back 
as 10 to 14 million years ago in Ramapithecus (Pilbeam, 1969; 
Simons, 1961, 1964, 1969). Among the early hominids of East 
and South Africa there are changes in nuchal musculature 
related in part to advanced degrees of bipedal locomotion, 
which itself is corroborated by the remains of the locomotor 
skeleton (pelvis, lower vertebral column, limb bones such as the 
femur, tibia and fibula, and various bones of the foot). Even the 
hand bones, at least of the East African hominids, show changes 
in musculoskeletal structure suggestive of manipulative abilities 
greater than those of any fossil or living ape or monkey. 

Why belabor these points? Because they show, whether or 
not the precentral gyrus appears on the surface of the endocast, 




FIG. 5. Occipital view of plaster replica of SK 1585 endocast. Scale equals 3 cm. 

that natural selection has long been operating on behavior, 
favoring neural organizations capable of servicing the new 
musculoskeletal complexes. 

This line of indirect evidence for brain reorganization need 
not be related only to motor or sensorimotor behavior, such as 
the various muscle contractions involved in bipedalism, but it 
must be taken to involve the whole adaptive complex (hunting, 
scavenging, carrying objects, and so on) in which these motor 
patterns are embedded and to include aspects of psychological 
restructuring as well. It is true that there is yet no way of 
comparing a gorilla endocast to that of an australopithecine or a 



8 




FIG. 6. Basal view of plaster replica of SK 1585 endocast. Scale equals 3 cm. 

Homo sapiens to show correlated changes between brain surface 
features and motor behavior. Endocasts may or may not reflect 
important adaptive changes in behavior and structure, but by 
themselves they cannot indicate whether the brain evolved 
before or after the sensorimotor changes. 

THE EVIDENCE 

Evidence from which I conclude that the brain has always 
been an important component of human evolution is as follows: 

1. Gross Morphology: Hominid endocasts show a human 
shape that is not found among a sample of 50 chimpanzee and 
gorilla endocasts. Although there can be considerable variation 
in endocasts of living pongids (figs. 9-16), none shows the 
combination of features seen on hominid endocasts. The 
differences are as follows: 
a. The height of the brain above the cerebellar lobes is almost 

always greater in hominid brains. Occasionally the brain of 



9 




FIG. 7. Dorsal view of Type 3 endocast, a gracile australopithecine from 
Sterkfontein. Note double-valleyed fracture in parietal lobe, squared-off shape of 
frontal lobe, and suggestion of heavy gyral and sulcal relief. (See Schepers, 1946.) 
Scale equals 3 cm. 



the pygmy chimpanzee, Pan paniscus, shows less flattening in 
height than that of either the gorilla or the chimpanzee (Pan 
troglodytes sp.) but it is not so high as that of the early 
australopithecines (table 1). 
b. The anterior tips, or poles, of the temporal lobes are 



10 




FIG. 8. Dorsal view of endocast of STS 60 from Sterkfontein. Scale equals 3 cm. 

distinctly more rounded and larger in hominids than in 
pongids (part of this is, of course, due to the different shape 
of the greater wing of the sphenoid and the dural sheath 
surrounding the tip of the lobe). 

c. The orbital surface of the frontal lobe is generally angled 
upward, with a more pointed and pronounced beak in pongid 
than in hominid brain casts. 

d. In pongid endocasts the position of the famous "lunate" or 
"simian" sulcus, which divides the primary visual cortex from 
the so-called parietal "association" cortex, is usually in a 
fairly anterior position (although less so than in cerco- 
pithecoids). Although only a few hominid endocasts [particu- 
larly the original Taung (1924) endocast] show the sulcus 



11 



clearly, it is definitely in a posterior, human-like position 
(figs. 3, 5). It is probably this feature, more than any other, 
that so firmly suggests cortical reorganization to a human 
pattern. This observation was first noted by Dart (1925), 
later by Schepers (1946), and was more or less verified by Sir 
Wilfred LeGros Clark (1947); a close examination shows no 
alternative position. 

e. The inferior border of the temporal lobe also shows 
enlargement, reflected in a smaller, or more acute, angle of 
the petrosal cleft. 

Taken together, these features form a Gestalt that is very 
difficult to demonstrate by linear measurements, as many 
physical anthropologists would wish. It is these 'Gestalten' 
that enable one to distinguish between pongid endocasts, 
such as between those of chimpanzees and gorillas, even 
though most measurements and indices tend to overlap. 

f. Finally, it is possible that there is more sulcal and gyral 
development in hominid cortices, particularly on the frontal 
lobe, than in pongid cortices; however, this is not easily 
measured on endocasts and is at best an impressionistic 
judgment. 

2. Gross Size: This parameter (or to follow Jerison, 1973, 
"statistic") is perhaps the crudest of all. The small absolute sizes 
of the australopithecine endocasts tended to deny them 
hominid status long after their discovery. Elsewhere I (Hollo- 
way, 1964, 1966a, 1968, 1970, 1972b) have detailed my 
observations on the signficance of this measurement of the 
brain. Some chimpanzees and most gorillas have larger brains 
than the early hominids (see, for example, Tobias's 1971 
compilations). The range of variation in normal present-day 
Homo sapiens is from about 1000 to 2200 cc, or about as 
much as the total evolutionary gain from Australopithecus 
africanus, at ca. 450 cc, to the average value of modern Homo 
sapiens of about 1400 cc. Yet there has never been any 
demonstration, among living populations, of a relationship 
between brain size (measured either by weight or volume) and 
behavior. Although some human microcephalics have brain 

12 




FIG. 9. Lateral views of rubber latex endocasts of (top) Pan paniscus, pygmy 
chimpanzee, (middle) Pan troglodytes, and (bottom) Gorilla gorilla. (Rubber latex 
endocasts made by author from specimens belonging to the American Museum of 
Natural History.) (See figs. 10 and 11 for occipital and dorsal views of same 
specimens.) Scale equals 3 cm. 



13 




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FIG. 13. Dorsal view of endocast of different, or another Pan troglodytes 
showing excellent gyral and sulcal markings. Arrows indicate anterior limit of lunate 
sulcus. (Rubber latex endocast made by author from a specimen at the American 
Museum of Natural History.) Scale equals 3 cm. 



volumes that gorillas, and perhaps a few large chimpanzees, 
might disdain, they do not exhibit simian behavior, but rather 
show the species-specific ability for symbolic language, albeit 
disadvantaged. 

The usefulness of this crude measure of the brain lies in its 
statistical utilization as a parameter from which other neural 
measures, such as neuron size, glial/neuron ratio, neural density, 
and dendritic branching may be calculated. All of these 
variables are closely tied in with behavioral variation, although 
it remains for future scientists to demonstrate this unambigu- 
ously (see Holloway, 1964, 1966a, 1966b, 1968; Jerison, 
1973). 

17 




FIG. 14. Endocast of modern Homo sapiens, lateral view. Note great height of 
cortex above cerebellum, expansion of temporal lobe in anterior and posterolateral 
margins, and slight slope of orbital surface on frontal lobe. (Rubber latex endocast 
made by author from specimen belonging to Columbia University.) Scale equals 3 cm. 

Gross brain size is also related to body mass and time, and 
thus it can be used in combination with these other variables to 
give us clues about changes in growth rates during evolution in 
particular phyletic lines. The study of brain -.body allometric 
relationships in different animal lines has had a long history and 
is a subject that is receiving considerable attention by modern 
scientists (see, for example, Jerison, 1973). So far, however, 
most of these studies have been concerned with comparisons 
between high-level taxa, such as between carnivores and 
herbivores, reptiles and birds, pongids and modern man. But if 
brain and body size can be measured with reasonable accuracy 
within a phyletic line, such as the Hominidae, the changes in 
allometric relationships with time can provide extremely im- 



18 




FIG. 15. Same specimen as figure 14, occipital view. Scale equals 3 cm. 

portant clues to selection pressures operating on variables such 
as growth rates of different parts of the body, encephalization, 
postnatal growth, and so on, which obviously have important 
biological relationships with social behavior and adaptation. In 
other words, another significant use of gross brain size, beyond 
that of simply indicating overall size increase, is as a key to 
other relationships that may have been more concerned with 
selection pressures. 

Unfortunately our samples for various hominid lineages are 
terribly small, and many specimens (e.g., the South African 
hominids) are not firmly dated; it is thus impossible to plot 
brain size against time in any accurate manner. If we could, the 
rates might give us some interesting clues to past selection 



19 




FIG. 16. Same specimen as figure 14, basal view. Scale equals 3 cm. 

pressures and dynamics (see Holloway, 1972b). Table 2 gives a 
number of newly determined endocranial capacities for various 
hominids. The methods used to arrive at these figures are given 
in the footnotes to this table. 

3. Relative Brain Size and Encephalization: There appears 
to be a lawful relationship between brain and body size in all 
vertebrate taxa (see Jerison, 1973, for a thorough review of this 
relationship). In general, following the principle of allometry, 
larger-bodied animals tend to have a proportionally smaller brain 
weight. It is possible to plot the size of the brain against the 
weight of the body on double-logarithmic graph paper and to 
discern some reasonably straight-line relationships. Regression 
lines are of the general form E = kP^, where E = brain weight, 
P = body weight, y = an exponent probably reflecting the 



20 



relationship between volume and surface area, and k = a 
constant, often taken to reflect "encephalization," or the 

relationship between brain :body weight ratios in different 
animals. Plotting different orders of vertebrates on the same 
graph tends to give an exponent of 0.66; for elosely related 
species the exponent usually falls between 0.20 and 0.30. 
Within the speeies, however, there seldom appears a relation- 
ship, but this is probably debatable. 1 The human brain is neither 
the smallest nor the largest in terms of relative size. Table 3 
gives a few examples of animals with large and small relative 
brain weights. This table does not show, however, the range of 
variation within each category for brain: body weight ratios, for 
which few published data exist. 

Using a large number of "basal" insectivores (representing the 
sort of primitive stock out of which the primates may have 
evolved), Stephan (1972) was able to construct a "basal" 
insectivore line, defined as log 10 h = 1.632 + 0.63 log 10 k. By 
substituting a primate's body weight in the equation (k), it is 
possible to solve for "h," which gives the expected brain weight 
of a "basal" insectivore with such a body weight. If this weight 
is then divided into the actual brain weight of the particular 
primate, an "index of progression," or measure of encephaliza- 
tion, results (table 4 shows a number of "progression indices" 
for different primates, including some fossil hominids). This last 
step requires making a hazardous assumption about the body 
weight of the fossil hominid. Nevertheless, allowing for maximal 
and minimal body weight, the South African gracile australopi- 
thecines fit either within the range for modern man or just 
below it, but always above the pongid range. This is indirect 
evidence for reorganization of these early hominid brains to a 

'Very little secure data exist for large samples of healthy individuals, which 
requires study by more sophisticated statistical methods, such as partial correlations. 
To date no such study has been published, not even in the excellent article by 
Pakkenberg and Voigt (1964) on the Danes. I give this warning because a preliminary 
analysis of a partial correlational study between the variables of age, weight, body 
height, and brain weight suggests more of a relationship between brain and body 
weight than is usually recognized. I hope to publish these results in the near future, 
thanks to the courtesy of Dr. Pakkenberg, who has given me the original data. 

21 



human pattern, but it does not tell us whether there is a general 
allometric increase in overall size or whether there has been 
differential development of particular elements of the brain. 

Still, these data are more relevant for understanding evolu- 
tionary change than are mere comparisons of gross brain size. It 
is a great pity that we do not as yet have a way to determine 
accurately the body weights of our hominid ancestors. If we did, 
we could plot these for particular lineages and, possibly, relate 
the resulting exponents to evolutionary selection pressures. 

Figure 17 and table 5 show a range of possible brain:body 
weight relationships, based on current estimates of hominid 
body weights (Tobias, 1967; Lovejoy and Heiple, 1970) that 
might have characterized stages of hominid evolution. Inter- 
pretation of selection pressures for increasing brain size varies, 
depending on whether the exponents linking the fossil hominid 
lineages are > 1.0, 1.0, 0.66, or less. The exponent 0.66 
characterizes most nonhominid mammals (Jerison, 1973), 

TABLE 1 

Some Crude Indices for Hominid Endocasts a 





Volume in 


Dare 


Dare 


L 


H 3 


Specimen 


Milliliters 


Larc 


L 


H 


V 


Taung 


404 


1.13 


1.48 


1.41 


1.41 


STS60 


428 


1.00 


1.35 


1.40 


1.29 


STS5 


485 


1.08 


1.39 


1.42 


1.27 


OH 5 


5 30 


1.47 


1.37 


1.45 


1.20 


SK 1585 


530 


1.73 


1.42 


1.43 


1.37 


ER732 


506 


1.06 


1.42 


1.48 


1.13 


OH 24 


590 


1.01 


1.29 


1.40 


1.32 


OH 13 


650 


1.17 


1.49 


1.48 


1.16 


OH 9 


1067 


1.05 


1.31 


1.55 


1.18 


OH 12 


727 


1.11 


1.41 


1.60 


0.97 


HE I 6 


943 


1.10 


1.33 


1.59 


1.02 


HE II 6 


815 


1.06 


1.35 


1.53 


1.08 


HE IV 6 


900 


1.00 


1.31 


1.64 


0.94 


HE VI 6 


855 


1.05 


1.33 


1.68 


0.97 


HEVII & 


1059 


1.07 


1.4! 


1.65 


0.92 


HE VIII 6 


1004 


0.98 


1.25 


1.61 


1.00 


ER 1470 c 


770 


1.04 


1.37 


1.36 


1.30 


Omo 338s 


427 


1.02 


1.37 


1.54 


1.03 



22 



TABLE ! - (Continued) 





Volume m 


I) arc 


1) arc 


L 


H 3 


Specimen 


Milliliters 


L arc 


L 


11 


V 


Pan paniscus 












<n = 8) 












average 


325 


0.99 


1.33 


1.46 


1.04 


range 


284-363 


0.97-1.01 


1.28-1.37 


1.36-1.54 


0.86-1.21 


Pan troglodytes 












(n = 29) 












average 


394 


0.96 


1.28 


1.47 


1.09 


range 


334474 


0.88-1.01 


1.20-1.34 


1.39-1.59 


0.95-1.23 


Gorilla gorilla 












(n= 36) 












average 


498 


0.98 


1.26 


1.53 


1.04 


range 


383-625 


0.94-1.04 


1.19-1.33 


1.39-1.67 


0.85-1.24 


Homo sapiens 












(n = 4) 












average 


1442 


1.10 


1.43 


1.40 


1.25 


range 


1324-1586 


1.04-1.14 


1.39-1.46 


1.35-1.46 


1.11-1.42 



Symbols: D arc = dorsal measurement between frontal and occipital poles; L arc = 
lateral measurement between frontal and occipital poles; L = chord length between 
frontal and occipital poles; H = chord length from vertex to lowest plane of temporal 
lobe; V = volume. 

a These figures clearly show that most hominid fossils (Homo erectus excepted) have 
a greater degree of cortical height relative to both length and volume than do the 
African pongids tested. 

ft The well-known platycephalyof the Indonesian H. erectus is clearly shown by the 
L/H value, the low D arc/L arc, D aic/L and H 3 /V ratios. 

c This specimen does not show a typical H. erectus pattern. 

"basal insectivores," and most lower primates (Stephan, 1972). 
This exponent suggests an allometric increase, where brain 
weight increases at a smaller rate than body weight. An 
exponent of approximately 1.0 indicates a constant brain :body 
weight ratio, suggesting selection pressure for brain weight to 
match body weight. An exponent greater than 1 .0 suggests selec- 
tion pressures for brain weight greater than that for body weight. 1 

'Of course, an exponent of 1.0 in hominids does mean an increase in brain size 
when compared with either a "basal" insectivore or vertebrate line where the 
exponent is about 0.66. 

23 



TABLE 2 
Endocranial Volumes of Reconstructed Hominid Specimens 









Endocranial 












Volume in 






Specimen 


Taxon 


Region 


Milliliters 


Method 


Evaluation 


Taung 


A. africanus 


South Africa 


440 c 


A 


1 


STS 60 


A. africanus 


South Africa 


428 


A 


1 


STS71 


A . africanus 


South Africa 


428 


C 


2-3 


STS 19/58 


A . africanus 


South Africa 


436 


B 


2 


STS 5 


A. africanus 


South Africa 


485 


A 


1 


MLD 37/38 


A. africanus 


South Africa 


435 


D 


1 


MLD 1 


? 


South Africa 


500±20 


B 


3 


SK 1585 


A . robustus 


South Africa 


530 


A 


1 


OH 5 


A . robustus 


East Africa 


530 


A 


1 


OH 7 


H. habilis 


East Africa 


687 


B 


2 


OH 13 


H. habilis 


East Africa 


650 


C 


2 


OH 24 


H. habilis 


East Africa 


590 rf 


A 


2-3 


OH 9 


H. erectus 


East Africa 


1067 


A 


1 


OH 12 


H. erectus (?) 


East Africa 


727 


C 


2-3 


ER406 


A . robustus 


East Africa 


510±10 


D 


2 


ER732 


A . robustus 


East Africa 


500 


A 


1 


ER 1470 


H. sp.? 


East Africa 


770 e 


A 


1 


HE1 


H. erectus 


Indonesia 


953^ 


A 


1 


HE 2 


H. erectus 


Indonesia 


815-f 


A 


1 


HE 4 


H. erectus 


Indonesia 


90(/ 


C 


2-3 


HE 6 (1963) 


H. erectus 


Indonesia 


855^ 


A 


2 


HE 7 (1965) 


H. erectus 


Indonesia 


1059-f 


C 


1-2 


HE 8 (1969) 


H. erectus 


Indonesia 


1004/ 


A 


1 



a A, direct water displacement of either a full or hemiendocast with minimal 
distortion and plasticine reconstruction; B, partial endocast determination, as 
described by Tobias (1967, 1971); C, extensive plasticine reconstruction, amounting 
to half the total endocast; D, determination based on the formula V = f Vz (LWB + 
LWH), described by MacKinnon et al. (1956), where L = maximum length, W = 
width, B = length, bregma to posterior limit of cerebellum, H = vertex to deepest part 
of temporal lobe and f appears to be a taxon specific coefficient. 

ft An evaluation of 1 indicates the highest reliability, 3, the lowest. 

Postulated for adult-the value of the actual specimen is 404 ml. 
Possible overestimate. 

Provisional estimate. 

■^These values are as yet unpublished and should be regarded as provisional. 



At the present stage of our knowledge, it is premature to go 
beyond this kind of simple exercise. Our samples are extremely 



24 



small, we have no good empirical evidence for any early 
hominid body weight and the values in figure 17 connect 
lineages that are geographically separated (i.e., the South 
African gracile Australopithecus with the East African Ilahilis 
with the East Asian Homo erectus with modern Homo sapiens). 
Nevertheless, these relationships between brain and body weight 
hold great promise for better understanding the dynamics of 
hominid evolution. Indeed, as is clear from figure 17, one can 
draw the lines in different ways, with constant slopes (i.e., 1.0) 
or with different slopes at different times. (See also Holloway, 
1974a.) The implications are extremely important, even though 
the basic data are admittedly weak, for the lines in figure 16 
demonstrate that a number of alternative hypotheses about 
hominid brain evolution can exist, and that any particular 
hypothesis is based on assumptions of body weight that cannot 
be empirically pinpointed. In any event they do show a human, 
rather than a pongid, pattern in terms of relative brain size and 
changes through time, which strongly suggests that hominid 
brain size increase and attending selection pressures were 
probably unique. 

TABLE 3 

Some Average Brain:Body Ratios for Various Animals 

Brain :body 
weight ratio 



Homo sapiens b 

Gorilla 

Chimpanzee 

Macaque, Rhesus 

Marmoset 

Squirrel monkey 

Elephant 

Whale 

Porpoise 



45 

200 

185 

170 

19 

12 

600 

10,000 

38 



"From Cobb, 1965. 

"Good tabulated data on ranges for healthy human adults is lacking. The excep- 
tion is one study on Danes by Pakkenberg and Voigt, 1964, p. 297, in which normal 
brain:body weight ratios are shown to vary from approximately 1:28 to 1:80. 



25 



TABLE 4 
Some Possible Brain Size: Body Weight Ratio and "Progression Indices" 









Brain : 


"Progression 




Average Brain 


Assumed Body 


Body 


Index" 


Specimen 


Size (ml.) 


Weight (Pounds) 


Ratio 


PRG/BG 


Gracile australopithecine 


442 


40 


1:41 


21.4 






50 


1 


62 


18.7 






60 


1 


51 


16.9 


Robust australopithecine 


530 


50 


1 


43 


22.3 






60 


1 


51 


19.9 






75 


1 


64 


16.9 






110 


1 


94 


12.8 


Homo sapiens 


1361 


150 


1 


45 


28.8 


Homo erect us 


930 


92 


1 


45 


26.6 






125 


1 


61 


22.0 



"Based on Stephan's, 1972, formula using a basal insectivore line (see text). 

Note: Maximum PRG/BG for gorilla is about 7.0, and for the chimpanzee, about 
12.0. See Stephan, 1972, for ranges. 

Maximum body weight of average gracile australopithecine (442 ml.) with 
PRG/BG of 12, is 100 pounds. That is, if we allow the "progression index" of 
Australopithecus to be the maximum chimpanzee value, the body weight is calculated 
to be 100 pounds, which is clearly too heavy, based on the postcranial materials we 
have thus far discovered for the gracile form of Australopithecus. 

4. Lateralization and Cerebral Hemispheric Dominance: 
Comparative neuroanatomy has not been able to demon- 
strate any definite difference between the human brain and 
the ape brain except on the basis of size. Absolute and relative 
brain sizes, plus quantitative differences in amount of cerebral 
cortex in certain lobes, such as the parietal and temporal, are all 
that have been defined. These are matters of continuity, as far 
as can be established at present. The cortico-cortical fasciculus 
occipito-frontalis, a long associational tract known to exist in 
the human brain, has not been distinguished in the chimpanzee 
or cercopithecoid brain (Bailey et al., 1943). This does not 
mean that an associational system does not exist between the 
posterior and frontal segments of the chimpanzee cortex, but 
only that it is probably not so developed as it is in Homo 
sapiens. Many more pongid specimens should be dissected 
before its presence or absence can be proved. 

26 



TABLE 5 

Brain:Body Weight Double-Log Relationships Based on the General F-ormula h = bk x , 

with Possible Slope Differences Depending on Brain and Body Weights Used 17 





Brain Volume 




Body Weight 






Specimen 


(ml.) 




(pounds) 




Slope 


A ustralopithecus 


450 


40 


50 


60 


1.0 


H. erectus 


930 


83 


103 


123 


1.0 


H. sapiens 


1361 


123 


150 


180 




Australopithecus 


450 


40 


50 


60 


0.6 


H. erectus 


930 


115 


143 


180 


0.6 


H. sapiens 


1361 


200 


200 


250 




Australopithecus 


450 


85-86 


- 


- 


1.92 


H. erectus 


930 


123 


- 


- 


1.92 


H. sapiens 


1361 


150 


- 


- 




A . africanus 


450 


50 


- 


- 


1.0 


H. habilis 


775 


86 


— 


— 


0.6 


H. erectus 


930 


114 


— 


— 


1.75 


H. sapiens 


1361 


140 


- 


- 





a Brain weights are held constant, the slopes varied and the resulting body weights 
determined by projection to the abscissa! axis, which is the body weight. 



The most singular difference known to exist at present is that 
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hemisphere seems dominant, in terms of language phenomenon, 
in the inferior parietal lobe (Wernicke's area), in the gyri and 
sulci of Heschl and in the third inferior frontal convolution, 
often known as Broca's area. The right hemisphere, particularly 
the parietal lobe, seems "dominant" for spatiotemporal and 



27 









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29 



visual integration. These attributes have long been discussed in 
the literature, but they have never been demonstrated by gross 
measurements, either on the brain or on endocasts of modern 
Homo sapiens. However, Geschwind and Levitsky (1968) have 
shown that when the temporal and parietal lobes are cut away, 
the left side shows strikingly enlarged convolutions, the gyri of 
Heschl, underneath. Astakhova and Karacheva (1970) have 
shown that differences between left and right hemispheres are 
present before birth. It is not possible to go into all the 
functional details, but they can be taken as a species-specific 
attribute of human brain structure, and by extension, of 
behavior. 

Do the fossil hominid endocasis show such differences? 
Unfortunately the endocasts of the South and East African 
australopithecines are seldom bilaterally complete, which pre- 
cludes any direct measurements. Gross measurements, such as 
lengths, arcs, breadths and heights, do not demonstrate any 
consistent asymmetries on complete endocasts. LeMay and 
Culebras (1972) have suggested that the Neanderthal brain cast 
from La Chapelle-aux-Saints shows laterality, but this depends 
on how carefully the Sylvian fissure is defined in its posterior 
course, a feature generally impossible to observe on most 
endocasts. 1 LeMay and Culebras's angioradiography of living 
humans does, however, show consistent left-right differences, 
but until a more accurate and sensitive method to measure 
endocasts of fossil hominids is found cerebral dominance in 
fossils cannot be proved. I am currently working on some of the 
newer Homo erectus fossils from Indonesia, on the basis of 
which a case may be made for cerebral dominance, but it is too 
early to be certain. The presence of stone tools, of primitive, 
but nevertheless standard patterns, at least 2.6 to 3.0 million 
years old, is suggestive of both lateralization and of primitive 
communication by a language based on symbols (Holloway, 
1969). 



'I have not been able to see this fissure clearly on any fossil hominid endocasts I 
have examined. 



30 



SUMMARY OF DIRECT AND INDIRECT EVIDENCE 

In summary, we find among the early australopithecine 
examples fairly clear-cut evidence for human, rather than ape- 
like, brain organization. This is based on the following evidence: 

1. The endocasts show a more human shape, particularly in 
the posterior migration of the lunate sulcus, which separates the 
primary visual cortex from the parietal association cortex, 
signifying an expanded associational cortical zone. The tem- 
poral lobe, so often implicated in memory mechanisms, is 
expanded in the anterior pole and in the inferior posterior 
region. The orbital rostrum is very unlike that of the apes, and 
there is a suggestion of an enlargement in the third inferior 
frontal convolution, the so-called Broca's area, which is involved 
in motor control of speech. 

2. Indirectly, the locomotor, manipulatory, dental, and total 
skeletal evidence indicates a human musculoskeletal orga- 
nization that presumably required neural reorganization to 
operate in human behavior patterns. 

3. The faunal associations suggest an adaptation based on 
scavenging and/or hunting for animal protein. The stone tools 
known from this early period are made to standard patterns. 
Both the faunal associations and stone tools are indications of 
human behavior requiring reorganization at almost all levels of 
the brain (Holloway, 1970), from sensorimotor integration and 
finesse, through set and attention variables, to memory (the 
organization of experience and the storage, recall and reconsti- 
tution of elements). 

4. Tentative brain :body ratios and encephalization indices 
support (but do not prove) a human brain organization. 

THE STAGES OF HOMINID BRAIN EVOLUTION: 
A POINT OF VIEW 

So far I have discussed both direct and indirect evidence to 
support the suggestion that the human brain had an early 
beginning regardless of its absolute size. All I have said thus far 
applies to endocasts, and thus to the brains of the early 

31 



hominids. Brains evolve in both material and social contexts. It 
is my contention that human social behavior has very old roots, 
not only in the sense that we have evolved from some primitive 
apelike lineage, but in the sense that human social behavioral 
evolution occurred early and was the major stimulus for further 
evolution since the time of the australopithecines. I would like 
to try to put together the story of the reorganization of the 
hominid brain, its great increase in size and the evolution of 
human behavior in a synthesis that avoids some of the simplistic 
one-to-one linear relationships that physical anthropologists are 
prone to make, such as that tools made the brain evolve or that 
tools replaced the canines. 

