Chapter III: Part 3

There is a third type of pain which modifies muscular action in a curious way. We have already stated that local pain serves an adaptive purpose. In this light let us now consider headache. Headache is one of the commonest initiatory symptoms of the various infections, especially of those infections which are accompanied by no local pain and by no local muscular action. In peritonitis, cholecystitis, pleurisy, arthritis, appendicitis, salpingitis, child-birth, in obstructions of the intestinal and the genito-urinary tract, in short, in those acute processes in which the local symptoms are powerful enough to govern the individual as a whole,--to make him lie down and keep quiet, refuse food and possibly reject what is already in the stomach,-- in all these conditions there is rarely a headache, but in the diseases in which local pain is absent, such as the exanthemata, typhoid fever, and auto-intoxication, which have no dominating local disturbances to act as policemen to put the individual to bed and to make him refuse food that he may be in the most favorable position to combat the oncoming disease, in such cases in which these masterful and beneficent local influences are absent we postulate that headache has been evolved to perform this important service.

On the hypothesis that it is good for the individual who is acutely stricken by a disease or who is poisoned by autointoxication to rest and fast, and that the muscular system obeys the imperial command of pain, and in view of the fact that the brain is not only in constant touch with the conditions of every part of the body but that it is also the controlling organ of the body, one would expect that in these diseases the major pain whose purpose it is to govern general muscular action would be located in the head and there we find it. How curious and yet how intelligible is the fact that, though a headache may be induced by even a slight auto-intoxication, an abscess may exist within the brain without causing pain. When an obliterative endarteritis is threatening a leg with anemic gangrene, or when one lies too long in the same position on a hard bed, there is threatening injury from local anemia, and as a result there is acute pain, but when the obliterative endarteritis threatens anemia of the brain, or when an embolism or thrombosis has produced anemia of the brain, there may be no accompanying pain. The probable explanation of the pain which results in the first instance and the lack of pain in the second is that in the former muscular action constitutes a self-protective response, but in the other it does not. Diseases and injuries of the brain are notoriously difficult to diagnosticate. This may well be because it has always been so well protected by the skull that there have been evolved within it few tell-tale self-protective responses, so that in the presence of injury and disease within itself the brain remains remarkably silent. It should occasion no surprise that there are in the brain no receptors, the mechanical stimulation of which can cause pain, because its bony covering has always prevented the adaptive implantation within it of contact pain receptors. Dr. Frazier tells me that in the course of his operations on the brains of unanesthetized patients he is able to explore the entire brain freely and without pain. From my own experience I am able to confirm Dr. Frazier's observation. In addition, the two-stage operation for the excision of the Gasserian ganglion provides an observation of extraordinary interest. If at the first seance the ganglion is exposed, but is not disturbed except by the iodoform gauze packing, then on the following day the gauze may be removed, the ganglion picked up, and its branches and root excised without anesthesia and without pain. The same statement and explanation may be made regarding the distribution of pain receptors for physical contact within the parenchyma of the liver, the gall-bladder, the abdominal viscera, the spleen, the heart, the lungs, the retroperitoneal tissue, the deep tissue of the back, the vertebrae, and in certain portions of the spinal cord. Just what is the distribution of the receptors for heat and for cold I am unable to state, but this much we do know, that without anesthesia the intestines may be cauterized freely without the least pain resulting, and in animals the cauterization of the brain causes no demonstrable change in the circulatory or respiratory reactions. It is probable therefore that the distribution of the pain receptors for physical contact and for heat are limited to those parts of the body that have been exposed to injurious contacts with environment.

Of special significance is the pain which is due to cold, which increases muscular tone and produces shivering. The general increase in muscular tone produces an interesting postural phenomenon: the limbs are flexed and the body bent forward, a position which probably is due to the fact that the flexors are stronger than the extensors. As muscular action is always accompanied by heat production, the purpose of the muscular contraction and the shivering is quite certainly caused by cold to assist in the maintenance of the normal body temperature.

