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Unit activity in temporal cortex during amygdaloid seizures in cats
ELECTROENCEPHALOGRAPHYAND CLINICALNEUROPHYSIOLOGY
UNIT
ACTIVITY
IN TEMPORAL
AMYGDALOID
CORTEX
221
DURING
SEIZURES IN CATS
Stll~IRO YAMAMOTO, M.D. 1
Department of Neurology and Neurosurgery, McGiU University and Montreal Neurological Institute, Montreal (Canada) (Received for publication: July 12, 1962)
INTRODUCTION
One characteristic phenomenon in temporal Iol,e seizures is flattening or desynchronization of the EEG at the onset of an attack, and this can also be produced by direct stimulation of the exposed uncus in patients undergoing surgical treatment for seizures (Jasper et el. 19S1). Experimentnily a similar EEG flattening has been shown, following electrical stimulation of the amygdaloid nucleus in the cat (Feindel and Gloor 1954; Kaada 1951; Ursin and Kaada 1960). The physiological significance of this phenomenon remains unknown. It may represent activation desynchronization as in the so-cniled~''arousal'' response (Arana-Iniguez et el. 1955; Ursin and Keada 1960). On the other hand, the amnesia and impaired mental functions which characterize the clinical seizure would suggest that such EEG flattening might express depression or interference with certain highly integrated cerebral functions. In the present study the behavior ofindividual cortical cells during seizures induced by amygdaloid stimulation in the cat is analyzed with microelectrodes. METHODS
The experiments were carried out on 51 cats. Surgical procedures were performed under ether anesthesia, with procainization of wound margins and pressure points. The animals were then immobilized by intermittent injections of flaxedil (geUemine triethiodide) except in 3 cases in which the high-spinal transection was carried out. Respiration was maintained artificially. After the initial injection of flaxedil or the high-spinal transection, a dose of 4 mg/kg of pentothal 1~ t address: Department of Sugpry, School of Medicine, University of Kanazawa, Kanazawa (Japan).
(thiopental sodium) was injected intravenously every 20 rain up to 12-16 mg/kg in total amount. The administration of pentothal minimized the epileptic activity which tendeJ to develop in animals subjected to repeated stimulation of the amygdala or the continuous activation pattern of the brain waves which usually occurred in curarized animals. Two pairs of bipolar wire electrodes as described by Deigado (1955) were stereotaxically introduced into the amygdala and the ventral hippcgampus ipeilateral to the exposed cortex. The electrodes in the amygdala were used for stimulation and those in the hippocampus for recording of the propagated after-discharge, The electrical stimulus to the amygdala was usually an 8-10 V, 5-msec pulse at 40/see for a period of 3 sec. The acoustic stimulus was a click, which was obtained by applying a rectangular voltage pulse (0.2-1.0 msec duration) to an electromagnetic type earphone. This was attached to an ear bar of the stereotaxic apparatus ipsilateral to the exposed cortex. The electrocorticogntm was recorded through a pair of silver electrodes separated at the tip by 5 mm and imbedded in a cortical stabilizer made of lucite curved to fit the contour of the brain. An opening was made in the stabilizer between the imbedded electrodes for passage of the microelectrode. The microelectrodes were micropipettes drawn to less than I ~ external diameter at the tip and filled with 3 M KCI (Caldwell and Downing 1955). The micrcelectrode was mounted in a mechanical micrometer ~nd connected with the input of a cathode follower (RCA 6AU6 in triode connection). The indifferent ei¢chode was screwed into the frontal bone. Potentials picked up by gross- and microEleetroenetph. din. Nturophy$1ol., 1963D]$: 221-229
222
S. YAMAMOTO
electrodes were amplified by CR-coupled amplitiers (Tektronix) and recorded by means of a 4-beam cathode-ray oscilloscope and a Grass camera. Ink-writer tracings were obtained simultancously by means of a~z Offner Type T EEG apparatus. In all the following illustrations, the upper beam is used for the surface. EEG, the second beam for the microelectrode recording
A
the recorded spikes often showed variations in amplitude and shape during a long continuous recording. RESULTS A most marked EEG flattening induced by amygdaloid stimulation was usually observed in the medial ectosylvian cortex, particularly in the
•
I See
500#V
