Chapter 7

If this be true, then these patients should exhibit behavior precisely contrary to that of those suffering from acute infection, that is, they should be constantly clearing their systems of these superabundant energizing materials by crying or laughing, and this is precisely what happens--the flood-gates of tears are open much of the time in Graves' disease--a disease of the emotions.

We have already interpreted pain as a phenomenon of motor activity. When pain does not lead to muscular activity it therefore frequently leads to crying or to moaning, just as tickling, which is equally an incentive to motor activity, results in laughter if it does not find full expression in action.

From the foregoing we infer that pain, the intense motor response to tickling, and emotional excitation are all primitive biologic reactions for the good of the individual, and that all have their origin in the operation of the great laws of evolution. If to this inference we add the physiologic dictum that the nervous system always acts as a whole, and that it can respond to but one stimulus at a time, we can easily understand that while diverse causes may integrate the nervous system for a specific action, if the cause be suddenly removed, then the result of the integration of the nervous system may be, not a specific action, but an undesigned muscular action, such as crying or laughter. Hence it is that laughter and crying may be evoked by diverse exciting causes. The intensity of the laughter or of the crying depends upon the intensity of the stimulus and the dynamic state of the individual.

The linking together of these apparently widely separated phenomena by the simple law of the discharge of energy by association perhaps explains the association of an abnormal tendency to tears with an abnormally low threshold for pain (Fig. 36). In the neurasthenic, tears and pain are produced with abnormal facility. Hence it is that, if a patient about to undergo a surgical operation is in a state of fear and dread before the operation, the threshold to all stimuli is lowered, and this lowered threshold will continue throughout the operation, even under inhalation anesthesia, because the stimulus produced by cutting sensitive tissue is transmitted to the brain just as readily as if the patient were not anesthetized. In like manner, the brain may be sensitized by the administration of large doses of thyroid extract prior to operation, the threshold to injury in such a case continuing to be low to traumatic stimuli even under anesthesia. Under the sensitizing influences of thyroid extract or of Graves' disease the effect of an injury, of an operation, or of emotional excitation is heightened. The extent to which the threshold to pain or to any other excitant is affected by Graves' disease is illustrated by the almost fatal reaction which I once saw result from the mere pricking with a hypodermic needle of a patient with this disease. As the result of a visit from a friend, the pulse-rate of a victim of this disease may increase twenty beats and his temperature rise markedly. I have seen the mere suggestion of an operation produce collapse. As the brain is thus remarkably sensitized in Graves' disease, we find that in these patients laughter, crying, emotional disturbances, and surgical shock are produced with remarkable facility.

I hope that even this admittedly crude and imperfect consideration of this subject will suggest the possibility of establishing a practical viewpoint as to the origin and purpose of pain, of tickling, and of such expressions of emotion as laughter and crying, and that it may help us to understand their significance in health and in disease.

THE RELATION BETWEEN THE PHYSICAL STATE OF THE BRAIN-CELLS AND BRAIN FUNCTIONS--EXPERIMENTAL AND CLINICAL[*]

[*] Address before The American Philosophical Society, April 18, 1913.

The brain in all animals (including man) is but the clearing-house for reactions to environment, for animals are essentially motor or neuromotor mechanisms, composed of many parts, it is true, but integrated by the nervous system. Throughout the phylogenetic history of the race the stimuli of environment have driven this mechanism, whose seat of power--the battery--is the brain.

Since all normal life depends upon the response of the brain to the daily stimuli, we should expect in health, as well as in disease, to find modifications of the functions and the physical state of the component parts of this central battery-- the brain-cells. Although we must believe, then, that every reaction to stimuli, however slight, produces a corresponding change in the brain-cells, yet there are certain normal, that is, non-diseased, conditions which produce especially striking changes. The cell changes due to the emotions, for example, are so similar, and in extreme conditions approach so closely to the changes produced by disease, that it is impossible to say where the normal ceases and the abnormal begins.

In view of the similarity of brain-cell changes it is not strange that in the clinic as well as in daily life, we are confronted constantly by outward manifestations which are so nearly identical that the true underlying cause of the condition in any individual case is too often overlooked or misunderstood. In our laboratory experiments and in our clinical observations we have found that exhaustion produced by intense emotion, prolonged physical exertion, insomnia, intense fear, certain toxemias, hemorrhage, and the condition commonly denominated surgical shock, produce similar outward manifestations and identical brain-cell changes.

It is, therefore, the purpose of this paper to present the definite results of laboratory researches which show certain relations between alterations in brain functions and physical changes in the brain-cells.