We have now discussed many of the causes of pain and in each instance we have found an associated muscular action which apparently serves some adaptive purpose (Figs. 24 and 25). If we assume that pain exists for the purpose of stimulating muscular reactions, we may well inquire what part of the nervous are is the site of the sensation of pain--the nerve-endings, the trunk, or the brain? Does pain result from physical contact with the nerve-endings, with the physical act of transmitting an impression along the nerve trunk, or with the process within the brain-cells by which energy is released to cause a motor act?

It seems most probable that the site of the pain is in the brain-cells. If this be so, then what is the physical process by which the phenomena of pain are produced? The one hypothesis that can be tested experimentally is that pain is a phenomenon resulting from the rapid discharge of energy in the brain-cells. If this be true, then if every pain receptor of the body were equally stimulated in such a manner that

{illust. caption = FIG. 25.--FEAR AND AGONY. "Amid this dread exuberance of woe ran naked spirits wing'd with horrid fear."-- Dante's "Inferno," Canto XXIV, lines 89, 90. all the stimuli reached the brain-cells simultaneously, the cells would find themselves in equilibrium and no motor act would be performed. But if all the pain receptors of the body but one were equally stimulated, and this one stimu-lated harder than the rest, then the latter would gain possession of the final common path, the sensation of pain would be felt, and a muscular contraction would result. It is well known that when a greater pain is thrown into competition with a lesser one, the lesser is completely submerged. In this manner the school-boy initiates the novice into the mystery of the painless plucking of hair. The simultaneous, but severe application of the boot to the blindfolded victim takes complete and exclusive possession of the final common path and the hair is painlessly plucked through the triumph of the boot stimulus over the hair stimulus in the struggle for the possession of the final common path. Another argument in favor of this hypothesis that pain is an accompaniment of the release of energy in the brain- cells is found in the fact that painless stimuli received through the special senses may completely submerge the painful stimuli of physical injury; for although the stimuli to motor action, which are received through the senses of sight, hearing, and smell, cause even more powerful motor action than those caused by physical contact stimuli, yet they are not accompanied by pain. Examples of this triumph of stimulation of the special senses over contact stimulation are frequently seen in persons obsessed by anger or fear, and to a less degree in those obsessed by sexual emotion. In the fury of battle the soldier may not perceive his wound until the emotional excitation is wearing away, when the sensation of warm blood on the skin may first attract his attention. Religious fanatics are said to feel no pain when they subject themselves to self-injury. Now, since both psychic and mechanical stimuli cause motor action by the excitation ofprecisely the same mechanism in the brain, and since the more rapid release of energy from psychic stimuli submerges the physical stimuli and prevents pain, it would seem that pain must be a phenomenon which is associated with the process of releasing energy by the brain-cells. Were physical injury inflicted in a quiescent state equal to that inflicted in the emotional state, great pain and intense muscular action would be experienced. Now the emotions are as purely motor excitants as is pain. The dynamic result is the same the principal difference being the greater suddenness and the absolute specificity of the pain stimuli as compared with the more complex and less peremptory stimuli of the emotions. A further evidence that pain is a product of the release of brain-cell energy is the probability that if one could pierce the skin at many points on a limb in such a manner that antagonistic points only were equally and simultaneously stimulated, then an equilibrium in the governing brain- cells would be established and neither pain nor motion would follow. An absolute test of this assumption cannot be made but it is supported by the obtainable evidence. We will now turn to a new viewpoint, a practical as well as a fascinating one, which can best be illustrated by two case histories: A man, seventy-eight years old, whose chief complaint was obstinate constipation, was admitted to the medical ward of the Lakeside Hospital several years ago. The abdomen was but slightly distended; there was no fever, no increased leukocytosis, no muscular rigidity, and but slight general tenderness. He claimed to have lost in weight and strength during the several months previous to his admission. A tentative diagnosis of malignant tumor of the large intestine was made, but free movements weresecured rather easily, and we abandoned the idea of an exploratory operation. The patient gradually failed and died without a definite diagnosis having been made by either the medical or the surgical service. At autopsy there was found a wide-spread peritonitis arising from a perforated appendix. A child, several years old, was taken ill with some indefinite disease. A number of the ablest medical and surgical consultants of a leading medical center thoroughly and repeatedly investigated the case. Although they could make no definite diagnosis they all agreed that the trouble surely could not be appendicitis because there was neither muscular rigidity nor tenderness. The autopsy showed a gangrenous appendix and general peritonitis. How can these apparently anomalous cases be explained? These two cases are illustrations of the same principle that underlies the freedom from pain which results from the use of narcotics and anesthetics, the same principle that explains the fact that cholecystitis may occur in the aged without any other local symptoms than the presence of a mass and perhaps very slight tenderness; and that accounts in general for the lack of