The localization of many of the cerebral functions, the discovery of a psychomotor tract, and the constant accessions to our knowledge of the physiology of the brain are throwing much light on the subject. But all efforts to localize the intellectual and moral functions of the brain, except generally to agree with the teachings of a century ago and to place them for the most part in the anterior and antero-lateral portions of the cortex, have thus far failed of success, the most careful observers still thinking that local lesions when apparently causing insanity do so by injuring the action of the brain as a whole, and not of any particular part. In some cases of insanity, with never anything like acute disease, where death occurs from the weakness of old age or some intercurrent malady, the brain does not present any recognizable difference from those of sane people whose brains have worn out with their bodies. In those forms of mental disease where changes are found, the most important and constant are in the cortex of the brain, especially in the fore, upper, and middle parts of the periphery, involving usually also the membranes. In beginning acute mania the condition of the blood affecting the brain or the pathological changes are probably as nearly identical with those in the acute stage of pneumonia, certain forms of typhoid fever, cerebro-spinal meningitis, and other diseases as the symptoms of the mania are now and then difficult to differentiate from those of the other diseases just mentioned. In rheumatism, syphilis, malarial poisoning, and Bright's disease with mania we find no distinctive pathological conditions to account for the maniacal symptoms. If asked whether there is a fixed lesion of the brain or any of its parts corresponding to given psychological changes, we should be obliged to say no, except in the case of incurable dementia. If asked whether there are important morbid changes corresponding with all cases of insanity, we can only say yes, sooner or later, in the majority of cases, and that there are certain destructive lesions, chiefly inflammatory, atrophic, and degenerative, which invariably mean marked deterioration of the mind. As regards diseases of other organs than the brain, the insane, like the sane, die of all of them, and in especially large numbers of pulmonary consumption.