In this section I wish to return to the original questions: How 
did the human brain evolve to its present state? How can we 
interpret the large increase in brain size from Australopithecus 
to modern Homo sapiens^. 

It is apparent that part of this increase must be related to 
increase in body size. Exactly how much is difficult to say, 
since it depends on which animal body and brain weights we 
compare with man and how we regard "extra" or "vital" 
neurons (Jerison, 1963, 1973). Taking the average human brain 
weight as 1450 grams and the average body weight as 150 
pounds, the following different calculations can be made: (1) 
Using Jerison's (1973, p. 44) equation of E = 0.07 P 2/3 
(E = brain weight, P = body weight) for higher vertebrates, we 
get an expected brain weight of 108 grams for Homo sapiens, 
leaving 1342 grams as "extra" (not related to body weight); (2) 
If we use Stephan's (1972) equation for "basal insectivores," 
the expected brain weight is 475 grams, leaving 975 grams as 
"extra"; (3) Jerison's (1973, p. 391) equation of E = 0.12 P 2/3 
for higher primates gives an expected brain weight of 223 
grams, leaving 1227 grams as "extra." 1 Both Jerison equations 



'I am using "extra" purely in the operational sense that it exceeds a weight based 
on a log-log regression with an exponent of roughly 0.6. I do not believe that any 
neural elements, are in any other sense "extra," whether in terms of weight or 
numbers of neurons. The so-called extras are part and parcel of the animal's adaptive 
behavioral repertoire! 

32 



leave us with the same degree of encephalization as the dolphin. 

Obviously these figures leave much to be desired, as the 
formulas are based on regressions relating only to living species. 
We would need to know the regressions for our fossil ancestors 
(Ramapithecus, Australopithecus, Homo erectus, etc.) to know 
what the increase in brain weight relative to body weight has 
been. If we use the mean of 442 cc. for the brain weight of the 
gracile australopithecines and 45 to 50 pounds as body weight, 
the braimbody weight ratio is about 1:45, roughly the same as 
modern Homo sapiens. If this ratio remains constant, i.e., at an 
exponent of 1.0, then none of the increase (ca. 1000 ml.) is 
"extra," at least in terms of the hominid regression equation. 

As can be seen, the figures can be used in various ways. It is 
all the more curious, then, that, contrary to most opinions 
(Jerison, 1963, 1973), the present data on neuron numbers in 
the primate cerebral cortex (see, for example, Shariff, 1953) do 
not indicate that the increase in brain size in Homo sapiens is 
primarily a result of hyperplasia, or the addition of large 
numbers of neurons. From Shariff s (1953) data, modern man 
seems to have about 1.25 times as many neurons as a healthy 
chimpanzee. Jerison's (1963, 1973) calculated "extra" cortical 
neurons are at total variance with Shariff s data, the only 
empirical evidence existing for primates. According to Jerison 
(1963), Homo sapiens has 2.2 times as many cortical neurons as 
a chimpanzee, yet his equations for "extra" neurons are derived 
from Shariffs empirical histological counts (see Holloway, 
1966a, 1974a, for a further critique). 1 

From limited neuropathological data, there is a suggestion 
that healthy chimpanzees and gorillas might have fewer mature 
functioning cortical neurons than human microcephalics (Hollo- 
way, 1964, 1968; Lenneberg, 1964, 1967). The behavioral 
repertoire of microcephalics is certainly limited, but many of 



'This preoccupation on mass can also be found in Count (1973), who transformed 
neuron numbers from base 10 to 2; i.e., humans have 2" neurons, while chimpanzees 
have 2 31 neurons. Count suggested that thus only two mitotic divisions separates the 
chimpanzee from the human brain. I strongly disagree with this interpretation. 



33 



them can use language, and their behavior is hardly simian. This 
further suggests some basic reorganization of the brain. 

Most scientists agree that the major increase in brain size is 
most likely related to hypertrophy, or increase in size, of the 
elements. The cortical neurons are generally large in man, there 
is a reduction in their density and an increase in both dendritic 
branching of the receptive processes of the neurons and in the 
number of neuroglial cells supporting the neurons. Thus, one 
important aspect of the large increase in brain size seems 
attributable to the reorganization of numerous component 
structures. That is why I believe comparisons based on cranial 
capacities alone are meaningless. One cc. of chimp or australo- 
pithecine cortex is not equivalent to one cc. of modern human, 
Neanderthal or Homo erectus cortex. It is changes in the spatial 
relationships between elements that provide our great neural 
complexity, for these result in an enormous number of synaptic 
contacts, or switching points (Holloway, 1964, 1966b, 1967, 
1968). 

The great increase in brain size can best be related, I believe, 
to a matrix of interacting variables of neural and behavioral 
complexity during the Pliocene and Pleistocene epochs that had 
an essentially positive feedback structure (see Holloway, 1967). 
The matrix involved a change in endocrine-target tissue inter- 
action, an increased postnatal dependence of offspring on 
parents, delayed maturation and the growing role of social 
programming on the brain. This interpretation is based on (1) 
observations regarding the effects of hormonal manipulations 
on such brain parameters as average cortical neuron size, neuron 
density, dendritic branching, glial/neural ratios, and cortically- 
mediated behavior; (2) phylogenetic and ontogenetic changes in 
cortical histology; and (3) the effects of enriched and deprived 
environments on cortical neuron histology. I (Holloway, 1964, 
1968) have reviewed this elsewhere and will not repeat the 
discussion here. The basic concordance in mammals between 
phylogenetic and ontogenetic development and extra environ- 
mental training on the one hand, and neurological changes- 
decreased neuron density, increased dendritic branching and 

34 



increased glial/ncural ratios in animals treated with growth 
hormone or thyroxin on the other, is illustrated in table 6. The 
table suggests a concordant picture of increase in brain 
complexity and cortically-mediated adaptive behavior. Thy- 
roidectomy and sensory deprivation, however, produce opposite 
results. 

TABLE 6 

Concordances of Different Lines of Evidence and Various Neural Parameters" 









Neural Parameters 














Cortically- 




Average 




Glial: 


Amount of 


Mediatcd 




Size of 


Neuron 


Neural 


Dendritic 


Adaptive 


Type of Evidence 


Neurons 


Density 


Ratio 


Branching 


Behavior 


Ontogenetic (growth) 


+ 


- 


+ 


+ 


+ 


Phylogcnetic 


+ 


- 


+ 


+? 


+ 


(within primates, 












related to brain size) 












Physiological manipulation 












1. throidectomy 


- 


+ 


_? 


- 


- 


2. administration 


+ 


- 


+ 


+ 


+ 


of thyroxin 












3. growth hormone 


+ 


- 


+ 


+ 


+ 


Environmental manipulation 












1. Sensory 


- 


+ 


- 


- 


- 


deprivation 












2. Environmental 


+ 


- 


+ 


+ 


+ 


complexity and 












training augmented 












(rats) (ECT vs. IC) 6 













a As the size of the neuron increases, so does its perikarya and cytoplasm, thereby 
requiring more neuroglial cells to service its metabolic needs. The additional size 
means reducing neural density, i.e., the number of neural nuclei in a standard size 
cube of cortical tissue. They are thus packed together less tightly. The increased 
neuron size also provides more cytoplasmic material for dendritic and axonal 
processes. Notice particularly that the hormonal evidence (all of it in vivo) matches 
the ontogenetic, phylogenetic, and environmental lines of evidence. 

''See Holloway, 1966a, and Rosenzweig, 1972, for details. 

Anthropological interpretations of the increase in brain size 
generally attempt to relate the increase in cranial capacity 
essentially to single aspects of evidence, such as tool-making, 



35 



hunting, language, etc. As the fossil hominids show an increase 
in endocranial volume, the archaeological record shows a 
concomitant increase in the range and sophistication of stone 
tool assemblages and in the size and kinds of animals hunted. A 
statistical correlation does not, of course, necessarily mean a 
causal connection. I find it very difficult, if not impossible, to 
draw a causal connection between brain size and stone tools or 
hunting habits. These must surely tie in more with social 
programming or learning than with an increase in neural 
elements. 

It would be a great oversimplification, if not a mistake, to 
relate cranial capacity in any linear or causal sense to the 
increasing complexity of stone tools during the Pleistocene. 
Early hominids accomplished more than simply making stone 
tools for future archaeologists' digs. Their tools were used in a 
variety of different environments, and their cooperative social 
behavior was an important part of adaptation to a hunting and 
gathering existence. Hunting and associated activities require a 
complex organization involving not only perceptual and motor 
skills, but an understanding of animals and their habits, plants, 
terrain, spoor, tracks, anatomy, butchering techniques, and 
perhaps storage. It is the total range of cultural adaptations that 
relates to brain increase; the making of stone tools is only one 
example, and of course, the most permanently recorded one. 

To the extent that the hunting of large animals involved 
cooperative enterprise, selection would certainly have favored 
behavioral mechanisms facilitating communication, including 
symbolic language. Language would have led to increased 
complexity of social interaction, involving appreciation of 
numerous related cues from social and material environments, 
and the control and inhibition of responses. In short, the 
increasing complexity of stone tools indicates other processes, 
but it cannot lead to more than educated guesses about the 
ecological complexity of selection pressures for human biosocial 
adaptations. (These relationships between tool-making and 
language, and hunting behavior and various levels of neural 



36 



structure have been examined in greater detail by Holloway 
1964, 1969, 1970.) 

Although the australopithecine brains were small, they were 
larger, both relatively and absolutely, than those of the 
chimpanzees, which probably had similar body weights. Be- 
tween the chimpanzee or the gorilla and man there is a large 
difference in the duration of the growth period. Maturation is 
complete in a chimpanzee at nine to 1 1 years, whereas in man it 
takes about 20 to 25 years. 

As yet we cannot look at a fossil and say at what age it 
became fully adult; but we must assume that growth rates and 
durations changed over the course of human evolution. One 
cannot get a brain to evolve in size without prolonging the 
period of its growth. Growth is a complex process involving 
interaction among genetic instructions for locus and timing, 
tissue differentiation, hormone environment (growth hormones, 
thyroxin, and androgens) and proper nourishment (including 
social nourishment). One of the organs most vulnerable to 
malnourishment is the growing brain, particularly during 
periods of mitotic division and nerve cell enlargement. The 
earliest evidence of increase in brain size in the fossil record 
coincides with the earliest evidence for utilization of protein- 
rich food (animal flesh). It seems an inescapable conclusion that 
there was an adaptive relationship between hunting and the 
evolution of the brain, mediated through longer periods of 
growth and dependence. 

A SPECULATIVE MODEL OF HOMINID EVOLUTION 

What follows is a set of speculations concerning the interrela- 
tions among a number of complex variables at different levels 
(anatomical, physiological, neuroanatomical, ecological, and 
social). The main purpose of this model is merely to show the 
matrix of variables that I believe must be considered if we are to 
have a clearer understanding of how the human brain evolved. 

Beginning with Ramapithecus (10 to 14 million years ago) 



37 



one can postulate that adaptations based on a savanna environ- 
ment (utilization of seeds, grass, and other vegetation) led to 
strong positive selection for bipedalism. I do not think we can 
speculate further without additional material. Consequently, 
my model starts after the Ramapithecus level of adaptation. 

Stage 1 : Early australopithecine phase. Major emphasis on social behav- 
ior adaptations, involving bipedalism, endocrine organization, and 
brain reorganization. 

Stage 2: Late australopithecine-"habiline" phase. Major emphasis on 
consolidation and refinement of Stage 1 . 

Stage 3: Late "habiline"-early Homo erectus to Neanderthal-sapiens 
phase. Emphasis on elaboration of cultural skills through a positive 
feedback relationship and brain enlargement. 

Stage 1 includes the rudimentary development of coopera- 
tive, sex-role-separated social groups resulting from endocrine 
changes involving hormones and target-tissues. There was a 
reduction of sexual dimorphism in tooth and skeletal size and 
an increase in epigamic features of secondary sexual characteris- 
tics such as permanent breasts and fat distribution. There were 
possibly other changes facilitating continuous sexual receptivity 
of the female and closer affective relations between the sexes. 
This complex of correlated anatomical, physiological, and 
behavioral changes led to greater sexual and social control 
associated with prolonged periods of postnatal dependence and 
learning. Changes in the interactions between hormones and 
target-tissues could have led to a reduction in aggressive 
components of behavior, sexual dimorphism in size and 
increased periods of growth with delayed maturation of skeletal 
development. These processes are mediated in a complex 
manner by the androgens and involve other hormones as well. 
The endocrine changes that led to the dimorphic features cited 
above could have played an important role in decreasing 
intragroup aggression, permitting groups to live more densely. 
In other words, the changes led to an increase in cooperative 
behavior (both among males and females and among males) that 
meant a stronger protection against both predators and other 
hominid groups. At the same time they affected growth rates, 



38 



accounting for longer periods of dependency and postnatal 
growth during which the brain showed an allometric increase. 
Associated with this complex of correlated changes are the 
developments of language (using a primitive symbol system) and 
hunting and scavenging (with a greater effective range due to 
more advanced bipedal locomotion). 

I regard the development of language as more closely bound 
up with social affect and control than with hunting behavior 
involving signaling and "object naming," although this does not 
mean that hunting could not have been a strong positive 
selection factor for language. 1 In addition to reorganization of 
social behavior and bipedal adaptation, there was a reorganiza- 
tion of the brain involving, minimally, a decrease in primary 
visual cortex on the convex cerebral surface and an increase in 
parietal and temporal association cortex, allowing for greater 
discrimination among complex cues of the environment and for 
extension of foresight and memory to cope more effectively 
with the savanna-type environment. Associated with these is the 
early manufacture of stone tools to extend the economic base. 
The tools may have been used to break bones to secure marrow 
and to detach peices of flesh or skin. They may also have been 
used as missiles to drive off carnivores from their kills. The 
latter behavior involved not only cooperation among group 
members, but skill in coordinating hand-eye movements and a 
complex appreciation of spatial-visual calculation. It is very 
tempting to relate this kind of behavior with the right 
hemisphere, known to be dominant in such coordination. 

Stage 2 includes refinement and elaboration of the changes in 
social behavior begun in Stage 1, as well as an increased 
dependence on social cohesion, language, and stone tools. 

'I do not agree that human cognition, and more particularly spoken and gestural 
communication are mainly cortical-to-cortical events, "liberated," so to speak, from 
limbic influences. Emotional involvement and tonus is always present in human 
communication, except perhaps in cases of psychopathology. This does not mean 
that evolutionary changes in cortical tissue and hemispheric relationships were not 
necessary. I only mean that those changes were not merely additive, but totally 
integrated with noncortical structures, particularly the thalamus, limbic structures, 
hippocampus, and reticular formation. 

39 



Bipedal locomotion was essentially fully human. There was 
both relative and absolute expansion of the brain, associated 
mainly with increased body size. There was greater efficiency of 
economic sharing and cooperation between the sexes, 1 provid- 
ing the basis for longer periods of postnatal dependency and 
learning, which initiated a feedback system between brain and 
cultural behavior. Language behavior became more strongly 
developed, and cognitive behavior of a more nearly human type 
developed, where language and tool-making arose from the same 
psychological structuring. There were true stone tool cultures at 
this stage, and language had prime importance in maintaining 
social cohesion and control and in "programming" offspring. 
Dependence on hunting increased and there was more success in 
stalking and hunting larger game. There was a selection for 
increased body size, bipedal agility and predictive abilities for 
more successful hunting. The social behavioral changes outlined 
in Stages 1 and 2 permitted longer male-male association for 
persistent hunting and for the protection of a more secure home 
base for females and young, who were providing small game and 
vegetables. The "initial kick," or "human revolution," is fully 
set and leads to Stage 3. 

In Stage 3 a positive feedback between brain development 
and cultural complexity was mediated through the increased 
periods of dependency and learning (which was taking place in a 
more complex and stimulating material and social environment) 
of the offspring. The major neural changes are those of size and 
refinement of the reorganized human brain (that is, sensori- 
motor, associative, extrapyramidal modulation, and cerebellar 
involvement in manual dexterity). This is not a stage of 
behavioral innovation, but an elaboration of "complexity- 
management" involving fineness of sensory discrimination and 
association between larger sets of past memories and skills (see 
Holloway, 1967). 

'No chauvinistic intents are harbored in the speculative model, in terms of either 
male or female superiority. I view the evolution of sex differences, both in behavior 
and morphology as complementary to human evolution, not as competitive or 
supraordinative. 

40 



It must be emphasized that I see these stages as gradual and 
continuous, with certain developments stressed more strongly in 
one stage than in another. My main point is to show that social 
behavior mechanisms have had a long development, beginning 
with the early hominids. In a sense, increase in brain size is 
minor compared to the evolution of the social matrix. Brain 
expansion finally depends on a solid behavioral foundation. My 
model takes into account both the skeletal remains and the 
cultural evidence and provides a base for synthesizing anatomi- 
cal, behavioral (social and individual), physiological, adapta- 
tional, and ecological variables. 

It is possible, I believe, to consider more molecular analyses 
within this model. At the level of neuroanatomy, one can 
suggest various brain regions that could be correlated with 
behavioral attributes such as set and attention, concentration, 
"memory" (permanence, quantity, facility, and strategy of 
recall), hand-eye and running coordination, mother-infant af- 
fect, babbling and reticular core reorganization, cerebral laterali- 
zation, play, curiosity, prolongation of prepubertal vividness of 
experience, memory, and so on. To do so, however, is far 
beyond the limits of this lecture. 

It must be understood that the analysis of endocranial casts 
alone cannot play more than a limited role in elaborating my 
hypothesis, or in supporting my speculations. The external 
morphology of endocasts provides clues, not proof, about past 
selection pressures, and these clues are fairly gross. The 
judicious use of endocasts, both as clues to neural reorganiza- 
tion and to changes of growth variables must await further 
discoveries with firm dates. While studies of australopithecine 
endocasts are in progress, it should be apparent that the 
specimens have potential use, both as clues to general events in 
hominid evolution and as morphological patterns for taxonomic 
purposes. The analysis given thus far shows, I believe, that the 
evolution of the brain has always been an integral part of 
hominid evolution and was not something that took place 
following other changes in different morphological sectors of 
the hominids. 

41 



Let me close by asserting my belief that human behavior is a 
long-standing evolutionary development, possibly more than 
three million years old. Human thought, aside from its more 
sophisticated scientific recency, is no late invention, but instead 
is very old. The human brain is both the product and cause of 
the evolution of human social behavior, and we should 
recognize that our brains are both the instruments and products 
of our sociality, the genesis of which was long in the making. 

ACKNOWLEDGMENTS 

I am grateful to Drs. Ian Tattersall and Lester Aronson and 
the American Museum of Natural History for honoring me with 
this lecture and for helping me with its publication. Much of the 
actual work on fossil specimens was carried out in Africa, 
Europe, and Indonesia with support from the National Science 
Foundation. Without the kindness and cooperation of Dr. P. V. 
Tobias at the University of Witwatersrand, South Africa, and 
Drs. Louis and Mary Leakey and Mr. Richard Leakey of the 
National Museum in Nairobi, Kenya, this work would not have 
been possible, and I am indebted to them and their staff for 
their help. I am similarly grateful to Dr. Teuku Jacob, Gadjah 
Mada University, Indonesia, and his staff for their courtesy, 
help, and hospitality; to Dr. Darwin Kadar, Section of Palaeon- 
tology, Geological Institute, Bandung, Indonesia; to Dr. G. H. 
R. von Koenigswald, Senckenberg Institute, Frankfurt, 
Germany. I owe special thanks to Dr. Alan Walker, now at 
Harvard University, for his cooperation, help, facilities, and 
friendship. Almost all the chimpanzee and gorilla specimens 
endocasted and studied were lent to me by the American 
Museum of Natural History, through the courtesy of Drs. Ian 
Tattersall and Richard Van Gelder, to whom I am most grateful. 
I thank Dr. Jeffrey Schwartz and Mr. Barry Cerf of Columbia 
University for their help in keeping me supplied with specimens, 
and Ms. Kate McFeely for typing the original manuscript. This 
research has also been supported by a Guggenheim Fellowship, 
for which the author is most grateful. 

42 



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45 



r;2bi A 

J35 

0.44 

974 



FORTY-FOURTH 
]jAMES ARTHUR LECTURE ON 
THE EVOLUTION OF THE HUMAN BRAIN 

1974 



PERSISTENT PROBLEMS IN 

THE PHYSICAL CONTROL 

OF THE BRAIN 

ELLIOT S. VALENSTEIN 



<? *• 



THE AMERICAN MUSEUM OF NATURAL HISTORY 
NEW YORK : 1975 



lit 






*? 










1869 
THE LIBRARY 



FORTY-FOURTH 

JAMES ARTHUR LECTURE ON 

THE EVOLUTION OF THE HUMAN BRAIN 



FORTY-FOURTH 
/JAMES ARTHUR LECTURE ON 
THE I VOLUTION OF THE HUMAN BRAIN 

1 9 74 



PERSISTENT PROBLEMS IN THE 
PHYSICAL CONTROL OF THE BRAIN 



ELLIOT S. VALENSTEIN 

Professor of Psychology and Neurosciencc 
University of Michigan, Ann Arbor 



THE AMERICAN MUSEUM OF NATURAL HISTORY 
NEW YORK : 1975 



JAMES ARTHUR LECTURES ON 
Till EVOLUTION OF 1111 HUMAN BRAIN 



Frederick I ilney . I'h< Brain in Relation to Behavior; March 15, 1932 

C. Unison Herrick, Brains as Instruments of Biological Values; April 6, 1933 

D. M. S. Watson, The Story o) Fossil Brains front Fish to Man; April 24, 1934 

C. U. Ariens Kappcrs. Structural Principles in the Nervous System, The Develop- 
ment of the Forebrain in Animals and Prehistoric Hitman Races, April 25, 1935 

Samuel T. Orton, Tlie Language Area of the Human Brain and Some of its 
Disorders; May 15, 1936 

R. W. Gerard, Dynamic Neural Patterns; April 15, 1 937 

Franz Weidenrcich, The Phylogenctic Development of the Hominid Brain and its 
Connection with the Transformation of the Skull; May 5, 1938 

G. Kingsley Noble, The Neural Basis of Social Behavior of Vertebrates; May 11, 
1939 

John F. Fulton, A Functional Approach to the Evolution of the Primate Brain; May 
2, 1940. 

Frank A. Beach, Central Nervous Mechanisms Involved in the Reproductive 
Behavior of Vertebrates; May 8, 1 94 1 

George Pinkley, A History of the Human Brain; May 14, 1942 

James W. Papez, Ancient Landmarks of the Human Brain and Their Origin; May 27, 
1943 

James Howard McGregor, The Brain of Primates; May 1 1, 1944 

K. S. Lashlcy , Neural Correlates of Intellect; April 30, 1945 

Warren S. McCulloch, Finality and Form in Nervous Activity; May 2, 1946 

S. R. Detwilcr, Structure-Function Correlations in the Developing Nervous System 
as Studied by Experimental Methods; May 8, 1947 

Tilly Fdinger, The Evolution of the Brain; May 20, 1948 

Donald O. Hcbb, Evolution of Thought and Emotion; April 20, 1949 

Ward Campbell Halstead, Brain and Intelligence; April 26, 1950 

Harry F. Harlow, The Brain and Learned Behavior ; May 10, 1951 

Clinton N. Woolsey, Sensory and Motor Systems of the Cerebral Cortex; May 7, 
1952 

Alfred S. Romer, Brain Evolution in the Light of Vertebrate History; May 21 , 1953 
Horace W. Magoun, Regulatory Functions of the Brain Stem; May 5. 1954 



*Fred A. Mettler. Culture and the Structural Evolution of the Neural System; April 
21, 1955 

*Pinckney J. Harman, Paleoneurologic, Neoneurologic, and Ontogenetic Aspects of 
Brain Phytogeny, April 26, 1956 

*Davenport Hooker, Evidence of Prenatal Function of the Central Nervous System in 
Man; April 25, 1957 

*David P. C. Lloyd, The Discrete and the Diffuse in Nervous Action; May 8, 1958 

*Charles R. Noback, The Heritage of the Human Brain; May 6, 1959 

*Ernst Scharrer, Brain Function and the Evolution of Cerebral Vascularization; May 
26, 1960 

Paul I. Yakovlev, Brain, Body and Behavior. Stereodynamic Organization of the 
Brain and of the Motility-Experience in Man Envisaged as a Biological Action 
System; May 16, 1961 

H. K. Hartline, Principles of Neural Interaction in the Retina; May 29, 1962 

Harry Grundfest, Specialization and Evolution of Bioelectric Activity; May 28, 
1963 

*Roger W. Sperry , Problems Outstanding in the Evolution of Brain Function; June 3, 
1964 

*Jose M. R. Delgado, Evolution of Physical Control of the Brain; May 6, 1965 

Seymour S. Kety, Adaptive Functions and the Biochemistry of the Brain; May 19, 
1966 

Dominick P. Purpura, Ontogenesis of Neuronal Organizations in the Mammalian 
Brain; May 25, 1967 

*Kenneth D. Roeder, Three Views of the Nervous System; April 2, 1968 

t Phillip V. Tobias, Some Aspects of the Fossil Evidence on the Evolution of the 
Hominid Brain; April 2, 1969 

*Karl H. Pribram, What Makes Man Human; April 23, 1970 

Walle J. H. Nauta, A New View of the Evolution of the Cerebral Cortex of Mammals; 
May 5. 1971 

David H. Hubel, Organization of the Monkey Visual Cortex; May 1 1, 1972 

Janos Szentagothai, The World of Nerve Nets; January 16, 1973 

Ralph L. Holloway, The Role of Human Social Behavior in the Evolution of the 
Brain; May 1, 1973 



* Published versions of these lectures can be obtained from The American Museum of 
Natural History, Central Park West at 79th St., New York, N.Y. 10024. 

-("Published version: The Brain in Hominid Evolution, New York: Columbia University 
Press, 1971. 



PERSISTENT PROBLEMS IN THE PHYSICAL 
CONTROL OF THE BRAIN 1 

INTELLECTUAL AND SOCIAL CLIMATE 
AND SCIENTIFIC DISCOVERY 

There is great temptation to dramatize scientific discoveries 
by picturing them as the result of sudden insights or lucky 
accidents. In actuality, this is seldom the entire story since most 
discoveries also reflect the intellectual and social climate of 
their time. The many potentially significant observations that 
were neglected or misinterpreted attest to the importance of a 
prepared mind. It is true, for example, that Luigi Galvani 
observed a suspended frog twitch in synchrony with flashes of 
lightning, but this event was significant because it occurred at a 
time of increasing interest in the relation of physical and 
biological phenomena. Galvani's observation occurred only a 
short time after Mesmer's suggestion that "animal magnetism" 
was the basis of what is now called hypnotism. Not very many 
years earlier, the Scottish anatomist John Hunter and the 
English physicist Henry Cavendish speculated that the study of 
such electric fish as the eel and torpedo (an electric ray fish) 
might help to explain the action of nerves in general. In fact, 
the part played by electric fish in the early history of 
bioelectricity and electrotherapy has been the subject of an 
interesting essay by Kellaway (1946). 