Fill. I Increased unit activityrecorded from auditory area. FlrJt trace, surfaceEEG. Sacor~dtrace, unit recordinll.Bottomtrace. EEG of hlppocempus.Four sectionsof record are continuous,Stimulation of emyfp~¼fs indicatedby stimulationartefact at end of first section. from the same cortical area (upward deflection representing neptivity), and the third beam for the EEG from the other portion of the cortex or for stimulation marks. Generally the time constant was 0.2 sac for the EEG and 0.005 sac for microelectrode recordin$. In the course of unitary recording, slight changes in amplitude or shape of spikes were often encountered. These were considered in most cases th~ result of movement of the microelec. trode (Mountcastle et aL 1957) induced by artificial respiration or change in blood pressure following amygdaloid stimulation (KMda 1951, Koikegami et aL 1953). The results of unitary recording treated in this report are limited to those obtained from well-isolated units, though
auditory area. This consisted of low-voltage highfrequency waves similar to the "EEG activation" pattern (Moruzzi and M u o u n 1949), In the somato-sensory cortex, on the other hand, the pattern was very often that of a continuous "arousal condition", which obscured the effect of amygdaloid stimulation. Therefore, microelec. trode recordings were mostly performed in the medial ectosylvian cortex, In only six animals the lower part of posterior ectosylv/an and sylvian corticies was studied, This area will be referred to hereafter as "temporal tip" (Stoil eta/. 1951). As seen in Fig. I and 2, the EEG activation in the medial ectosylvian cortex usually developed almost immediately after the start of amysdaloid stimulation and lasted for 20-50 sac. On the FJeemsmeeph.dt~. N~quop~sJol., 1963, 15:221-229
CORTICALUNITS DURING A]g[YGDALOIDSEIZURES
...... ......
~.3
5oo,,v
F~ 2
Activation of unit started from onset of arayl;daloid stimulation. Sporadic bunts of very hilh frequency ~ m seen durins ~ o f ~ ! f l ~ frequency, Indications are as in Fill. !.
•
"
|
.m
! $ec
Fill. 3 Continuous epilsptic unit discharp. First and second traces in each section of record are as in Fill. 1. Bottom tmoe in first sw--tion indicstes click stimuli at I/inc. On and off of amylldslotd stimulation am tndicsted by arrows in first and second sections. Unit was driven by click stimuli and responded to llmylldaloid stimulation with continuous oellular epikptic dischllrp during period of EEO activation. This was ee~'6pAaleIsold preparation without curarizatinn.
other hand, the propagated after-discharge in the hippocampus developed gradually and subsided in 3-7 sec. In only 3 animals, however, a gradual development of the EEG activation was found in the medial ectosyivian cortex (upper tracing
of Fig. 6). In all the records taken from the area of temporal tip, propagation of epileptic afterdischarge or theta.wave-like slow waves were seen during a period of 3-13 sec following amygdaloid stimulation, and the EEG activation ap£1¢clroenceph. din. Neurophyslol., 1963, 15:221-229
224
s. Y A ~ O r o
peared thereafter. In the case shown in Fig. 4, EEG recordings were made in the temporal tip (posterior ectosylvian gyrus) and the auditory area. In the cortex of temporal tip, slow waves which appeared during a period of 4 see after amygdaloid stimulation were considered to be a propa a typi
A. Spontaneous unit activity Effects of a m y ~ o i d s ~ t i o n on unit activity were classified into ~ categories. (a) Increase in frequency of the unit disdmrge. This was observed in 83 out of 146 units (56.8%). Fig. I illustrates one of the typical example~. The
2 SOO~uV
I $eo
Fig. 4 Delayed f~ilitation of unit activity. Ftnt trace, EEG of lower part or posterior ecto,ylvlan i~rus.
Second trace, unit recording from rome cortical am. Bottom trace, IEI~Gof auditory area. Re~ords at bottom of flluro were obtained 40 ~ after amy~aloid ,timu¼tion, lation of the amygdala. In the auditory area, on the other hand, fast waves (30 c/sec) developed immediately after stimulation. These were considered as EEG "activation" although their voltage was not suppressed.
I. Unit activity The activity of the units was analyzed during the EEG activation induced by amygdaloid stimulation: 116 in the medial ectosylvian cortex, and 30 in the temporal tip. They were distributed in the depths of O.4 to 2.4 a m , altho~tgh encountered most frequently at 0.7 to i.8 mm. The voltage of the re':orded spike discharges ranged from 200/~V to 10 mV; 65 per cent of them were initially positive, and the others initially negative.
stimulation, reaching its maximum in 2 xc, and returned to its previous level when the EEG activation was about to subside. Fig. 2 is a sample record from another unit in the same area of the same animal as in Fig. I. This unit started to be activated almost from the beginning of amylgdaIoid stimulation, with latency of approximately 30 reset, looking as though it was responding to each stimulation pulse. After the end of the stimulation this increased activity continued for more than 18 sec: at 2 and 5 sec after the end of the stimulation, there appeared two burst~ of high-frequency spike discharge preceded by highamplitude transient spikes. The latter mayprobably have been caused by movements and the corresponding bursts be due to injury of the unit.