Fear.--Our experiments have shown that the brain-cell changes due to fear may be divided into two stages: First, that of hyperchromatism-- stimulation; second, that of hypochromatism--exhaustion (Figs. 5 and 13). Hyperchromatism was shown only in the presence of the activating stimuli or within a very short time after they had been received. This state gradually changed until the period of maximum exhaustion was reached--about six hours later. Then a process of reconstruction began and continued until the normal state was again reached.

Fatigue.--Fatigue from overexertion produced in the brain-cells like changes to those produced by fear, these changes being proportional to the amount of exertion (Fig. 4). In the extreme stage of exhaustion from this cause we found that the total quantity of Nissl substance was enormously reduced. When the exertion was too greatly prolonged, it took weeks or months for the cells to be restored to their normal condition. We have proved, therefore, that in exhaustion resulting from emotion or from physical work a certain number of the brain-cells are permanently lost. This is the probable explanation of the fact that an athlete or a race-horse trained to the point of highest efficiency can reach his maximum record but once in his life. Under certain conditions, however, it is possible that, though some chromatin is forever lost, the remainder may be so remarkably developed that for a time at least it will compensate for that which is gone.

Hemorrhage.--The loss of blood from any cause, if sufficient to reduce the blood-pressure, will occasion a change in the brain-cells, provided that the period of hypotension lasts for more than five minutes. This time limit is a safeguard against permanent injury from the temporary hypotension which causes one to faint. If the hemorrhage be long continued and the blood-pressure be low, there will be a permanent loss of some of the brain-cells. This explains why an individual who has suffered from a prolonged hemorrhage will never again be restored to his original powers.

Drugs.--According to their effect upon the brain-cells, drugs may be divided into three classes: First, those that stimulate the brain-cells to increased activity, as strychnin (Fig. 37); second, those that chemically destroy the brain-cells, as alcohol and iodoform (Figs. 38 and 39); third, those that suspend the functions of the cells without damaging them, as nitrous oxid, ether, morphin. Our experiments have shown that the brain-cell changes induced by drugs of the first class are precisely the same as the cycle of changes produced by the emotions and by physical activity. We have found that strychnin, according to the dosage, causes convulsions ending in exhaustion and death; excitation followed by lassitude; stimulation without notable after-results; or

{illust. caption = A, Section of Cerebellum of Normal Dog. C, Section of Cerebellum of Dog after Repeated Doses of Strychnin. FIG. 37.-- BRAIN-CELLS SHOWING STAGE OF HYPERCHROMATISM FOLLOWED BY CHROMATOLYSIS RESULTING FROM THE CONTINUATION OF THE STIMULUS. (Camera lucida drawings.)increased mental tone; while the brain-cells accurately display these physiologic alterations in proportional hyperchromatism in the active stages, and proportional chromatolysis in the stages of reaction. The biologic and therapeutic application of this fact is as obvious as it is important.

In our experiments, alcohol in large and repeated dosage caused marked morphologic changes in the brain-cells which went as far even as the destruction of some of the cells (Fig. 39). Ether, on the other hand, even after five hours of administration, produced no observable destructive changes in the brain-cells.

The effect of iodoform was peculiarly interesting, as it was the only drug that produced a rise of temperature. Its observed effect upon the brain-cells was that of wide-spread destruction.

Infections.--In every observation regarding the effect of pyogenic infections on dogs and on man we found that they caused definite and demonstrable lesions in certain cells of the nervous system, the most marked changes being in the cortex and the cerebellum (Fig. 40). For example, in fatal infections resulting from bowel obstruction, in peritonitis, and in osteomyelitis, the real lesion is in the brain-cells. We may, therefore, reasonably conclude that the lassitude, the diminished mental power, the excitability, irritability, restlessness, delirium, and unconsciousness which may be associated with acute infections, are due to physical changes in the brain-cells.

Graves' Disease.--In Graves' disease the brain-cells show marked changes which are apparently the same as those produced by overwork, by the emotions, and by strychnin. In the postmortem examination of one advanced case it was found that a large number of brain-cells were disintegrated beyond the power of recuperation, even had the patient lived. This is undoubtedly the reason why a severe case of exophthalmic goiter sustains a permanent loss of brain power.

