METABOLISM OF THE CENTRAL NERVOUS SYSTEM IN VIVO 



>8 5 3 



system, the electrical activity is an almost quantita- 

 tive indicator of the degree of functional activity; 

 and in such nervous structures as the sympathetic 

 ganglia or postganglionic axons ( 1 7, 55, 110, 111, 113), 

 increased electrical activity produced by electrical 

 stimulation is definitely associated with an increased 

 consumption of oxygen. On the other hand, in the 

 central nervous system the over-all electrical activity 

 of heterogeneous units cannot always be readily 

 interpreted in terms of over-all functional activity. 

 Therefore, in the central nervous system the relation- 

 ship between functional activity and metabolic 

 rate is less easily determined. Convulsive activity, 

 hardly a normal condition, has often been resorted 

 to as evidence of increased functional activity 



In the cerebral cortex of the cat, Davies and co- 

 workers by means of the oxygen electrode found 

 increases in oxygen utilization following electrical 

 stimulation (21) or during convulsions (22) induced 

 by pentylenetetrazol. Since the increased oxygen 

 consumption either coincided with or followed the 

 onset of convulsions, it was interpreted that the 

 elevated metabolic rate was the result of the in- 

 creased functional activity produced by the con- 

 vulsive state. Geiuier ct Magnes (51) observed a simi- 

 lar relationship in the perfused eat brain during 

 pentylenetetrazol and strychnine convulsions. Despite 

 the increased oxygen consumption, glucose uptake 

 in the perfused cat brain is markedly reduced during 

 the convulsion but is enhanced immediately after- 

 ward (52). In the lightly anesthetized monkey, 

 Schmidt and co-workers (162) found an excellent 

 correlation between cerebral oxygen uptake and 

 cerebral functional activity, the latter judged by 

 muscular movements, ocular reflexes, character of 

 respiration and level of arterial pressure. Changes in 

 cerebral functional activity either occurred spon- 

 taneously, were caused by altering cerebral blood 

 flow by means of hemorrhage, transfusion or epineph- 

 rine infusion, or were induced by convulsant (picro- 

 toxin, pentylenetetrazol, nikethamide) or depress. mt 

 (thiopental) drugs. Cerebral oxygen consumption rose 

 to double the resting level during convulsions and 

 was depressed to half the resting level in the post- 

 convulsive state. Narcotic doses of thiopental lowered 

 the metabolic rate about the same amount. In human 

 beings no observations during convulsions have been 

 made, but Kety and his associates (103) found simi- 

 larly reduced cerebral metabolic rates in the mentally 

 depressed state immediately following electroshock- 

 induced convulsions. This reduction could not be 



attributed to insufficient cerebral blood flow which, 

 although reduced, was still adequate. 



Indeed, in human studies, convincing correlations 

 between cerebral metabolic rate and mental activity 

 have been obtained in a variety of pathological states 

 of altered consciousness (39, 92). Graded reductions 

 in cerebral oxygen consumption have been found to 

 lie associated with comparably graded reductions 

 in mental alertness down to the level of coma in 

 conditions such as diabetic acidosis and coma (99), 

 uremic coma (73, 155), hepatic coma (39, 192), 

 acute alcoholic intoxication (8), anesthesia (83, 193), 

 cerebral ischemia due to shock (42) or increased 

 intracranial pressure (102), neurosyphilis (74, 138), 

 and organic dementia of various causes 1 1 1 v (see 



table 1 I. 



On the other hand, normal or physiological altera- 

 tions in mental functions do not appear to be as- 

 sociated with any alterations in oxygen consumption 

 of the brain as a whole. During natural sk-ep (121) 

 and the performance of mental arithmetic (177), 

 conditions which according to the electrocnccphal- 

 ographic patterns are associated with decreased and 

 increased cortical aetivitv, respectively, the over-all 

 cerebral metabolic rate is unchanged. In schizo- 

 phrenia in which mental functions are qualitative!) 

 though not necessarily quantitatively altered, one 

 studv reported a fall in cerebral metabolic rate in 

 eases of long duration ((13), but others have found no 

 differences from normal (103, 178). Some evidence is 

 available that anxiety ma) in some circumstances be 

 associated with an accelerated cerebral metabolic 

 rate (92, [73) but this effect may be secondary to the 

 calorigenic action on the brain of increased circulating 

 amounts ol epinephrine (104, 17 ; Tin- hick of 

 correlation between physiological alterations in men- 

 tal activity and over-all cerebral metabolic rate is not 

 necessarily evidence against a relationship between 

 functional aetivitv and metabolic rate in the central 

 nervous system. In the pathological states, large 

 segments of the brain are probably affected func- 

 tionally in the same direction. In the physiological 

 alterations in mental aetivitv, the activity of only a 

 small portion may lie changed; or, as is more likely 

 in a heterogeneous organ like the brain in which so 

 many parts are functionally inversely related, there 

 may be simply a redistribution of the patterns of 

 activity among the various component parts so that 

 the net metabolic rate of the brain as a whole may be 

 only negligibly changed, if at all. Such heterogeneity 

 during changes in mental function have been demon- 

 strated as regards the blood flow in studies of the 