Galvani's observations, therefore, were not entirely acci- 
dental. It is certain that Galvani did not suspend a frog between 
a wire attached to a lightning rod and a rod immersed in a well 
by mere chance. He was very much aware of Benjamin 
Franklin's demonstration that atmospheric electricity could be 

'A comprehensive discussion of the historical, scientific, and ethical considera- 
tions related to the physical control of the brain was presented by Valenstein (1973). 
The research reported in the present paper was supported by NIMH Research Grant 
2 ROl MH20811-03. 



tapped in a harmless manner. This particular frog experiment 
was clearly only one of many Galvani designed to study the role 
of electricity in biological phenomena. Many of these experi- 
ments involved the observation that a frog's muscle would 
twitch when touched with metal probes. The lively dispute 
between Galvani and the physicist Allesandro Volta that took 
place between 1790 and 1798 was over interpretation. Galvani 
argued for the existence of "animal electricity," whereas Volta 
argued for "metallic electricity" and claimed that the dissimilar 
metals used in most of Galvani's experiments produced an 
electric force that caused the muscles to contract. This 
controversy shaped much of the research on the nervous system 
during the early part of the nineteenth century. By 1848 when 
du Bois-Reymond published his book, Investigations of Animal 
Electricity, and Helmholtz had shown that the speed of nerve 
conduction was very different from that of electric current, the 
controversy had disappeared. 

The value of electrical stimulation to study the nervous 
system, however, increased in importance with the passage of 
time. The technique, which had been applied primarily to the 
crural nerve and gastrocnemius muscle of the frog, began to be 
applied directly to mammal brains. Legend has it that while 
dressing the head wounds of soldiers, Eduard Hitzig observed 
that their muscles twitched on the side of the body opposite the 
injury. The 1870 report by Fritsch and Hitzig describing the 
frontal lobe regions of dogs from which electrical stimulation 
could evoke bodily movement is traditionally attributed to this 
accidental observation. As Doty pointed out, there is no truth 
in this legend despite the number of writers who delight in 
repeating it. Fritsch and Hitzig had become embroiled in the 
controversy over specific versus holistic representation of func- 
tions within the brain, particularly the cerebral cortex. Many in- 
vestigators were using electrical stimulation to settle the issue but 
the results were often confusing because it was not yet appreciated 
that Galvanic (direct) current destroyed nerve tissue. (Du Bois- 
Reymond had already developed an inductorium for providing 
alternating or faradic current, but it was not universally used.) 



Fritsch and Hitzig concluded that their results showed clearly 
that "some pyschological functions and perhaps all of them . . . 
need certain circumspect centers of the cortex." David Ferrier 
reached the same conclusion a few years later as a result of his 
electrical stimulation of the monkey cortex. Friedrich Goltz, on 
the other hand, argued for holism by describing dogs that were 
still capable of moving all their limbs after removal of virtually 
half the brain. The literature of the period provides much 
support for the statement attributed to Alfred Binet, "Tell me 
what you are looking for and I'll tell you what you will find." 

Even the first known attempt at psychosurgery must be 
examined against the background of the localization contro- 
versy. In 1891, Gottlieb Burckhardt, the director of the insane 
asylum at Prefargier, Switzerland, reported the results of 
removing part of the cortex of six "demented" patients. He 
said: "Who sees in psychoses only diffuse illness of the 
cortex . . . for him it will naturally be useless to remove small 
parts of the cortex in the hope to influence a psychosis 
beneficially by this means. One has to be as I am, of a different 
opinion. That is, our psychological existence is composed of 
single elements, which are localized in separate areas of the 
brain .... Based on these considerations and theories expressed 
earlier, I believe one has the right to excise such parts of the 
cortex, which one can consider starting points and centers of 
psychological malfunctions and furthermore, to interrupt con- 
nections whose existence is an important part of pathological 
processes." 

Controversies about localization are still with us, but of 
course at a more sophisticated level. Stereotaxic techniques and 
reliable methods for permanently implanting electrodes have 
made it possible to undertake behavioral (psychological) studies 
over long periods of time. Earlier controversy was about simple 
motor responses; current arguments often focus on the localiza- 
tion of relatively complex motivational states. The intellectual 
and social climate also influences contemporary research, but it 
is difficult to achieve adequate perspective when one is very 
close to a scene. Nevertheless, it is helpful to try. I believe I can 



discern two major influences that have shaped brain stimulation 
studies from 1950 to the present. One of these involves the 
attempt to accumulate evidence demonstrating that electrical 
stimulation of discrete subcortical brain areas can evoke natural 
drive states. The other influence, which stems directly from the 
first, has been the preoccupation with brain stimulation as a 
technique for controlling behavior. 

For psychologists interested in studying the process of 
learning, the early 1950s was a time of increasing disillusion- 
ment with theories based on changes in hypothetical drive states 
assumed to take place in the brain. (Indeed, this was a period 
when it was often maintained that CNS, the common abbrevia- 
tion for the central nervous system, in reality meant the 
"conceptual nervous system.") These drive-reduction learning 
theories, as they are called, emphasized that we learn only (or in 
the weaker versions of the theory, we learn best) those 
stimulus-response connections that are associated with changes 
in level of drive state. Although it was recognized that 
peripheral body factors may contribute to drive state, a number 
of experiments had made it evident that drives such as hunger 
and thirst did not depend upon intensity of stomach contrac- 
tions, dryness of mouth, or other obvious bodily cues. Drive 
states, therefore, were presumed to be represented mainly by 
the level of activity in functionally specific neural systems 
within the brain. However, this conclusion was inferential, and 
therefore the properties of drive, the major variable in the 
theory, had to be inferred and could not be measured. The field 
was rapidly degenerating into unresolvable arguments of little 
interest to anyone not indoctrinated into this specialty. 

Drive-reduction theorists desperately needed some new input 
into their system. Although the Swiss physiologist Walter Hess 
had received a Nobel prize by this time, the details of his 
German publications were not well known in the United States. 
Hess had been stimulating the diencephalon in cats, using a 
technique that permitted him to study the responses evoked in 
awake, relatively unrestrained animals. Most of his observations 
were directed toward understanding the regulation of so-called 



autonomic responses such as changes in pupil size, blood 
pressure, heart rate, respiration, and the like. When Hess was 
invited to speak at Harvard in 1952, a number of people became 
aware tor the first time that some of his studies seemed to 
demonstrate that electrical stimulation of certain areas in the 
diencephalon could suddenly make peaceful cats aggressive or 
satiated cats hungry. These reports were seized upon, for they 
seemed to provide a means to manipulate drives and to measure 
them directly. 

Neal Miller (1973, pp. 54-55) reflected on his initial interest 
in brain stimulation studies and described it as follows: 

'if 1 could find an area of the brain where electrical 
stimulation has the other properties of normal hunger, would 
the sudden termination of that stimulation function as a 
reward? If I could find such an area, perhaps recording from it 
would provide a way of measuring hunger which would allow 
me to see the effects of a small nibble of food that is large 
enough to serve as a reward, but not large enough to produce 
complete satiation. Would such a nibble produce a prompt, 
appreciable reduction in hunger, as demanded by the drive- 
reduction hypothesis?" 

This certainly does not reflect the sophistication of Miller's 
current thinking on the problem, but it does illustrate the 
earlier intellectual climate that produced a need to find 
similarities between such behaviors as eating, drinking, and 
aggression when elicited by brain stimulation, and the same 
behaviors when motivated by natural internal states. What was 
found was that eating, drinking, grooming, gnawing, aggression, 
foot-thumping, copulation, carrying of young, and many other 
behaviors could be triggered by brain stimulation. What was 
claimed was that discrete brain centers were identified which, 
when stimulated electrically, would evoke specific and natural 
states such as hunger, thirst, sexual appetite, and maternal 
drives. Tests were designed to emphasize the naturalness of the 
evoked states and dissimilarities were disregarded or dismissed 
as experimental noise. A personal experience illustrates the 
influence of the prevailing bias. When reporting at a meeting 



that the same brain stimulus frequently evoked eating, drinking, 
and other behaviors, I noted that these and other observations 
raised some serious questions about the belief that natural drive 
states were evoked. A colleague attending the session told 
me that he had made similar observations several years 
earlier, but as they interfered with the planned experiments, 
the testing conditions were arranged so that the stimu- 
lated animals had no chance to express these "irrelevant" 
behaviors. 

In addition to overlooking behavioral observations inconsis- 
tent with the assumption that natural drive states could be 
duplicated by stimulating single points in the brain, several 
other trends characterized the period from 1955 to 1970. There 
was a tendency to rush into print with every new observation of 
a different behavior that could be evoked by brain stimulation. 
The competition for priority of discovery and the need to 
demonstrate progress to the granting agencies often interfered 
with any serious attempt to understand the relation between 
brain stimulation and behavior change. One active researcher 
remarked to me that he would not be "scooped" again, 
bemoaning the fact that someone had published an article 
describing a new behavior that could be evoked by brain 
stimulation before he had. The list of such behaviors kept 
growing. One other factor that had a major impact was the 
belief that each evoked behavior was triggered from different 
and discrete brain sites. In some cases, reports encouraging the 
growth of this belief actually presented no anatomical informa- 
tion, but despite this deficiency, there was little hesitancy in 
using loosely defined anatomical terms (really pseudoanatomi- 
cal) such as the "perifornical drinking area." Some reports 
presented very complete histological data, but where the 
authors emphasized the separateness of brain areas eliciting 
different behaviors, others with a different bias could just as 
readily see diffuse localization and considerable overlap. In 
total, the impression was created that a large number of natural 
motivational states could be reliably controlled by "tapping 
into" discrete brain sites. 



POPULARIZATION OF RESEARCH 

As the reports of these experiments began to be dissemi- 
nated, a number of other distortions were introduced. These 
accounts fed the growing fear that this new brain technology 
might be used to control human behavior. The emphasis on 
control, by numerous demonstrations of behavior being turned 
"on and off" and by selective and oversimplified descriptions of 
these demonstrations in the popular press, has had the 
predictable effect. The possibility of behavior control by 
various brain interventions has become a popular topic for 
novels, television shows, movies, magazines, feature articles in 
newspapers, and even essays purporting to describe life in the 
not too distant future. Michael Crichton's The Terminal Man is 
only one of many novels that have used this theme. It may be 
no exaggeration to say that this story may have a greater impact 
(because it is believed by more people) than Mary Shelley's 
Frankenstein. Taking a different tack, an article that appeared 
in Esquire magazine described a government of the future, an 
"electroligarchy," where everyone is controlled by electrodes 
(Rorvik, 1969). It is not necessary to demonstrate that all this 
material is believed by everyone, or even by most people, in 
order to recognize that the virtual bombardment from the 
media has had a profound effect. 

Even the material meant only for amusement, and not 
intended to be taken seriously, gradually begins to become a 
part of our serious thinking and influences our perception of 
interpersonal relations. A New York Times article dated 
September 12, 1971, described the scientists who: "have been 
learning to tinker with the brains of animals and men and to 
manipulate their thoughts and behaviors. Though their methods 
are still crude and not always predictable, there can remain little 
doubt that the next few years will bring a frightening array of 
refined techniques for making human beings act according to 
the will of the psychotechnologist.' , 

With more drama and expressing less reservation, Perry 
London (1969, p. 37) a professional psychologist, stated that 



All the ancient dreams of mastery over man and all the tales of zombies, 
golems, and Frankensteins involved some magic formula, or ritual, or 
incantation that would magically yield the key to dominion. But no 
one could be sure, from the old Greeks down to Mrs. Shelley, either by 
speculation or vivisection, whether there was any door for which to 
find that key . . . This has been changing gradually, as knowledge of the 
brain has grown and been compounded since the nineteenth century, 
until today a whole technology exists for physically penetrating and 
controlling the brain's own mechanisms of control. It is sometimes 
called "brain implantation," which means placing electrical or chemical 
stimulating devices in strategic brain tissues . . . These methods have 
been used experimentally on myriad aspects of animal behavior, and 
clinically on a growing number of people . . . The number of activities 
connected to specific places and processes in the brain and aroused, 
excited, augmented, inhibited, or suppressed at will by stimulation of 
the proper site is simply huge. Animals and men can be oriented toward 
each other with emotions ranging from stark terror or morbidity to 
passionate affection and sexual desire . . . Eating, drinking, sleeping, 
moving of bowels or limbs or organs of sensation gracefully or in spastic 
comedy, can all be managed on electrical demand by puppeteers whose 
flawless strings are pulled from miles away by the unseen call of radio 
and whose puppets made of flesh and blood, look "like electronic 
toys," so little self-direction do they seem to have. 

It is little wonder that the feeling of being controlled by 
surreptitiously implanted brain devices has become an increas- 
ingly common delusion in paranoia. 

While many people emphasize the potential misuse of these 
new brain-manipulating techniques, there are some who have 
stressed what they believe is their positive potential. They see in 
them a possible cure not only for intractable psychiatric 
disorders, but for intractable social problems as well— particu- 
larly those related to violent crimes and wars. This potential of 
brain intervention to achieve desirable ends has been expressed 
by Kenneth Clark in his presidential address to the 1971 
convention of the American Psychological Association: Clark 
suggested that "we might be on the threshold of that type of 
scientific biochemical intervention which could stabilize and 
make dominant the moral and ethical propensities of man and 
subordinate, if not eliminate, his negative and primitive behav- 
ioral tendencies." 

Proposals of this type can best be discussed after a more 



realistic foundation is prepared for critically examining the 
capacity of physical techniques to modify brain-behavior 
relationships. 

A CRITICAL EXAMINATION OF THE EVIDENCE 

It should be recognized from the outset that evidence limited 
to the demonstration of inhibition or evocation of some 
behavior pattern can be very misleading. Such demonstrations 
convey the impression that there is a simple and predictable 
relationship between specific brain sites and complex behavior 
patterns. Also, the implication that only one behavior is 
influenced by the electrical stimulation encourages the infer- 
ence that the control is very precise and selective. 

It might not be inappropriate to begin the critical examina- 
tion with a demonstration that is familiar to most people, 
Delgado's (1969) purported demonstration of brain stimulation 
inhibiting aggressiveness in a bull. An article in the New York 
Times (September 12. 1971) described the event as it is 
typically reported: "Dr. Delgado implanted a radio-controlled 
electrode deep within the brain of a brave bull, a variety bred to 
respond with a raging charge when it sees any human being. But 
when Dr. Delgado pressed a button on a transmitter, sending a 
signal to a battery-powered receiver attached to the bull's horns, 
an impulse went into the bull's brain and the animal would 
cease his charge. After several stimulations, the bull's naturally 
aggressive behavior disappeared. It was as placid as Ferdinand." 

Although this interpretation is commonly accepted, there is 
actually little evidence supporting the conclusion that the 
stimulation had a specific effect on the bull's aggressive 
tendencies. A viewing of the film record of this demonstration 
should make it apparent to all but the most uncritical observer 
that the stimulation forced the bull to turn in circles in a very 
stereotyped fashion. This should not surprise anyone familiar 
with the brain, as the stimulating electrode was situated in the 
caudate nucleus, a structure known to play an important role in 
regulating bodily movements. It is true that the bull's aggressive 



charges were stopped for a short period, but there is no 
evidence that it was because aggression was inhibited. Rather, 
because it was forced to turn in circles every time it came close 
to its target, the confused bull eventually stopped charging. 
Patients receiving caudate nucleus stimulation also display 
various types of stereotyped motor responses. Sometimes all 
movement is stopped in an "arrest response," so that a person 
instructed to continue tapping a table may be immobilized by 
the stimulation with his hand in midair (Van Buren, 1966). 
Destruction of the caudate nucleus in cats and other animals has 
been reported to produce a syndrome called obstinate progres- 
sion, a curious phenomenon characterized by persistent walking 
movements even when an animal's head may be wedged into a 
corner (Mettler and Mettler, 1942). In humans, movement 
disorders such as the spasticity and tremors seen in Parkinson's 
disease have frequently been linked to caudate nucleus 
pathology. 1 

Caudate stimulation has also been reported to cause confu- 
sion and to interfere with speech (Van Buren, 1963). There are 
several animal studies indicating that caudate stimulation 
interferes with the normal habituation of responses to novel 
stimuli when they are presented repeatedly, e.g., Deadwyler and 
Wyers (1972), and Luria (1973) have suggested that in humans 
the caudate nucleus is important for focusing attention because 
of its role in selectively inhibiting responses to irrelevant 
stimuli. Kirkby and Kimble (1968) reported that rats have 
difficulty inhibiting responses in passive avoidance tests follow- 
ing damage to the caudate nucleus, and Rosvold, Mishkin, and 
Szwarcbart (1958) have concluded that this structure is 

1 Plotnik and Delgado (1970) have presented evidence that stimulation of the 
caudate nucleus, putamen, gyrus pyriformis, and gyrus rectus may inhibit the threat- 
ening grimaces in monkeys that normally followed tail shock. Although only a mini- 
mum amount of data were presented, these changes in the monkeys' behavior did not 
seem to be accompanied by motor disturbances or general disorientation. Although 
the report suggests that stimulation of some structures may inhibit the expression of 
aggressive displays at current intensities that do not produce gross motor disturb- 
ances, there is no reason to assume that the large number of other functions believed 
to be regulated by these brain areas were unaffected. 

10 



involved in delayed alternation and visual discrimination perfor- 
mance of monkeys. 

Many more functions of the caudate nucleus are described in 
the scientific literature, but a cataloguing of them all is not 
necessary for our present purpose. It should be clear, however, 
that we will not advance very far in our attempt to analyze the 
contribution of the caudate nucleus to behavior if we restrict 
ourselves to listing the complex behaviors affected by electrical 
stimulation. What is needed is a testing program designed to 
characterize functional changes with increasing precision by 
dissecting out the elements common to behaviors appearing to 
be very different. 

The fact that it is possible to inhibit or evoke different 
complex behaviors by electrical stimulation has led some people 
to conclude that specific behaviors might be modified by 
destroying the neural area around the tip of the stimulating 
electrode. Thus, using the electrode implanted in the bull's 
caudate nucleus to destroy a portion of this structure would be 
expected to alter the aggressive temperament of that animal. 
Although the specific experiment has not been done, there is no 
reason to believe that this would be the case. Destruction of the 
caudate nucleus does not change the aggressive tendencies of 
other animals, but it may produce various movement deficits or 
impairments on tasks requiring a selective inhibition of sensory 
and motor processes and the connections between them. 1 
Similarly, if one destroys the hypothalamic area that evokes 
aggressive behavior in a cat or rat, under an electrode, no change 
in natural aggressivity is induced unless the area destroyed is so 
extensive that the animal is incapable of any behavior at all. 
Even after surgical isolation of the entire hypothalamus, a cat is 
still able to display integrated attack and rage responses when 

1 None of this evidence is meant to argue against the possibility that parts of the 
caudate nucleus may be more involved in one type of process than in another. It has 
been shown that specific parts of the caudate nucleus receive input from the orbital 
frontal, the dorsolateral frontal, or the inferotemporal cortex, and the deficits that 
follow selective destruction of portions of this complex structure differ accordingly 
(Divac, Rosvold, and Szwarcbart, 1967). The behavioral manifestations of these 
deficits, however, vary with the demands of the situation. 

11 



provoked, as Ellison and Flynn (1968) have demonstrated. 
Earlier, Hess described his disappointment at not being able to 
modify a behavior elicited by stimulation even after destroying 
the tissue around the electrode. He said: 

"This step, involving the use of the same electrodes, seemed 
to be most promising, inasmuch as we expected that a 
comparison of stimulation and destruction effects would 
provide us with a reciprocal confirmation in the sense of a plus 
or minus effect. In reality, however, the results were disappoint- 
ing. Today we know why. Since our procedure aimed for the 
greatest possible precision, we often produced only correspond- 
ing small foci of coagulation. As is shown by the stimulation 
study, however, even the best demarcated 'foci' are relatively 
diffuse" (Hess, 1957, p. 43). 

Luria (1973, pp. 33-34) commented that localization of 
complex functions in specific regions of the brain is always 
misleading. What is needed, he said is to "ascertain by careful 
analysis which groups of concertedly working zones of the brain 
are responsible for the performance of complex mental activity; 
what contribution is made by each of these zones to the 
complex functional system." 

Luria also noted that though it is appropriate to speak of the 
secretion of bile as a function of the liver, insulin secretion as a 
function of certain cells in the pancreas, and the transduction of 
light by photosensitive elements in the retina, when we speak of 
such functions as digestion or perception, "it is abundantly 
clear that [they] cannot be understood as a function of a 
particular tissue." Similarly, Luria (1973) quoted Pavlov on the 
question of a "respiratory center." "Whereas at the beginning we 
thought that this was something the size of a pinhead in the 
medulla . . . now it has proved to be extremely elusive, climbing 
up into the brain and down into the spinal cord, and at present 
nobody can draw its boundaries at all accurately." 

The idea that the brain is organized into discrete compart- 
ments whose function corresponds to our social needs is simply 
not in accord with reality. The brain does not work that way. A 
concept such as aggression is a man-made abstraction and it 

12 



therefore should not be expected to exist as a separate entity in 
the nervous system. Many parts of the nervous system play roles 
in regulating what most of us would label aggressive behavior 
and each of these parts also plays a role in regulating other 
aggression, and copulation. Even though all of these behaviors 
point. These investigators destroyed a small amount of the 
hypothalamic tissue in a rat by means of a specially designed 
knife and reported changes in eating, drinking, irritability, 
aggression, and copulation. Even though all of these behaviors 
were not affected equally, the possibility of modifying a large 
number of behaviors by destroying even a small amount of 
brain tissue is quite clear. In drawing conclusions from brain 
stimulation experiments, what is almost invariably overlooked is 
that just about every area of the brain is involved in many 
different functions and all but the simplest functions have 
multiple representation in the brain. 

The eagerness to believe that discrete and natural motiva- 
tional states such as hunger can be manipulated by brain 
stimulation has resulted in a selective perception of even some 
of the pioneering work in this field. For example, although Hess 
is consistently mentioned as having produced bulimia by 
hypothalamic stimulation, it sometimes seems that his classic 
papers are not read so often as they are cited. Hess (1957, p. 
25) actually said the following: "Stimulation here produces 
bulimia. If the animal has previously taken neither milk nor 
meat, it now devours or drinks greedily. As a matter of fact, 
that animal may even take into its mouth or gnaw on objects 
that are unsuitable as food, such as forceps, keys, or sticks. " 
(Italics mine.) 

It must be recognized that most hungry cats are more 
discriminating than Hess's brain-stimulated animals. 

In the studies from my own laboratory, it has been shown 
that the behavior evoked by brain stimulation is very different 
from behavior motivated by natural states. A stimulated animal 
may eat one type of food, but not the food it normally eats in 
its home cage (fig. 1 ). or it may not eat even the same food if it 
is changed in texture, as when food pellets are offered as a 

13 



ground mash. Stimulated animals may drink water from a 
drinking tube, but not from an open dish (fig. 2), and the taste 
preferences of an animal drinking in response to stimulation 
differ from those of a thirsty animal (fig. 3). Most important 
from the point of view of behavior control (or lack of it), the 
elicited behavior may change even in response to identical brain 
stimulation. A rat that drinks only in response to stimulation, 
for example, may start to eat when stimulated at a later time 
(figs. 4, 5). Moreover, the brain sites from which eating and 
drinking may be evoked are much more widespread than is 
usually implied. There is no anatomically discrete focus for this 
phenomenon, although there are brain areas where the proba- 
bility of evoking eating and drinking is very low (Cox and 
Valenstein, 1969). In 1973 Reis, Doba, and Nathan reached a 
similar conclusion. These investigators found that they could 
evoke grooming, eating, and predatory behavior (depending on 
the intensity of the stimulating current) from almost all 
electrodes placed in the fastigial nucleus of the cat's cerebellum. 
Since the behaviors invariably appeared in the same order as the 
stimulus intensity was increased, regardless of the electrode 
placement within the fastigial nucleus, the investigators con- 
cluded (op. cit., p. 847): "Thus, it is the intensity of the 
stimulus and not the location of the electrode which is one of 
the determinants of the identity of the behavior. Second, the 
observation that the nature of the behavior evoked from a single 
electrode at a fixed stimulus intensity could be changed by 
altering the availability of goal objects (such as food or prey) is 
another demonstration that the locus of the electrode is not 
critical. Thus, our findings suggest that the behavioral responses 
from fastigial stimulation are probably not due to excitation of 
discretely organized neural pathways." 

The conclusion to be drawn from these experiments is 
certainly not that stimulation at any brain sites can evoke any 
behavior if the contingencies are arranged appropriately or that 
stimulation at different sites all evoke the same general state. 
These misinterpretations continue to appear in print although 
we have made an effort to be clear on these points. Valenstein, 

14 



20 



i 5 



100% 



o 10 



^ 



0% 0% 



© 



MLH 



0% 0% 




^ Col Dog Food 
^ Food Pellets 

I Water 



Stimulation with 

Cot - Dog Food 

Removed 



© 



© 



ALL GOAL OBJECTS PRESENT 

TESTS 



© © © 

CAT -DOG FOOD ABSENT 



FIG. 1 . Behavior evoked by brain stimulation in a testing situation involving 
choices. During initial 3 tests, rats received brain stimulation in the presence of 
commercial cat-dog food, their regular food pellets, and a water bottle. Stimulation 
evoked eating cat-dog food only. Then cat-dog food was removed. We assumed that if 
stimulation evoked a hunger state animals would readily switch to eating food pellets. 
Instead, stimulation gradually evoked drinking with increasing regularity (see fig. 5). 
After stimulation evoked regular drinking three additional tests with food pellets and 
a water bottle were administered. Animals drank almost every time stimulation was 
given. Stimulus parameters were invariably the same. Each test consisted of 20 stimu- 
lations (20 sec. duration). Maximum score for any one behavior was 20, but animals 
could display more than one behavior during a single 20-second stimulation period. 
(Data from Valenstein, Cox, and Kakolewski, 1968b.) 

Cox, and Kakolewski (1970, p. 30) said: "We are not suggesting 
that any elicited response may substitute for any other, but 
rather that the states induced by hypothalamic stimulation are 
not sufficiently specified to exclude the possibility of response 
substitution." And Valenstein (1969, p. 300) said, "[it] is not 
meant to imply that it will not be possible to differentiate the 
effects of stimulation at different hypothalamic regions, but 
rather that the application of specific terms such as hunger, 
thirst and sex may not be justified." 

It seems clear that some behaviors are more likely to be 



15 



20 



100% 



100% 



15 



Q 

Id 

o 10 



5- 



3 
O 



90% 



0% 



0% 



M Water in Bottle 

I Water in Dish 

^^ Food Pellets 



Drinking Experience 
from Water Dish 



Stimulation with 

Water Dish and 

Food Pellets 



0% 



^ 




© © © 

WATER DISH ABSENT 



© © © 

WATER BOTTLE ABSENT 



TESTS 



FIG. 2. Behavior evoked by brain stimulation in a testing situation. During initial 
tests, rat drank from water almost every time stimulation was administered, but did 
not drink water from a dish or eat food pellets. Afterward, the animal drank all the 
water from a dish for three days (this was natural drinking; no brain stimulation was 
administered) before periodic stimulation in the presence of the water dish and food 
pellets were initiated. It was assumed that if thirst had been induced by stimulation 
during initial tests, rat would rapidly switch to drinking water from dish when stimu- 
lated. Instead, stimulation gradually evoked eating of food pellets. During three 
stimulation tests with water dish and food pellets available, rat did not drink, but ate 
food pellets during most of stimulation trials. Stimulus parameters were invariably 
the same. Each test consisted of 20 stimulations (20-sec. duration). Maximum score 
for any one behavior was 20, but animals could display more than one behavior 
during a single 20-second stimulation period. (Data from Valenstein, Kakolewski, and 
Cox, 1968.) 



interchangeable than others. This probably reflects the role of 
the sensory, motor, and visceral changes induced by the 
stimulation in channeling behavior in certain directions. Although 
these bodily changes do not duplicate natural motivational states, 
they do play an important role in determining the types of behav- 
ior that will Or will not be seen during stimulation. 



