Electrocortical manifestations of epilepsy in monkey

E L E C T R O C O R T I C A L M A N I F E S T A T I O N S OF EPILEPSY I N M O N K E Y 1 E. EIDELBERG, M.D., 2 B. KONIGSMARK, M.D. a and J. D. FRENCH, M.D. University of California at Los Angeles, School of Medicine and Veterans Administration Hospital, Long Beach, Calif. (Received for p u b l i c a t i o n : J u n e 9, 1958)

INTRODUCTION It has been shown in previous work on cortical epileptogenesis in monkeys that there is a definite p a t t e r n of distribution of the excitability of the cortex to convulsions induced by direct electrical stimulation ( F r e n c h et al. 1956). The precentral " m o t o r " areas had the lowest and the occipital cortex the highest threshohl for seizure induction, with the frontal lobe, anterior temporal pole and parietal cortex occupying an intermediate position in the gradient of excitability (fig. 1). It was also shown in a following paper (Livingston et al.) that the partial isolation. by subpial cireumseetion without undercutting,, of a seo'ment of the motor cortex induced changes both in the excitability and capacity for seizure spread from the area so prepared, as well as from the area exactly homotopic to it in the eontralateral hemisphere, although this latter region had not been interfered with directly in any form. Moreover, this contralateral homotopic area showed spontaneous spiking and an increased capacity for seizure induction after the operation. 4 The purpose of the experiments reported here was to explore the nature of the phenomena nnderlying the different exeitability of various cortical areas as well as those responsible for the enhancement of excitability in the area homotopic to a ehronieally ciremnseeted eortical locus. A lead was provided by Abdullah and Magoun's (1957) finding that seizures induced either by Metrazol or high frequency electrical stimulation of the

cortex in eats iuterfered with pote~Mals evoked by local cortical stimulation which, according to one proposal, are due to dendritic activity in the cortex (Chang 1951, 1952). A close relationship between dendritic de t,olarization and seizure discharges has also been proposed by Brazier (1955) who sl~ggests that epileptic spikes might be genen,~ed in the apieal dendrites of the cortex. To assess the role of dendritic depolarization in epileptogenesis, prelimin~lry studies were made in monkeys of eortie, l responses evoked by stimulation of the thalamie relay nuclei (augmenting response), ,f the diffusely projecting thalamic nuclei ',recruiting response), of contralateral surface loci (eallosal response) and of local surface, loci (local or direct eortieal response). T h , last were found to be most easily handled an, I consistent and, since they have been shown to indicate dendritic activity, were selected to" this study. METHODS

The experiments reported here were made on 14 monkeys (Macaca m u l a t t a l In 11 of these, subpial eircumsection of ~n area of cortex approximately 1 square eenl imeter was made either in the motor or premotor cortex of one hemisphere by a procedure' described in detail elsewhere (Livingston t/ al.). All animals had recovered full vigor when the definitive experiment was made 10-30 days later. When made in the motor ,;ortex, the cireumsection was always placed in the arm area so that observations could be standardized. These monkeys displays,[ slight to moderate distal brachial monopa~esis post1 A i d e d b y g r a n t s f r o m 15. S. P u b l l e t l e a l t h operatively, usually with eomple!,? recovery Servlee a n d t h e F o r d F o u n d a t i o n . after a few days. 2 Lederle I n t e r n a t i o n a l Fellow, L i m a , P e r u . 3 IT. S. P u b l i c H e a l t h R e s e a r c h Fellow. F o r the definitive experiments, terminal 4 W e shall a p p l y h e r e f r o m t h e t e r m homotopie evaluation in operated animals and control to t h a t area. which is s y m m e t r i e a l l y placed in the examination in 3 unoperated monkeys, traopposite h e m i s p h e r e , to a e i r e u m s e c t e d locus. [1213

