Since emotional reactions in the higher vertebrates depend on individual experience and are aroused in man, in addition, by complex symbols, one would expect that the hypothalamus could be excited from the cortex.
In experiments with topical application of strychnine on the cerebral cortex, the transmission of impulses from the cortex to the hypothalamus was demonstrated.
Moreover, the responsiveness of the hypothalamus to nociceptive stimulation is greatly increased under these conditions.
Even more complex and obviously cortically induced forms of emotional arousal could be elicited in monkey A on seeing monkey B (but not a rabbit) in emotional stress.
A previously extinguished conditioned reaction was restored in monkey A and was associated with typical signs of emotional excitement including sympathetic discharges.

It seems to follow that by and large an antagonism exists between the paleo- and the neocortex as far as emotional reactivity is concerned, and that the balance between the two systems determines the emotional responsiveness of the organism.
In addition, the neocortical-hypothalamic relations play a great role in primates, as Mirsky's interesting experiment on the "communication of affect" demonstrates.
But even in relatively primitive laboratory animals such as the rat, sex activity closely identified with the hypothalamus and the visceral brain is enhanced by the neocortex.
MacLean stressed correctly the importance of the visceral brain for preservation of the individual and the species, as evidenced by the influence of the limbic brain (including the hypothalamus) on emotions related to fight and flight and also on sexual functions.
It should be added that in man neocortical-hypothalamic interrelations probably play a role in the fusion of emotional processes with those underlying perception, memory, imagination, and creativity.

Previous experiences are obviously of great importance for the qualitative and quantitative emotional response.
The visceral brain as well as the neocortex is known to contribute to memory, but this topic is beyond the scope of this paper.

13.

Hypothalamic balance and its significance

After this brief discussion of neo-, paleocortical, and cortico-hypothalamic relations, let us return once more to the problem of hypothalamic balance and its physiological and pathological significance.
Facilitatory processes take place between neocortex and hypothalamus via ascending and descending pathways.
Thus cortico-fugal discharges induced by topical application of strychnine to a minute area in the neocortex summate with spikes present in the hypothalamus and cause increased convulsive discharges.
On the other hand, the temporary reduction in hypothalamic excitability through the injection of a barbiturate into the posterior hypothalamus causes a lessening in frequency and amplitude of cortical strychnine spikes until the hypothalamic excitability is restored.
Apparently, a positive feedback exists between the posterior hypothalamus and the cerebral cortex.
Consequently, if for any reason the hypothalamic excitability falls below the physiological level, the lessened hypothalamic-cortical discharges lead to a diminished state of activity in the cortex with consequent reduction in the cortico-fugal discharges.
Obviously, a vicious cycle develops.
This tendency can be broken either by restoring hypothalamic excitability directly or via cortico-hypothalamic pathways.
It is believed that drug therapy and electroshock involve the former and psychotherapy the latter mechanism.

Before we comment further on these pathological conditions, we should remember that changes in the state of the hypothalamus within physiological limits distinguish sleep from wakefulness.
Thus, a low intensity of hypothalamic-cortical discharges prevails in sleep and a high one during wakefulness, resulting in synchronous EEG potentials in the former and asynchrony in the latter condition.
Moreover, the dominance in parasympathetic action (with reciprocal inhibition of the sympathetic) at the hypothalamic level induces, by its peripheral action, the autonomic symptoms of sleep and, by its action on the cortex, a lessening in the reactivity of the sensory and motor apparatus of the somatic nervous system.
With the dominance of the sympathetic division of the hypothalamus, the opposite changes occur.
Since electrical stimulation of the posterior hypothalamus produces the effects of wakefulness while stimulation of the anterior hypothalamus induces sleep, it may be said that the reactivity of the whole organism is altered by a change in the autonomic reactivity of the hypothalamus.
Similar effects can be induced reflexly via the baroreceptor reflexes in man and animals.

Of particular importance is the study of the actions of drugs in this respect.
Although no drugs act exclusively on the hypothalamus or a part of it, there is sufficient specificity to distinguish drugs which shift the hypothalamic balance to the sympathetic side from those which produce a parasympathetic dominance.
The former comprise analeptic and psychoactive drugs, the latter the tranquilizers.
Specific differences exist in the action of different drugs belonging to the same group as, for instance, between reserpine and chlorpromazine.
Important as these differences are, they should not obscure the basic fact that by shifting the hypothalamic balance sufficiently to the parasympathetic side, we produce depressions, whereas a shift in the opposite direction causes excitatory effects and, eventually, maniclike changes.
The emotional states produced by drugs influence the cortical potentials in a characteristic manner;
synchrony prevails in the EEG of the experimental animal after administration of tranquilizers, but asynchrony after application of analeptic and psychoactive drugs.

The shock therapies act likewise on the hypothalamic balance.
Physiological experiments and clinical observations have shown that these procedures influence the hypothalamically controlled hypophyseal secretions and increase sympathetic discharges.
They shift the hypothalamic balance to the sympathetic side.
This explains the beneficial effect of electroshock therapy in certain depressions and a shift in the reaction from hypo- to normal reactivity of the sympathetic system as shown by the Mecholyl test.
Some investigators have found a parallelism between remissions and return of the sympathetic reactivity of the hypothalamus to the normal level as indicated by the Mecholyl test and, conversely, between clinical impairment and increasing deviation of this test from the norm.
Nevertheless, the theory that the determining influence of the hypothalamic balance has a profound influence on the clinical behavior of neuropsychiatric patients has not yet been tested on an adequate number of patients.
The Mecholyl and noradrenalin tests applied with certain precautions are reliable indicators of this central autonomic balance, but for the sake of correlating autonomic and clinical states, and of studying the effect of certain therapeutic procedures on central autonomic reactions, additional tests seem to be desirable.