Eiecln~em',~p&din. Nemophysiol., 1963, IJ: 221-229
CORTICALUNrlB DURING AMYGDALOIDSEIZURES
However, the same phenomena as shown in Fig. 2 could be observed in 4 records taken from the same unit at lO-min intervals. Fig, 3 is a sample record of a single unit which responded to a click stimulus and was activated during the period of EEG activation with a continuous firing at a freq~ of over 300/see. This unit could be activated in the ~ w a y by a ~ n d amygdaloid
225
wave-like after-discharge. Thereafter there was an enhancement of unit activity which appeared to be associated with EEG activation, However, the appearance of propagated after-discharge in thi~ area was found to be not always associated with an arrest of the unit activity. Co) Decrease m frequency of the unit discharge. This was encountered in 23 out of 146 units
500~V
I See Fig. $ D~reaud unit activityfollowingamyldaloid stimulation.Indicationsare as in Fill. I. stimulation performed after a sufficiently Ions interval, It should be noted, however, that such a long lasting high.frequen~ u n i ~ discharge was e n c o u n ~ only in ent~plmle Do[J eats without curarization. Upon repeated amygdaloid stimulation, such animals tended to show an epileptic state characterized by continuous cortical seizure discharges, intense salivation, mastieatory movements, etc. In 11 units in the 8r¢~lpof"in¢reased"activ ity, it took for the activity to increase 1 see or longer after the end of amygdaloid stimulation. Five ofthese eleven units were found in the cortex of temporal tip. In this area, results were rather complicated, since the propagated after-discharge preceded a simple EEG activation. The record of Fig. 4 obtained from such region showed a blocking of unit activity during the propagated theta-
(15.8 ~). In the ease of Fig. $ the EEG activation started from the onset ofamygdaloid stimulation and continued about 20 sec during which period a decrease in unit activity was seen. In this type of neuron the unit activity could be depressed repeatedly by repeated stimulation, and a temporary arrest of unit discharge was seen during a period from I-9 see after stimulation. (c) No change infrequency of the unit discharfe. Forty out of 146 units (27.4%) did not modify their firing pattern either during or following amygdaloid stimulation c~pable ofeliciting EEG activation.
B. Evoked unit response The most common effect of amygdaloid stimulation on the neurons which responded to a click stimulus in the primary auditory area was Electroenccph. din. NGurophysiol., 1963, 13:221-229
226
$. YAMAMOTO
i See
500,V
Fis. 6 EfYectsof 8mygdaloid stimulation upon unit response to click stimuU. First trace, EEG of primary ~,uditory urea. Second trace, unit recording from nine cortical urea. Bottom trace, marks of click stimuli. Recordsobtained 50 se~ after umygclaloid stimulation are in bottom section of tSrure.
a decrease in the threshold and an increase in the spikes in response to the click were seen. In the number of spikes, while the amplitude of surface record or 2 see after amygdaloid stimulation evoked pote,~tial was always decreased. In the (Fig. 7, 2S), it can be seen that the evoked unit sample record shown in Fig. 6, sub-threshold A dO 88 click stimuli (80~ of threshold voltap) were applied at a frequency of 2/No. About 2 see after the end of amygdaloid stimulation, an EEG activation developed and the unit ~gan not only to respond to each click stimulus, but also to discharge spontaneously. These phenomena continued for about 50 see and returned to the pre. vious state when the EEG activation gradually subsided. A slight change in spike shape du~ng the recording in this ease seemed to be due to slight movements of the microeleetrode relative to brain tissues and the unit was considered to be the same. In the ease shown in Fig, 7, a sub- Effects of an~lldaloidstimulationupon o~ok~l sur/~ poten+.~ and unit response to click stimulL First truce maximal strength of click stimulation was used of each frame, surface poteatbd ;.n prima~ auditory area to evoke a unit response. After amygdaloid respondit~ to submuxima! click stimulus. ,~coad trlu:e, stimulation, a depression of the surface potential unit responsesfrom samecortk:l urea. A, control record. was seen. During this period ofdepre~ed surface 2,5, 5,5, 12,5,2USand 40S: records 2, 5, 12, 20und dOsee end of an~lldaloid stimulation. Signal or click evoked potential, a development of spontaneous after stimulus is indicated by upward smalldeflectionon time unit discharge and an increase in number of scale shown in frame of 1:5, Ebetroe~epb. din. NemW~yslol., 1963, 15:221-229
CORTICALUNITS DUgIIqG AMYGDALOIDMEIZURES