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cheotomy and bilateral craniectomy were performed u n d e r ether anesthesia and the head was secured in the stereotaxie frame. Cranieetomy was necessarily extensive and all of the cerebral convexity was exposed except for the anterior p a r t of the t e m p o r a l and inferior temporo-occipital regions. Flaxedil @ was administered intravenously (10 m g / h o u r , average dose), respirations being maintained artificially. Monophasic square pulses (0.01 - 0.03 reset., 20-120V.) were delivered f r o m a Grass $4-0 stimulator and isolation unit through a concentrie p a i r of stainless steel electrodes with 1 ram. tip-barrel distance. The tip was made to p e n e t r a t e the cortex until the bared end of

with a Grass recording camera. The frequency-response band of the preamplifiers was set for each response so ~s to minimize interference without distortio~t of the signal. To obtain more complete ini!ormation concerning differences in the res],onses obtained in the various areas studied, cl~.~rent intensity was progressively increased whi~e the duration of the pulses remained unchanged. D a t a so obtained permitted plotting ~.f strength-response curves (fig. 3), the abeissae represent]ng intensity of current and tile ordinate indicated baseline-to-peak ampli:o.de of the responses. The effect of volt~,.4'e increments upon latency of response was also measured and plotted in the same way. In a few cases

SUSCEPTIBILITY OF CORTEX TO SEIZURE DISCHARGE

Fig. 1 Diagrams of the monkey brain show the difference in threshold voltag,.. for electrically-induced seizures in various cortical areas (From Frenc:~ Gernandt and Livingston 1956). the barrel contracted the cortical surface. The barrel was always the cathode. Recording was u n i f o r m l y monopolar-differential, employing a balanced p a i r of leads, on each wound m a r g i n as reference. The pickup electrode was a chlorided-silver ball resting lightly on the surface 3 ram. away f r o m the stimulating electrodes. Another ehlorided-silver ball electrode was placed 2 ram. away from the recording electrode and led off to ground to minimize stimulus artifacts. Responses evoked by single shock stimuli were delivered through two Grass P~ RC coupled p r e a m p lifiers to a DuMont 333 double-beam cathoder a y oscilloscope where they were p h o t o g r a p h e d

recordings of the spontaneous E C G aetivit~ were made f r o m multiple loc.i over the con. vexity by means of a Grass ~[odel I I I amplifier and inkwriter. Recording sites selected for s t u d y were widely disseminated over both hemispheres front occipital to frontal pole, in all experiments, always symmetrically opposed points were studied in each animal. P a r t i c u l a r attention was directed to the effect of the preliminary operative intervention u p o n responses in the cortical locus eireumseeted and in that area homotopie to it on the contralateral motor or p r e m o t o r cortex. I n these experiments bilateral respons,~s were recorded

ELECTROCORTICAL ~fANIFESTATIONS

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(a) A~i~aIs without a preuious circumsection The a p p e a r a n c e of the local ,?ortical response exhibited some features o l; similarity

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cortical cells. The completeness of the corpus callosum section was also verified.

before and a f t e r surgical division of the corpus callosum in order to assess possible tonic influences mediated by callosal systems upon dendritic depolarization. Comparable assessments of induced homotopie depolarizations were made a f t e r the circumsected zone was injected with 2 per cent procaine, u n d e r c u t or removed.

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,/' V :Fig. 2 Records of local cortical responses taken in points of A to F on the cortex of a single animal. Stimulation intensities were the same in all areas (0.01 msec. single shocks). The shaded zone C indicates a point homotopie to a cireumsection on the opposite hemisphere.

A t the t e r m i n a t i o n of each experiment, serial sections of the circumsected locus were studied in order to determine the extent of the cuts and the integrity of the remaining

wherever evoked on the cortical surface although i m p o r t a n t variations, to be described later, were striking. An initial positive deflection, which commonly increased in amplitude