well-expressed disease phenomena in senility and in infancy. The reason why the aged, the very young, and the subjects of general paresis show but few symptoms of disease is that in senility the brain is deteriorated, while in infancy the brain is so undeveloped that the mechanism of association is inactive, hence pain and tenderness, which are among the oldest of the associations, are wanting. Senility and infancy are by nature normally narcotized. The senile are passing through the twilight into the night; while infants are traversing through the dawn into the day. Hence it is that the diagnosis of injury and disease in the extremes oflife is beset by especial difficulties, since the entire body is as silent as are the brain, the pericardium, the mediastinum, and other symptomless areas. For the same reason, when a patient who is seriously ill with a painful disease turns upon the physician a glowing eye and an eager face, and remarks how comfortable he feels, then the end is near. This is a brilliant and fateful clinical mirage. When one reflects on the vast amount of evidence as to the origin and the purpose of pain, he is forced to conclude that pain is a phenomenon of motor stimulation, and that its principal role is the protection of the individual against the gross and the microscopic enemies in his environment. The benefits of pain are especially manifested in the urgent muscular actions by means of which the body moves away from physical injury; obstructions of the hollow viscera are overcome; rest is compelled in the acute infections-- the infected points are held rigidly quiet, the muscles of the abdomen are fixed, and harmful peristalsis is arrested in peritonitis; while there is absolutely no pain in the diseases or injuries which affect those regions of the body in which in the course of evolution no pain receptors were placed, or in those diseases in which muscular inhibition or contraction is of no help. In a biologic sense pain is closely associated with the emotional stimuli, for both pain and the emotions incite motor activity for the good of the individual. The frequent occurrence of post-operative and post- traumatic pain is accounted for by the fact that the operation or the injury has lowered the threshold of the brain- cells to trauma; the brain and not the local sensitive field is the site of the pain. I have found that, by blockingthe field of operation with local anesthesia, post-operative pain is diminished; that is, since the local anesthesia prevents the strong stimuli of the trauma from reaching the brain, its threshold is not lowered. There is a close resemblance between the phenomena of pain habit, of education, of physical training, of love and of hate. In education, in pain habit, in all emotional relations, a low brain- cell threshold is established which facilitates the reception of specific stimuli; all these processes are motor acts, or are symbolic of motor acts, and we may be trained to perceive misfortune and pain as readily as we are trained to perceive mathematical formulae or moral precepts. In each and every case, readiness of perception depends, as it seems to me, upon a modified state of the brain-cells, their threshold especially, the final degree of perception possible in any individual being perhaps based on the type of potential molecules of which the brain is built. We must believe also that every impression is permanent, as only thus could an individual animal or a man be fitted by his own experience for life's battles. LAUGHTER AND CRYING What is laughter? What is its probable origin, its distribution, and its purpose? Laughter is an involuntary rhythmic contraction of certain respiratory muscles, usually accompanied by certain vocal sounds. It is a motor act of the respiratory apparatus primarily, although if intense it may involve not only the extraordinary muscles of respiration, but most of the muscles of the body. There are many degrees of laughter, from the mere brightening of the eyes, a fleeting smile, tittering andgiggling, to hysteric and convulsive laughter. Under certain circumstances, laughter may be so intense and so long continued that it leads to considerable exhaustion. The formation of tears is sometimes associated with laughter. When integrated with laughter, the nervous system can perform no other function. Crying is closely associated with laughter, and in children especially laughter and crying are readily interchanged. We postulate that laughter and weeping serve a useful purpose. According to Darwin, only man and monkeys laugh (Fig. 26); other animals exhibit certain types of facial expression accompanying various emotions, but laughter in the sense in which that word is commonly used is probably an attribute of the primates only, although it is probable that many animals find substitutes for laughter. The proneness of man to laughter is modified by age, sex, training, mental state, health, and by many other factors. Healthy, happy children are especially prone to laughter, while disease, strong emotions, fatigue, and age diminish laughter. Women laugh more than do men. The healthy, happy maturing young woman perhaps laughs most, especially when she is slightly embarrassed. What causes laughter? Good news, high spirits, tickling, hearing and seeing others laugh; droll stories; flashes of wit; passages of humor; averted injury; threatened breach of the conventions; and numerous other causes might be added. It is obvious that laughter may be produced by diverse influences, many of which are so unlike each other that it would at first sight seem improbable that a single general principle underlies all. Before presenting a hypothesis which harmonizes most of the facts, and which mayoffer an explanation of the origin and purpose of laughter, let us return for a moment to some previous considerations-- that man is essentially a motor being; that all his responses to the physical forces of his environment are motor; {illust. caption = FIG. 26.--LAUGHING CHIMPANZEE. "Mike," the clever chimpanzee in the London Zoo, evidently enjoys a joke as well as any one else. (Photo by Underwood and Underwood, N. Y.)}

