"93° 



II \M)Ii(l(lK OK PHYSIOLOGY 



NEUROPHYSIOLOGY in 



to be strictly one of liver metabolism. So far, the 

 disease can be controlled if the infant is put on a 

 phenylalanineTow diet within the first few months of 

 life; in time, perhaps, replacement rather than with- 

 holding maneuvers will become possible. 



Insufficiency, of vitamin B 6 is associated with seizure 

 states. Pyridoxine has been found effective in treating 

 infantile convulsions (48), and will promptly relieve 

 seizures induced in man or animals by lack of 

 pvridoxal due to either B 6 dietary insufficiency or 

 interference with the action of the pyridoxine kinase 

 (or binding of pvridoxal phosphate) by such anti- 

 metabolites as methoxypyridoxine (75) or toxopyrimi- 

 dine (251), or by the convulsant thiosemicarbazides 

 1 j ■;oi. Pvridoxal phosphate, in turn, is the coenzyme 

 for the decarboxylase that, among other reactions, 

 forms gamma amino butyric acid (GABA) from 

 glutamic acid; mi a sufficient decrease in this leads to 

 decreased GABA. This amino acid, in its turn, may 

 be related to inhibition (Sokoloff), and does alter 

 dendritic potentials [e.g. of Purkinje cells, according to 

 Grundfest and Adey el al. (4)] and neuron thresholds. 

 Thus a clear sequence exists from several convulsant 

 conditions through decreased pyridoxal-P, GABA, 

 membrane potential, neuron threshold, to actual 

 spike discharges (158). 



Unfortunately, there is other evidence dissociating 

 the convulsant action of these drugs from changes in 

 brain concentration of pyridoxal-P or GABA [e.g. 

 Rosen tt al. (251 ), Terzuolo et al. (277)]; so the issue 

 remains clouded. Indeed, the common story of re- 

 lating chemical actions to functional effects has been 

 one of early simplicity and later doubt. The role of 

 acetylcholine in neural function, still uncertain (95, 

 IOO, 103, 215) more than a decade after the intro- 

 duction of diisopropylfluorophosphate, supposed to 

 1 h a specific inhibitor, but not full) so (34), is a case 

 in point. A further example is the evidence for low 

 ATP [and CrP and membrane potential and 

 threshold (150)] as an alternate to GABA as ,1 basis 

 for convulsions. In a strain of mice susceptible to 

 audiogenic seizures, a defect in adeninctriphosphatase 

 appeared just during the seizure-prone period (1). 

 And, hi course, pyridoxine is involved in man) other 

 reactions besides GABA formation, including even 

 those involving the catechol amines and indoles. 



In the widespread disease or diseases known as 

 schizophrenia, the picture is fai less clear; but there 

 is growing evidence thai here also metabolic errors 

 ma) dominate the picture. A strong hereditar) factor 

 has been demonstrated (154, 155; bui see 1 (.6) I his 

 might aci through .1 disturbance in phosphate me- 



tabolism, lor evidence is now converging on a general 

 cellular error in the handling of organic phosphates, 

 seen especially in nucleotides of red blood corpuscles 

 (28, 123, 124, 223; Ling, N. S. & Gerard, manuscript 

 in preparation). Other biochemical and physiological 

 abnormalities have been described in schizophrenia 

 by Richter (244), Kruse (164), Folch-Pi (74), Cole 

 & Gerard (47), in which see especially the chapter by 

 Domino, McGeer & McGeer (20;) and Rubin (255), 

 but most of these are still moot in the view of Kety 

 (157); and, in any event, such a discussion is beyond the 

 scope of this chapter. 



STRUCTURAL ORGANIZATION 



Topography and Topology 



The more than 10 billion neurons in the brain 

 are not distributed uniformly in space nor connected 

 with one another to form random networks. To 

 some extent, perhaps a large one, the location of gra) 

 and white and the positioning of neuron clusters 

 is an accident of the evolutionary process. II the 

 primitive neuraxis had additional coordinating 

 neurons superposed at the front end, with express 

 pathways to connect these with more caudal parts 

 of the body, it is understandable why the gra) is 

 on the uuiside of the hemispheres and the white on 

 the outside of the spinal cord. With various distance 

 receptors appropriately gathered at the front end 

 of the body, after bilateral symmetry and an antero- 

 posterior gradient established a front end, then the 

 special neuron accumulations for transmitting the 

 increased information and later lor integrating it 

 would also be clustered as special bumps and nuclei 

 near one another in the head. 



But the actual architecture max well influence 

 functioning by its geometr) or topograph) as well 

 .is b) its topology; in fact, ii almost certainl) does. 

 We are told that the cortex is convoluted to gain 

 addition, il surface for the expanding neuron popu- 

 lation. Bui il the extra neurons were accommodated 

 l>\ thickening the Layer of cones, rather than by 

 extending it, there would be no need lor infolding. 

 Nor is ii likel) that the folding is related 10 a need 

 lor proximit) between pial vessels and neurons 

 plent) of highly active neural m.issr- are reached 

 b) penetrating vessels. Moreover, other neural 



[gregates increase as three-dimensional masses with 



high inner connectivity. Rather, ii seems that effec- 

 tive functioning demands that lite conical neurons 