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E. EIDELBERG, B. K O N I G S M A R K and J. D. F R E N C H

characteristically exhibited lower thresholds and steeper strength-response curves than did those recorded from other reg]~,ns (fig. 3). Contrasting sharply with p,~tentials evoked in the motor cortex were those elicited in the occipital region (fig. 2F). t t e r e thresholds were hia'h and the negative d ~[lection rarely achieved an amplitude of 300 f,~V. The wave, when it occurred at all, appea:'ed as a broadbased hump with a peak-time ],~tency of 20-25 msee. Responses evoked in other ,.ortieal loci exhibited characteristics which represented tra,'~

with increments in ~oltage, consistently followed the shock artifact. This wave was succeeded immediately by a negative deflection which always exhibited greater magnitude and duration. Irregularities in the decline of this response occasionally occurred but no other consistent events were discernible. Clearly, the negative deflection was dominant, and unless otherwise indicated, subsequent reference to evoked responses will always allude to this wave. Marked differences could be demonstrated in the amplitude and latency of local cortical responses elicited in various cortical loci. In

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:Fig. 3 Intensity-response curves show differences in excitability of four loci (~ the cortex. Note that homotopie point C showed highest amplitude !E~ response to all stimuli.

the motor area responses exhibited high amplitude and short latency and the magnitude of responses in the arm area were consistently higher than were those in other regions of the motor cortex (fig. 2C). The average amplitude of responses evoked here was 1000 ~V. when tested to maximal shocks, while comparable potentials elsewhere in the motor cortex rarely exceeded 800 uV. (fig. 2D). These negative deflections in the motor cortex appeared as narrow-based high waves which reached peak amplitude 8-12 msec. after the stimulus artifact. Additionally motor cortical responses

sitions between the extremes of those elicited in motor and occipital regions. Commonly, the p r e f r o n t a l area was as um~xcitable as the occipital pole (fig. 2A), although, occasionally, high amplitude responses were recorded particularly near the anterior end of the arcuate sulcus. The pos-(~entral gyrus, parietal cortex and posterior-superior temporal regions were slightly more responsive (fig. 2E). The premotor amt frontal oeulomotor regions were distinctly more excitable (fig. 2B). Itere, responses approached in latency and appearance those elicited in the

ELECTROCORTICAL MANIFESTATIONS OF EPILEPSY IN MONKEY motor cortex although amplitudes r a r e l y exceeded 600 t~V. I n each p r e p a r a t i o n responses were obtained always at symmetrically opposite loci in both hemispheres, so that each series of responses had its own internal control. This was done as the only possible means of securing some reliability in the data, since the absolute amplitudes of the responses tended to v a r y f r o m animal to animal, due at least in p a r t to minor differences in the electrical characteristics of the electrodes employed. W h a t we considered significant was that the same p a t t e r n of distribution of amplitude of response was present in all cases and t h a t the difference between the responses on symmetrically opposite loci was never greater than l0 per cent.

(b) Animals with previous circumsection of t/~e premotor cortex No consistent difference was observed between responses evoked in the contralateral area homotot)ie to the circumsection and those elicited in neighboring cortex. Inside the cireumsected area itself potentials were often difficult or impossible to elicit due probably to the t r a u m a and scar of the previous operation. There was no evidence that responses couht cross the limits of the circmnsection, for potentials were never evoked to stimuli applied either outside or inside the cortical island by electrodes placed on the alternate side of the existing cuts.

(el A~imals with previous circumsection of the motor corte.T Confirming previous results

(Livingston

et al.), inkwriter recording commonly revealed the presence of spontaneous fast, low amplitude spiking in the eircumsected area and from a point homotopic to it contralaterally. Except in one instance, no consistent, recognizable, h)cal cortical responses were obtained when both the stimulating and recording electrodes were placed inside the limiting cuts. The exceptional case displayed rooderately low amplitude responses with latencies comparable to those exhibited by u n o p e r a t e d segments of motor cortex. in all experiments, striking changes appeared in the contralateral area homotopie to