16 



100 



? 90 



K 80 - 



o 70 - 



60 - 



o 50 - 



3 40 - 



u 30 - 



20 - 



D 



IVofer 

30 % Glucose 
N = 9 



WATER 
DEPRIVED 



DRINKING ELICITED BY 
HYPOTHALAMIC STIMULATION 



FIG. 3. Preference for water and glucose by rats receiving brain stimulation and 
the same animals being deprived of water for 48 hours. All rats initially drank water 
when stimulated but did not eat. In a two-bottle choice test, they preferred glucose 
during brain stimulation, but water when thirsty. (Data from Valenstein, Kakolewski. 
and Cox. 1968.) 

To date, the direct effects of stimulation have been relatively 
neglected. Although it is often stated that stimulation does not 
produce behavior changes unless the appropriate stimulus is 
available, such changes are actually often neglected even when 
the data suggest their importance. For example, the first 
description of drinking evoked by brain stimulation contained a 
strong suggestion that motor responses may have been more 
important in directing behavior than any presumed thirst state. 
In his report. Greer (T955. pp. 60-61 ) said: 

Stimulation of the animal began 24 hours after the electrodes were 
implanted. It was immediately apparent that the animal was under great 
compulsion to perform violent "licking" activity when a current was 
passed between the hypothalamic electrodes. In response to stimula- 
tion, it would stand on its hind legs and run vigorously around the glass 
enclosed circular cage, licking wildly at the glass wall. This behavior 



17 



would cease immediately upon shutting off the current. If the voltage 
were slowly increased, licking would gradually become more vigorous. 
With stimulation continuing by timer control, the reaction of the 
animal changed during the first night. The water bottle containing 200 
ml was found completely empty at 9 a.m. even though it had been 
filled at 6 p.m. the previous evening. It was now found that stimulation 
would result in violent drinking activity. The non-specific licking 
response had been lost. As soon as the current was turned on, the 
animal would jump for the water bottle and continue to drink avidly 
until the switch was turned off. If the water bottle was removed and 
the current then turned on, the rat would go back to its "licking" 
behavior of the previous day, but would immediately transfer it to 
drinking behavior when the water bottle was replaced. 



100% 100% 100% 




© © © 

ALL GOAL OBJECTS PRESENT 



© © © 

WATER REMOVED 
TESTS 



© 



© 



© 



ALL GOAL OBJECTS PRESENT 



FIG. 4. Behavior evoked by brain stimulation in a choice situation. Initially, 
animal drank only when stimulation was given (first 3 tests). After periodical 
stimulation in the presence of food and a wooden block (for gnawing), but without 
water bottle, rat gradually began to eat food pellets. Next three tests demonstrated 
that stimulation evoked regular eating. Last 3 tests demonstrated that even when 
tested with water bottle present, stimulation elicited eating as well as drinking. 
Stimulus parameters were invariably the same. Each test consisted of 20 stimulations 
(20-sec. duration). Maximum score for any one behavior was 20, but animals could 
display more than one behavior during a single 20-second stimulation period. (Data 
from Valenstein, Kakolewski, and Cox, 1968a). 

Visceral changes produced by the stimulation may also play a 
role in determining the behavior evoked by brain stimulation. 
For example, Folkow and Rubinstein (1965) contrasted the 
visceral changes produced by hypothalamic stimulation that 
evokes eating with those changes produced by electrodes 
evoking rage reactions. Among the prominent bodily changes 



18 



Coling 

Drinking 



Stimulation 

without 

reed 




FOOD ond WATER PRESENT 



20 25 30 35 

ONLY WATER PRESENT 
TESTS 



45 50 

FOOO ond WATER PRESENT 



FIG. 5. Gradual development of behavior evoked by brain stimulation. Rat was 
tested shortly after first demonstration of eating in response to stimulation. In more 
than 10 successive tests, eating was evoked by brain stimulation with increasing 
regularity. Although water was available, stimulation never evoked drinking. Animal 
was then given periodic stimulation for one-week period until it started to drink in 
response to stimulation. In more than 40 tests, rat drank in response to stimulation 
with increasing regularity. During last 10 tests, both food and water were present. 
During most tests rat ate and drank when stimulation was administered, although 
drinking gradually became dominant evoked response. Stimulus parameters were invar- 
iably the same. Each test consisted of 20 stimulations (20-sec. duration). Maximum 
score for any one behavior was 20, but animals could display more than one behavior 
during a single 20-second stimulation period. (Data from Valenstein, 1971.) 



produced by stimulation that caused rats to eat were a marked 
increase of intestinal motility and change in stomach volume 
plus mild increases in blood pressure and heart rate. The pattern 
was different when rage was evoked; intestinal and gastric 
motility were inhibited, and the blood pressure and blood 
distribution patterns differed from those produced by elec- 
trodes that evoked eating. 

Ball (1974) also stressed the importance of visceral changes 
for evoked eating. In rats displaying this response, Ball 
sectioned the vagus nerve at a point close to where it innervates 
the stomach. He reported that the stimulus threshold for 
elicitation of eating was raised significantly even after the 
animals recovered from surgery and were eating the normal 
amount of food in their home cage. Even though the thresholds 
increased, it was clear that the visceral changes controlled by 



this branch of the vagus nerve were not necessary for the 
evoked behavior, as stimulation continued to evoke eating. 
Similarly, as noted earlier, Reis, Doba, and Nathan (1973) 
reported that electrical stimulation of the rostral fastigial 
nucleus of the cat's cerebellum elicited either grooming, 
feeding, or killing of a rat, depending on the intensity of 
stimulation used. The magnitude of the cardiovascular responses 
(heart rate and blood pressure) differed for each of the three 
behaviors evoked, but the behaviors were still displayed after 
these visceral responses were blocked by an injection of 
phentolamine. It is evident from the many important studies by 
Flynn and his colleagues (see Flynn, Edwards, and Bandler, 
1971) that brain stimulation produces many different sensory, 
motor, and visceral changes. Apparently the blocking of one or 
two of these changes is not likely to be very disruptive once an 
elicited behavior has become established. These bodily changes, 
however, may play an important role in channeling behavior 
during the initial brain stimulation experience. 

In addition to producing bodily changes, the positive or 
aversive motivational effects evoked by brain stimulation may 
also serve to channel behavior and determine which behaviors 
are interchangeable. Plotnik (1974) summarized the motiva- 
tional consequences of 174 brain stimulation sites in monkeys. 
The motivational effects were determined by tests that mea- 
sured whether an animal sought out escaped from or was 
indifferent to the brain stimulation. It was found that 1 17 sites 
were neutral, 22 were positive or rewarding, and 35 were 
aversive or negative. All 14 points that elicited aggressive 
behavior directed at other monkeys had aversive motivational 
properties, although the converse was not true. Plotnik views 
the elicited aggression as "secondary aggression" produced by 
reaction to an aversive stimulus. In such cases, it would be as 
misleading to conclude that there was a direct relationship 
between natural aggression and the brain site stimulated as there 
would be to conclude the same about the soles of the feet 
because an electric shock delivered to them produces fighting 
between animals caged together. The point is well illustrated by 

20 



Black and Vandcrwolf (1969, p. 448), who reported that a 
foot-thumping response could be evoked in the rabbit by 
stimulation of diverse brain sites (in the hypothalamus, thala- 
mus, central gray, septum, reticular formation and fornix- 
fimbria). Rather than postulate the existence of a complex 
"thumping circuit" in the rabbit brain, they noted that 
thumping could be elicited by foot shock and concluded that 
"thumping behavior in the rabbit is a fear or pain response. " 

The significance of the motivational properties of brain 
stimulation is made clearer by distinguishing predatory from 
aggressive behaviors. In cats and rats, hypothalamic stimulation 
has evoked both types of behaviors. In these animals, a 
predatory, stalking behavior (called "quiet biting attack" in the 
rat), which is well directed at an appropriate prey, has been 
distinguished from a diffusely directed "affective rage attack" 
(Wasman and Flynn, 1962; Panksepp, 1971). Stimulation at 
sites that evoke the predatory (or appetitive) behavior has been 
shown to also evoke positive or rewarding effects (Panksepp, 
1971), whereas stimulation at sites evoking "affective attack" 
has been demonstrated to be aversive (Adams and Flynn, 1966). 
In primates, the elicited aggression is intraspecific, resembling 
fighting rather than predatory behavior, and is evoked pri- 
marily, if not exclusively, by stimulation having aversive 
motivational properties. 1 Although the evidence is inadequate, 
aggression provoked by brain stimulation in humans also seems 
to occur only in cases of stimulation having aversive conse- 
quences (see Valenstein, 1973, for a review of this literature). 
Considerations such as these, suggesting that certain behaviors 
are compatible with aversive and others with positive states, 
may set limits on the behaviors that can be evoked by a 
particular brain electrode. 

Although the somatic and motivational effects produced by 

1 Robinson, Alexander, and Browne (1969) reported one instance where stimula- 
tion elicited aggressive attacks on another monkey and also supported self-stimula- 
tion behavior. This suggests that brain stimulation that elicits intraspecies aggression 
may be motivationally positive. However, as self-stimulation was tested with brief 
(0.5 sec.) stimulus trains and aggression was elicited by relatively long (10-40 sec.) 
stimulus trains, this exception may be more apparent than real. 

21 



brain stimulation make it more likely that one group of 
behaviors will be evoked rather than another, these factors are 
by no means sufficient to determine completely the specific 
behavior displayed or the motivational states induced. Environ- 
mental factors and individual or species characteristics can also 
be very important determinants. An experiment from my own 
laboratory demonstrates this point and also illustrates how 
easily one can be misled by first impressions in brain stimula- 
tion experiments. 

Figure 6 illustrates a two-compartment chamber used to test 
the behavior of rats receiving rewarding hypothalamic stimula- 
tion (Phillips et al., 1969). The equipment was so arranged that 
when the rat interrupted the photo cells on the right side of the 
chamber, brain stimulation is turned on and remained on until 
the animal interrupted the photo cell in the left compartment. 
In an amazingly short time, the rat learned to play the game, 
running to the right side and turning the stimulation on for a 
period, then running to the opposite side and turning the 
stimulation off. This behavior was repeated rapidly over and 
over again. The rat was stimulating its own brain and apparently 
enjoying it— at least it continued doing it. 

At this point, we placed food pellets on the right, the 
stimulation side. After a brief period, the rat started to pick up 
the pellets when stimulated and carry them (as pictured in fig. 
6) to the opposite side of the chamber, where they were 
dropped as soon as the brain stimulation was turned off. We 
were fascinated by this unexpected turn of events, as it seemed 
possible that we had stumbled on a region of the rat's brain that 
regulated food-hoarding behavior. At least that is what we were 
thinking until we investigated a little further. When we 
substituted rubber erasers and pieces of dowel sticks, the rat 
carried them just as readily. If we mixed the edible and inedible 
objects together, the rat did not discriminate between them. It 
carried both. This was a very strange type of food-hoarding 
behavior! Next we placed some rat pups on the right side and 
found that these also were carried to the other side. It dawned 
on us that had we started with the rat pups and gone no farther, 

22 



we would have been convinced thai we were activating the brain 
structures that controlled the pup-retrieval component of 
maternal behavior. Probably we would have found it difficult to 
resist speculating about the significance of the fact that males 
carried pups as readily as females. 




FIG. 6. Rat carrying wooden dowel stock from stimulation (right) to nonstimula- 
tion (left) side of test chamber. (In this variation of the basic experiment, animals 
were given a choice between receiving hypothalamic stimulation with or without the 
opportunity to carry objects; they chose the former.) (Data from Phillips et al., 1969: 
figure reproduced from Valenstein, Cox, and Kakolewski, 1970.) 

Once the rats started carrying objects regularly, they would 
pick up and carry almost anything in response to the stimula- 
tion. When stimulated, the compulsion to carry became so 
strong that the rats carried parts of their own bodies when all 
the objects were removed. A rat picked up its tail or a front leg 
with its mouth and carried it over to the other side where it was 
"deposited" as soon as the stimulation was turned off. 

Finally, we found that if the very same stimulation was 
delivered to the rat's brain under different conditions, objects 
were no longer carried. We programmed the equipment to 
deliver the same temporal pattern of stimulation the rat had 
previously self-administered, controlled now by a clock rather 
than by the rat's position. This procedural change resulted in 
the possibility that the animal could be stimulated any place in 
the test chamber rather than the stimulation being turned on 



23 



and off consistently in different parts of the chamber. Under 
these conditions the identical electric stimulus, delivered to the 
same brain site through the same electrode, no longer evoked 
object-carrying even if the animal was directly over several of 
the objects when the stimulation was turned on. 

We believe that the answer to this puzzling phenomenon lies 
partly in the rat's tendency to carry objects (food, pups, even 
shiny objects) from an open field, where the rat is vulnerable 
and therefore highly aroused, back to the relatively secure and 
calming environment of the nest site. When stimulation is 
delivered regularly in certain parts of the rat's life space and 
turned off regularly in other parts, it not only produces 
alternating arousal and calming states, but links these states to 
specific parts of the environment. In addition, because rats 
prefer to turn off even rewarding brain stimuli after a period of 
time (Valenstein and Valenstein, 1964), they are forced to 
move back and forth in the test chamber. Taken all together, we 
may have inadvertently duplicated all the internal and external 
conditions that exist when a rat makes repeated forays from its 
nest site to the outside world. 

Admittedly, this explanation is speculative. It is clear, 
however, that the behavior produced by stimulation is not 
determined in any simple fashion by the location of the 
electrode in the brain. (Actually, we achieved the same results 
with electrodes in different rewarding sites.) The behavior 
produced by the stimulation can only be understood by 
considering the natural propensities of the rat in the environ- 
mental conditions in which it is tested. 

BRAIN STIMULATION IN HUMANS AND OTHER PRIMATES 

If the response to brain stimulation is variable in inbred rats, 
it is certainly much more variable in monkeys and humans. In 
monkeys, for example, brain stimulation may initiate drinking 
when the animal is confined to a restraining chair. However, 
when the stimulation is administered when the monkeys are in a 
cage and not restrained, they do not drink, even though they 

24 



may be sitting within inches of the water dispenser when the 
stimulation is administered (Bowden, Galkin, and Rosvold, In 
press). In humans, brain stimulation may evoke general emo- 
tional states that are somewhat predictable in the sense that 
certain areas tend to produce unpleasant feelings and other 
areas tend to produce positive emotional states. Patients may 
report feeling tension, agitation, anxiety, fear, or anger, or they 
may describe their feelings as being very pleasant or relaxed. 
Different patients report different feelings from stimulation of 
what is presumed to be the same brain area, and the same 
person may have very different experiences from identical 
stimulation administered at different times (see Valenstein, 
1973, for a review of this literature). The impression that brain 
stimulation can evoke the identical emotional state repeatedly 
in humans is simply a myth, perhaps perpetuated in part 
because of its dramatic impact. Janice Stevens et al. (1969, p. 
164) stressed this variability: "Subjective changes were elic- 
itable in similar but not identical form repeatedly on the same 
day, but often were altered when stimulation was carried out at 
the same point on different days. " 

Many people have the impression that the results of brain 
stimulation are predictable because of the reports that the same 
visual hallucinations and memories can be evoked repeatedly by 
brain stimulation. It is true that Wilder Penfield, who operated 
on the temporal lobes of patients suffering from intractable 
epilepsy, had emphasized that electrical stimulation of this 
brain region may repeatedly evoke the same memory. Consider- 
able excitement was generated by reports that these evoked 
memories had the fidelity of tape recording playbacks of past, 
forgotten experiences. Indeed, on the basis of these reports, a 
few psychoanalysts began to speculate about the neural basis of 
repressed memories (Kubie, 1953). What was generally over- 
looked, however, was that Penfield had reported that the same 
response could be evoked within a minute or two, but a 
different response was obtained after a longer period (see 
Penfield and Perot, 1963). The similarity of this conclusion to 
that of Stevens et al. (1969) is apparent. Moreover, recent 

25 



studies have made it clear that the occurrence of these evoked 
memories is rare and when they do occur it can usually be 
shown that they were determined by what was on the patient's 
mind or some other aspect of the situation when stimulation 
was administered (Van Buren, 1961; Mahl et al., 1 964). 

Even relatively simple motor and sensory responses to 
stimulation of specific areas of the cerebral cortex of primates 
may vary with time and individuals. When Leyton and 
Sherrington (1917) reported their observations following corti- 
cal stimulation of the chimpanzee, orang-utan, and gorilla, they 
noted considerable evidence of "functional instability of corti- 
cal motor points." Not only did thresholds vary and stimulation 
of a particular brain site produce either extension or at other 
times flexion of the same joint, but the muscles involved 
sometimes also changed. Leyton and Sherrington reported that 
often a particular response became dominant and was elicited 
from a variety of cortical points that had previously given very 
different responses. They also observed that stimulation of the 
same cortical points produced different responses from differ- 
ent individuals and even from opposite hemispheres within the 
same individual. This is not to deny that there was general 
agreement as to the parts of the frontal cortex most likely to 
produce movement of some kind in specific muscle groups, but 
Leyton and Sherrington emphasized that the details of the 
movements would not be the same if the experiment were 
repeated. Observations of this type have also been made 
following stimulation of the human cortex. Penfield and 
Boldrey (1937, p. 402) noted that stimulation at a point on the 
post-central gyrus, which does not elicit a particular response, 
may gain this capability if it is tested after stimulating a brain 
point that does evoke the response. Similar observations of 
variation of responses have been reported following electrical 
stimulation of sensory cortical areas in humans. Penfield and 
Welch (1949), for example, noted that if a brain site evoked 
sensations seeming to originate in the thumb, the same 
stimulation might later evoke sensations experienced as coming 
from the lips if the stimulation had been preceded by activation 

26 



of another site that evoked lip sensations. These authors have 
called such variability "deviation of sensory response." Libet 
(1973) discussed the variability in human response to electrical 
stimulation in more detail. 

It is totally unrealistic to believe that stimulation of a 
discrete point in the brain will invariably elicit the same 
memory, emotional state, or behavior. The changes produced 
by the stimulation depend upon what is going on in the rest of 
the brain and in the environment at the time. The understand- 
able need in science to eliminate variability and demonstrate 
control over phenomena may, when applied to the study of the 
brain, distort reality by concealing the very plasticity that is an 
essential aspect of adaptive behavior. 

CONTROL OF HUMAN BEHAVIOR: FACT AND FANTASY 

No discussion of electrical brain stimulation and behavior 
control would be complete without considering the existence of 
rewarding brain stimulation. As everyone surely knows by now, 
Olds and Milner (1954) accidentally discovered about 20 years 
ago that electrical stimulation of certain brain structures can 
serve as an effective reward for rats. Subsequent studies of the 
behavior of rats and other animals indicated, in many different 
ways, that pleasurable sensations can be evoked by brain 
stimulation (see Olds, 1973). No other single discovery in the 
brain-behavior field has produced more theoretical speculation 
than the phenomenon that animals are highly motivated to 
stimulate their own brains. Clarke's reaction (1964, pp. 200- 
201) to this discovery is representative: 

Perhaps the most sensational results of this experimentation, which 
may be fraught with more social consequences than the early work of 
the nuclear physicists, is the discovery of the so-called pleasure or 
rewarding centers in the brain. Animals with electrodes implanted in 
these areas quickly learn to operate the switch controlling the 
immensely enjoyable electrical stimulus, and develop such an addiction 
that nothing else interests them. Monkeys have been known to press the 
reward button three times a second for eighteen hours on end, 
completely undistracted either by food or sex. There are also pain and 

27 



punishment areas of the brain; an animal will work with equal 
singlemindedness to switch off any current fed into these. 

The possibilities here, for good and evil, are so obvious that there is no 
point in exaggerating or discounting them. Electronic possession of 
human robots controlled from a central broadcasting station is 
something that even George Orwell never thought of, but it may be 
technically possible long before 1984. 

In part, because the pleasurable reactions have been produced 
by direct stimulation of the brain and involve electronic 
gadgetry, there is a tendency to conjure up images of "pure 
pleasure 1 ' that are completely irresistible. It should surprise no 
one that science fiction writers have seized this phenomenon as 
a theme for their stories. In Larry Niven's story (1970), for 
example, the presumed omnipotence of rewarding brain stimu- 
lation is at the very center of the "perfect crime." The story 
takes place in the year 2123 and Owen Jennison's body has just 
been discovered under conditions that appear to indicate a 
suicide, but the death actually was the result of a carefully 
planned murder: 

Owen Jennison sat grinning in a water stained silk dressing gown. A 
month's growth of untended beard covered half his face. A small black 
cylinder protruded from the top of his head. An electric cord trailed 
from the top of the cylinder and ran to a small wall socket. 

The cylinder was a droud, a current addict's transformer. 

It was a standard surgical job. Owen could have had it done anywhere. 
A hole in his scalp, invisible under the hair, nearly impossible to find 
even if you knew what you were looking for. Even your best friends 
wouldn't know, unless they caught you and the droud plugged in. But 
the tiny hole marked a bigger plug set in the bone of the skull. I 
touched the ecstasy plug with my imaginary fingertips, then ran them 
down the hair-fine wire going deep into Owen's brain, down into the 
pleasure center. 

He had starved to death sitting in that chair. 

Consider the details of the hypothetical murder. Owen Jennison is 
drugged no doubt-an ecstasy plug is attached — He is tied up and 
allowed to waken. The killer then plugs Mr. Jennison into a wall. A 
current trickles through his brain, and Owen Jennison knows pure 
pleasure for the first time in his life. 

28 



He is left tied up for, let us say, three hours. In the first few minutes he 
would be a hopeless addict. 

No more than three hours by our hypothesis. They would cut the ropes 
and leave Owen Jennison to starve to death. In the space of a month 
the evidence of his drugging would vanish, as would any abrasions left 
by ropes, lumps on his head, mercy needle punctures, and the like. A 
carefully detailed, well thought out plan, don't you agree? 

The readiness to believe that artificial stimulation of the 
brain can evoke such intense and irresistible pleasures reveals 
more about our desires than about our brain. Routtenberg and 
Lindy (1965) did demonstrate that some rats actually starved 
themselves to death because they continued to stimulate their 
brains rather than eat. However, one can be terribly misled by 
the popular accounts of this experiment. In the actual experi- 
ment, rats with electrodes implanted in rewarding brain 
structures were given only one hour a day to press a lever for 
food. It was necessary for them to eat during that hour in order 
to stay alive. After the rats were on this feeding schedule for a 
period, they were given a second lever that offered brain 
stimulation as a reward. Some of them spent so much time on 
this second lever that they did not receive sufficient food to 
keep them alive until the next day's hourly session. This is quite 
different from the picture most people have in mind about what 
took place. In the special conditions of a brief test designed to 
emphasize the controlling power of brain stimulation, some of 
the rats were apparently not able to anticipate the consequences 
of choosing the brain stimulation lever. Under conditions 
providing rats with free access to brain stimulation and food, 
they never starve themselves. In fact, they eat their usual 
amount of food (Valenstein and Beer, 1964). 

Rewarding brain stimulation is not equally compelling for all 
species. In humans, it does not seem capable of inducing an 
irresistible, pleasurable experience. Robert Heath, who is 
probably more experienced than anyone else with the pleasura- 
ble reactions brain stimulation can evoke in humans, has 
commented that it does not seem able to induce a euphoria 
equal to that produced by drugs (personal commun.). This is 

29 



not to deny that patients have reported feeling considerable 
pleasure during brain stimulation or that they were willing to 
repeat the experience, particularly after receiving the impression 
that this was part of the therapeutic program. (See Valenstein, 
1973, for a review of the reports of pleasure evoked by brain 
stimulation in humans.) Brain stimulation has evoked orgasms, 
but there is a tendency to attach too much significance to this. 
It is usually overlooked that, as with masturbation, brain 
stimulation that produces an orgasm does not continue to be as 
pleasurable afterward. 

The emotional state induced in humans by brain stimulation 
varies with the emotional and physical condition of the patient. 
(Heath, John, and Fontana, 1968, p. 168) stated that "When the 
same stimulus was repeated in the same patient, responses 
varied. The most intense pleasurable responses occurred in 
patients stimulated while they were suffering from intense pain, 
whether emotional and reflected by despair, anguish, intense 
fear or rage, or physical, such as that caused by carcinoma. The 
feelings induced by stimulation of pleasure sites obliterated 
these patients' awareness of physical pain. Patients who felt well 
at the time of stimulation, on the other hand, experienced only 
slight pleasure. " (Italics mine.) 

The existence of circuits in the brain that can induce both 
pleasure and arousal may be telling us something important 
about neural mechanisms that have evolved to help focus 
attention, to increase involvement in a task, and to facilitate the 
consolidation of memories (see discussion in Valenstein, 1973, 
pp. 40-44). There are speculations that malfunctioning of these 
reward circuits is responsible for such psychiatric conditions as 
depression and schizophrenia (see Stein, 1971). Such specula- 
tion leads to more research that ultimately will increase our 
understanding of how the brain regulates behavior. This is very 
unlikely to be the consequence of the proposals to use brain 
stimulation to control behavior. 

It would be difficult to fabricate a better example of the 
distortions that can result from a preoccupation with behavior 
control than that contained in a proposal, apparently seriously 

30 



advanced, by [ngraham and Smith ( 1972). These two criminolo- 
gists suggested that techniques are available for maintaining a 
surveillance on paroled prisoners and for controlling their 
behavior. They propose that implanted devices could be used to 
keep track of the location of the parolee and his physiological 
state while remotely operated brain stimulation could deliver 
either rewards or punishments or it could control behavior in 
other ways. For example, Ingraham and Smith (1972, p. 42) 
suggested the following scenario. 

"A parolee with a past record of burglaries is tracked to a 
downtown shopping district (in fact, is exactly placed in a store 
known to be locked up for the night) and the physiological data 
reveals an increased respiration rate, a tension in the muscula- 
ture and an increased flow of adrenalin. It would be a safe 
guess, certainly, that he was up to no good. The computer in 
this case, weighing the probabilities, would come to a decision 
and alert the police or parole officer so that they could hasten 
to the scene; or, if the subject were equipped with an implanted 
radiotelemeter, it could transmit an electrical signal which could 
block further action by the subject by causing him to forget or 
abandon his project." 

It is impossible to be certain, but it seems unlikely that 
anyone would approve such a plan. The more serious problem is 
the amount of creative energy diverted from the search for 
realistic solutions to important social problems by this type of 
thinking. It sometimes seems that difficulties in implementing 
necessary social changes encourage people to search for solu- 
tions in a fantasy world. 