that thoughts and words even are symbolic of motor acts; that in the emotions of fear, of anger, and of sexual love the whole body is integrated for acts which are not performed. These integrations stimulate the brain-cells, the ductless glands, and other parts, and the energizing secretions, among which are epinephrin, thyroid and hypophyseal secretions, are thrown into the blood-stream, while that most available fuel, glycogen, is also mobilized in the blood. This body-wide preparation for action may be designated kinetic reaction. The fact that emotion is more injurious to the body than is muscular action is well known, the difference being probably caused by the fact that when there is action the above-mentioned products of stimulation are consumed, while in stimulation without action they are not consumed and must be eliminated as waste products. Now these activating substances and the fuel glycogen may be consumed by any muscular action as well as by the particular muscular action for which the integration and consequent stimulation were made; that is, if one were provoked to such anger that he felt impelled to attack the object of his anger, one of three things might happen: First, he might perform no physical act but give expression to the emotion of anger; second, he might engage in a physical struggle and completely satisfy his anger; third, he might immediately engage in violent gymnastic exercises and thus consume all the motor-producing elements mobilized by the anger and thus clarify his body.

In these premises we find our explanation of the origin and purpose of laughter and crying, for since they consist almost wholly of muscular exertion, they serve precisely such clarifying purposes as would be served by the gymnastic exercises of an angry man. As it seems to me, the muscular action of laughter clears the system of the energizing substances which have been mobilized in various parts of the body for the performance of other actions (Figs. 27 to 29). If this be true, the first question that presents itself is, Why is the respiratory system utilized for such a clarifying purpose? Why do we not laugh with our feet and hands as well? Were laughter expressed with the hands, the monkey might fall from the tree and, if by the feet, man might fall to the ground. He would at least be ataxic. In fact, laughter has the great advantage of utilizing a group of powerful muscles which can be readily spared without seriously interfering with the maintenance of posture. Laughter, however, is only one form of muscular action which may consume the fuel thrown into the blood by excitation. That these products of excitation are often consumed by other motor acts than laughter is frequently seen in public meetings when the stamping of feet and the clapping of hands in applause gives relief to the excitation (Fig. 30). Why the noise of laughter? In order that the products of excitation may be quickly and completely consumed, the powerful group of expiratory muscles must have some resistance against which they can exert themselves strongly and at the same time provide for adequate respiratory exchange. The intermittent closure of the epiglottis serves this purpose admirably, just as the horizontal bars afford the resistance against which muscles may be exercised. The facial muscles are not in use for other purposes, hence their contractions will consume a little of the fuel. An audience excited by the words of an impassioned speaker undergoes a body-wide stimulation for action, all of which may be eliminated by laughter or by applause (Fig. 31).

