MAN'S INTERVENTION IN INTRACEREBRAL FUNCTIONS
Extract from a medical report of 1967
by Jose M.R. Delgado,
Department of Psychiatry,
Yale University, School of Medicine
New Haven, Connecticut

        Recent technical developments allow an increasing control of
biological functions by electronic instrumentation.  Heart rate,
urination, muscle contraction, audition, blood pressure, and other
functions may be influenced instrumentally.  Following this trend,
techniques are being developed for the investigation and manipulation of
intracerebral mechanisms in animals and in man.
        The newly developed electronic methodology will have important
applications for epilepsy, intractable pain, involuntary movements, and
mental illness.  The greatest challenge, however, is the possibility
that we might substitute, at least in part, human intelligence for
natural choice in man's design of man's highest quality: mental
functions.  A further step in our technological intervention into the
human body is the increasing control of biological functions by
electronic instrumentation.  The clinical success of electrical driving
of the heart in patients with cardiac block has been widely acclaimed.
The bladder has been stimulated by implanted electrodes to produce
urination in cases of permanent spinal block.  A method has recently
been described for placing leads in the auditory nerve to circumvent
deafness caused by inner ear damage.  An electrical current, applied to
the depressor nerve of the carotid sinus, has been used as a permanent
artificial bias to lower blood pressure in hypertensive patients.
        The brain has an extraordinary anatomical and physiological
complexity, and results of its stimulation depend on the position of the
electrodes, parameters of excitation, history of the organism,
environmental circumstances, and other little known factors.  In
addition, when exploring intracerebral physiology we are reaching not
only for the soma but for the psyche itself.  This is the greatest
challenge in the study of cerebral functions which has two main aspects:
        (a)     The acquisition of basic knowledge in order to
understand the physical and chemical mechanisms related to mental and
behavioral manifestations.
        (b)     The development of new approaches for the treatment of
cerebral disturbances.
        In animals and in man the inside of the brain is like an ocean
through which we can navigate without visibility by relying on
instrumental guidance.  Cerebral maps have been complied, oriented
according to stereotaxic coordinates which permit the blind placement of
electrodes within any desired structure.  Assemblies of very fine wires,
guided mechanically by micromanipulators, are introduced through a small
opening made in the skull.  As the electrodes are implanted for days or
months, studies may be carried out in completely awake subjects while
engaged in spontaneous normal activity.
        In humans, implanted electrodes are now used in major hospitals
for the diagnosis and treatment of difficult cases of epilepsy,
involuntary movements, organic pain, anxiety, and other illnesses.  The
presence of electrodes in the brain is not harmful or even
uncomfortable, and patients live a normal life in their own homes.
Repeated exploration of the brain in fully conscious subjects is part of
the necessary study to orient treatment and to control their illness,
and at the same time it provides important information about
correlations between brain physiology, mental activity, and behavioral
performance.  Basic experimentation is conducted in several animal
species, and because of their relative biological closeness to man,
monkeys have been particularly useful subjects.

Radio Stimulators
        In the present electronic age when we are in radio communication
with orbiting capsules and with the stars, it should not be too
difficult to establish radio contact with the inside of the brain.
Actually, however, until recently we lacked suitable instrumentation.
Refined electronic knowledge certainly is available, but the present
orientation of civilization is to direct a large part of our economic
and intellectual resources toward the conquering of outer space and
similar enterprises while paying much less attention to exploration of
the inner space of the brain.  To change this situation it is necessary
to understand the importance and the possibility of manipulating
cerebral physiology, which is, after all, the basis of human
personality.  This field has fundamental medical, social, and even
philosophical implications and should attract the intelligent
collaboration of the best electronic engineers.  since 1959, I have been
interested in the development of suitable instrumentation, and my
initial design of a rather simple, reliable, single channel stimulator
has provided interesting behavioral information.  For the last year, a
new three channel system, developed in collaboration with Mr. Per Hals,
has been successfully used in our monkey colonies.
        It should be expected that in the immediate future, use of
microminiaturization and integrated circuits will allow greater
reduction in size and increase in sophistication of cerebral
radio-stimulators.

Programmed Stimulators
        Some studies of brain physiology require cycles of repeated
prolonged stimulation.  For example, excitation of the lateral
hypothalamus in cats for 0.5 seconds every 5 seconds for 1 hour daily,
for 10 days, increased the intake of food 10 times above control levels.
In other experiments in cats, stimulation of the basolateral amygdala
for 5 seconds, every 15 seconds, for 24 hours, produced a significant
and lasting decrease of food intake.  These programs for excitation may
be easily set in the radio-transmitter, but it is more practical to
establish the program in the stimulator carried by the animal.  The
advantage of the programmed stimulator is that it is self contained and
does not depend on a radio-link, and therefore the mobility of the
subject is not limited, which is an important castration in possible
application of this unit for ambulatory therapy in humans.  A similar
method has been used to modify the functional activity of the depressor
nerve of the carotid sinus dogs, and subsequently also in man, in order
to reduce excessive levels of blood pressure.  This methodology has
great scientific and clinical importance, and results already obtained
demonstrate that the set point of biologically self-regulated mechanisms
may be artificially modified by low level continuous stimulation of the
appropriate neural tissue.