Hopefully, it is clear by now that the responses that can be 
evoked from stimulating discrete brain areas are too variable 
and affect too many different functions to be useful in 
behavior-control schemes. The evoked behavior depends on 
what is going on elsewhere in the brain, individual and species 
characteristics, and is very much influenced by situational 
factors. Those who prefer to think only in terms of control may 
be very disappointed to learn this. Those who think that the 
basic concern of science is understanding may find it useful to 

31 



be reminded of the complex relationship between brain and 
behavior. 

It is not surprising that biological solutions to social problems 
have been discussed most frequently in the context of control- 
ling violence. This discussion, and some actual proposals, have 
taken very different forms. In his address to the American 
Psychological Association mentioned earlier, Kenneth Clark also 
stated: 

Given the urgency of the immediate survival problem, the psychological 
and social sciences must enable us to control the animalistic, barbaric 
and primitive propensities in man and subordinate these negatives to 
the uniquely human moral and ethical characteristics of love, kindness 
and empathy. We can no longer afford to rely solely on the traditional 
prescientific attempts to contain human cruelty and destructiveness. 

Given these contemporary facts, it would seem that a requirement 
imposed on all power-controlling leaders, and those who aspire to such 
leadership, would be that they accept and use the earliest perfected 
form of psychotechnological, biochemical intervention which would 
assure their positive use of power and reduce or block the possibility of 
using power destructively. It would assure that there would be no 
absurd or barbaric use of power. It would provide the masses of human 
beings with the security that their leaders would not sacrifice them on 
the altars of their personal ego (Presidential Address, American 
Psychological Association, 1971). 

Undoubtedly Kenneth Clark is seriously concerned about 
possible misuse of the enormous capabilities for destruction 
that exist. His speech and the types of solutions he proposes 
make it apparent that he has been greatly influenced by the 
experiments interpreted as revealing discrete neural circuits 
regulating aggression. Stripped to its essentials, his proposal 
appears as a modern variant of phrenology, a belief that the 
brain is organized into convenient functional systems that 
conform to our value-laden categories of behavior. Clark seems 
to believe that we need only to exorcise those critical regions of 
the brain that are responsible for undesirable behavior, or to 
suppress them biochemically, and goodness will dominate. 
Mankind will be saved by a "goodness pill." The great impact of 
the many distorted descriptions of the power of brain control 

32 



techniques becomes especially evident when even social sci- 
entists accept the questionable hypotheses that wars are mainly 
caused by man's animal-like aggressive tendencies and that 
biological intervention offers a practical way to prevent them. 
Clark has not suggested any specific biological intervention, so 
it is not possible to discuss his proposal in any detail. The 
situation is different with the proposal advanced by Vernon 
Mark and Frank Ervin. 

Mark and Ervin (1970) stressed the magnitude of the 
problem of violence in the United States and the belief that a 
biological approach can make a significant contribution toward 
finding a solution. The following are typical of a number of 
statements from their book. 

"Violence is, without question, both prominent and preva- 
lent in American life. In 1968 more Americans were the victims 
of murder and aggravated assault in the United States than were 
killed and wounded in seven-and-one-half years of the Vietnam 
War; and altogether almost half a million of us were the victims 
of homicide, rape, and assault." 

They introduced their book (1970) with the Preface that 
"We have written this book to stimulate a new and biologically 
oriented approach to the problem of human violence." In the 
foreword to the book, William Sweet, a neurosurgeon affiliated 
with Harvard University and the Massachusetts General Hospital 
and a frequent collaborator of Mark and Ervin, expressed "the 
hope that knowledge gained about emotional brain function in 
violent persons with brain disease can be applied to combat the 
violence-triggering mechanisms in the brains of the non- 
diseased." Clearly, a biological solution to the problem of 
violence is sought. 

Mark and Ervin suggested that abnormal brain foci in the 
amygdala are responsible for a significant amount of violent 
crimes. They believe that these abnormal foci often respond to 
internal and external stimuli by triggering violent behavior. 
Mark and Ervin have implanted stimulating electrodes in 
patients that display a history of episodic violence and claim to 
be able to locate the "brain triggers" by determining the area 

33 



from which violent behavior can be evoked. The treatment 
consists of destroying the area believed to be responsible for the 
abnormal behavior. 

The relevance of temporal lobe structures for aggressive 
behavior can be traced back to the seminal studies of Kliiver 
and Bucy (1939), although there were several earlier reports 
that contained similar observations (for example, Brown and 
Shafer, 1888; Goltz, 1892). Most investigators now believe that 
the temporal lobes and particularly the amygdala nuclei play an 
important, although complex, role in the expression of aggres- 
sion, but Kliiver and Bucy and all subsequent investigators have 
emphasized the very many different behavioral changes that 
follow destruction of this brain region in animals (see Valen- 
stein, 1973, pp. 131-143). 

In addition to a "taming" of monkeys (and other animals) 
after temporal lobe ablation, hypersexuality, increased orality, 
and a so-called psychic blindness 1 have also been observed. 
Others have emphasized the emotional "flatness" of the 
amygdalectomized animal (e.g., Schwartzbaum, 1960). The 
behavior changes may take very different forms, even diametri- 
cally opposite expression, under different circumstances. Amyg- 
dalectomized monkeys may become less aggressive toward man, 
but as Rosvold, Mirsky, and Pribram (1954) reported, the 
changes in dominance patterns between animals may be more 
dependent on the history of their social interactions than on the 
particular brain area destroyed. 

Arthur Kling and his colleagues have recently reported even 
more striking evidence of the fallacy of describing complex 
change in response tendencies by such shorthand expressions as 
"increased tameness" (Kling, Lancaster, and Benitone, 1970; 
Kling, 1972). Kling captured and amygdalectomized wild 
monkeys in Africa and on Caijo Santiago near Puerto Rico. 
Control monkeys that were captured and released rejoined their 



1 "Psychic blindness" refers to a loss of higher integrative visual functions rather 
than to a loss in visual acuity. 



34 



troupe although sonic initial fighting was necessary. Before 
they were released, the amygdalectomized monkeys seemed 
tamer when approached by the experimenters, but when 
released into their own troupe they were completely unable to 
cope with the complexities of monkey social life. The behavior 
of the amygdalectomized monkeys was often inappropriate. 
Sometimes they displayed aggression toward dominant animals, 
a trait never exhibited before. In not too long a period, all the 
amygdalectomized monkeys either were driven from or re- 
treated out of the troupe and eventually either died of 
starvation or were killed by predators. These observations 
demonstrate the multiplicity of behavioral changes that usually 
occur following brain lesions and the dependency of these on 
environmental conditions. In this context, it is interesting that 
the compulsive sexual mounting commonly observed in amyg- 
dalectomized monkeys housed in the laboratory was not seen 
under natural conditions. 

The results of amygdalectomy in humans have been less 
systematically studied. These operations have been performed 
on patients exhibiting aggressive, hyperkinetic, and destructive 
behavior, usually (but not always) accompanied by temporal 
lobe epilepsy. While hypersexuality and orality have been 
observed to occur postoperatively in humans, most neurosur- 
geons claim these symptoms are rare and when they occur they 
subside after several months (see Valenstein, 1973, pp. 209-233, 
for a review of the clinical literature). Although "psychic 
blindness" has not been reported, there exist only a few serious 
studies of intellectual changes following amygdalectomy in 
humans. In one study, Ruth Andersen (1972) tested 15 patients 
after amygdalectomy, and even though 13 of them had 
undergone only unilateral operations, she reported evidence of a 
loss of ability to shift attention and respond emotionally. 
Anderson (1972, p. 182) concluded, "Typically the patient 
tends to become more inert, and shows less zest and intensity of 
emotions. His spontaneous activity tends to be reduced and he 
becomes less capable of creative productivity. 

"With these changes in initiative and control of behavior, our 

35 



patients resemble those with frontal lesions. It must be pointed 
out, however, that the changes are very discrete and there is no 
evidence of serious disturbance in the establishment and 
execution of their major plans of action. 

"Presumably he will [function best] in well-structured 
situations of a somewhat monotonous and simple character." 

Typically, amygdalectomy in humans involves destruction of 
an appreciable proportion of this structure. For example, 
Heimburger, Whitlock, and Kalsbeck (1966) and Balasubra- 
maniam, Kanaka, and Ramamurthi (1970) estimated that they 
had destroyed more than 50 percent of the amygdala on each 
side. In view of the animal literature and Ruth Andersen's 
observations, one might suspect that had adequate postopera- 
tive testing been generally used, intellectual and emotional 
deficits would have been detected more often. Mark and Ervin 
(1970, p. 70) implied that their lesions need not be large 
because of the use of stimulating electrodes to locate the 
discrete focus that is triggering the violence. They argued that 
postoperative deficits would be minimized by the smaller, more 
selective stereotaxic lesions their technique makes possible. For 
example: "tiny electrodes are implanted in the brain and used 
to destroy a very small number of cells in a precisely 
determined area. As a surgical technique, it has three great 
advantages over lobectomy: it requires much less of an opening 
in the surfaces of the brain than lobectomy does; it destroys less 
than one-tenth as much brain tissue; and once the electrodes 
have been inserted in the brain, they can be left without harm 
to the patient until the surgeon is sure which brain cells are 
firing abnormally and causing the symptoms of seizures and 
violence." 

It is important, therefore, to examine critically the validity of 
the claim that electrical stimulation is a reliable means of 
locating a "brain trigger of violence." 

A few years ago, while studying the elicitation of behavior by 
hypothalamic electrodes, we noticed an interesting trend (Cox 
and Valenstein, 1969). In each of the rats we had implanted 
two electrodes, one on each side of the midline, but usually not 

36 



symmetrically placed. We observed that in a number of animals 
the same response was evoked from very different placements, 
whereas in other animals either different or no specific behavior 
was elicited from electrodes that often seemed to be in the same 
locations (fig. 7). We concluded that within certain anatomical 
limits, a "prepotent response" tendency of the animal (Valen- 
stein, 1969) appeared to be a more important determinant of 
the behavior evoked than the exact location of the electrode in 
the brain. 





"'"^0^ 44AAL 


15AAL 1SAAR 


Behavior: BotiaalE). 


Drink ;-.j ■; D), Gnawing (G) 


Left(L) Electrode 


Electron 


Strong D 


Strong 


Intermediate E+D 


iit< E*D 


Intenediite E 


! i -it* E 


Strong D 


Strong D 


Intermediate G 


Strong G 


Strong D 


Strong D 



FIG. 7. Illustration of different anatomical locations for two electrodes that 
evoked the same behavior in a given animal. (Data from Valenstein, Cox, and Kako- 
lewski, 1970. Brain diagrams from Konig and Klippel, 1963.) 

Many were skeptical of our conclusion and cited examples 
from the literature or from their own laboratory experiences 
that demonstrated that two electrodes could evoke different 
behaviors in the same animal. We had never denied this, but had 
argued that many electrodes evoke states that are sufficiently 



37 



similar, yet not specifically identifiable, so that the stimulated 
animal's behavioral characteristics become a major determinant 
of the effects produced by stimulation. Additional information 
has been accumulating supporting our impression. In a recent 
study using monkeys, it was noted that drinking was elicited 
initially in some by only a few electrodes, but over time an 
increasing number of electrodes situated at different brain sites 
gained the capacity to evoke drinking. Stimulation at an equally 
varied distribution of sites in other monkeys did not evoke 
drinking. Some monkeys seem to respond to brain stimulation 
at many different sites by drinking, whereas others do not 
(Bowden, Galkin, Rosvold, In press). A similar conclusion may 
be drawn from an earlier study by Wise (1971) in which rats 
were implanted with electrodes capable of being moved up and 
down within the brain (fig. 8). It was found that in some rats 
eating and drinking were continuously evoked as the electrode 
was advanced over a large dorsoventral portion of the hypo- 
thalamus, but in other rats, these behaviors were not observed 
in response to stimulation at any site (fig. 9). 




FIG. 8. Sketch of an electrode assembly that can be raised and lowered in the 
animal's brain. (See Wise, 1971 , for details.) 



38 



Panksepp (1971, p. 327) has also provided information that 
supports our "prepotency hypothesis. " He has studied the elicita- 
tion of mouse-killing responses in rats and has concluded thai 




FIG. 9. Path of electrodes used to explore brain for regions evoking eating and 
drinking. Electrodes were advanced in 0.5 mm. steps descending along the path of the 
tract. Upper sections show paths of electrode penetrations that did not evoke eating 
or drinking. In lower sections, both eating and drinking were evoked from all posi- 
tions between upper and lower circles. Each electrode was placed in a different 
animal. (See Wise, 1971, for more details.) 



the ability to elicit mouse-killing by stimulating the brain of a 
rat ". . . interacted with the behavioral typology of individual 
animals, animals normally inclined to kill mice were more likely 
to kill during hypothalamic stimulation than nonkillers. Thus, 
the electrically elicited response was probably not determined by 
specific functions of the tissue under the electrode but by the 
personality of the rat." 



39 



In regard to humans, Kim and Umbach (1973) reported the 
effects of stimulating the amygdala of aggressive and nonaggres- 
sive patients. They concluded that during amygdala stimulation 
of aggressive patients ''aggressiveness increased, whereas no 
aggressive reaction was observed in non-violent cases. Thus the 
amygdaloid complex seems not to be specific for anxiety alone 
or for aggression alone, and shows no specificity of the 
subnuclei for these emotional states." 

There is little reason, therefore, to believe that brain 
stimulation is a reliable technique for locating discrete foci that 
trigger violence even if such foci exist. In the violence-prone 
patients sent to Mark and Ervin, violence can be triggered by a 
great number of brain stimulation sites and probably also by a 
pinch on the skin. The ability of stimulation techniques to 
ferret out a "critical focus" is far from what it has been touted 
to be. Indeed, the fact that Mark and Ervin found it necessary 
to make bilateral lesions to produce any significant effect 
strongly suggests that no "critical focus" was found. Also 
supporting this interpretation is the fact that the bilateral 
lesions are usually made progressively larger until the desired 
behavior change is believed to have been achieved. Although 
Mark and Ervin have presented their approach very seductively 
by implying that they can locate and eliminate small and 
discrete "brain triggers of violence," in actual practice they 
seem to be performing "standard" bilateral amygdalectomies. 

There is little doubt that there are well-documented cases 
where the onset of assaultive behavior can be traced to temporal 
lobe damage. There is also little doubt that there are cases 
where, by all reasonable standards, surgery has led to consider- 
able improvement in behavior (Gloor, 1967). There has, 
however, been a gross exaggeration of the amount of violence 
that can be attributed to brain pathology. The evidence 
presented by Mark and Ervin is extremely weak. It consists 
mainly of a recitation of parallel statistics on the numbers of 
murders, rapes, assaultive acts, automobile accidents, and 
assassinations, on one hand, and the number of cases of 
epilepsy, cerebral palsy, mental retardation, and other indica- 

40 



tions o\ brain damage, on the other. Not only arc no causal 
connections established, but the statistical evidence does not 
support the conclusion that the correlation of brain damage and 
violence is high. 1 Mark and Ervin have also bolstered their 
general argument by implying that brain pathology was the 
cause in such dramatic and violent incidents as the Charles 
Whitman shooting from the University of Texas tower. 2 

Totally neglected in their description was Whitman's personal 
history, which could readily have provided an explanation for 
his violence without any brain pathology. Nor was there any 
mention that Whitman's carefully laid plans did not conform to 
the pattern of sudden, unprovoked, episodic violence that Mark 
and Ervin have described as characteristic of those with 
abnormal brain foci. It may be relevant to point out that 
according to the newspapers. Whitman's brother was shot to 
death in a barroom dispute not too long ago. Is it likely that a 
temporal lobe tumor was the cause here, too? 

There is a danger that the frustration produced by the 
inability to effectively reverse the accelerating rate of violence 
will cause those whose minds run toward simplified behavior- 
control schemes to accept the delusion that biological solutions 
are available for what are primarily social problems. The varying 
amount of violence prevalent at different times and in different 
societies makes it clear that violence is primarily a social 



1 The older neurological and psychiatric literature often contained statements that 
epileptics, particularly temporal lobe epileptics, are prone to violence. Most neurolo- 
gists today refute the earlier figures. Current estimates of the incidence of violence 
among epileptics ranges between 1 and 4 percent and if corrections are made for age 
(onset of temporal lobe epilepsy is later than for other epilepsies) the relationship is 
no higher for the temporal lobe subgroup. Rodin (1973) induced seizure in 150 
epileptic patients using the EEG activating drug, bemigride. He reported that there 
was no incident of aggressive behavior during or after the psychomotor automatisms 
that occurred in 57 of the patients. He argued that the often-reported relationship 
between aggression and psychomotor epilepsy has been exaggerated. 

2 It had been frequently stated that a cancerous tumor (glioblastoma multiforme) 
was situated in the amygdala. Actually, because of the mishandling of the brain at the 
time of autopsy, the location of the tumor was never clearly established (Frank 
Ervin, personal commun.). 

41 



phenomenon. If drug-related crimes are excluded, most of the 
present upsurge in violence can be related to the rejection of 
previously accepted social roles, the large numbers of people 
who do not believe they have a vested interest in the stability of 
our society, and the increasing belief that our institutions 
cannot or will not initiate the changes that are needed. These 
are not easy problems to remedy, but we will surely be in 
serious trouble if a number of influential people become 
convinced that violence is mainly a product of a diseased brain 
rather than of a diseased society. 

PSYCHOSURGERY 

The current controversy over what has been called the 
"resurgence of psychosurgery" places a responsibility on those 
of us studying the brain and behavior— whether or not we 
welcome the opportunity— to offer some light in the midst of all 
this heat. Anyone who has participated in a public discussion of 
this issue realizes that psychosurgery is one of those topics on 
which most people prefer to have one soul-satisfying emotional 
outburst rather than attempt to draw conclusions from very 
complex and often conflicting data. While I have nothing 
against emotional catharsis, there is an obligation to examine 
the logic of the arguments and the relevant evidence as 
impartially as possible, if we are to make a contribution to 
something besides our own psychological well-being. Some of 
the political and social arguments that have been introduced 
have aroused such passion that people are forced to take sides 
on these issues and in the process forget that there may be a 
patient in desperate need of help. It is possible to make only a 
few remarks and I offer these in an effort to set the stage for 
some constructive dialogue by placing the problem in perspec- 
tive. The serious ethical and legal questions concerning in- 
formed consent, adequate review of experimental medical 
procedures, and operations on children or those committed to 
psychiatric and penal institutions cannot be discussed here (see 
Shapiro, 1974, and Valenstein, 1973). 

42 



No discussion on this topic would be complete without at 
least one person arguing against psychosurgery by reminding us 
that the brain is the seat of our personality, humanity, 
creativity, capacity to Learn, to experience emotion, and even of 
our soul. 1 It is certainly true that if we remove the brain all of 
these capacities will be lost, with the possible exception of the 
soul. I do not want to appear facetious or to denigrate these 
human qualities, but 1 want to emphasize that we must talk 
about particular parts of the brain and the functions that are 
regulated by these parts. It is well known that many people 
have had localized brain tumors removed with little, if any, 
detectable loss in these human capacities. 

It is often argued that psychosurgery is unique in that 
healthy tissue is destroyed for a presumed therapeutic purpose. 
In truth, however, psychosurgery is really not that unique in this 
regard. There are several medical procedures that involve the 
destruction of healthy tissue in order to accomplish some 
therapeutic advantage. For example, removal of a normal 
endocrine gland to arrest some pathological process is not 
uncommon. Unquestionably, there are important differences 
between removing an endocrine gland, where replacement 
hormonal therapy is possible, and destroying part of the brain, 
but there also exist procedures other than psychosurgery that 
involve destruction of normal brain tissue. It is instructive to 
consider a few such examples. 

Dr. Irving Cooper of St. Barnabas Hospital in New York has 
done more than 10,000 brain operations on patients suffering 
from such movement disorders as Parkinsonian tremors, various 
types of spasticity, and choreoathetosis. While not everyone 
concurs. Cooper (1969) reported a high percentage of success. 

1 For example, the preamble to a bill controlling psychosurgery passed in June, 
1973, by the Oregon State legislature (Senate Bill 298) reads: "Whereas it is acknowl- 
edged that the human brain is the organ which gives man his unique qualities of 
thought and reason, personality and behavior, emotion and communication. And, 
indeed, is that unique structure importing to man his soul and ethical being; and 

"Whereas these things being so, the free and full use of brain is the absolute and 
inalienable right of each individual, a prerequisite for making choices, possessing 
insight and judgement, and in health providing for the exercise of citizenship . . ." 

43 



In all likelihood, Cooper destroyed healthy brain tissue (in the 
ventral thalamus or basal ganglia) as he freely admits in his 
writings. It is important to appreciate that in many instances 
there is some loss of function unrelated to the regulation of 
movement that is incurred. For example, in one review Cooper 
and his colleagues (Cooper et al., 1968) pointed out that 
following surgery 58 percent of the patients suffer "mild," and 
28 percent "moderate," deficits in speech articulation, phona- 
tion, and even the selection of appropriate words. The danger of 
such undesirable side effects does not necessarily rule out a 
therapeutic procedure. The risks must be weighed against the 
possible benefits. 

To cite a different example. Many cases of temporal lobe 
epilepsy are classified as idiopathic— that is, of unknown origin. 
Indeed, Dr. Wilder Penfield of the Montreal Neurological 
Institute wrote that he believed that in a number of instances 
the basic disorder may actually exist in some subcortical region 
and be projected to the temporal lobe. Nevertheless, there are 
many people with excellent credentials and extensive experi- 
ence who would agree that the removal of a restricted part of 
the temporal lobe has helped patients with otherwise intractable 
episodes of seizures, although here too undesirable side effects— 
in some cases serious— are not unknown. 

In other cases of intractable epilepsy the cutting of the 
corpus callosum, the most extensive fiber connections between 
the two sides of the brain, has significantly decreased the 
incidence of seizures according to Drs. Bogen and Vogel of the 
California College of Medicine. No one believes that the corpus 
callosum in these patients was not perfectly normal before 
surgery. Here too there were deficits produced by the surgery. 
Sperry and his colleagues, for example, have demonstrated 
striking deficits in these "split-brain" people, but it takes special 
testing to reveal them (see Gazzaniga, 1970). Postoperatively, 
the patients function quite well in normal life situations, 
certainly much better than when they were plagued by a 
number of grand mal seizures every day. 

Admittedly these surgical procedures are controversial and 

44 



drugs have decreased the need for them. It should be noted, 
however, that many would argue that these surgical techniques 
are still very helpful for the elimination of some intractable 
symptoms and that a loss-benefit analysis would justify their 
use. Therefore, with respect to the issue of destroying healthy 
tissue, psychosurgery should not be thought of as a unique 
therapeutic practice. It is more realistic to view it as one end of 
a continuum differing mostly on the clarity of the diagnosis 
rather than the treatment. 

It is true that as of now there is virtually no reliable evidence 
linking psychiatric disorders to brain pathology. 1 It is important 
to note, however, that there are few brain scientists prepared to 
rule out the possibility that significant relationships between 
psychiatric condition and brain abnormalities may be found in 
the future. One of the difficulties thus far encountered in the 
search for a relationship is that evidence of pathology in the 
nervous system is much more subtle than it is in other organs. It 
certainly is possible that functional abnormalities in the brain of 
psychotic patients can never be detected by the relatively low 
magnification of the light microscope. It has been reported that 
the electron microscope has revealed significant defects in the 
fine aborizations of neurons in the brains of some mental 
defectives. It is possible that the greater degree of magnifica- 
tion afforded by the electron microscope may reveal structural 
abnormalities in selective regions of the brains of some 
psychiatric patients. 

Unless one argues for the independence of mind and body, 
the possibility of structural or biochemical abnormalities cannot 
be ruled out. It should be noted that even if regional brain 
abnormalities are found, it is not necessary to assume that these 
were the initial cause of the psychiatric disorder. Abnormal 



1 Dr. Fred Plum's recent observation that "schizophrenia has been the graveyard of 
many neuropathologists" refers to the fact that a large number of early pathologists 
wasted much of their professional lives pursuing false leads. These leads could not be 
substantiated by others or were shown to be brain artifacts resulting from the deteri- 
orated physical condition of long term institutionalized patients (see Kety and 
Matthysse, 1972). 

45 



brain functioning could be a by-product of abnormal behavior 
produced by environmental contingencies. Nevertheless, once 
produced, such brain functioning could play a major role in 
maintaining abnormal behavior, emotionality, and thought 
processes. We certainly do not object to this type of reasoning 
when applied to disorders that we label psychosomatic. When a 
substantial number of neuroscientists believe that brain abnor- 
malities, perhaps of a biochemical nature, will eventually be 
linked to some psychiatric disorders, measures that close the 
door to future investigation of this possibility should be 
discouraged. 1 

Still another argument raised is that the rationale for 
psychosurgery, that is, the physiological evidence that justifies 
the procedure, is very primitive. This is true enough and I have 
discussed the problem in detail elsewhere (Valenstein, 1973). 
We should observe, however, that a number of medical 
treatments is based on the empirical evidence that they work 
despite the fact that understanding of the physiological mecha- 
nisms responsible for their action are not available. If we 
demanded a good rationale for all medical treatment we would 
not even use aspirin, not to mention psychopharmacological 
drugs and electroconvulsive shock treatment. (Incidentally, 
despite considerable criticism of the possible overuse of 
electroconvulsive treatment and its poorly understood mecha- 
nisms for inducing change, the majority of psychiatrists 
maintain that it is still the most effective way of arresting some 
cases of very severe depression.) 

Judging from accounts in the popular news media, the issue 
that has caused the most concern is the charge that psychosur- 

'Of interest here is a recent poll of the Society tor Neuroscience, an organization 
that includes among its members most of the leading brain scientists in this country. 
Of the 873 respondents, 74% (16% disagreed and 10% had no opinion) expressed the 
belief that psychosurgery should be available to patients suffering from incapacitating 
mental disorders provided adequate safeguards are taken. A great majority (76%) of 
the members felt, however, that a commission should be established "to promulgate 
guidelines for selecting and evaluating patients, for certifying that there is a recog- 
nized functional disorder, for determining that psychosurgery is an appropriate last 
resort, for obtaining informed consent and for follow-up and record keeping." 

46 



gery may be used as a political instrument to control people 
particularly so-called militant blacks. These charges have been 
accepted as true and repeated by many people who have made 
no effort to check the facts. My own view, after carefully 
surveying the literature and doing some direct checking, is that 
the charges cannot be substantiated and that they were really 
demagogic attempts to add emotional fire to the issue and to 
secure political allies. 1 It is clear that we have to be vigilant and 
monitor carefully the practices in state and private institutions 
where there may be disproportionate representations based on 
race, social class, or sex. As real and as serious as that problem 
may be, however, it is quite different from some of the charges 
we have been hearing. It should be noted that a substantial 
proportion of the 500 to 600 psychosurgical patients operated 
on in the United States each year are not institutionalized, but 
are private patients referred by psychiatrists. 