Insomnia.--The brains of rabbits which had been kept awake for one hundred hours showed precisely the same changes as those shown in physical fatigue, strychnin poisoning, and exhaustion from emotional stimulation. Eight hours of continuous sleep restored all the cells except those that had been completely exhausted. This will explain the permanent ill effect of long-continued insomnia; that is, long-continued insomnia permanently destroys a part of the brain-cells just as do too great physical exertion, certain drugs, emotional strain, exophthalmic goiter, and hemorrhage. We found, however, that if, instead of natural sleep, the rabbits were placed for the same number of hours under nitrous oxid anesthesia, not only did the brain-cells recover from the physical deterioration, but that 90 per cent. of them became hyperchromatic. This gives us a possible clue to the actual chemical effect of sleep. For since nitrous oxid owes its anesthetic effect to its influence upon oxidation, we may infer that sleep also retards the oxidation of the cell contents. If this be true, then it is probable that inhalation anesthetics exert their peculiar influence upon that portion of the brain through which sleep itself is produced. If nitrous oxid anesthesia and sleep are chemically identical, then we have a further clue to one of the primary mechanisms of life itself; and as a practical corollary one might be able to produce artificial sleep which would closely resemble normal sleep, but which would have this advantage, that by using an anesthetic which interferes with oxidation the brain-cells might be reconstructed after physical fatigue, after emotional strain, or after the depression of disease.

In the case of the rabbit in which nitrous oxid was substituted for sleep, the appearance of the brain-cells resembled that in but one other group experimentally examined--the brain-cells of hibernating woodchucks.

Insanity.--Our researches have shown that in the course of a fatal disease and in fatal exhaustion, however produced, death does not ensue until there is marked disorganization of the brain tissue. In the progress of disease or exhaustion one may see in different patients every outward manifestation of mental deterioration, manifestations which, in a person who does not show any other sign of physical disease, mark him as insane. Take, for example, the progressive mental state of a brilliant scholar suffering from typhoid fever. On the first day of the gradual onset of the disease he would notice that his mental power was below its maximum efficiency; on the second he would notice a further deterioration, and so the mental effect of his disease would progress until he would find it impossible to express a thought or to make a deduction. No one can be philanthropic with jaundice; no one suffering from Graves' disease can be generous; no mental process is possible in the course of the acute infectious diseases. Just prior to death from any cause every one is in a mental state which, if it could be continued, would cause that individual to be judged insane. If the delirium that occurs in the course of certain diseases should be continued, the patient would be judged insane. In severe cases of Graves' disease the patient is insane. Individuals under overwhelming emotion may be temporarily insane. Every clinician has seen great numbers of cases in which insanity is a phase of a disease, of an injury, or of an emotion. The stage of excitation in anesthesia is insanity. The only difference between what is conventionally called insanity and the fleeting insanity of the sick and the injured is that of time. We may conclude, therefore, what must be the brain-picture of the person who is permanently insane. This _a priori_ reasoning is all that is possible, since the study of the brain in the insane has thus far been confined to the brains of those who have died of some disease. And it is impossible to say which changes have been produced by the fatal disease, and which by the condition which produced the insanity. The only logical way by which to investigate the physical basis of insanity would be to make use of the very rare opportunities of studying the brains of insane persons who have died in accidents.

Our experiments have proved conclusively that whether we call a person fatigued or diseased, the brain-cells undergo physical deterioration, accompanied by loss of mental power (Figs. 40 to 43). Even to the minutest detail we can show a direct relationship between the physical state of the brain-cells and the mental power of the individual, that is, the physical power of a person goes _pari passu_ with his mental power. Indeed, it is impossible to conceive how any mental action, however subtle, can occur without a corresponding change in the brain-cells. It is possible now to measure only the evidences of the effects on the brain-cells of gross and violent mental activity. At some future time it will doubtless be possible so to refine the technic of brain-cell examinations that more subtle changes may be measured. Nevertheless, with the means at our disposal we have shown already that in all the conditions which we have studied the cells of the cortex show the greatest changes, and that loss of the higher mental functions invariably accompanies the cell deterioration.

A MECHANISTIC VIEW OF PSYCHOLOGY[*]

[*] Address delivered before Sigma Xi, Case School of Science, Cleveland, Ohio, May 27, 1913, and published in _Science_, August 29, 1913.

Traditional religion, traditional medicine, and traditional psychology have insisted upon the existence in man of a triune nature. Three "ologies" have been developed for the study of each nature as a separate entity--body, soul, and spirit--physiology, psychology, theology; physician, psychologist, priest. To the great minds of each class, from the days of Aristotle and Hippocrates on, there have come glimmerings of the truth that the phenomena studied under these divisions were interrelated. Always, however, the conflict between votaries of these sciences has been sharp, and the boundary lines between them have been constantly changing. Since the great discoveries of Darwin, the zoologist, biologist, and physiologist have joined hands, but still the soul-body-spirit chaos has remained. The physician has endeavored to fight the gross maladies which have been the result of disordered conduct; the psychologist has reasoned and experimented to find the laws governing conduct; and the priest has endeavored by appeals to an unknown god to reform conduct.

