another in the form of contraction known as shivering; and a third, giving rise to heat as the only important phenomenon. The heat produced by muscles in ordinary or general muscular acts and in repair and growth is a mere incident to activity; but the heat arising during shivering is undoubtedly a specific product-i. e., the object of the shivering is a production of heat (see p. 433). If the nerve-fibres which convey the impulses that cause shivering be ordinary motor fibres, then these fibres are not only motor fibres, but specific thermogenic fibres in so far as they are connected with heatproduction by this act. There are also, apparently, fibres which are entirely distinct from the motor fibres, and which convey impulses that give rise to heat-production as a specific product, and even in the entire absence of motor phenomena. Thus, in a curarized animal in which all motor activity of the skeletal muscles is abolished, an enormous increase of heat-production may occur (Reichert) which cannot satisfactorily be explained in any other way than by assuming the existence of such specific thermogenic fibres. Our information at present is, however, so limited that we can do scarcely more than speculate.

Our knowledge of the character of the afferent fibres which carry impulses that reflexly affect thermogenesis is very unsatisfactory. There can be no doubt that sensory impulses arise in various parts of the organism, especially in the skin, which exercise important influences upon the heat-producing processés. Thus, cooling the skin reflexly excites heat-production, which cannot be attributed to indirect influences upon other functions, but whether or not there exist specific afferent thermogenic fibres is not known. It is possible that the temperature nerves of the skin, the cold and the heat nerves, may be responsible for reflex excitation or depression of heat-production.

The Thermogenic Centres.-The existence of specific thermogenic centres has for many years been conceded, but it has only been recently that hypothesis has given place to fact. The most important results of recent research may be generalized as follows: (1) That the irritation of the skin by heat or cold is followed by marked changes in thermogenesis, which effects are to a certain extent entirely independent of vasomotor and other incidental changes, and which, therefore, are due in part to an increase of heat-production dependent directly upon efferent thermogenic impulses. (2) That injury or excitation of certain parts of the brain is followed by an increase of heat-production. (3) That injury or excitation of certain other parts of the brain is followed by diminished heat-production. (4) That injury of the spinal cord may be followed by an increase or decrease of heat-production which cannot be entirely accounted for by vaso-motor and other attendant alterations. (5) That after operations upon certain parts of the cerebro-spinal axis there follows an increase or decrease in the quantity of CO, formed, indicating a corresponding effect on the heat-producing processes.

The results of recent calorimetric work show that there are definite regions of the cerebro-spinal axis which are apparently specifically concerned in thermogenesis; that the effects of excitation or destruction of each region are more

or less characteristic; and that the different regions seem to be so intimately related to one another as to constitute a co-ordinate mechanism. Certain of these regions when irritated give rise, as a direct result, to increased thermogenesis, hence they are of the nature of thermo-accelerator centres; and others to diminished thermogenesis, hence are thermo-inhibitory centres. Both kinds of centres seem to be associated with and to govern a third kind which is distinguished as the general or automatic thermogenic centres. The mechanism may be theoretically expressed in this form: The general thermogenic centres may be regarded as maintaining by virtue of independent activity a fairly constant standard of thermogenesis, and as being influenced to increased activity by the thermo-accelerator centres and to diminished activity by the thermo-inhibitory centres. The finer or smaller variations in thermogenesis are presumably effected by the general centres, whereas the grosser variations are probably effected by the influences of the thermo-accelerator and thermo-inhibitory centres. Specific heat-centres (thermogenic and thermolytic) have by various observers been held to exist in certain regions of the brain cortex, in the base of the brain just in front of and beneath the corpus striatum, in the corpus striatum, in the septum lucidum and the tuber cinereum, in the optic thalamus, in the corpora quadrigemina, in the pons and medulla oblongata, and in the spinal cord. Some of these centres have been regarded as being thermogenic and others as being thermolytic. Many errors in deduction have, however, been made because of the many inherent difficulties attending experimentation upon the cerebro-spinal axis, and because almost all the methods used necessarily involve injury or excitation of contiguous parts. The methods adopted of studying these various regions have been chiefly destruction or injury by means of a probe, actual cautery, excision, and the injection of cauterants; by transverse incisions across the cerebro-spinal axis so as to separate higher from lower portions of the cerebro-spinal axis; and by excitation by small punctures, electricity, etc.