In the minds of many, psychosurgery is thought of as a 
behavior-control technique of potentially wide applicability 
rather than as an experimental therapeutic procedure for 
intractable psychiatric disorders. This belief has had a very 
significant influence on legislation presently being considered. 
For example, in the proposed federal legislation (H.R. 6852) 

1 To the best of my knowledge, the person most responsible for this belief is the 
psychiatrist Peter Breggin. Breggin has charged that "these brain studies are not 
oriented toward liberation of the patient. They are oriented toward law and order 
and control-toward protecting society against the so-called radical individual." In his 
statement attacking psychosurgery, which was read into the Congressional Record 
(February 24, 1972, vol. 18, no. 26), Breggin implied that Dr. O. J. Andy, a Missis- 
sippi neurosurgeon, concealed that he was operating mainly on blacks. This and 
similar charges have been repeated by many people as well as in such magazines as 
Ebony (Mason, 1973) apparently without troubling to check the facts. However, in 
answer to my inquiry, Dr. Andy wrote that of the approximately 40 psychosurgical 
operations he has performed, only 5% (i.e., 2 cases) were black. At a symposium on 
psychosurgery at the 197 3 American Psychological Association Meeting in Montreal, 
Dr. William Scovillc, the outgoing president of the International Psychosurgical Asso- 
ciation, stated that he has never performed psychosurgery on a black person. The 
speculation by Mark. Sweet, and Ervin (1967) that the more violent participants in a 
riot may have some brain pathology has undoubtedly caused much anxiety about 
future applications. Nevertheless, their psychosurgical patient population does not 
reflect any racial bias. 

47 



outlawing psychosurgery these procedures are defined as brain 
surgery for the purpose of: 

"(A) modification or control of thoughts, feelings, actions, or 
behavior rather than the treatment of a known and diagnosed 
physical disease of the brain; 

"(B) modification of normal brain function or normal brain 
tissue in order to control thoughts, feelings, action, or behavior" 

Similar wording can be found in other proposed legislation or 
legislation that has already been passed. Clearly the concern 
that these techniques will be used to control people has 
provided a good part of the motivational impetus behind such 
legislation. It is understandable that black congressmen and 
women are among the leading supporters of the above legisla- 
tion. Apparently, they have been convinced that psychosurgery 
is a technique for controlling behavior that has been or is likely 
to be selectively used against one segment of the population. It 
is most important that precedent-setting legislation aimed at 
curtailing experimental medical procedures be considered care- 
fully and not hastily framed in response to a distorted 
representation of the problem. 

This critique of many of the common arguments against 
psychosurgery should not be construed as my support for 
these surgical procedures. My reasons for presenting this point 
of view are twofold. On the one hand, I believe that if 
psychosurgery is criticized on the wrong grounds the legislative 
remedies may take a form that would establish a dangerous 
precedent. Also, a criticism of irrelevant arguments or unsub- 
stantiated charges can help to focus our attention on what 
should be the main issue, namely, Can destruction of a part of 
the brain be justified on therapeutic grounds? This question is 
easier to ask than to answer. Even if all the data on the 
consequences of a particular psychosurgical procedure were in 
agreement and their meaning unambiguous, it would still be 
possible to reach opposite conclusions because of personal 
weights assigned to gains and losses in different capacities. Is a 
flattening of emotional responsiveness, for example, balanced 
by freedom from a crippling anxiety? 

48 



It is not possible for me to present any firm eonclusions, let 
alone to substantiate them, on the approximately one-dozen 
different brain operations that eould be called psychosurgery. 
Raising some of the main problems that will have to be faced in 
evaluating any psychosurgical procedure may serve some useful 
purpose. To begin, we have to face the likelihood that the 
results of any brain operation probably will always contain an 
element of unpredictability that will not be completely elimi- 
nated by any increased technical precision. This is true in part 
because the ramifications of destroying any part of the brain 
must depend upon the total personality of the patient, or if you 
prefer, on the total neuronal context that must mediate the 
impact of destruction of any one part of the brain. Moreover, 
there is usually some compensation for loss in function 
following brain damage, but the amount of compensation varies 
with individuals for a great number of reasons we cannot go 
into at this time. 

Another problem in evaluating psychosurgery is that the 
available evidence leaves much to be desired. In the first place, 
most of the testing of patients following psychosurgery was 
done at a time when the patient population and the surgical 
procedures were different from those that exist today. The 
older prefrontal lobotomy procedures destroyed much larger 
brain areas than do the current so-called fractional operations. 
Although most of the older operations involved rotating surgical 
knives inside the brain in order to disconnect large areas of the 
prefrontal cortex, present-day techniques may limit destruction 
to an area 3 to 5 mm. in diameter. There is also little doubt that 
the more modern methods of stereotaxic surgery make it 
possible to reach specific brain targets with much more 
precision than was previously possible. 

No purpose is served by reviewing in detail the results of the 
older prefrontal lobotomy procedures. The results were ex- 
tremely variable and one can without difficulty find evidence 
on both sides of the controversy. There is evidence in the 
literature demonstrating a blunting of emotional responsiveness, 
lowering of performance on at least some parts of IQ tests, an 

49 



inability to maintain goal-directed behavior, the triggering of 
epileptic seizures, and other neurological problems following 
prefrontal lobotomy. There are also a number of studies that 
reported significant psychiatric improvement following the 
operations, no IQ loss, and an increased ability to hold a job. 
Some of the studies that reached this positive conclusion 
involved relatively long-term follow-ups and some, such as those 
conducted by the Connecticut Lobotomy Committee or the 
British Board of Control Study, included substantial samples of 
patients (Moore et al., 1948). The Columbia-Greystone study, 
which involved more than 50 participating investigators and a 
battery of 35 psychological tests (selected from a list of more 
than 100 that were considered), concluded that there was no 
evidence that topectomy (one type of prefrontal operation) 
produced any permanent loss in learning ability, memory, 
creativity, imagination, intellectual achievement, social or ethi- 
cal attitudes, or even sense of humor (see Mettler, 1949, 1952; 
Landis, Zubin, and Mettler, 1950). These studies can all be 
criticized on various methodological grounds; the test instru- 
ments were probably insensitive to important changes in 
behavioral capacities, and the estimates of improvement often 
gave exaggerated weighting to the elimination of behavior 
troublesome to the hospital staff or society in general while 
placing considerably less emphasis on the qualitative aspects of 
the postoperative adjustment level. 

While we can learn much from examining the older prefrontal 
lobotomy literature— particularly in respect to methodological 
points in the way such studies should or should not be 
conducted— it is not possible to apply specific conclusions to 
the brain operations performed today. Very different brain 
areas are often involved, even where the surgery is still directed 
at prefrontal areas. There are fewer studies reporting results 
following selective damage to limbic and hypothalamic struc- 
tures. It is probably safe to conclude that the added precision of 
the newer operations has resulted in many fewer instances of 
gross behavioral deterioration, or neurological side-effects such 
as epilepsy. However, our information about the emotional and 

50 



intellectual changes produced by the newer psychosurgical 
procedures is very inadequate. 

Neurosurgeons have neither the training nor the time to 
conduct the type of studies needed to evaluate adequately the 
changes produced by their brain operations. Postoperative 
changes are usually reported in gross terms listing percentages 
of patients exhibiting different degrees of improvement in 
poorly defined categories ranging from "completely cured" 
to "no change." There are few examples where postoperative 
evaluative tests were designed to measure changes in those 
capacities that animal studies have emphasized as likely to be 
altered. Indeed, many neurologists and neurosurgeons have 
displayed an amazing "tunnel vision" toward animal studies. 
They have been quick to see clinical applications in animal 
studies, but often quite blind to the results that should have 
cautioned them against the operation and influenced their 
evaluative procedures. A few examples are offered to illustrate 
this point. 

There is some familiarity with the circumstances that 
encouraged Egas Moniz, the Portuguese neurologist and Nobel 
laureate, to initiate prefrontal lobotomy. It will be recalled that 
at the International Neurology Congress in London in 1935 
Carlyle Jacobsen presented his results on the behavior changes 
in chimpanzees following destruction of their frontal lobes. 
Prior to the operation, one of the chimpanzees— the now- 
famous Becky— had a temper tantrum every time she made a 
mistake in the testing situation. After frontal lobe surgery, 
however, she showed no evidence of emotional disturbance 
under similar circumstances. Moniz was sitting in the audience, 
and according to John Fulton, the session chairman: "Dr. 
Moniz arose and asked if frontal lobe removal prevents the 
development of experimental neurosis in animals and elimi- 
nates frustrational behavior, why would it not be feasible to 
relieve anxiety states in man by surgical means." The main 
thrust of Jacobsen's presentation, namely, that the operated 
animals were no longer able to perform certain problem-solving 
tasks (particularly those involving delayed responses) was 

51 



ignored. Within three months, Moniz had persuaded his neuro- 
surgical colleague, Almeida Lima, to operate on their first 
patient. 

Anterior cingulotomy is another psychosurgical procedure 
used by several surgeons today. Here, too, a careful reconstruc- 
tion of the history reveals a striking "tunnel vision." John 
Fulton's description of the animal experiments by Wilbur Smith 
(1945) and Arthur Ward (1948) in a number of influential 
speeches had a direct influence on the adoption of cingulotomy 
procedures by a number of people in England, France, and in 
the United States. Fulton reported that following cingulotomy 
monkeys became tamer. A closer examination of Ward's 
description of the postoperative behavior of the monkeys 
reveals the inadequacy of the term "tameness" to summarize all 
the changes that occurred. For example, Ward said: 

there is an obvious change in personality. The monkey loses its 
preoperative shyness and is less fearful of man. It appears more 
inquisitive than the normal monkey of the same age. In a large 
cage with other monkeys of the same size, such an animal shows no 
grooming behavior or acts of affection towards its companions. In fact, 
it treats them as it treats inanimate objects and will walk on them, 
bump into them if they happen to be in the way, and will even sit on 
them. It will openly eat food in the hand of a companion without being 
prepared to do battle and appears surprised when it is rebuffed. Such an 
animal never shows actual hostility to its fellows. It neither fights nor 
tries to escape when removed from a cage. It acts under all 
circumstances as though it had lost its "social conscience." This is 
probably what Smith saw and called "tameness." It is thus evident that 
following removal of the anterior limbic area, such monkeys lose some 
of the social fear and anxiety which normally governs their activity 
and thus lose the ability to accurately forecast the social repercussions 
of their own actions. 

Perhaps the most striking example of "tunnel vision" comes 
from a psychosurgical procedure that involves destruction of 
the ventromedial hypothalamus in persons diagnosed as pedo- 
philic homosexuals, that is, men who seek out sexual opportuni- 
ties with young boys. Dr. F. Roeder and his colleagues at the 
University of Gottingen in Germany received their inspiration 
while watching a film at another International Neurology 
Congress, held in Brussels in 1957 (Roeder et al., 1971, 1972). 

52 



Roedcr described his response to this film which depicted the 
hypersexual behavior of cats amygdalectomized by Leon 
Schreiner and Arthur Kling. "the behavior of male cats with 
lesions of the amygdalar region in some respects closely 
approached that of human perversion. The films convinced us 
that there was a basis for a therapeutic stereotaxic approach to 
this problem in man. 1 ' Roeder was referring to work on cats by 
Arthur Kling which demonstrated that ventromedial hypotha- 
lamic lesions eliminated the hypersexuality previously produced 
by amygdala lesions. Roeder and his colleagues proceeded to 
make stereotaxic lesions in the ventromedial hypothalamic 
nucleus in man. Based on experience with a relatively small 
patient population studied in a cursory way, Roeder and his 
associates reached the disquieting if not shocking, conclusion 
about their surgical procedure that "there is no doubt that 
experimental behavioral research has afforded us a basic method 
to eliminate or to control pedophilic homosexuality by means 
of an effective psychosurgical operation in the area of the sex 
behavior center." Those of us who study the brain and behavior 
in animals know of the voluminous literature implicating the 
ventromedial hypothalamic nucleus in endocrine regulation, 
appetite, and many other functions. There is also good evidence 
that irritability and aggressiveness can be produced by lesions in 
this area. However, once the focus was directed at sexual 
behavior, the other important behaviors regulated by this brain 
area were ignored. 

Similar comments could be made in reference to a recent 
report on producing stereotaxic lateral hypothalamic lesions to 
combat obesity in humans (Quaade, 1974). As Marshall (1974) 
pointed out in a comment on Quaade's report, the lateral 
hypothalamus is not specifically involved in "monitoring the 
energy needs of the organism and transforming such informa- 
tion into an urge to eat." In animals, lateral hypothalamic 
damage also produces sensory changes leading to inattentiveness 
to external stimuli and impairment in sexual activation, learning 
ability, and memory. 

A point that apparently has to be made over and over again is 

53 



that there are very few parts of the brain that control only one 
behavior. People studying a given area of the brain may 
emphasize either control of appetite, aggression, endocrine 
balance, or sexual behavior, and so forth, depending on their 
own interests. I have stressed this "tunnel vision" problem 
because it illustrates the danger of superficial contacts between 
experimentalists and clinicians. There are many consequences of 
this lack of communication. Obviously, in some instances, 
operations should never have been performed. In a great many 
instances, behaviors and capacities that should have been 
assessed were completely neglected in the postoperative eval- 
uation of patients. What is needed is not some hastily conceived 
legislation that may set a precedent hindering all investigations 
in experimental medicine. We clearly need better controls to 
protect patients, but it must be recognized that this cannot be 
accomplished unless more meaningful interactions between 
research scientists and clinicians are established. 



54 



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Valenstein, E. S., V. C. Cox, and J. W. Kakolewski 

1968a. Modification of motivated behavior elicited by electrical stimulation of the 
hypothalamus. Science, vol. 159, pp. 1119-1121. 

1968b. The motivation underlying eating elicited by lateral hypothalamic stimula- 
tion. Physiol. Behavior, vol. 3, pp. 969-971. 

1970. Reexamination of the role of the hypothalamus in motivation. Psychol. 
Rev., vol. 77, pp. 16-31. 

61 



Valenstein, E. S., J. W. Kakolewski, and V. C. Cox 

1968. A comparison of stimulus-bound drinking and drinking induced by water 
deprivation. Communications Behavior Biol., pt. A, vol. 2, pp. 227-233. 

Valenstein, E. S., and T. Valenstein 
1964. Interaction of positive and negative reinforcing neural systems. Science, vol. 
145, pp. 1456-1458. 

Van Buren, J. M. 

1961. Sensory motor and autonomic effects of mesial temporal stimulation in 
man. Jour. Neurosurg., vol. 18, pp. 273-288. 

1963. Confusion and disturbance of speech from stimulation in the vicinity of the 
head of the caudate nucleus. Ibid., vol. 20, pp. 148-157. 

1966. Evidence regarding a more precise localization of the posterior frontal- 
caudate arrest response in man. Ibid., vol. 24, pp. 416-417. 

Ward, A. A., Jr. 
1948. The anterior cingular gyrus and personality. Res. Publ. Assoc. Nerv. Ment. 
Dis., vol. 27, pp. 438-445. 

Wasman, M., and J. P. Flynn 

1962. Directed attack elicited from hypothalamus. Arch. Neurol., vol. 6, pp. 
220-227. 

Wise, R. A. 

1971. Individual differences in effects of hypothalamic stimulation: the role of 
stimulation locus. Physiol. Behavior, vol. 6, pp. 569-572. 



62 



£0 I .^ 

35 

.46 

76 



* ^V^C^^^*>%^pi 



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FORTY-SIXTH 
1 JAMES ^.RTHUR LECTURE ON 
THE EVOLUTION OF THE HUMAN BRAIN 

fTH 



WHAT SQUIDS AND OCTOPUSES 

TELL US 
ABOUT BRAINS AND MEMORIES 



JOHN Z. YOUNG 



THE AMERICAN MUSEUM OF NATURAL HISTORY 
NEW YORK : 1977 









fffc 






Museum of a, 




1869 
THE LIBRARY 



FORTY-SIXTH 

JAMES ARTHUR LECTURE ON 

THE EVOLUTION OF THE HUMAN BRAIN 



FORTY-SIXTH 

JAM IS ARTHUR LECTURE ON 

I III EVOLUTION OF 1 111 HUMAN BRAIN 



WHAT SQUIDS AND OCTOPUSES 

TELL US 
ABOUT BRAINS AND MEMORIES 



JOHN Z. YOUNG 

Professor Emeritus and Honorary Fellow 
University College, London 



THE AMERICAN MUSEUM OF NATURAL HISTORY 
NEW YORK : 1977 



ADD , k m-?-7 




JAMES ARTHUR LECTURES ON 
THE EVOLUTION OF THE HUMAN BRAIN 



Frederick Tilney, The Brain in Relation to Behavior; March 15, 1932 

C. Judson Herrick, Brains as Instruments o) f Biological Values; April 6, 1933 

D. M. S. Watson, Hie Story of Fossil Brains from Fish to Man; April 24, 1934 

C. U. Ariens Kappers, Structural Principles in the Nervous System; The Develop- 
ment of the Forebrain in Animals and Prehistoric Human Races; April 25, 1935 

Samuel T. Orton, The Language Area of the Human Brain and Some of its 
Disorders; May 15, 1936 

R. W. Gerard, Dynamic Neural Patterns; April 15, 1937 

Franz Weidenreich, The Phylogenetic Development of the Hominid Brain and its 
Connection with the Transformation of the Skull; May 5, 1938 

G. Kingsley Noble, The Neural Basis of Social Behavior of Vertebrates; May 11, 
1939 

John F. Fulton, A Functional Approach to the Evolution of the Primate Brain; May 
2, 1940 

Frank A. Beach, Central Nervous Mechanisms Involved in the Reproductive 
Behavior of Vertebrates; May 8, 1 94 1 

George Pinkley, A History of the Human Brain; May 14, 1942 

James W. Papez, Ancient Landmarks of the Human Brain and Their Origin; May 27, 
1943 

James Howard McGregor, The Brain of Primates; May 11, 1944 

K. S. Lashley, Neural Correlates of Intellect; April 30, 1945 

Warren S. McCulloch, Finality and Form in Nervous Activity; May 2, 1946 

S. R. Detwiler, Structure-Function Correlations in the Developing Nervous System 
as Studied by Experimental Methods; May 8, 1947 

Tilly Edinger, The Evolution of the Brain; May 20, 1948 

Donald O. Hebb, Evolution of Thought and Emotion; April 20, 1949 

Ward Campbell Halstead, Brain and Intelligence; April 26, 1950 

Harry F. Harlow, The Brain and Learned Behavior; May 10, 1951 

Clinton N. Woolsey, Sensory and Motor Systems of the Cerebral Cortex; May 7, 
1952 

Alfred S. Romer, Brain Evolution in the Light of Vertebrate History; May 21, 1953 

Horace W. Magoun, Regulatory F"unctions of the Brain Stem; May 5, 1954 



*Fred A. Mettler, Culture and the Structural Evolution of the Neural System; April 
21, 1955 

*Pinckney J. Harman, Pale one urologic, Neoneurologic, and Ontogenetic Aspects of 
Brain Phytogeny; April 26, 1956 

* Davenport Hooker, Evidence of Prenatal function of the Central Nervous System in 

Man; April 25, 1957 

*David P. C. Lloyd, The Discrete and the Diffuse in Nervous Action; May 8, 1958 

*Charles R. Noback, Die Heritage of the Human Brain; May 6, 1959 

*Ernst Scharrer, Brain function and the Evolution of Cerebral Vascularization; May 
26, 1960 

Paul I. Yakovlev, Brain, Body and Behavior. Stereodynamic Organization of the 
Brain and of the Motility -Experience in Man Envisaged as a Biological Action 
System; May 16, 1961 

H. K. Hartline, Principles of Neural Interaction in the Retina; May 29, 1962 

Harry Grundfest, Specialization and Evolution of Bioelectric Activity; May 28, 1963 

*Roger W. Sperry, Problems Outstanding in the Evolution of Brain function; June 3, 
1964 

*Jose M. R. Delgado, Evolution of Physical Control of the Brain; May 6, 1965 

Seymour S. Kety, Adaptive functions and the Biochemistry of the Brain; May 19, 
1966 

Dominick P. Purpura, Ontogenesis of Neuronal Organizations in the Mammalian 
Brain; May 25, 1967 

*Kenneth D. Roeder, Three Views of the Nervous System; April 2, 1968 

t Phillip V. Tobias, Some Aspects of the fossil Evidence on the Evolution of the 
Hominid Brain; April 2, 1969 

*Karl H. Pribram, What Makes Man Human; April 23, 1970 

VValle J. H. Nauta, A New View of the Evolution of the Cerebral Cortex of 
Mammals; May 5, 1971 

David H. Hubel, Organization of the Monkey Visual Cortex; May 11, 1972 

Janos Szentagothai, The World of Nene Nets; January 16, 1973 

* Ralph L. Holloway, The Role of Human Social Behavior in the Evolution of the 

Brain;Mny 1, 1973 

*Elliot S. Valenstein, Persistent Problems in the Physical Control of the Brain; May 
16, 1974 

^Marcel Kinsbourne, Development and Evolution of the Neural Basis of Language; 
April 10, 1975 

*John Z. Young, What Squids and Octopuses Tell Us About Brains and Memories, 
May 13,1976 

^Unpublished. 

*Published versions of these lectures can be obtained from The American Museum of 
Natural History, Central Park West at 79th St., New York, N. Y. 10024. 

t Published version: The Brain in Hominid Evolution, New York: Columbia Univer- 
sity Press, 1971. 



WHAT SQUIDS AND OCTOPUSES TELL 
US ABOUT BRAINS AND MEMORIES 

NEW TECHNIQUES FOR STUDIES OF THE BRAIN 

To reach a better understanding of the human brain we need 
to develop new ways of thinking and talking about the nervous 
system in general. All our knowledge of nerve fibers and their 
synapses proves to be something of a disappointment when we 
try to explain complex forms of behavior, such as that of man. I 
have believed for many years that to overcome this difficulty 
we must try to describe as fully as possible the behavior pat- 
terns and the whole nervous system. When I began research, I 
thought that it might be possible to do this for lampreys and 
after making some studies went so far as to write what would 
now be called a research program with this in view. But on fur- 
ther consideration, I decided that both the behavior and struc- 
ture of the brain of these animals were too difficult to study, 
mainly for technical reasons. Moreover in 1929, for the first 
time, I became acquainted with octopuses and squids and quite 
soon decided that their nervous systems seemed likely to pro- 
vide sufficient complexity to be interesting and sufficient ac- 
cessibility for anatomical study and experiment. It is not too 
much to make the claim that this hope was well founded, as 
we now have some understanding of all parts of the cephalopod 
nervous system. We also have a lot of information about their 
behavioral capacities— at least in the laboratory; less, unfortu- 
nately, in their native state in the sea. 

It may seem to be a vain and unjustified claim that we un- 
derstand cephalopod brains so well. Of course, there is an im- 
mense amount that we should like to know. But I hope that 
the effort to substantiate this claim may serve to bring out 
both the extent and the limitations of our knowledge of all 
brains, including that of man. It may show how what we mean 
by "understanding the brain" has changed over the last 50 

1 



years since this research began. This may prove to be quite a 
useful exercise not only in the history of neuroscience but in 
the study of the relations of science and technology in general. 
We can recognize four major changes of scientific method 
and capabilities since 1929 that have especially influenced neu- 
rology. 

1. Reliable methods of recording small changes in electrical ac- 

tivity have become widely available. With these we can 
follow events in nerves and brains with a very high degree 
of resolution in time. Resolution in space can also be pre- 
cise, but is limited to a few places in the brain at a time. 

2. Electronmicroscopy has provided us with the power to study 

the structure and organization of neurons with a very high 
degree of resolution in space. This, unfortunately, is pos- 
sible only by accepting very poor resolution in time. We 
cannot follow changes from moment to moment with the 
electron microscope. 

3. Chromatography provides us with the power to study the mi- 

crochemical composition of tissues, estimating quantities 
of substances that are present in very small amounts, 
though again with rather poor resolution in both space and 
time. Fluorescence microscopy has also been particularly 
helpful in the study of the nervous system because of its 
capacity to reveal selectively the course of tracts contain- 
ing biologically active amines. 

4. Finally, during this period mankind has enormously enlarged 

his mathematical powers of computation. Computers help 
us to bring together the vast masses of data provided by 
other techniques. Besides their help with arithmetical 
operations, it is even more important that computers have 
led to great advances in our understanding of the operations 
of communication and control which, until recently, were 
considered only by using the language of subjective psy- 
chology. 
Knowledge of the nervous system has profited from these ad- 
vances. My own detailed contributions have mostly been in 



humbler fields, using older techniques of histology and psy- 
chology. But through developments that we have sponsored in 
the Department of Anatomy at University College, London, I 
have been near the beginning of several of these four major new 
developments of technique and have been able to find helpers 
in applying them to cephalopods. 

THE BRAIN AS A HIERARCHICAL SOMATOTOPIC COMPUTER 

Our aim is to try to understand the nervous system as a 
whole. Let us therefore begin with the last of the new techniques 
mentioned. Cybernetics can tell us how to think of the brain as 
a hierarchical computer, somatotopically organized (Arbib, 
1972). The idea of hierarchy in the nervous system was intro- 
duced by the clinician Hughlings Jackson long ago, and cyber- 
netic analysis shows that it is really an essential feature of any 
organization that uses much information to accomplish a pur- 
pose, whether it be an army or an octopus. Hierarchy allows 
each level to receive only that part of the information that is 
relevant for the decisions it must take. This is magnificently 
illustrated by octopuses (fig. 1). Each of the eight arms carries 
hundreds of highly mobile suckers and the movements of 



- 







■ } 




FIG. 1. An octopus swimming forward to attack a crab. 



these, and of the whole arm, are controlled by nerve cells lying 
in ganglia within the arm. There are altogether 350 million cells 
in the arms as compared with only 150 million in all the rest of 
the nervous system (Young, 1971). The suckers are the enlisted 
men of the cerebral army, and their local nerve cells are the 
noncommissioned officers. Individual isolated arms are capable 
of quite complicated coordinated movements, for example 
acting either to draw objects in or to reject them. These periph- 
eral centers are thus the next layer of members of the hier- 
archy and can act independently. They are the regiments of 
the cerebral army, and the nerve cells placed along the center of 
each arm are the junior officers who control them. They receive 
information from individual suckers and order them to act in 
particular sequences. 

The brain contains lower motor centers, comparable with our 
own spinal cord (fig. 2), and these control movements of all 
the arms when working together and of the mantle, which acts 
by jet propulsion. Electrical stimulation of these centers will 
produce movements of the relevant parts, including changes of 
color by the chromatophores (Boycott and Young 1950; Boy- 
cott, 1961). To pursue our analogy we here have regimental and 
brigade headquarters. They receive relevant information from 
the arms and send orders to them. However, these centers nor- 
mally operate under the control of still higher motor centers in 
the basal supraoesophageal lobes. These basal lobes have struc- 
ture strikingly like our own cerebellum, but before we can un- 
derstand their working we must begin to think more carefully 
about what tasks the nervous system has to do, and what we 
mean when we say that it sends information, instructions, or 
commands. 

COMMUNICATION AND CONTROL BY THE NERVOUS SYSTEM 

Since the last century it has been usual to think of the nerves 
as agents of communication, following the analogy of telegraph 
wires. But what do they communicate? Neurophysiologists have 
been cautious and confused about this ever since the time Des- 



visual learning 



-"^■C vertical lobe 



touch learning 



V'v--\' 

(/ movement 
} - of eyes 
^and body •> 




FIG. 2. Longitudinal sagittal section of the brain of an octopus. 

cartes spoke of nerves with the analogy of pulling on wires to 
ring bells or of animal spirits traveling along hollow tubes. 