response seem-., to he maqked by a massive spontaneous unit discharge. In the next two x~-cords (5S and 123), there was an increase in number of spikes of unit response. Such an increased unit activity returned to the previous level about 40 sec after amygdaloid stimulation (40S). In only one case a decrease in the number of spikes of unit response was found to be associated with that of the surface evoked potential. In the unit shown in Fig. 8, the unit response of control record consisted of a group of eady sp~kes followed by long-latency discharge by about 140 msec. Four sec after amygdaloid stimulation, the long-latency discharge was abolished, and the number of early spikes decreased (Fig. 8, 4S). Return to the previous level was obtained 20 sec after stimulation (20S). A
4S
1RS
227
sponded to the maximal development of the propagated seizure discharge in the hippocampus. DISCUS|OH
The EEG activation during amygdaloid seizure in cats was considered by Arana-lniguez et al. (1955) as an EEG arousal through excitation of the reticular activating system. Ursin and Kaada (1960) also noted that the EEG activation occurred with behavioral "attention" and both could be produced by stimulation with stimulus strength insufficient to produce a seizure discharge at the site of stimulation in the amygdala. Patterns of unit activity obtain¢.~! from the temporal cortex of the cat in response to amygdaloid stimulation varied considerabt~ from cell to cell. A frequency increase of the .~lx)ntaneous s~)ikes was found in over 50~0 of units, while the remaining ones s h o ~ d no change in their activity, and only in about 15~ a decease in their firing frequency was observed. Also for the units responding to click stimuli, the most common change was "facilitation". A similar finding on the unit activity was also obtained from the somatosensory and visual cortices during EEG activation induced by peripheral or reticular stimulation (Akimoto et al. 1961; Saito et al. 1957). The unit activity in the present study indicates, however, that the cortical mechanisms during amygdaloid seizures are rather more complicated than those involved in a simple "arousal" reaction. The changes in pattern of cortical unit activity following amygdaloid stimulation is of a build-up type requiring a considerable latency, and an unusu.~lly high.frequency firin$ often develops. It has been noted that the propagation of seizure discharge from the amygdaloid region occurs through the septum and the head of,'.audate nucleus to the mesencephalon, with inclusion of the whole diencephalon, hypothalamus and thalamus (Ajmone Marsa~l and Stoll 1951; Andy and Mukawa 1960; Arana-lniguez et al. 1955; Gloor 1957; Stoll et al. 1951). A gredual development of change in unit activity following amygdaloid stimulation may be ~^plained by the delay of propagation of the seizure disct,trge from the amygdala to subcortical structures, since the period of the maximal change in unit activity was.found to be coincident with that of
NIE/Nm 10 met
|OOpV
FiJ. 8 I)~reese in both'~voked surface potential and unit dis.
~arlM in response to click stimulus foliowins amy~aloid stimulation. Indications are m in Fig. 7. II, Relationship between EE6 activation, unit activity and propagated hippocamixt! seizure dis. dmrge The release of the unit activity from the effects, either fncilitatory or inhibitory, of the amygdaIoid stimulation, was found to occur almost coincidently with the return of the EEG activity to the resting pattern. This parallelism, however, was not absolute. The EEG activation usually developed almost sintuitaneou~ly with the onse~ of" amygdaloid stimulation. It was a consistent finding for the units characterized by increase of their firing frequency that the maximal effects would occur 2-5 sec after the ,nd of amygdaloid stimulation; this time approximately corre-
Electroenceph. din. Heurophyslol., 1903, 15:221-229
228
s. YAb[AMOTO
propagated seizure discharge occurring in the hippocampns. A similar but more prolonged pro~gation of discharge is assumed to exist in the brain stem (Andy and Mukawa 1960; AranaInigucL et al. 1955; Gloor 1957). These consideIations suggest that when the amygdala is stimulated with strong intensities, the cortex is affected ~rough two n~cchanisms; one is a mere arousal reaction which develops with a short latency after amygdaloid stimulation, the other being a profound subcortieal involvement which is affected by the propagated seizure discharge. A spread of amygdaloid seizures to the cerebral cortex in cats has been noted to be confined to the areas corresponding to the anterior temporal and insular cortices in primate (AranaIniguez eta/. 