Let us test this hypothesis by some practical examples. The first is an incident that accidentally occurred in our laboratory during experiments on fear which were performed as follows: A keen, snappy fox terrier was completely muzzled by winding a broad strip of adhesive plaster around his jaw so as to include all but the nostrils. When this aggressive little terrier and the rabbit found themselves in close quarters each animal became completely governed by instinct; the rabbit crouched in fear, while the terrier, with all the ancestral assurance of seizing his prey, rushed, upon the rabbit, his muzzle always glancing off and his attack ending in awkward failure.

This experiment was repeated many times and each time provoked the serious-minded scientific visitors who witnessed it to laughter. Why? Because the spectacle of a savage little terrier rushing upon an innocent rabbit as if to mangle it integrated the body of the onlooker with a strong desire to exert muscular action to prevent the cruelty. This integration caused a conversion of the potential energy in the brain-cells into kinetic energy, and there resulted a discharge into the blood-stream of activating internal secretions for the purpose of producing muscular action. Instantly and unexpectedly the danger passed and the preparation for muscular action intended for use in the protection of the rabbit was not needed. This fuel was consumed by the neutral muscular action of laughter, which thus afforded relief.

A common example of the same nature is that encountered on the street when a pedestrian slips on a banana peel and, just as he is about to tumble, recovers his equilibrium. The onlookers secure relief from the integration to run to his rescue by laughing. On the other hand, should the same pedestrian fall and fracture his skull the motor integration of the onlookers would be consumed by rendering physical assistance--hence there would be no laughter. In children almost any unexpected phenomenon, such as a sudden "booing" from behind a door, is attended by laughter, and in like manner the kinetic reaction produced by the innumerable threats of danger which are suddenly averted, a breach of the conventions, a sudden relief from acute nervous tension; a surprise--indeed, any excitant to which there is no predetermined method of giving a physical response-- may be neutralized by the excitation of the mechanism of laughter.

In the same way the laughter excited by jokes may be explained. An analysis of a joke shows that it is composed of two parts-- the first, in which is presented a subject that acts as a stimulus to action, and the second, in which the story turns suddenly so that the stimulus to action is unexpectedly withdrawn. The subject matter of the joke affects each hearer according to the type of stimuli that commonly excites that individual. Hence it is that a joke may convulse one person while it bores another, and so there are jokes of the classes, bankers' jokes, politicians' jokes, the jokes of professional men, of the plebeian, of the artist, etc. If the joke fails, the integration products of the excitation may be used in physical resentment (Fig. 32).

Another type of laughter is that associated with the ticklish points of certain parts of the body, the soles of the feet and certain parts of the trunk and of the abdomen. The excitation of the ticklish receptors, like pain, compels self-defensive motor acts. This response is of phylogenetic origin, and may be awakened only by stimuli which are too light to be painful. In this connection it is of interest to note that a superficial, insect-like contact with the skin rarely provokes laughter, and that the tickling of the nasal, oral, and pulmonary tracts does not produce laughter. The ticklish points that cause laughter are rather deeply placed, and a certain type of physical contact is required to constitute an adequate stimulus. That is, the contact must arouse a phylogenetic association with a physical struggle or with physical exertion. In the foot, the adequate stimuli for laughter are such contacts as resemble or suggest piercing by stones or rough objects.. The intention of the one who tickles must be known; if his intention be playful, laughter results, whereas if injury be intended, then an effort toward escape or defense is excited, but no laughter. If deep tickling of the ribs is known to be malicious, it will excite physical resentment and not laughter. Self-tickling rarely causes laughter for the reason that auto-tickling can cause only a known degree of stimulation, so that there results no excessive integration which requires relief by the neutral muscular activity of laughter. In fact, one never sees purposeful acts and laughter associated. According to its severity, an isolated stimulus causes either an action or laughter. The ticklish points in our bodies were probably developed as a means of defense against serious attacks and of escape from injurious contacts.