During the last century and the present one, physiologists 
have mostly described the activity of nerves by using unques- 
tioningly the phrases "nerve impulse" or "action potential," but 
now we can see that these are rather ambiguous and indeed eva- 



sive terms. This will sound like rank heresy, especially coming 
from me since the giant nerve fibers of the squid have told us 
more about nerve impulses than any other nerve fibers have 
done (fig. 3). I came upon them by chance while studying squid 
ganglia for another purpose. The cells related to them had in- 
deed been seen by Williams in 1909. But there had been no fur- 
ther mention of the cells in the literature, and no one had seen 
the giant fibers themselves. In 1936 at Woods Hole we were 
able to prove that these huge channels are nerve fibers and fig- 
ure 4 shows some of the earliest records of their action poten- 
tials. The function of these enormous nerves is to elicit contrac- 
tion of the sac that produces the propulsive jet. The arrange- 
ment ingeniously provides that both sides of the mantle and its 
nearer and distant parts all contract together (fig. 5). 

If the function is so well understood, what do I mean by say- 
ing that the concept of an impulse or action potential is ambig- 
uous? What's in a name? In this context of the giant fiber sys- 
tem I agree that it does not matter much. An activity spreads 





ft 






FIG. 3. Transverse section of one of the stellar nerves of a squid. There are many 
small nerve fibers and one giant fiber. 



> 

E 



FIG. 4. Oscillograph record of the electrical changes accompanying a sequence of 
nerve impulses in a squid's giant nerve fiber. The discharge has been set off by plac- 
ing oxalic acid on one end of the fiber. Note that the impulses are all the same height. 
The time-markers show 1/5 or l/100th sec. 



along the nerve fibers and we can tell rather precisely how it is 
initiated by a synapse in the stellate ganglion and propagated to 
start off a muscular contraction. We can even show that one 
nerve impulse produces one pulse of the jet, so we can say that 
the action of single cells in the nervous system produces a par- 
ticular behavioral act by the whole squid. This is good progress 
in understanding. We can go further and apply it to mammals 
where, in a monkey trained to press a lever, single cells of the 
cerebral cortex show electrical activity before the movement be- 
gins (Evarts et al., 1971). Thus we get a good idea of how the 
nervous system is made up of nerve cells each of which has a 
distinct function. 

This sounds fine and is indeed true. The principle on which 
all nervous systems are built is that of multichannel communica- 
tion. Each nerve fiber carries only one sort of message, either in- 
ward from a sense organ or outward to produce some action by 
a muscle or gland. Each fiber thus carries only a small amount 
of information. To carry large amounts of information inward 
and to produce varied and subtle behavior, very large numbers 
of fibers are needed, each having a different "function." The 
trouble is that in the more interesting parts of the brain we 
cannot specify what the "function" is. So when we say that 
when we see red certain nerve fibers from the eye transmit some- 
thing called nerve impulses we do not really know what we 
are saying. In what sense do nerve impulses transmit redness? 




■a <n 



To answer this we must look more carefully at what we mean 
when we say that the nervous system serves for communica- 
tion. We are using words borrowed from human activities in 
which a sender has a message calling for some action that he 
expects from a recipient. He passes signals in what we call a 
code along a channel to the receiver, who decodes it and selects 
the required action from the repertoire, or set, of programs 
available. There are very many fascinating things we could say 
about this situation. For the present, notice firstly that the ac- 
tivity of communication presupposes an aim or purpose that is 
to be achieved by choosing the right program from a set. Fur- 
ther it makes use of some arbitrary code of signals, preset by 
past history and "understood" by transmitter and receiver. Liv- 
ing things are the only systems that we know of that maintain 
themselves by communication in this way. So what we are 
doing is to use the words that have been developed to describe 
human social life to describe all living things. For the present 
we are concentrating on nervous messages themselves, and we 
notice that the analogy suggests that they be called signals in 
a code. Physiologists are beginning to talk about nerve im- 
pulses in this way but curiously enough the physiologists who 
win Nobel Prizes for the study of nerve fibers seldom, or never, 
use words such as "code" or "symbol." They stick to the dear 
old terms "nerve impulse" and "action potential." They have in- 
deed been able to find out a very great deal about the physical 
changes that are involved in the transmission of the nerve mes- 
sage, without thinking much about what the message communi- 
cates. To be unkind one might say it was like giving a Nobel 
Prize for Literature to people who had advanced knowledge of 
typewriters, or of ink, or perhaps of radio transmission! I may 
say that many of my best friends are Nobel Prize winners— at 
least they have been until now! 

But there are two further turns of the screw that physiolo- 
gists must suffer. The significance of signals in a code is that 
they symbolize the matters to be communicated. If we are to 
describe the effects of our nerve impulses properly, in this 
analogy we must say that they are significant because they are 



symbols, that is, they stand for or represent either some event 
in the outside world or some inner need or some action to be 
performed at the decoding end of a communication channel. 
We say that a sign or a signal becomes a symbol or representa- 
tion for something else when it has the effect upon us of that 
something. A traditional picture of a horse symbolizes horse for 
us; but the horse in Picasso's "Guernica" does more, it sym- 
bolizes also fear and horror. 

I claim, therefore, that we shall learn to understand better 
how the nervous system works if we consider how the opera- 
tions of each part of it represent or symbolize either some 
change in the inner or outside world or some instruction for 
action, passing outward from the brain to the muscles or glands. 
Let us then see what the various parts of the nervous system 
in our cephalopods serve to symbolize. 

SYMBOLS FOR GRAVILY AND MOVEMENT 

Cephalopods, like other animals, arrange their behavior 
in such a way as to respect the demands of gravity. To be able 
to do this they have within themselves parts which by their 
physical structure symbolize gravity and movement. These 
are, as it were, little models of those features of the universe. 
Cephalopod statocysts are based on principles surprisingly simi- 
lar to those used by vertebrates, including man (fig. 6). Like our 
own inner ear, they combine receptors for maintaining orienta- 
tion with respect to gravity with others that are sensitive to the 
angular accelerations due to movement of the animals. 

The gravity receptors illustrate well the principles involved in 
symbolization. To meet the task of correct orientation in rela- 
tion to the earth's surface, there is present in the statocyst a 
little model to represent gravity, a stone hanging upon sensory 
hairs. These hairs send streams of action potentials whose pat- 
tern thus symbolizes the position of the animal in relation to 
gravity. The connections of these nerve fibers must be meticu- 
lously arranged to ensure that the various muscles pull to pre- 



10 



/ 



mac. prin. mac. n. sup 




FIG. 6. The statocyst of the squid Loligo, as seen from in front. The calcium salts 
in the statoliths (the gravity stones) make them opaque. There is one very large one 
on each side, composed of crystals of aragonite. This stone lies in the transverse plane 
attached to sensory hairs of the macula princeps (mac. prin.). There are two other 
patches of sensory cells, carrying numerous small crystals. The macula neglecta su- 
perior (mac. n. sup.) lies nearly in the sagittal plane, the macula neglecta inferior 
(mac. n. inf.) in an oblique horizontal plane. 

cisely the correct extent to hold the animal upright (fig. 7). If 
the statocysts are destroyed this is no longer possible. Notice, 
then, that the model serves to allow the action system of the 
animal to maintain its proper relation with the rest of the world— 
the essential feature of living. 

For the detection of angular accelerations the cephalopods 
have ridges of sensory hairs, the cristae, carrying very light 
flaps, the cupulae. The cristae run along the sides of the stato- 
cyst sac in four directions, at right angles to each other (fig. 8). 
When the animal turns, the displacement of the wall relative to 
the fluid contents of the statocyst moves the cupula of one or 
more of the ridges according to the direction of movement. The 
signals set up by the hair cells of the crista thus represent the 



11 




FIG. 7. Drawings by M.T. Wells to show how pupil of a normal octopus is always 
held horizontal (a-e). In f and g, are shown the positions of the pupils in an animal 
from which both statocysts had been removed. 

animal's own movements. By their connections these nerve fi- 
bers then initiate compensatory movements, especially of the 
eye muscles. 

This system is obviously similar to that of our own semi- 
circular canals. It is indeed striking that in the more active ceph- 
alopods, such as the squids, the statocyst has become divided 
up and curved into shapes that in effect constitute actual 
canals. Our three semicircular canals serve to represent angular 
accelerations in three planes of space. What are the squids doing 
with four cristae? It may be that the answer is that with the 
fourth they detect linear acceleration forward or backward. 
These animals can move readily in these two directions, which 
is a feat not easily achieved even by their rivals the fishes. 
Budelmann (1975) has shown that the cristae are indeed capa- 
ble of responding to linear acceleration (unlike the semicircular 
canals). 



12 



a.c. 




FIG. 8. Statocyst of the fast -moving squid Loligo, seen from above. The stato- 
liths shown in figure 6 have been removed. The white outlines show the course of the 
crista (ridge) of sensory cells (cr) mainly for detecting angular accelerations. The 
ridge runs (on each side) across in front, along the side, across the back and then 
up in the vertical plane. The cavity has curved sides and is divided up by a number of 
projections (a.c.=anticristae). The effect is a restriction of fluid movement similar to 
that accomplished by the semicircular canals in vertebrates. 

It is interesting to note that in octopuses and other cephalo- 
pods that do not make rapid turning movements the whole sys- 
tem is changed. The sac is very large and the anticristae are re- 
duced or absent, leaving a single volume of fluid whose inertia 
gives greater sensitivity to slow movements (fig. 9). So in every 
animal the structure and connections of the sense organs have 
come to represent the environment in which it lives. Notice that 
the model that the animal contains represents not only the fea- 
tures of the world but also the actions that the animal must it- 
self perform to keep alive. The models in the brain are not static 
pictures, they are the written plans and programs for action. In 
squids the giant cells that produce the jet lie very close indeed 
to the statocyst. If the animal is suddenly disturbed it imme- 
diately produces a jet. This plan of action does not have to 



13 




FIG. 9. The statocyst of the slow-moving squid Taonius, seen from above. The 
macula (mac.) and its stones are quite different from those of Loligo. The sac is 
large and the anticristae (a.c.) are small and few, so that the cavity is not divided up 
into "canals." K. is Kolliker's canal, a blind ciliated tube of unknown function ;cr = 
crista. 

be learned. It is written into the inherited wiring pattern. 

In man and other vertebrates the cerebellum is a very im- 
portant part of the system for control of movement. We have 
recently realized that there are lobes in the brains of cephalo- 
pods that contain large numbers of very small parallel fibers, 
strikingly like those of our own cerebellum (figs. 10, 11). We 
do not yet understand the full significance of these arrange- 
ments but a possible explanation is that the fine fibers serve 
to represent time (Braitenberg, 1967). They conduct very 
slowly and this may determine the braking action that termi- 
nates a movement. Many actions of the muscles are ballistic, 
in the sense that the ending of their contraction is determined 
when it begins and not by any feedback en route. 

In ourselves the ear has the further function of detecting 
sound. Cephalopods seem to have no capacity for responding 
to vibrations, except those of very low frequency. This is very 
strange since water transmits vibrations that could have very 



14 




med. bas 
fins 
chromatophores 



mantle 



eye-muscles 



funne 



FIG. 10. A diagram of the brain of a squid showing the four sets of fine parallel 
fibers, somewhat similar to those in the vertebrate cerebellum. The suboesophageal 
lobes lie below and control the various movements as shown. The cerebellum-like 
lobes lie above them and are called the anterior basal (a.bas.), median basal (med. 
bas.) and peduncle lobes (ped.). The parallel fibers run in different planes; two sets 
are in the anterior basal lobe, one in each of the others. Notice that these lobes send 
fibers to the lower motor centers. 

great symbolic value and indeed the fishes, great rivals of the 
cephalopods for domination of the waters, hear very well. 



LEARNING SYMBOLIC VALUES 

All the behavioral responses we have considered so far have 
been the consequence of connections laid down during develop- 
ment, but cephalopods are provided also with considerable 
powers of learning. Far less of course than in mammals or man 
but still enough to provide us with much information about the 
processes that are involved in memory formation. It is here 
that it becomes especially important to pay attention to our 
conceptual framework and language. The essence of learning is 
the attaching of symbolic value to signs from the outside world. 
Images on the retina are not eatable or dangerous. What the eye 

15 




FIG. 1 1. Section of the peduncle lobe of a squid showing the fine parallel fibers. 
Stained by the Golgi method, which picks out a few fibers. The photograph has been 
retouched. 

can provide is a tool by which, aided by a memory, the animal 
can learn the symbolic significance of events. The record of its 
past experiences then constitutes a program of behavior appro- 
priate for the future. 

Octopuses have two separate memory systems. One allows 
them to make appropriate responses to things that they see; the 
other does the same for the tactile and chemical properties of 
objects touched by the arms (fig. 12). These systems lie at the 
top of the hierarchy of nerve centers in the sense that they 
make the decisions as to which movements shall be executed by 
the lower parts. To revert to our military metaphor, they are 
the General Staff. They receive intelligence from the outside 
world and then write plans for programs of action by the whole 
army, in the light of their memory records of past experience. 

With the visual system an octopus can learn to make attacks 
at one shape but to retreat from another. With the touch system 



16 



vert. sup. fr 

Attack" /"| ^V~? 



raw in" inf. fr. 



optic lobe 



eye 




arms 



funnel 



FIG. 12. Diagram of the brain of an octopus showing the parts that make up the 
two memory systems. The two are outgrowths from the superior buccal lobe, which 
controls the eating system (sup. bucc). The inferior frontal system (inf. fr.) receives 
information from the arms and provides a memory regulating which objects are 
drawn in. The superior frontal (sup. fr.) and vertical (vert.) lobes are part of the visual 
memory, serving to decide which objects should be attacked for food. 

he can learn to discriminate degrees of roughness and also 
chemical differences, detected by the suckers (Wells and Wells, 
1956; Wells, 1963) (fig. 13). 

The visual system has features again surprisingly like those of 
vertebrates in their principles of operation, in spite of great dif- 
ferences in detailed anatomy. We can see from these principles 
the stages that are necessary for the learning of symbolic signif- 
icances by vision or touch. 

FEATURE DETECTORS 



The first essential is to have sensors that are competent to 
extract relevant information from the world. We know little 
about the physiology of these in cephalopods but something of 
their anatomy. There are cells with receptive fields in the outer 
parts of the optic lobes that seem suited to detect contours, as 

17 



<^<*NrH £*}£*! 






i^|% g?§f*% 



FIG. 13. Series of plastic spheres used for training octopuses to distinguish various 
degrees of roughness. 

do cells of the visual cortex of mammals (fig. 14). Octopuses 
can be trained to react differentially to rectangles with vertical 
and horizontal orientations. It is probable that these features 
are detected by the receptive fields of these second-order visual 
cells, which seem to be tuned to receive signals from rows of 
optic nerve fibers. We note that such a system depends on a de- 
tailed somatotopic projection from the sensory surface of the 
eye. This presents a literal map of outside events, from which 
the brain then records certain features as it writes the programs 
that will determine its future actions. Moreover, these feature 
detectors lie in a layered system of neuronal processes, the 
plexiform layer, which is surprisingly like the layered structure 
of the vertebrate retina (fig. 15). Contributing to this layered 
neuropil are great numbers of amacrine and horizontal cells, 
with processes limited to the plexiform layer. Some extend over 
long distances, others are quite short, and we have as yet no 
information as to how any of them operate. Their presence, 
however, in essentially the same relations in cephalopods and 



18 




Res- 



Res.+ 



FIG. 14. Diagram of the optic lobe of an octopus to show the system by which it 
is suggested that visual contours are detected and memory records made that will 
control future behavior. Clas. V. and clas. H. are the "classifying cells," which 
respond to particular visual features (e.g., vertical or horizontal rectangles). The 
octopus can be trained to attack or avoid either of these, so the pathways from them 
msut lead to motor systems for attack and retreat. Following an attack the animal 
will receive either food or pain. The suggestion is that signals from the lips (food) or 
from the body (pain), besides promoting attack or retreat, will activate the small 
cells, which produce an inhibitory transmitter and block the unwanted pathway, 
leading to greater use of that which is "correct." The memory cells (mem.) only 
discharge if they receive signals both from the classifying cells and from the indicators 
of results (Res.+ and Res.-). The system is shown biased as it would be if the horizon- 
tal rectangle had been given food and the vertical shocks. 

vertebrates should surely help us to find the principles that are 
involved in the extraction of significant visual features. Pribram 
(1971) has suggested that such systems recall the logical organi- 
zations necessary for encoding by and/or gates. We can also sur- 
mise from the work of Dowling and Werblin (1969) on the 
retina of the mud-puppy (Necturus) that these elaborate net- 
works operate essentially as analogue computers, using patterns 
of graded electrical signals to compute from the patterns that 
are sent to them from the retinal receptors suitable all-or-none 
signals to pass on to the next stage in the brain. 

Unfortunately, we know rather little about how to pursue 
such signals, either in cephalopods or vertebrates, to the points 



19 




FIG. 15. Photograph of a section of the surface of the optic lobe of an octopus, 
showing how it resembles the vertebrate retina. There are outer and inner granule cell 
layers (o. gr. and in. gr.), with a plexiform layer between (plex.). The optic nerve 
fibers come in from the right (o.n.). They have disappeared from the upper part of 
the figure where some of them had been cut some days previously. The inner 
tangential bands of fibers in the plexiform zone (tan.) are the receiving dendrites of 
the "classifying cells" shown in figure 14. They have remained intact. Cajal's silver 
stain. 



20 



at which the changes occur that constitute the writing of a new 
action program by the memory mechanism. In squids we can 
say that there are only one or two further synapses between the 
feature detectors and the giant cells. Therefore, although the 
optic lobes are indeed large and complex, there is no need to 
suppose that any very elaborate system of operations has to in- 
tervene between detection and behavior, even in learned behav- 
ior. 

However, somewhere in this pathway there must be the possi- 
bility of an alteration in connection patterns, if that is the 
mechanism by which the memory system works. I have sug- 
gested that this is done by the operation of a switch system that 
reduces the probability of using one pathway in favor of the 
other (fig. 14). It may be that once one path begins to be used 
rather than the other there will also be a subsequent increase in 
its availability, perhaps by added synaptic connections or effi- 
cacy, as has been suggested, following Cajal (1895, see 1953 p. 
887), by many workers (e.g., Hebb, 1949; Young, 1950). But 
whatever mechanism is used to establish the symbolic value of 
some set of nervous signals, it must involve a reduction of the 
number of possible behavioral responses. The octopus can orig- 
inally react either positively or negatively to a horizontal 
rectangle; his experience restricts him to only one of these re- 
sponses. A given signal cannot symbolize both something good 
and bad. I have suggested that the switching of each single neu- 
ronal pathway constitutes a unit of memory or mnemon. It is 
the single "word" of the writing that constitutes the new pro- 
gram of action. The octopus is a very simple creature and per- 
haps it learns only single words. We have to learn not only 
words but whole "sentences," indeed whole "books," which 
constitute the action programs that become written in our 
memories. 

For the establishment of symbolic value it is essential that 
the results of action can be referred to a standard, which must 
ultimately be set by the genetic composition, the historical in- 
formation encoded in the DNA. Such signals of the results of 
action come from the taste systems on the one hand and the 

21 



pain systems, producing aversive responses, on the other. We do 
not know much about them in octopuses but there is evidence 
that if they are prevented from reaching to the appropriate 
parts of the brain no learning is possible. We notice that these 
nerve impulses, like all others, are symbolic, in this case sym- 
bolizing internal states that are either satisfactory or unsatis- 
factory for life. The symbolic value is established by the long 
sequence of selections that have produced appropriate DNA. 
Those organisms that do not have an appropriate taste for food 
and life or skill in avoiding pain do not survive. 

The anatomy suggests that in the octopus, as in vertebrates, 
special patterns of connection are used to allow these reference 
signals to meet with those coming from the outside world. In 
both the visual and touch memory systems of the octopus there 
are lobes in which this interaction can take place (fig. 16). The 



sup.fr. -^ 




-.1 . 



*%i& 



FIG. 16. Photograph of sagittal section through the front part of the brain of an 
octopus, showing the inferior frontal (inf. fr.), superior frontal (sup. fr.) lobes, and 
superior buccal lobe (sup. bucc). These serve to mix signals of taste (from the lips) 
with those from the arms and optic lobes (respectively). The two lobes have similar 
structures, with many interweaving bundles, allowing for the mixing. Cajal's silver 
stain. 



22 



output of the lobes in both cases passes through a further lobe 
consisting of large numbers of very small cells, the vertical or 
subfrontal lobes (fig. 17). Many lines of investigation have 
shown that these lobes are involved in the process of recording 
in the memory, but are not absolutely essential for it. Their 
action seems to be particularly in restraining the animals from 
performing actions that are likely to be damaging. The numer- 
ous minute cells in these lobes can be seen with the electron 
microscope to be packed with synaptic vesicles (fig. 18). How 
they operate remains a very interesting question. 

In general we can say that if learning consists in increasing 
the probability of performing certain "correct" actions when 
symbols appear, then it is necessary to have inhibitory systems 
to restrain the performance of other actions. A multichannel 
system such as this operates by means of a maximum ampli- 
tude filter in which many elements may be active but only the 
most active takes control (Taylor, 1964). It is suggested that the 
cerebral cortex contains systems that act in this way. Perhaps 
the prefrontal lobes in particular have a restraining influence in 




pain 



FIG. 17. Diagram of some connections of the median superior frontal (med. sup. 
fr.) and vertical lobes (vert.) of an octopus as shown by electronmicroscopy. The 
short amacrine cells in the vertical lobes are packed with synaptic vesicles. They are 
influenced by the fibers from the superior frontal and also by those entering from 
below and probably signalling pain. They influence larger cells leading to the 
subvertical lobe (subv.) and so back to the optic lobes (opt.). 



23 



WT& 




FIG. 18. Electronmicrographs of synaptic contents in the superior frontal (on 
right) and vertical (left) lobes of an octopus. The synapses in the former are between 
incoming fibers (e) and cell processes (cp.). In the vertical lobe the amacrine trunks 
(amt.) receive synapses from the axons of the superior frontal (s.f.b.) and transmit to 
spines (sp.) of cells that carry signals away from the lobe. 

man, allowing the performance of such delicately graded actions 
as those of effective speech in a social context. 

Human brains, like those of octopuses, must contain reference 
systems to determine which lines of action are likely to be suc- 
cessful in maintaining life. We can indeed begin to see some evi- 
dence that they operate in ways rather like those described. 
Ungerstedt (1971) and others have shown that there are systems 
of aminergic pathways leading upward from centers in the 
medulla to the hypothalamus and on to the limbic system and 
frontal cortex (fig. 19). These pathways, such as that beginning 
in the nucleus coeruleus, come from regions where fibers from 
the taste buds enter the brain. Crow and his colleagues have pro- 
duced evidence that rats with lesions to this pathway cannot 
learn to run a maze for food reward (Anlezark, Crow, and 
Greenaway, 1973). Moreover, with electrodes implanted in 
these regions animals will press repeatedly for self-stimulation. 
There are controversies about these experiments, but it seems 
very probable that we are approaching here close to the core of 
many problems that have worried mankind for centuries, and 
do so still. The reference signals that come from these path- 
ways, and from the hypothalamus, provide the aims and objec- 
tives of our lives and the course of our learning. Of course crude 



24 




loc. c. 



FIG. 19. Diagram of the ascending pathways on the rat's brain that use the 
transmitter noradrenaline. They begin in the locus coeruleus (loc. c.) and other 
centers in the hind brain. From here they ascend to the cerebellum (cb.), hypo- 
thalamus (hyp.) and finally reach to the cerebral cortex (cort.), olfactory bulb (ol.) 
and hippocampus (hip.). The terminal areas are shaded (after Ungerstedt, 1971). 

rewards do not necessarily enter into every associational act, 
especially in man. We have acquired more subtle systems of re- 
ward to supplement those of taste and pain. Nevertheless, we 
begin to see how life depends upon symbolic signs of life values, 
which are used to give symbolic significance to the signals we 
receive from the outside world. 



25 



LITERATURE CITED 

Anlezark, G.M., T.J. Crow, and A. P. Greenaway 

1973. Evidence that noradrenergic innervation of the cerebral cortex is necessary 
for learning. Jour. Physiol. London, vol. 231, pp. 119-120. 

Arbib, M.A. 
1972. The metaphysical brain. New York, WileyTnterscience. 

Boycott, B.B. 

1961. The functional organization of the brain of the cuttlefish, Sepia officinalis. 
Proc. Royal Soc, vol. 152, pp. 503-534. 

Boycott, B.B. and J.Z. Young 

1950. The comparative study of learning. Symp. Soc. Exp. Biol., vol. 4, pp. 432- 
453. 

Braitenberg, V. 

1967. Is the cerebellar cortex a biological clock in the millisecond range? Progr. 
Brain Res., vol. 25, pp. 334-346. 

Budelmann, B.-U. 

1975. Gravity receptor function in cephalopods with particular reference to 
Sepia officinalis. Fortsch. Zool., vol. 23, pp. 84-96. 

Cajal, S.R. 
1953. Histologie du Systeme nerveux (facsimile of French edition of 1909). Ma- 
drid, Instituto Ramon y Cajal. 

Dovvling, J.E., and F.S. Werblin 

1969. Organization of retina of the mudpuppy Necturus nee turns. 1. Synaptic 
structure. Jour. Neurophysiol., vol. 32, pp. 315-338. 

Evarts, E.V., E. Bizzi, R.E. Burke, M. Long, and W.T. Thach, Jr. 

1971. Central control of movement. Neurosci. Res. Program Bull., vol. 9, pp. 2- 
170. 

Hebb, D.O. 

1949. The organization of behavior. New York, John Wiley. 
Pribram, K.H. 

1971. Languages of the brain. New Jersey, Prentice Hall. 
Taylor, W.K. 

1964. Cortico-thalamic organization and memory. Proc. Royal Soc. B., vol. 159, 
pp. 466-478. 

Ungerstedt, U. 

1971. Stereotaxic mapping of the monomine pathways in the rat brain. Acta 
Physiol. Scand., vol. 367 (Suppl.), pp. 148. 

26 



Uclls. M.J. 

1963. Taste or touch: some experiments with Octopus. Jour. Exp. Biol., vol. 40, 
pp. 187-193. 

Wells. M J. .and J.Wells 

1956. Tactile discrimination and the behavior of blind Octopus. Pubbl. Staz. 
zool. Napoli., vol. 28, pp. 94-126. 

Williams, L.W. 

1909. The anatomy of the common Squid Loligo pealii, Lesueur. Leiden, Brill. 

Young, J.Z. 

1939. Fused neurons and synaptic contacts in the giant nerve fibres of cephalo- 
pods. Phil. Trans. Royal Soc. vol. 229, pp. 465-503. 

1950. Doubt and certainty in science. Clarendon Press, Oxford. 

1971. The anatomy of the nervous system of Octopus vulgaris. Oxford, Clarendon 
Press. 



27 



SN2&1.4 
• J35 
10.4-7 
1977 



FORTY-SEVENTH 
I JAMES ARTHUR LECTURE ON 
THE EVOLUTION OF THE HUMAN BRAIN 



AN EVOLUTIONARY INTERPRETATION 

OF THE 
PHENOMENON OF NEUROSECRETION 



BERTA SCHARRER 



THE AMERICAN MUSEUM OF NATURAL HISTORY 
NEW YORK : 1977 



xo 






*fi 



A* 




V 



% 



1869 
THE LIBRARY 



FORTY-SEVENTH 

J WHS ARTHUR U C I I Rl ON 

THE EVOLUTION OF THE HUMAN BRAIN 



AN EVOLUTIONARY INTERPRETATION 

OF THE 
PHENOMENON OF NEUROSECRETION 



BERTA SCHARRER 

Professor of Anatomy and Seuroscience 
Albert Einstein College of Medicine. New York 



THE AMERICAN MUSEUM OF NATURAL HISTORY 
NEW YORK : 1978 



FORTY-SEVENTH 

JAMES ARTHUR LECTURE ON 

THE EVOLUTION OF THE HUMAN BRAIN 



The author's studies reported in the present paper have been 
supported by Research Grants NB-05219, NB-00840, and 5 POl- 
NS-07512 from the U.S.P.H.S. and by N.S.F. Grant BMS 
74-12456. 