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the circumsected motor cortex. The local cortical responses at this site were ,,onsistently higher in amplitude t h a n were potentials evoked either at the same site in control animals or in the adjacent leg and face areas (fig. 2, 3). There was no appreci;Lble change in the latency of these responses. These augmented responses were unchanged by section of the corpus callosum. Additio~ally, they were not influenced when the e ~'cumsected site was injected with procaine, 1 ndercut or removed by suction. Anatomical examination of t t c operated site revealed, in all cases, that the ciremnseetion had effectively isolated th( island of motor cortex from s u r r o u n d i n g tisq/e leaving intact white m a t t e r at the base. , l some instances, owing to hemorrhage and scar, these basal connections were considera)ly smaller t h a n the surface area enclosed b,c the cuts. Comparable changes were also app~ rent iu the cortex itself, although viable and a p p a r e n t l y functional tissue p r o m i n e n t l y persisted. DISCUSSION These investigations suggest a i,ossible association between factors leadin~ to highly developed local cortical responses and those responsible for epileptogenesis. Ce~'tainly cortical cell populations which respon, led to local repetitive stimulation by cxhibitin~ after-discharge also displayed evoked n e g ~ i v e potentials of high voltage in respous,' to single shocks. Conversely, loci resistan, to afterdischarge showed only a relatively limited capacity to generate these potentials. 3,Ioreover, a parallel between responsiveness t(, single and to repetitive shocks could be exte.~ded to include cortical sites of intermediate ,.xeitability. The distribution of high a m p i t u d e local responses over the hemisphere fmlnd in this s t u d y is comparable to that of t~-anscallosal potentials described by Curtis (1!i~0) in the eat and monkey and by Chang' . 1953) and Peacock (1957) in the eat. The s~rface negative phase in the latter (callosal), like that of the local cortical response, has beet~ a t t r i b u t e d to dendritic depolarization (Chang 1952, 1953; Clare and Bishop 1956). ,qtudi(~s in which surface recording and re,it analysis were made simultaneously in the s~Jme cortical

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area have suggested t h a t induced dendritic depolarization or even spontaneous negative waves in the E E G are associated with increase in f r e q u e n c y of p r o p a g a t e d unit responses in the u n d e r l y i n g area ( B r o o k h a r t and Zanehetti 1956; Calma and A r d u i n i 1954; Chang 1951; Whitlock ct al. 1953). Such observations supp o r t the proposal t h a t dendritic depolarization relates to the excitability of the somaaxon (Bishop and Clare 1955; Clare and Bishop 1956; Eceles 1951; P u r p u r a and G r u n d f e s t 1956). Therefore, since the evoked responses observed in the present study probably represent dendritic depolarization, it seems possible that the ]atter m a y relate to epileptogenesis as well as to normal excitability. Against this view J u n g and TSmfies (1950) have observed that local cortical responses disappear during seizure activity in the same area which they i n t e r p r e t e d as indicating normal inhibitory activity ( " B r e m swellen"). While their experimental observations have been confirmed by others, among them Abdullah and Magoun (1957), we would be more prone to agree with the latter a u t h o r ' s interpretation, namely that the disappearance of " a x o d e n d r i t i c " evoked potentials during seizures m a y well represent a kind of " b u s y - l i n e " effect due to the involvement of dendritic structures in the generation of seizm'e potentials. This would l~e more in line with the data reported in this p a p e r and with A d r i a n ' s conclusion that the negative waves of the direct cortical response must represent depolarization, not hyperpolarization, of structures oriented radially to the cortical surface. Additional s u p p o r t for the proposal t h a t abnormal dendritic depolarization is closely related to seizure production stems f r o m the observation reported here that abnormally large local cortical responses are found in surface loci which are rendered abnormally epileptogenic. A previous report revealed that a contralateral point homotopic to a locus of chronically circumseeted motor cortex displayed abnormal spiking and increased tendency for exhibiting afterdischarge upon direct stimulation (Livingston et al.). These ob-