In classifying these centres we are governed by the results which follow excitation and destruction. When irritation or destruction directly affects thermogenesis, the centre is regarded as being thermogenic, but if heat-dissipation is the process directly affected, the centre is regarded as being thermolytic. In classifying thermogenic centres we would regard the centre as being a general thermogenic centre if it is capable, after the destruction of other thermogenic centres, of causing the normal output of heat; a thermo-accelerator centre is distinguished by the fact that excitation increases thermogenesis, while destruction does not diminish thermogenesis, unless the centre happens to be active at the time, and further by the fact that after its destruction the normal output of heat may continue; a thermo-inhibitory centre is distinguished by a decrease of heat-production following stimulation and by the absence of any permanent effect on thermogenesis when the centre is destroyed. The general or reflex thermogenic centres are undoubtedly continuously active, the degree of activity varying according to the immediate demands of the organism for heat; while the thermo-accelerator and thermo-inhibitory centres are prob

ably only intermittently active, coming into play when the general centres are of themselves unable to effect a sufficiently rapid compensation.

While it must be admitted that our knowledge of the precise locations, physiological peculiarities, and correlations of the thermogenic centres is by no means complete, we have at our disposal some most important and significant data. The general thermogenic centres have been shown by Reichert1 to be located in the spinal cord. The thermogenic centres in the brain are either thermo-accelerator or thermo-inhibitory. Thermo-accelerator centres probably exist in the caudate nuclei (possibly also in the tuber cinereum and optic thalami), pons, and medulla oblongata.2

Excitation of any one of these regions is followed by a pronounced rise of heat-production; destruction of any one region may or may not be followed by a decrease of heat-production, and if a decrease does occur it may in most cases be attributed to incidental causes, such as shock and other attendant conditions. The centre which is common to the pons and medulla is for the most part probably located in the latter, but it is not so powerful in its influences on thermogenesis as the thermo-accelerator centres in the basal regions of the cerebrum. These cerebral centres are affected by agents which have little or no effect on the heat centres of the spinal cord. Thermo-inhibitory centres have been located in the dog in the region of the sulcus cruciatus and at the junction of the supra-sylvian and post-sylvian fissures.3 Irritation of either of them is followed by a decrease of heat-production, while their destruction may be followed by a transient increase of heat-production. The cruciate centre is the more powerful. None of these cerebral centres exercises any influence on thermogenesis after section of the spinal cord at its junction with the medulla oblongata.

Theoretically, these centres are associated in this way: The general thermogenic centres are in the spinal cord, and while they are perhaps impressionable to impulses coming to them through various sensory nerves, they are not apparently in the least influenced by cutaneous impulses caused by changes in external temperature nor by changes of the temperature of the blood. It is not improbable that these centres are in the anterior cornua of the spinal cord. The thermo-accelerator and thermo-inhibitory centres are connected with the general centres by nerve-fibres, the former influencing the general centres to increased activity, and the latter to diminished activity. The thermo-accel

1 University Medical Magazine, 1894, vol. v. p. 406.

2 Reichert: University Medical Magazine, 1894, vol. 6, p. 303. Ott: Journal of Nervous and Mental Diseases, 1884, vol. 11, p. 141; 1887, vol. 14, p. 154; 1888, vol. 15, p. 85; Therapeutic Gazette, 1887, p. 592; Fever, Thermotaxia, and Calorimetry, 1889. Aronsohn and Sachs: Pflüger's Archiv für Physiologie, 1885, Bd. 37, S. 232. Girard: Archives de Physiologie normale et pathologique, 1886, t. 8, p. 281. Baginsky und Lehmann: Virchow's Archiv für Physiologie, 1886, Bd. 106, S. 258. White: Journal of Physiology, 1890, vol. 11, p. 1; 1891, vol. 12, p. 233. Baculo: Centri temici, 1890, 1891, and 1892. Tangl: Pflüger's Archiv für Physiologie, 1895, Bd. 68, S. 559. Schultze: Archiv für experimentelle Pathologie und Pharmakologie, 1890, Bd. 43, S. 193.

3 Wood: "Fever," Smithsonian Contributions to Knowledge, 1880, No. 357. Ott: Journal of Nervous and Mental Diseases, 1888.

erator and thermo-inhibitory centres seem to be especially affected by cutaneous impulses which are generated by changes in external temperature, and to be influenced by alterations of the temperature of the blood. It is doubtless through these centres that changes in external and internal temperature are able to affect the heat-producing processes. Presumably both an increase of temperature of the blood and cutaneous impulses generated by an increase of external temperature excite the thermo-inhibitory centres, and thus inhibitory impulses are sent to the general centres, lessening their activity; on the other hand, both a fall of temperature of the blood and cutaneous impulses generated by cold presumably excite the thermo-accelerator centres and thus cause impulses to be sent to the general centres, exciting them to greater activity.