Anger, fear, and grief are also strong excitants and, therefore, are stimuli to motor activity. It is obvious that whatever the excitant the physico-chemical action of the brain and the ductless glands cannot be reversed--the effect of the stimulus cannot be recalled, therefore either a purposeful muscular act or a neutralizing act must be performed or else the liberated energy must smoulder in the various parts of the body.

It is on this hypothesis that the origin and the purpose of laughter and crying may be understood. Even a superficial analysis of the phenomena of both laughter and crying show them to be without any external motor purpose; the respiratory mechanism is intermittently stimulated and inhibited; and the shoulder and arm muscles, indeed, many muscles of the trunk and the extremities are, as far as any external design is concerned, purposelessly contracted and released until the kinetic energy mobilized by excitation is utilized. During this time the facial expression gives the index to the mental state.

Crying, like laughter, is always preceded by a stimulation to some motor action which may or may not be performed (Figs. 33 and 34). If a mother is anxiously watching the course of a serious illness of her child and if, in caring for it, she is stimulated to the utmost to perform motor acts, she will continue in a state of motor tenseness until the child recovers or dies. If relief is sudden, as in the crisis of pneumonia, and the mother is not exhausted, she will easily laugh if tired, she may cry. If death occurs, the stimulus to motor acts is suddenly withdrawn and she then cries aloud, and performs many motor acts as a result of the intense stimulation to motor activity which is no longer needed in the physical care of her child. With this clue we can find the explanation of many phenomena. We can understand why laughter and crying are so frequently interchangeable; why they often blend and why either gives a sense of relief; we can understand why either laughter or crying can come only when the issue that causes the integration is determined; we can understand the extraordinary tendency to laughter that discloses the unspoken sentiments of love; we can understand the tears of the woman when she receives a proposal of marriage from the man she loves; we can understand why any averted circumstance, such as a threatened breach of the conventions, which would have led to embarrassment or humiliation, leads to a tendency to laughter; and why the recital of heroic deeds by association leads to tears, On the other hand, under the domination of acute diseases, of acute fear, or of great exhaustion, there is usually neither laughter nor crying because the nervous system is under the control of a dominating influence as a result of which the body is so exhausted that the excess of energy which alone can produce laughing or crying is lacking.

A remarkable study of the modification of laughter and crying by disease is found in that most interesting of diseases--exophthalmic goiter. In this disease there is a low threshold to all stimuli. That the very motor mechanism of which we have been speaking is involved, is shown by an enormous increase in its activity. There is also an increase in the size of certain at least of the activating glands--the thyroid and the adrenals are enlarged and overactive and the glycogen-producing function of the liver is stimulated. The most striking phenomenon of this disease, however, is the remarkable lowering of the brain thresholds to stimuli. In other words, in Graves' disease the nervous system and the activating glands-- the entire motor mechanism--are in an exalted state of activity.

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.

The response to contact stimuli then depends always on the presence of nociceptors in the affected part of the body and to the type of the contact. Powerful response is made to crushing injury by environmental forces; to such injuring contacts as resemble the impacts of fighting; to such tearing injuries as resemble those made by teeth and claws (Fig. 9). On the other hand, the sharp division of tissue by cutting produces no adaptive response; indeed, one might imagine that the body could be cut to pieces by a superlatively sharp knife applied at tremendous speed without material adaptive response.

These examples indicate how the history of the phylogenetic experiences of the human race may be learned by a study of the position and the action of the nociceptors, just as truly as the study of the arrangement and variations in the strata of the earth's crust discloses to us geologic history.