servations were confirmed in the present report and it was demonstrated, moreover, that such epileptogenic loci homotopic to chronic motor circumsections displa~,.d abnormally large local cortical responses. A u g m e n t e d epileptogenesi~ in the cont r a l a t e r a l homotopic area could conceivably result either f r o m distorted callosal or other influences initiated in the cir,~umseeted locus or f r o m some focal alteration of function in the homotopic area itself. The, fact that the augmented local cortical r e s p m s e elicited in the homotopic site was mfinflueneed by elimination of possible input~ f r o m the circumsected zone speaks strongl~ in favor of the latter possibility. I t is a com~,~on clinical observation that epileptogenic le,ions m a y elicit focal discharge at the outse~ but, as time passes, the epileptic process l m d s to become more generalized. The experS~aents reported here suggest that such spread of seizure activity is the result of enhance(i excitability induced in cell masses remote f',}m a discharging focus but connected with it by intimate association pathways. Such : ' ? m o t e loci appear not only to be hypersus.eptible to seizures arising in the original f(,d~s, but, under certain circumstances, to be e qmble of elieiting convulsive activity theresa.Ires. This phenomenon would a p p e a r to ~,qate to experiments reported by Speran-l~y (1943) in which local freezing of the ,.ortex resulted in seizure induction and .
ELECTROCORTICAL MANIFESTATIONS OF EPILEPSY IN MONKEY SUMMARY 1. Studies were made on the local cortical potentials evoked in different areas of the monkey brain. These potentials a p p e a r e d as p r e d o m i n a n t l y surface-negative waves, and consistent p a t t e r n s in the a p p e a r a n c e and amplitude of the responses were exhibited by each area studied. Maximal voltages characterized the " m o t o r a r e a " , while minimal deflections were found in the p r e f r o n t a l and occipital cortex, intermediate values were present in other areas. 2. Correlation was found to exist between the excitability of cortical loci to single-shock stimuli as manifested by local cortical responses and to high-frequency stimulation as indicated by seizure a f t e r discharges. 3. W h e n enhanced epileptogenesis was induced in a locus of the motor region by chronically circumsecting an area of cortex in a m i r r o r site on the opposite hemisphere, increased responsiveness to single shocks was observed in the remote cortical locus. This epileptogenie effect was not due to tonic influences f r o m the cireumseeted area since its excision or proeainization or callosal section did not alter the a u g m e n t e d response. 4. The concept of dendritic depolarization as an index of neuronal excitability was discussed in relation to observed variations in the local cortical response. I t was proposed that this concept could conceivably be extended to account for differences in seizure susceptibility exhibited b y various cortical regions.

1. Une 6tude a 6t6 faite des potentiels eorticaux 6voqu6s en plusieurs aires cortieales. Ces potentiels sont surtout des ondes " s u r face-n6gatives" et chaque aire corticale 6tudi6e a montr6 des r6ponses d ' u n comportement et d ' n n e amplitude assez constante. Les voltages les plus 61ev6s 6taient enregistr6s an nivean de l'aire motriee. Le cortex frontal et occipital pr6sentaient les d6flections les moins 61ev6es, et des valeurs interm6diaires 6talent not6es dans les autres aires. 2. Une corr61ation a 6t6 6tablie entre l'excitabilit6 des aires cortieales p o u r des stimuli '~ choc isol6, mise h l'6videnee p a r la r6ponse