The treatment of the literature was greatly facilitated by Bibli- 
ographia Neuroendocrinological compiled and edited by Dr. 
Mary Weitzman, and supported by Grant No. 1 ROl LM 02327 
awarded by the National Library of Medicine, U.S.P.H.S., 
DHEW. 



JAMES ARTHUR LECTURES ON 
THE EVOLUTION OF THE HUMAN BRAIN 



Frederick Tilney. The Bruin in Relation to Behavior, March 15, 1932 

C. JtldsOi] Herrick, Brains as Instruments of Biological Values; April 6. 1933 

D. M. S. Watson. The Story of Fossil Brains from Fish to Man; April 24, 1934 

C. U. Aliens Kappers, Structural Principles in the Nervous System; The Development of 
the Forehrain in Animals and Prehistorie Human Races; April 25, 1935 

Samuel T. Orton, The Language Area of the Human Brain and Some of its Disorders; 
May 15. 1936 

R. W. Gerard, Dynamic Neural Patterns; April 15, 1937 

Franz Weidenreich. The Phylogenetic Development of the Hominid Brain and its Connec- 
tion with the Transformation of the Skull; May 5, 1938 

G. Kingsley Noble, The Neural Basis of Social Behavior of Vertebrates; May 11, 1939 

John F. Fulton, A Functional Approach to the Evolution of the Primate Brain; May 2, 
1940 

Frank A. Beach, Central Nervous Mechanisms Involved in the Reproductive Behavior of 
Vertebrates; May 8, 1941 

George Pinkley. A History of the Human Brain; May 14, 1942 

James W. Papez, Ancient Landmarks of the Human Brain and Their Origin; May 27, 
1943 

James Howard McGregor, The Brain of Primates; May 11, 1944 

K. S. Lashley, Neural Correlates of Intellect; April 30, 1945 

Warren S. McCulloch, Finality and Form in Nervous Activity; May 2, 1946 

S. R. Detwiler, Structure-Function Correlations in the Developing Nervous System as 
Studied by Experimental Methods; May 8, 1947 

Tilly Edinger, The Evolution of the Brain; May 20, 1948 

Donald O. Hebb. Evolution of Thought and Emotion; April 20, 1949 

Ward Campbell Halstead, Brain and Intelligence; April 26, 1950 

Harry F. Harlow. The Brain and Learned Behavior; May 10, 1951 

Clinton N. Woolsey, Sensory and Motor Systems of the Cerebral Cortex; May 7, 1952 

Alfred S. Romer, Brain Evolution in the Light of Vertebrate History; May 21, 1953 

Horace W. Magoun, Regulatory Functions of the Brain Stem; May 5, 1954 

*Fred A. Mettler, Culture and the Structural Evolution of the Neural System; April 21, 
1955 

*Pinckney J. Harman, Paleoneurologic, Neoneurologic, and Ontogenetic Aspects of Brain 
Phylogeny; April 26, 1956 



*Davenport Hooker, Evidence of Prenatal Function of the Central Nervous System in 
Man; April 25, 1957 

*David P. C. Lloyd, The Discrete and the Diffuse in Nervous Action; May 8, 1958 

*Charles R. Noback, The Heritage of the Human Brain; May 6, 1959 

*Ernst Scharrer, Brain Function and the Evolution of Cerebral Vascularization; May 26, 
1960 

Paul I. Yakovlev, Brain, Body and Behavior. Stereodynamic Organization of the Brain 
and of the Motility-Experience in Man Envisaged as a Biological Action System; May 
16, 1961 

H. K. Hartline, Principles of Neural Interaction in the Retina; May 29, 1962 

Harry Grundfest, Specialization and Evolution of Bioelectric Activity; May 28, 1963 

*Roger W. Sperry, Problems Outstanding in the Evolution of Brain Function; June 3, 
1964 

*Jose M. R. Delgado, Evolution of Physical Control of the Brain; May 6, 1965 

Seymour S. Kety, Adaptive Functions and the Biochemistry of the Brain; May 19, 1966 

Dominick P. Purpura, Ontogenesis of Neuronal Organizations in the Mammalian Brain; 
May 25, 1967 

*Kenneth D. Roeder, Three Views of the Nervous System; April 2, 1968 

tPhillip V. Tobias, Some Aspects of the Fossil Evidence on the Evolution of the Hominid 
Brain; April 2, 1969 

*Karl H. Pribram, What Makes Man Human; April 23, 1970 

Walle J. H. Nauta, A New View of the Evolution of the Cerebral Cortex of Mammals; 
May 5, 1971 

David H. Hubel, Organization of the Monkey Visual Cortex; May 11, 1972 

Janos Szentagothai, The World of Nerve Nets; January 16, 1973 

*Ralph L. Holloway, The Role of Human Social Behavior in the Evolution of the Brain; 
May 1, 1973 

*Elliot S. Valenstein, Persistent Problems in the Physical Control of the Brain; May 16, 
1974 

a Marcel Kinsboume, Development and Evolution of the Neural Basis of Language; April 
10, 1975 

*John Z. Young, What Squids and Octopuses Tell Us About Brains and Memories, May 
13, 1976 

*Berta Scharrer, An Evolutionary Interpretation of the Phenomenon of Neurosecretion; 
April 12, 1977 



^Unpublished. 

*Published versions of these lectures can be obtained from The American Museum of 
Natural History, Central Park West at 79th St., New York, N. Y. 10024. 

tPublished version: The Brain in Hominid Evolution, New York: Columbia University 
Press, 1971. 



AN EVOLUTIONARY 

INTERPRETATION OF THE 

PHENOMENON OF NEUROSECRETION 



INTRODUCTION 

Almost 50 years ago, Ernst Scharrer (1928) made a discovery 
that was received by the scientific community with great skepti- 
cism, if not with outright rejection. It marked the beginning of a 
scientific adventure that has given rise to one of the most chal- 
lenging pursuits in neurobiological research, the results of which 
have been dramatic. Based on cytological observations in a tele- 
ost fish, Phoxinus laevis, he postulated that certain groups of 
distinctive cells in the hypothalamus ("neurosecretory neurons") 
engage in secretory activity to a degree comparable to that of 
endocrine gland cells. He further suggested that this activity may 
be related to hypophysial function. 

A search in the literature yielded but one comparable report 
calling attention to the occurrence of "glandlike" nerve cells in 
another part of the central nervous system, the spinal cord of 
skates (Speidel, 1919). Subsequent studies demonstrated the al- 
most ubiquitous occurrence of such neurons throughout the ani- 
mal kingdom. Yet, for many years to come, the spotlight 
remained on the hypothalamic neurosecretory centers of the ver- 
tebrate series. The elucidation of their close affiliation with the 
pituitary gland eventually gave rise to a new discipline, neuroen- 
docrinology. 

However, recognition of these unusual neural elements repre- 
sents a challenge to the neuron doctrine, according to which 
nerve cells are most commonly thought of as being designed for 
the reception of stimuli, the generation and propagation of bio- 
electrical potentials, and the rapid, synaptic transmission of sig- 
nals to contiguous recipient cells. "Conventional" neurons make 
only very restricted use of chemical mediators in the form of 
special neurotransmitters and certain other regulatory substances. 



1 



In contrast, the primary activity of the classical neurosecretory 
cell consists of the manufacture of a distinctive (proteinaceous) 
product in sufficient quantity to function in a hormonal capacity. 
Furthermore, its axon terminates, without establishing synaptic 
contact, in close proximity to the vascular system. No wonder 
that, because of these "aberrant" attributes, neurosecretory phe- 
nomena were long looked at askance and frequently brushed off 
as signs of degenerative or postmortem changes. Today, this 
mistrust no longer exists, as will become apparent in the follow- 
ing discussion. 

An important step forward was the demonstration that the 
"posterior lobe hormones," e.g., vasopressin, are derived from 
peptidergic neurosecretory nuclei of the hypothalamus and are 
transported by axoplasmic flow to the posterior pituitary where 
they are released into the general circulation (Bargmann and 
Scharrer, 1951). At last, the endocrine nature of some of these 
neuroglandular elements had been established. 

But even then a vexing question remained. Why should the 
body make use of nerve cells to provide hormonal messengers in 
order to reach terminal effector sites such as the kidney? This 
conceptual difficulty stems from the established custom of classi- 
fying neuroculatory and glandular functions as two distinctly 
separate categories. In reality, there are cogent reasons for bridg- 
ing this gap, based largely on evidence that is implicit in the 
evolutionary history of integrative systems. 

PHYLOGENY OF NEURAL SYSTEMS OF COMMUNICATION 

A careful consideration of the phylogenetic, and to some ex- 
tent the ontogenetic, development of such informational systems 
has made it increasingly clear that the manufacture and release of 
secretory products is an old and fundamental attribute of neuronal 
elements. The evolutionary approach, featured in this article, is 
based on the premise that the most elementary integrative mecha- 
nisms existing today may resemble those of our remote ancestors 
(Pavans de Ceccatty, 1974). 

By reason of its phylogenetic derivation from a pluripotential 
epithelial element, the primitive nerve cell can be viewed as a 



functionally versatile structure, endowed with the capacity to 
dispatch both long distance and localized chemical signals. This 
concept is supported by a substantial body of information on 
neuroregulatory mechanisms encompassing all multicellular ani- 
mals (see Lent/., 1968; Highnam and Hill, 1977). Starting with 
the simplest forms among them, we find in sponges a reticular 
neuroid tissue complex whose components do not yet satisfy all 
the criteria of nerve cells. The first primitive neurons with ele- 
mentary synaptic contacts appear in the lowest eumetazoans, the 
eoelenterates. 

What seems important in the context of the present analysis is 
that in both groups some of the cells mentioned display cytologi- 
cal signs of neurosecretory activity. The cytoplasmic granules 
observed here are comparable to those of higher animals in that 
they stain with alcian blue and, in electron micrographs, appear 
electron dense and membrane-bounded with diameters of 
1,000-1.700 A (Pavans de Ceccatty, 1966; Lentz, 1968; Davis, 
1974). Neurosecretory granules are abundant in the nervous sys- 
tem of planarians. In the ganglia of annelids more than one-half 
of all neurons are of the neurosecretory type. 

Even more relevant is the fact that distinctive hormonal func- 
tions as well as other "nonconventional" neuroregulatory roles 
can be ascribed to the neurosecretory neurons of these lower 
invertebrates. Tests with isolated neurosecretory granules of the 
coelenterate Hydra reveal that their content regulates growth and 
differentiation, especially during regeneration (Lentz, 1968). This 
neuromediator also seems to participate in the induction of 
gametogenesis and sexual differentiation (Burnett and Diehl, 
1964). Similarly, neurosecretory control, over a distance, of 
growth during development and regeneration and of certain re- 
productive events has been demonstrated in planarians (Lentz, 
1968; Grasso and Benazzi, 1973) and in annelids (Hauenschild, 
1974). 

The salient point is that in none of these primitive invertebrates 
have "regular," i.e., nonneural glands of internal secretion been 
identified. Therefore, at this level of differentiation, the nervous 
system seems to be the only agency available for carrying out all 
of the existing endocrine functions. Neurohormones thus hold the 



rank of the phylogenetically oldest integrative long-distance mes- 
sengers, and the endocrine type of coordination accounts for a 
relatively large sector of neuronal activities in lower inverte- 
brates. In other words, far from being a latecomer and a rare 
exception, the neurosecretory neuron dates back to the very be- 
ginning of the development of neural structures. Furthermore, its 
versatility indicates that it has remained closer to the nerve cell 
precursor than has the more specialized "conventional" neuron. 

In the course of evolution the scene shifts in more than one 
direction. Not only is there a staggering increase in the number 
of neurons, as primitive nervous systems give way to more and 
more elaborate structures but, in the most advanced forms, the 
vast majority of "conventional" nerve cells engage in interneuro- 
nal synaptic transmission involving the release of tiny, precisely 
metered amounts of chemical transmitter substances. Some of 
these special messengers are used over and over again. There- 
fore, in these billions of neurons, the demands for secretory 
activity have become greatly reduced. 

Another, equally important, evolutionary change in design is 
the evolvement of extraneuronal hormone sources. The structural 
and functional attributes of the endocrine apparatus have long 
been thought to be as clearly defined as have those of neurons. 
Yet, the dividing line is by no means complete, on account of the 
neuroectodermal origin of peptide-producing endocrine cells to be 
discussed below. According to this concept (Pearse, 1976), the 
relationship between the neuronal and nonneuronal hormone 
sources of the hypothalamic-hypophysial complex is even closer 
than formerly recognized, since both share their origin from the 
same precursor cells in the ventral neural ridge. However, in 
spite of this embryonic background, the cells of the ade- 
nohypophysis should not be classified as neural elements. They 
have crossed over to join the ranks of the endocrine system. This 
process of metamorphosis entails the loss of structural and 
cytochemical neural attributes and the acquisition of endocrine 
qualities which these polypeptide-hormone-secreting cells share 
with the rest of the endocrine apparatus. 

The evolvement of this second integrative system that special- 
izes in hormonal communication, making use of various types of 



chemical messengers, argues against the need for blood-borne 

neurochemical mediators in higher animals. Quite obviously, its 
existence should relieve neurons from doing double duty. 

NEUROENDOCRINE INTERACTIONS 

In reality neurohormones do not become obsolete after the 
acquisition, by arthropods and vertebrates, of an endocrine appa- 
ratus proper. Instead they take over a novel and highly significant 
role, that of mediation between the two systems of integration. 
As has been pointed out repeatedly in the past (Scharrer, 
1970-1974), the neurosecretory neuron, having retained its dual 
capacity, is ideally suited and programmed for this special task. 

In view of this shift in functional significance, the question 
raised earlier, concerning the raison d'etre of first-order neurohor- 
monal mechanisms even in the most highly developed organisms, 
now appears in a different light. Such one-step systems, e.g., the 
control of water metabolism by vasopressin, have certainly be- 
come overshadowed by those constituting the all-important neu- 
roendocrine channel of communication. They do not even seem 
to be obligatory. Yet, their existence makes sense in an evolu- 
tionary perspective, i.e., when interpreted as carryovers from 
systems operating by necessity in phylogenetically less advanced 
forms. 

NONNEUROHORMONAL PEPTIDERGIC ACTIVITIES 

A rather unexpected and challenging result of the detailed 
ultrastructural analysis of the neuroendocrine axis in vertebrates 
and invertebrates was the realization that not all the neurosecre- 
tory neurons dispatch their messenger substances via the general 
or the special portal circulation. There are, in fact, several recog- 
nized modes of neurochemical communication that are neither 
strictly neurohumoral (synaptic) nor neurohormonal (blood- 
borne). One such mechanism is the long known regulation of 
tissue growth and maintenance, by "neurotrophic substances" 
(see Smith and Kreutzberg, 1976). The chemistry and extracellu- 
lar pathway of these diffusible substances released from sensory 
and motor fibers are still uncertain. 



Information on nonvascular extracellular avenues available to 
peptidergic neurosecretory messengers is more precise. These 
variants include the cerebrospinal fluid (see Rodriguez, 1976), 
zones of extracellular stroma, and even narrow "synaptoid" gaps. 
Axons laden with neurosecretory material can be observed to 
penetrate the glandular parenchyma of the adenohypophysis as 
well as the corpus allatum of insects. In both organs synaptoid 
release sites occur in close vicinity to, or even in contiguity with, 
their apparent cells of destination. Furthermore, such spatial rela- 
tionships are not restricted to endocrine elements, but are also 
found in a variety of somatic structures, among them various 
exocrine gland cells and muscle fibers. 

Perhaps the most unexpected informational systems are those 
in which neurosecretory neurons establish synapse-like relation- 
ships with other neurons, some of which may themselves be of 
the nonconventional type (see Scharrer, 1976). The realization 
that, at least in certain special situations, peptidergic neurosecre- 
tory mediators may operate in a manner comparable to that of 
neurotransmitters has added a new and important facet to the 
"gestalt" of the classical neurosecretory neuron. The existence of 
these several intermediary possibilities for the transfer of informa- 
tion by neurosecretory cells has clarified their relationship with 
the more conventional neuronal types. Consequently, the sharp 
dividing line originally thought to separate conventional from 
classical neurosecretory neurons no longer exists. Now the modes 
of operation of classical neurosecretory neurons actually blend 
into a continuum of diverse neurochemical activities. 

NONCONVENTIONAL INTERNEURONAL COMMUNICATION 

What makes the discovery of synaptoid structures between 
neurons intriguing is that they go hand in hand with increasing 
physiological evidence in support of the concept that nonconven- 
tional (peptidergic) neuroregulators may modulate certain forms 
of synaptic interneuronal communication. This broader neu- 
rotropic activity will undoubtedly turn out to represent a novel 
and important form of information transfer with far-reaching bio- 
medical implications (see, for example, Constantinidis et al., 



1974; Sterba. 1974; Broun and Vale. 1975; Plotnikoff ct al.. 
1975; Prange et al.. 1975a. 1975b; Vincent and Arnauld. 1975; 
Brownstein et al.. 1976; Guillemin. Ling and Burgus. 1976; Lote 
et al.. 1976). 

To cite an example of such known activities among the hypo- 
physiotropic hormones, or factors. TRF (thyrotropin releasing 
factor) has a modulating effect on synaptic, especially mono- 
aminergic. transmission. Apparently, this role evolved before that 
of controlling thyrotropin release, and it seems to be of a more 
general importance (Grimm-J0rgensen. McKelvy and Jackson. 
1975; McCann and Moss. 1975; Waziri, 1975; see also Nicoll, 
1977). A broader role for the posterior lobe hormone vasopressin, 
or fragments thereof, is that demonstrated by de Wied and his co- 
workers (1976) and involved in the control of various forms of 
behavior. Moreover, effects that differ from conductance changes 
evoked by conventional neurotransmitters can be elicited in cer- 
tain neurosecretory neurons of molluscs by the application of 
vasopressin and related peptides (Barker and Gainer. 1974). Fi- 
nally, there is new and intriguing evidence that two specific 
neuronal pentapeptides (enkephalins. Hughes et al.. 1975) func- 
tion as endogenous analgesics presumably by suppressing excita- 
tory synaptic signals implicated in the perception of pain (see 
Snyder, 1977). 

BIOCHEMICAL EVOLUTION OF NEUROSECRETORY 
MEDIATORS 

The evolutionary interpretation of the phenomenon of neu- 
rosecretion presented here is not based on morphological and 
physiological evidence alone. It can be further substantiated by 
tracing the biochemical history of neurosecretory mediators, even 
though the picture is still incomplete. 

Among the general trends that are beginning to emerge are the 
following. In contrast to those used in much smaller amounts by 
conventional nerve cells, the chemical messengers operating in 
classical neurosecretory neurons of both vertebrates and inverte- 
brates are proteinaceous in nature. Furthermore, the biologically 
active polypeptides of many neurosecretory neurons are bound by 



noncovalent forces to special carrier proteins, called neurophysins 
(see Walter, 1975; Watkins, 1975; Acher, 1976b), which are 
primarily responsible for the selective stainability of neurosecre- 
tory material throughout the animal kingdom. Aside from serving 
as carrier molecules, these proteins may play an active role of 
their own (Pilgrim, 1974). 

Much information is being amassed on the occurrence and 
precise localization of such neuropeptides and their affiliated 
neurophysins within the neurosecretory systems of a variety of 
animals by the use of immunochemical, especially immu- 
noelectron-microscopic methods (see McNeill et al., 1976; Ude, 
1976; Zimmerman, 1976). In addition, synthetically produced 
neurohormones and their analogs are becoming available in in- 
creasing numbers. These advances offer valuable tools for the 
differential determination of the relationships and functional roles 
of these substances. 

There is substantial support for the concept that the characteris- 
tic products of presently existing neurosecretory neurons have a 
common evolutionary origin. Gene duplication, modification, and 
cleavage of ancestral proteinaceous molecules are presumed to 
have been involved in the development of chemical entities with 
more and more diversified functional properties (see Wallis, 
1975). 

This process seems to be reflected by the fact that enzymatic 
dissociation is responsible for the biosynthesis of most, if not all, 
biologically active peptides known today (Tager and Steiner, 
1974; Acher, 1976b). For example, the active nonapeptides stored 
in the mammalian posterior lobe and the corresponding carrier 
proteins are apparently not synthesized as such in the perikarya of 
the respective hypothalamic neurons but are cleaved from a pre- 
cursor of higher molecular weight (Sachs et al., 1969; Gainer, 
Same and Brownstein, 1977). The fact that both components 
make a strikingly sudden and simultaneous appearance early dur- 
ing fetal development (Pearson, Goodman and Sachs, 1975) sup- 
ports the view that they share the same macromolecular pre- 
cursor. Moreover, the impressive structural similarity throughout 
the entire vertebrate series of neurohypophysial hormones (Heller, 
1974; Carraway and Leeman, 1975; Wallis, 1975; Acher, 1976a) 



as well as their corresponding neurophysins (Capra and Walter, 
1975; Acher. 1976b; Zimmerman, 1976) suggests that their pres- 
ent preeursor moleeules (prohormones) are derived from closely 
related ancestral proteins. 

The same type of lineage can be claimed for hypophysiotropic 
factors, the amino acid sequences of which are contained in 
parent compounds of higher molecular weight. For example, 
nonapeptides with hormonal activities of their own can play the 
role of precursor for short-chain principles, such as the tripeptide 
MIF (MSH-release inhibiting factor, melanostatin), a neurohor- 
mone with different functional capacities (Walter, 1974; Reith et 
al., 1977). Parenthetically, another unexpected feature about 
nonapeptides is the recently reported presence of vasopressin, 
unaccompanied by neurophysin, in a cell line from a human lung 
carcinoma (Pettengill et al., 1977). 

Information on analogous proteinaceous compounds in inverte- 
brates is still sporadic. Nevertheless, histochemical and biochemi- 
cal parallelisms can be recognized. For example, a chromato- 
phorotropin that was chemically identified in crustaceans shows a 
close resemblance to some of the small hypophysiotropic peptides 
of mammals (Fernlund and Josefsson, 1972; Carlsen, Christensen 
and Josefsson, 1976). Furthermore, a chemically synthesized oc- 
tapeptide was shown to elicit pigment concentration in two types 
of crustacean chromatophores in vitro and in vivo (Josefsson, 
1975). A similar fully identified neuropeptide is the adipokinetic 
hormone of insects (Stone et al., 1976). Another case in point is 
the recent demonstration of immunoreactive TRF (thyrotropin 
releasing factor) in the ganglia of some gastropods (Grimm- 
J0rgensen, McKelvy and Jackson, 1975) where, for obvious rea- 
sons, its function could resemble only the extrahypothalamic 
activities demonstrated in vertebrates. An indication of the occur- 
rence of such nonconventional interneuronal communication is 
the recent observation (Takeuchi, Matsumoto and Mori, 1977) 
that certain neurons of the snail Achatina are differentially af- 
fected by fragments of some enzymatically treated nonapeptides, 
e.g., oxytocin and vasotocin. 

Finally, are there common denominators in the biosynthetic 
and functional features of classical neurosecretory materials and 



of other biologically active peptides produced by neurons and/or 
glandular elements derived from neuroectodermal precursors (an- 
terior pituitary and other members of the APUD cell series, 
Pearse, 1976; Pearse and Takor Takor, 1976)? 

In underscoring the neuroembryological and cytochemical fea- 
tures shared by these cells, Pearse' s intriguing concept clarifies 
the multiple occurrence, both within and outside the adult ner- 
vous system, of a variety of regulatory peptides, including Sub- 
stance P, enkephalins, endorphins, and several hypophysial 
hormones. Therefore, all of these peptides may also have in 
common the mode of their molecular evolution. 

An example in support of this proposition is the mounting 
evidence for the derivation of several such peptides with distinc- 
tive physiological properties from a larger parent molecule, the 
formerly enigmatic pituitary hormone /3-lipotropin (Li, 1964). 
Among its subunits the endorphins (Goldstein, 1976; Guillemin, 
1977) are currently receiving much attention because of their 
analgesic and behavioral effects. The N-terminal of a-endorphin, 
a short sequence (amino acid residues 61 through 65) apparently 
representing the analgesically active core, precisely matches that 
of methionine enkephalin, one of the two specific neuronal pen- 
tapeptides already referred to (Cox, Goldstein and Li, 1976; 
Guillemin, 1977; Guillemin, Ling and Burgus, 1976). Therefore, 
these endogenous opiates could be generated from the prohor- 
mone /3-lipotropin, either within the brain or in the pituitary, in 
which case they could reach their sites of action via the circula- 
tion or the cerebrospinal fluid (Reith et al., 1977). 

There are also several indications of functional parallelisms. 
One is the demonstration that, in company with several hypo- 
physiotropic polypeptides, enkephalin and endorphin (Dupont et 
al., 1977; Simantov and Snyder, 1977) as well as Substance P 
(Kato et al., 1976) elicit the release of growth hormone, ACTH, 
FSH, and prolactin. Another is that Substance P, like enkephalin, 
endorphin, and several hypophysiotropins, may act as a modula- 
tor of neuronal activity (see Zetler, 1976). 

Neither enkephalins nor opiate receptors have thus far been 
found among invertebrates (Snyder, 1977). Nevertheless, the fea- 
tures that all the biologically active peptides known to date have 

10 



in common add up to the following generalization. In the course 
o\' a long evolutionary history, ancestral macromolecular proteins 
have given rise to a variety of related compounds. Multiple sites 
of cleavage and molecular modulation seem to have resulted in 
the acquisition and dissociation of diverse, e.g., hormonal, neu- 
rotransmitter-! ike, and carrier functions, whereby one active prin- 
ciple may act in more than one capacity. These possibilities, 
borne out by phylogenetic and ontogenetic considerations, illus- 
trate the principle of biochemical economy. 

CONCLUSIONS 

An examination of the evolutionary history of neural tissue, 
and its pluripotentiality in primitive animals, points up its special 
glandular attributes. The old inherited capacity for secretory ac- 
tivity seems to have been put to use in multiple and specialized 
ways at consecutive levels of the evolutionary scale. Therefore, 
the spectrum of available neurochemical mediators and of modes 
of information transfer that digress from standard synaptic trans- 
mission is more diversified than previously assumed, even in 
higher forms. Hormones derived from neural elements have re- 
mained indispensable even after the appearance of the endocrine 
system proper. The most unorthodox neurosecretory cells giving 
rise to these blood-borne proteinaceous messengers, as well as 
those signaling at closer range, have found their place within the 
range of existing variants. Now that the versatility of the hypo- 
thalamic neurosecretory centers and their major role in neuro- 
endocrine integration have been clarified, current interest can turn 
to extrahypothalamic neuropeptides. This nonconventional minor- 
ity seems to have a relatively wide distribution within and outside 
the central nervous system and to function in remarkable ways. 
Further exploration of the glandular aspects of neuronal function 
and their relationship with peptide-hormone-producing cells of 
neuroectodermal origin holds much promise. 



11 



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17