It was assumed that the shift in autonomic hypothalamic balance occurring spontaneously in neuropsychiatric patients from the application of certain therapeutic procedures follows the pattern known from the sleep-wakefulness cycle.
A change in the balance to the parasympathetic side leads in the normal individual to sleep or, in special circumstances, to cardiovascular collapse or nausea and vomiting.
In both conditions the emotional and perceptual sensitivity is diminished, but no depression occurs such as is seen clinically or may be produced in normal persons by drugs.
The fundamental differences between physiological and pathological states of parasympathetic (and also of sympathetic) dominance remain to be elucidated.

Perhaps a clue to these and related problems lies in the fact that changes in the intensity of hypothalamic discharges which are associated with changes in its balance lead also to qualitative alterations in reactivity.
A state of parasympathetic "tuning" of the hypothalamus induced experimentally causes not only an increase in the parsympathetic reactivity of this structure to direct and reflexly induced stimuli, but leads also to an autonomic reversal: a stimulus acting sympathetically under control conditions elicits in this state of tuning a parasympathetic response!
Furthermore, conditioned reactions are fundamentally altered when the hypothalamic sympathetic reactivity is augmented beyond a critical level, and several types of behavioral changes probably related to the degree of central autonomic "tuning" are observed.
If, for instance, such a change is produced by one or a few insulin comas or electroshocks, previously inhibited conditioned reactions reappear.
However, if these procedures are applied more often, conditioned emotional responses are temporarily abolished.
In other studies, loss of differentiation in previously established conditioned reflexes resulted from repeated convulsive (metrazol) treatments, suggesting a fundamental disturbance in the balance between excitatory and inhibitory cerebral processes.

It has further been shown that: (1) an experimental neurosis in its initial stages is associated with a reversible shift in the central autonomic balance;
(2) drugs altering the hypothalamic balance alter conditioned reactions;
(3) in a state of depression, the positive conditioned stimulus may fail to elicit a conditioned reaction but cause an increased synchrony instead of the excitatory desynchronizing (alerting) effect on the Aj.
These are few and seemingly disjointed data, but they illustrate the important fact that fundamental alterations in conditioned reactions occur in a variety of states in which the hypothalamic balance has been altered by physiological experimentation, pharmacological action, or clinical processes.

14.

On the physiological basis of some form of psychotherapy

The foregoing remarks imply that the hypothalamic balance plays a crucial role at the crossroads between physiological and pathological forms of emotion.
If this is the case, one would expect that not only the various procedures just mentioned which alter the hypothalamic balance would influence emotional state and behavior but that emotion itself would act likewise.
We pointed out that emotional excitement may lead to psychosomatic disorders and neurotic symptoms, particularly in certain types of personality, but it is also known that the reliving of a strong emotion ("abreaction") may cure a battle neurosis.
This phenomenon raises the question whether the guidance of the emotions for therapeutic ends may not have an even wider application in the area of the neuroses.
Being a strictly physiological procedure, one may expect from such a study additional information on the nature of the emotional process itself.

Wolpe's experiments and therapeutic work lie in this area.
He showed convincingly that anxiety is a learned (conditioned) reaction and is the basis of experimental and clinical neuroses and assumed, therefore, that the neuronal changes which underlie the neuroses are functional and reversible.
An important observation of Pavlov served as a guide post to achieve such a reversibility by physiological means.
In a conditioning experiment, he demonstrated the antagonism between feeding and pain.
A mild electrical shock served as a conditioned stimulus and was followed by feeding.
The pain became thus the symbol for food and elicited salivary secretion (conditioned reflex).
Even when the intensity of the shocks was increased gradually, it failed to evoke any signs of pain.
Since strong nociceptive stimuli produce an experimental neurosis during which the animals fail to eat in the experimental situation, Wolpe thought that he could utilize the feeding-pain antagonism to inhibit the neurotic symptoms through feeding.
Appropriate experiments showed that this is, indeed, possible.
He then applied this principle of reciprocal inhibition to human neuroses.
He took advantage of the antagonism between aggressive assertiveness and anxiety and found a relatively rapid disappearance of anxiety when the former attitude was established.

For the interpretation of these significant investigations, it should be remembered that reciprocal relations exist in the hypothalamus with respect to autonomic and somatic functions which are closely associated with the emotions.
The feeding-pain antagonism seems to be based on this reciprocal relation between the tropho- and ergotropic systems.
Furthermore, a functional antagonism exists between an aggressive attitude and a state of anxiety.
Although in both emotions sympathetic symptoms are present, different autonomic-somatic patterns underlie aggression and anxiety, respectively, as indicated by the rate of the excretion of the catecholamines, the state of the muscle tone, and the Mecholyl test.
The psychological incompatibility of these emotional states seems to be reflected in, or based on, this marked difference.

15.

Concluding remarks

In our attempt to interpret the emotions in their physiological and pathological range, we emphasized the importance of the degree of activity of the parasympathetic and sympathetic divisions of the hypothalamic system and their influence on the inhibitory and excitatory systems, respectively.
We stressed the reciprocal relation of these systems with respect to the autonomic-somatic downward discharge as well as regarding the hypothalamic-cortical discharge.
Although we are still far from a complete understanding of these problems, as a first approximation, it is suggested that alterations in the hypothalamic balance with consequent changes in the hypothalamic-cortical discharges account for major changes in behavior seen in various moods and states of emotions in man and beast under physiological circumstances, in experimental and clinical neurosis, and as the result of psychopharmacological agents.
In view of the important role which emotional disturbances play in the genesis of neurotic and psychotic disorders and the parallelism observed between autonomic states and psychological behavior in several instances, it is further suggested that a hypothalamic imbalance may play an important role in initiating mental changes.