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corticalc locale et entre l'exeitabilit~ des aires eorticales pour des stimuli h haut(~ fr6quence, raise en ~videnee p a r une post-d,~,~harge @ileptique. 3. Une @ileptog6nSse augn,,nt~e dans une certaine r~gion de l'aire n,,trice peut 6tre obtenue dans une pr6paratio,, ehronique en isolant p a r cireoneision, dans l'aire motrice controlat6rale et homologue ~lne certaine aire du cortex. Ceei a comme effet d'abaisser le seuil d'exeitabilit6 p o u r des ,hoes isol~s. Cet effet 6pileptog~ne ne semble I,as 6tre dfi h des influences toniques de l'aire ainsi isol6e puisque l'excision ou ]a procainisa: ion de cette aire ou encore nne section du corp- calleux ne ehangeait pas la r6ponse augment.~.~. 4. Une discussion est faite d( la d6polarisation dendritique comme index de l'excitabilit6 ncuronique en relation ave. les variations des r@onses corticales loeal,~s q u ' o n a observ6es. La proposition est fail,, que ectte notion p o u r r a i t 6tre employee uti],mcnt pour expliquer les diff6rences de ]a sen.ibilit6 convulsive des aires corticales distinct 's. ZUSAMMENt~ASSUNG 1. Untersuehungen w u r d e n a u ~ e f f i h r t an !oka]en, kortikalen Potentialen, welche in verschiedenen Regioneu des A f f e n g e h i r n s ausgelSst wurden. Diese Potential,. ersehienen als vorwiegend oberfliichen-negalive Wellcn und reproduzierbare T y p e n von l~eizantworten in Bezug auf A u f t r e t e n und Amplitude wurden in jeder untcrsuchten Rindenregion angetroffen. Die hSehsten A m p l i l u d e n wurden in der motorischen Region beobaehtet, w~ihrenddem minimale E n t l a d u n g , n i m frontalen u n d okzipitalen K o r t e x angetroffen wurden. Intermedi~ire W e r t e wu:'den in anderen Area]en gemessen. 2. Es wurde festgestellt, da.~ eine Beziehung besteht zwischen der E~'regbarkeit yon Rindenarealen in A n t w o r t :luf Einzelsehoeks, wc]che lokale Rindem,.izantworte erzeugen, und derjenigen in A~twort auf hochfrequente Reizung, welehe (.ine epileptische N a c h e n t l a d u n g zur Folge hat. 3. Eine erhShte K r a m p f b e r e i t s c h a f t konnte erzeugt werden in einem Areal der motorisehen Rinde, wenn ein Rindenfeld in spiegel-

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E. E I D E L B E R G , B. K O N I G S M A R K and J. D. F R E N C H

bildlieher Lokalisation in der kontralateralen Hemisphiire in einem chronischen Experiment umschnitten wurde. Nach einer solchen Umschneidung wurde eine erhShte Antwortbereitschaft zu Einzelschoeks im entfernten kortikalen Feld beobachtet. Dieser epileptogene Effekt war nieht bedingt durch tonisehe Einfliisse welche yon der umschnittenen Rindenregion ausgingen, da Exzision oder Prokainisierung dieser Region, sowohl als auch Durchseheidung des Balkens die erhShte Reizbarkeit in der kontralatera]en Hemisphere nicht beeinflusste. 4. Die Theorie, dass dendritische Depolarisation ein Index der neuronalen Reizbarkeit darstellt, wird besproehen, wobei Bezug genommen wird auf die beobaehteten Ver~nderungen der lokalen kortikalen Reizantwort. Es wird vorgesehlagen, dass diese Theorie vielleieht ausgedehnt werden kSnnte, um die untersehiedliehe Krampfbereitsehaft versehiedener Rindenfelder zu erkliiren. REFERENCES

ARDULLAtL A. :F. and MaGOUN, H. W. E f f e c t of induced seizure discharge upgn evoked cortical potentials. Fed. Proe., 1957, 16: 1. ARDlTINL A. nnd WHITLOCK, D. B. Spike discharge in the pyramidal system during recruitment waves. J. Neurophysiol., 1953, 16 : 430-436. BISHOP, G. I{. and CLARE, ~V[. ]-I. Facilitation and recruitment in dendrites. EEG Clin. Neurophysiol., 1955, 7: 486-489. t~RAZIER, ~ . A. ]~. Neuronal structure, brain potentials and epileptic discharge. Epilcpsia I I I , 1955, 4 : 9-18. BROOKtIART, J. 1V[. and ZANCttETTI, A. The relation between electrocortical waves and responsiveness of the corticospinal system. EEG Clin. Ne~rophysiol., 1956, 8: 427-444. CAL),IA, ~. and ARDUINI, A. Spontaneous and induced activity in the pyramidal units. J. Neurophysiol., 1954, 17 : 321-335. CHANG, H. T. Dendritic potential of cortical neurons produced by direct electrical stimulation of the cerebral cortex. J. Neurophysiol., 1951, 14: 1-21. CHANG, I:[. T. Cortical neurons, with particular reference to apical dendrites. C. Spr. Har. Syrup. Quant. Biol., 1952, 17: 189-202. CHANG, H. T. Cortical response to activity of callosal neurons. J. Neurophysiol., 1953, 16: 117131.