The great impulse to a deeper and keener study of man's relation, not only to man, but to the whole animal creation, which was given by Darwin, has opened the way to the study of man on a different basis. Psychologists, physicians, and priests are now joining hands as never before in the great world-wide movement for the betterment of man. The new science of sociology is combining the functions of all three, for priest, physician, and psychologist have come to see that man is in large measure the product of his environment.

My thesis to-night, however, will go beyond this common agreement, for I shall maintain, not that man is in _*large measure_ the product of his environment, but that environment has been the actual CREATOR of man; that the old division between body, soul, and spirit is non-existent; that man is a unified mechanism responding in every part to the adequate stimuli given it from without by the environment of the present and from within by the environment of the past, the record of which is stored in part in cells throughout the mechanism, but especially in its central battery--the brain. I postulate further that the human body mechanism is equipped, first, for such conflict with environment as will tend to the preservation of the individual; and, second, for the propagation of the species, both of these functions when most efficiently carried out tending to the upbuilding and perfection of the race.

Through the long ages of evolution the human mechanism has been slowly developed by the constant changes and growth of its parts which have resulted from its continual adaptation to its environment. In some animals the protection from too rough contact with surroundings was secured by the development of an outside armor; in others noxious secretions served the purposes of defense, but such devices as these were not suitable for the higher animals nor for the diverse and important functions of the human race. The safety of the higher animals and of man had to be preserved by some mechanism by means of which they could become adapted to a much wider and more complex environment, the dominance over which alone gives them their right to be called "superior beings." The mechanism by the progressive development of which living beings have been able to react more and more effectually to their environment is the central nervous system, which is seen in one of its simplest forms in motor plants, such as the sensitive plant and the Venus fly-trap, and in its highest development only in the sanest, healthiest, happiest, and most useful men.

The essential function of the nervous system was primarily to secure some form of motor activity, first as a means of securing food, and later as a means of escaping from enemies and to promote procreation. Activities for the preservation of the individual and of the species were and are the only purposes for which the body energy is expended. The central nervous system hag accordingly been developed for the purpose of securing such motor activities as will best adapt the individuals of a species for their self-preservative conflict with environment.

It is easy to appreciate that the simplest expressions of nerve response-- the reflexes--are motor in character, but it is difficult to understand how such intangible reactions as love, hate, poetic fancy, or moral inhibition can be also the result of the adaptation to environment of a distinctively motor mechanism. We expect, however, to prove that so-called "psychic" states as well as the reflexes are products of adaptation; that they occur automatically in response to adequate stimuli in the environment; that, like the reflexes, they are expressions of motor activity, which, although intangible and unseen, in turn incite to activity the units of the motor mechanism of the body; and finally, that any "psychic" condition results in a definite depletion of the potential energy in the brain-cells which is proportionate to the muscular exertion of which it is the representative.

That this nerve mechanism may effectively carry out its twofold function, first, of self-adaptation to meet adequately the increasingly complicated stimuli of environment; and second, of adapting the motor mechanism to respond adequately to its demands, there have been implanted in the body numerous nerve ceptors-- some for the transmission of stimuli harmful to the mechanism-- nociceptors some of a beneficial character--beneceptors; and still others more highly specialized, which partake of the nature of both bene- and nociceptors--the distance ceptors, or special senses.

A convincing proof that environment has been the creator of man is seen in the absolute adaptation of the nociceptors as manifested in their specific response to adequate stimuli, and in their presence in only those parts of the body which throughout the history of the race have been most exposed to harmful contacts. We find they are most numerous in the face, the neck, the abdomen, the hands, and the feet; while in the back they are few in number, and within the bony cavities they are lacking.

Instances of the specific responses made by the nociceptors might be multiplied indefinitely. Sneezing, for example, is a specific response made by the motor mechanism to stimulation of nociceptors in the nose, while stimulation of the larynx does not produce a sneeze, but a cough; stimulation of the nociceptors of the stomach does not produce cough, but vomiting; stimulation of the nociceptors of the intestine does not produce vomiting, but increased peristaltic action. There are no nociceptors misplaced; none wasted; none that do not make an adequate response to adequate stimulation.

Another most significant proof that the environment of the past has been the creator of the man of to-day is seen in the fact that man has added to his environment certain factors to which adaptation has not as yet been made. For example, heat is a stimulus which has existed since the days of prehistoric man, while the _x_-ray is a discovery of to-day; to heat, the nociceptors produce an adequate response; to the _x_-ray there is no response. There was no weapon in the prehistoric ages which could move at the speed of a bullet from the modern rifle, therefore, while slow penetration of the tissues produces great pain and muscular response, there is no response to the swiftly moving bullet.