The Mechanism concerned in Thermolysis.-The loss of heat by the body is in a large measure incidental to attendant conditions and is not a reflex result of the activity of a thermolytic mechanism; in other words, the loss occurs essentially by virtue of the same conditions as would cause inanimate bodies to lose heat. The living homothermous organism differs as regards the loss of heat from dead matter, chiefly in that the rapidity with which heatdissipation occurs is regulated to a material extent by vital processes. The regulation of the loss of heat is effected by the operations of a complex mechanism—that is, one consisting of a number of distinct although correlated parts. A study of this mechanism, which is designated the thermolytic mechanism, includes a consideration of all of the processes by which heat is lost, of the nervous mechanisms which govern them, and of the conditions which affect them, but especially of those processes and mechanisms which act reciprocally in conjunction with the thermogenic mechanism to maintain the mean bodily temperature. Practically all of the heat lost by the organism occurs by radiation and conduction from the skin, by the evaporation of water from the skin and lungs, and in warming the food, drink, and inspired air. From these facts we believe that mechanisms which affect the blood-supply to the skin, the quantity of sweat secreted, the condition of the surface of the skin, and the quantity of air inspired must in a large measure regulate thermolysis. For instance, if the temperature of the organism be materially increased there occur increased activity of the heart, peripheral vascular dilatation, increased respiratory activity, and (except in fever) an increase in the secretion of sweat. The increase of the activity of the heart together with the dilatation of the cutaneous blood-vessels increases the quantity of blood supplied to the skin; the cutaneous blood-vessels are dilated, exposing a larger surface of blood to the cooler external surroundings, and thus materially favoring the loss of heat by radiation; the increase in the quantity of sweat is favorable to an increase in the amount of water evaporated, and thus to a larger loss of heat in this way; an increase of respiratory activity means a larger volume of air respired, a greater expenditure of heat in warming the air and in the evaporation of water from the lungs. In man the pilo-motor mechanism plays a subsidiary and unimportant part in the regulation of heatdissipation, but in some lower animals, as in certain birds, it is of considerable importance. The thermolytic mechanism therefore includes the cardiac, vaso

motor, respiratory, sweat, and pilo-motor mechanisms. All these are affected directly or indirectly by the temperature of the blood and skin. An increase in the temperature of the blood and skin excites all of them so that changes are brought about which favor heat-loss. The respiratory movements especially may be rendered intensely active, and in certain animals to such a marked degree that they may become more frequent than the heart-beats.

Thermotaxis.-Thermotaxis or heat-regulation is effected by reciprocal changes in heat-production and heat-dissipation brought about by the intervention of the thermogenic and thermolytic centres, just as the regulation of arterial pressure is effected by the reciprocal relations of the cardiac and vaso-motor mechanisms. If heat-production is more active than heatdissipation, thermolysis is so affected that the heat-loss is increased, and thus the mean bodily temperature maintained; if heat-production is subnormal, heat-dissipation also falls. Similarly, if heat-dissipation is increased, the heat-producing processes are excited to greater activity to make up the loss; conversely, if heat-dissipation is decreased, heat-production also tends to be decreased. These reciprocal actions depend essentially or wholly upon the influence of cutaneous impulses and the temperature of the blood. For instance, an increase of the temperature of the blood increases the activity of the thermolytic processes, thus effecting a compensation. If we subject an animal to a moderately cold atmosphere, as in the winter, heat-dissipation is increased, but cutaneous impulses are generated which excite the thermogenic centres so that heat-production is also increased, and thus the bodily temperature is maintained practically unaffected. It is only under abnormal conditions or under conditions of intense muscular activity that this reciprocal relationship is so disturbed that changes in one process are not quickly compensated for by changes in the other.

Thermotaxis is effected in a large measure reflexly, especially by cutaneous impulses generated by external cold and heat, both thermogenic and thermolytic processes being affected. Cold applied temporarily, as in the form of a douche, bath, sponging, etc., causes constriction of the cutaneous capillaries. This lessens both the quantity and temperature of the blood passing through the skin, the effect of which tends to decrease the dissipation of heat by radiation and conduction. Moreover, a lessened blood-supply causes the skin to become poorer in fluid, so that the conduction of heat from the warmer inner parts is lessened. The conductivity of the skin is further decreased by the action of the pilo-motor muscles, which when in contraction or in a state of greater tonicity render the skin tenser and thus press out the blood and tissue juices. The secretion of sweat is diminished, so that the quantity of heat lost in the vaporization of water is decreased. On the other hand, heat-dissipation tends to be materially increased by the greater radiation of heat due to the greater difference between the temperature of the body and of the douche, bath, etc., and the tendency to an increase in this way is much greater than the opposite tendency depending upon the factors above noted, therefore heat