CLARE,•. ~:[. and BISHOP, G. It. Petentiat wave mechanisms in cat cortex. EEG Clin. Neurophysiol., 1956, 8: 583-602. CURTIS, H. J. Intercortical connections of corpus eallosum as indicated by evok,:.~l potentials. J. Neurophysiol., 1940, 3 : 4 0 7 - 4 1 3 ECCLES, J. C. Interpretation of action potentials recorded in the cerebral cortex. EEG Clin. Ne~rophysiol., 1951, 3: 449-464. EYZAGUIRRE, C. and KUFFLER, S. K. Processes of excitation in the dendrites a~,,1 soma of single and isolated sensory nerve cG.Fls in the lobster and crayfish. J. Gen. Physiol.. 1955, 39: 87-119. FRENCH, J. D., GERNANDT, B. E. a~,d LIVINGSTON, R. B. Regional differences in se ~ure susceptibility in monkey cortex. A M A Arch. Neurol. Psychiat., 1956, 75: 260-274. GRUNDFEST, It. Electrical inexcit~tility of synapses and some consequences in the (,.ntral nervous system. Physiol. Rev., 1957, 37 : 3:;7-361. JUNG, R. und TSNNIES, S. F. IIirr,elektrische Untersuehungen fiber Entstehung u~Jd Erhaltung von Krampfentladungen: die Vorzfingc am Reizort und die Bremsfahigkeit des ~ehirns. Arch. f. Psychiat., 1950, 185: 701-735. LI, C. L. and JASPER, H. H. Mi( roelectrode studies of the electrical activity of ihe cerebral cortex of the cat. J. Physiol., 1953, : ] i : 117-140. LIVINGSTON, l~. 1~.~ :FRENCH, J. D . KONIGSI~IARK, B.~ RICHLAND, 1~2. J. and ABDULI ~H, A. F. Experimental studies in cortical el,ileptogcncsis. (In press.) NAUTA, W. J. H. Terminal distrfi*utiou of some afferent fibers in the cerebral ~,:rtex. Anat. Rec., 1954, 118: 333. PEAC0CK, S. 3& Activity of am,.rior suprasylvian gyrus (cat) in response to trt, nscallosal afferent volleys. J. Ncurophysiol., 1957, 20: 140-155. PERL, E. 1:~. and WHITLOCK, D. G. Potentials evoked in cerebral somatosensory re~ion. J. Neurophysiol., 1955, i8: 486-501. PURPURA, D. P. and GRUNDFEST, ~'1. Nature of dendritic potentials and synaptic mechanisms in cerebral cortex of cat. J. Neur¢/d~ysiol., 1956, 19: 573-595. SI~IOLL,D. A. Dendritic organizat,.n in the neurons of the visual and motor corti,.es of the cat. J. Anat., 1953, 87: 387-408. SPERANSKY, A. D. A Basis for t),,' Theory of Medicine. International Publishers. New York, 1943. TEASDALL,R. D. and STAVRAKY, G. W. Responses of deafferented spinal neurones l,, corticospinal impulses. J. Neurophysiol., 1953. 16: 367-375. WARD, A. A. and JENKNER,F. L. The bulbar reticular formation and tremor. Trans. liner. Neurol. Ass., 1953, 78: 36-38. WHITLOCK, D. Cr.~ ARDUINI~ A. ;md MORUZZI, G. Microelectrode analysis of the pyramidal system during transition from sleep ro wakefulness. J. Ncurophysiol., 1953, 16: 414-421~.

Reference: EIDELBERG,E., KONIGSMARK,B. and FREXCH, J. D. Electrocortical manifes~(tions of epilepsy in monkey. EEG Clin. Neurophysiol., 1959, 11: 121-128. c4~i~