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.