Radio Injectors
        Neuronal activity is the product of a multitude of phenomena
which may be influenced by electrical and chemical means.  The use of
electricity has a long history in neurophysiology, while the application
of chemicals directly into the brain is more difficult and has had a
limited acceptance.  The recent development of cerebral biochemistry and
psychopharmacology has promoted great interest in the study of
cerebra-biochemical correlations and the possible clinical use of
intracerebral injections.  From the experimental point of view,
behavioral investigations in animals require individual freedom, and for
this purpose methods have been designed for remote control
administration of drugs.  The animals are equipped with mutilated
electrodes attached to fine tunings, forming assemblies called
"chemitrodes" which are permanently implanted into the brain.
Administration of chemicals is performed with a specially designed
"chemitrode pump", which measures 40 x 18 mm. and weighs only 10 grams,
and consists of two lucite compartments separated by an elastic
membrane.  One side is filled with synthetic spinal fluid or any other
solution to be injected, and the adjoining side is filled with a
solution of hydrozoan.  When a current is passed through the latter
compartment, gas is released and its pressure pushes the drug to be
injected through the chemitrode.
        It is well known that the brain generates electrical activity
which can be recorded by means of electrodes in contact with the scalp,
or even better, implanted within the cerebral tissue.  It is also known
from the investigations of other authors, that the process of learning
is accompanied by reliable changes in the electrical activity of the
hippocampus, and that decision making, conditioning, and instrumental
responses have detectable signs of electrical activity in specific
cerebral structures.  We should expect to establish new correlations
between spontaneous - or evoked - behavioral manifestations and pattern
of electrical activity within determined structures.
        This type of investigation is clearly of great interest, and
several companies are now offering instrumentation of multichannel
recording of biological data including heart activity, temperature,
blood pressure, muscle activity, brain activity, and other phenomena.
Technology in this area is advancing rapidly and we may expect solutions
to these problems in the near future.  Telemetry is only of secondary
interest in the present article which deals mainly with brain
stimulation.
        The possible use of biological or atomic batteries does not seem
to be practical in the next few years but could be an excellent solution
in the more remote future.  . . . .  For therapeutic purposes, bilateral
stimulation of symmetric areas of the brain has many advantages.  In
addition, active areas are usually multiple.  A compromise is necessary
between the practicality and convenience of controlling many areas of
the brain, and four channels of stimulation seem to be reasonable
number.
        The anatomical and physiological mechanisms underlying motility,
emotions, memories, desires, and behavioral responses in general, are
inside the circuitry of the central nervous system, which until recently
could be reached exclusively through sensory inputs.
        Development of the methodology described above for the
exploration of the depth of the brain represents an artificial path for
extrasensory communication with neurons.  Electrical stimulation of
cerebral areas with play a role in emotional responses usually evoked
not a stereotyped movement as described in the previous paragraphs, but
a change in the general reactivity toward environmental inputs.  For
example, in monkeys, radio-stimulation of the tegmentum, central gray,
middling thalamus, and other areas of the brain related to
offensive-defensive manifestation produced results which depended on the
hierarchical status of the stimulated animal and on the social
situation.  When this type of stimulation was applied to the boss of the
colony, his aggressive behavior was preferentially directed against a
particular monkey, usually an unfriendly male, and never against the
female who had been his favorite companion and palmate.  The boss'
increased aggressiveness depended on electrical stimulation of the
brain, while the details of his aggressive performance and the direction
of hostility were determined by his previous experience and by the
location and the reaction of the other animals.  Instincts are
genetically determined and are among the most solid patterns of response
which exist in the brain.  electrical stimulation, however, is able to
modify instinctive behavior, as demonstrated in some of our experiments.
Mother-infant relations are well established in rhesus monkeys, the
mother spent most of her time hugging her baby, nursing, grooming, and
taking continuos care of him.  This relation was disrupted as soon as
the mesencephalon was radio-stimulated, and the mother was induced to
adopt an offensive attitude, circling rapidly and biting different parts
of her body.  She completely lost her interest in the baby, and ignored
his tender calling and attempts to approach her, after 10 seconds of
brain stimulation, this unnatural attitude persisted for about 10
minutes, after which the mother gradually regained interest in holding
the little monkey in her arms, only to abandon him again as soon as
cerebral stimulation was repeated.

MAN'S DESIGN OF MAN
        While primitive societies adapted to the environment by taking
refuge in cavies and eating natural products, civilized man has
continuously tried to modify the environment according to his needs, and
recently has begun to alter his own biology, producing taller races,
increasing the span of life, and controlling his own reproduction.
Following this trend, we have started to influence the physiological
basis of the mind, and scientific investigation has established the
principle that:
        We can experiment with intracerebral mechanisms responsible for
the onset, development and maintenance of specific behavioral and mental
functions.  We are certainly facing ethical, philosophical and practical
problems not exempt from risks, but we should also expect important
medical applications of the new methodology to epilepsy, intractable
pain, involuntary movements, and mental illness.
        The greatest challenge, however, is the possibility that we
might substitute - at least in part - human intelligence for natural
choices in man's design of man's highest quality: mental functions.
        This investigation was supported by research grants from the
United States Public Health Services, M2004, and the Office of Naval
Research, Number 609(48).

Reference:  the only one not  of Jose M. Delgado's papers:
Adey, W.R., Dunlop, C.W., and Hendrix, C.E.  Hippocampal slow waves.
Distribution and phase relationship in the course of approach learning.
Arch. Neurol. Chicago. 3:74-90, 1960.
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