1955; Gloor 1957). The unit activity during the propagated aAer-discharge, epileptic or them-wave-like, obtained in the temporal tip area in the present study was quite variable, so that a definite conclusion regarding this problem was not obtained. Some of the instances of high-frequency firing observed in the present study could probably be interpreted as a sign of damaged neurons. Actually, in many eases, units were lost in a few seconds after amygdaloid stimulation and, in such cases, their activity was usually characteristic of injury discharge. This was most likely due to movement of the brain tissue with changes in the blood pressure resulting from amygdaloid stimu. l,~tion (Kaada 1951; Koikegami et al. 1953). Although for other units the high.frequency discharge also appeared sunestively similar to an injury discharge ~he ~bove described phenomena could be produced repeatedly in the same unit by repeated stimulation. Adischarge at over 300/ sac seems indeed to be a manifestation of cellular seizure discharge (Baumjartner 1954). If this interpretation is correct, it may be important to note that cellular "seizure" can occur in the cortex while the EEG shows a simple activation pattern during amygdaloid seizures. Under a state ofarousal reaction, a depression of ~-qr~hcepotentials evoked by click stimuli was noted by Bremer (1953). Most neurons in the primary auditory area which responded to click stimuli in the p~sent study reacted to amygdaloid stimulation with a decrease of the threshold and an increase in number of spikes, while the cur-
responding surface potentials were depressed. The phenomena of a decreased threshold and increased ~ring of the unit may explain some of the behavioral reaction (such as "attention") following amygdaloid stimulation. However, the development of an irregular spontaneous unit discharge or an excessively long.lasting unit response might provide some explanation for the phenomenon of confusion or other behavioral automatisms in the psychomotor seizures. It seems conceivable that automatic irrational behavior and amnesia which characterize amygdaloid seizures in man may be caused by inhibition or blocking of neuronal circuits in the ternporal neocortex. The results of the present study in the cat suggest, however, that "inhibition" has a relatively minor role in amygdaloid stimulation. A blockade of physiological function of the cortex due to hyperactivity of neurons seems a mo~c likely mechanism of the psychomotor seizure. SUMMARY !. Unit activity of the media; and posterior ectosylvian and posterior sylvian cortices following amygdaloid stimulation with activation of the cortical EEG was studied in 51 cats. 2. Stimulation of the amygdala could produce a cortical electrographtc effect consisting of a low voltage, fast and asynchronous activity having characteristics of the "arousal" pattern. This phenomenon was most marked in the medial ectosylvian cortex, i.e. the auditory area, in the eat immobilized by flaxedil or hiah4pinal tran. section. 3. During EEG activation which followed amygdaloid stimulation, an increase of the spontaneous unit activity was found in the l a r ~ t number of units O6,8Yo), the next one showing no change in activity (27.4~'0), and the units whose activity was depmmed were encountered with least frequency (!$.8Yo). 4, In most cases, the change in unit activity was maintained during the EEG activation. In
those units exhibiting facilitatory effect, their maximal firing frequency occurred in 2-5 sac after the end of amygdaloid stimulation, in rather close coincidence with the appearance of the propagated aSter-discharge in tt= hippoeampus. 5. Surface-evoked potentials in the primary Eteetvoencepb, din. Nm~u~stol,, 1~3, 1.5: 211-2~
CORTICAL UNITS DURING AMYGDALOIDSEIZURES auditory a r e a in response to d i c k stimuli were always depressed temporarily after amygdaloid stimulation, which however, tended to "facilit a t e " the unit response by decreasing its threshold to click stimuli and increasing the n u m b e r o f spikes. 6. Some neurons in the primary auditory area reacted to a m y g d a l o i d stimulation with very highfrequency firins, their pattern being suggestive o f cellular epileptic discharge during the period o f E E G activation. This m a y indicate a sub-epileptic state o f the cortex rather than a simple arousal reaction. I wish to exp~gss my ~inccre gratitude to Dr. H. H. Jasper for his guidanoe and help in preparing and carrying out this study. I am indebted to Dr. P. Gloor for his invaluable advice. My grateful thanks are also due to Dr. K. Iwama for helpful criticism of the manuscript. REFERENCES
AJMONE MAMAN, C. and STou., J. [;ubcortical connections of the temporal pole in relation to temporal lobe seizures. AreA. Neurol. Psychiat. (Chic.), 19[;1, 66. 669-686. Agtt,toxo, H., [;Afro, Y. and NAKAMURA,Y. Effects of arousal stimuli on evoked neuronal activities in cat's visual cortex. In R. JuNo and H. Koamtuua (Editors), Freiburg symlmslum on the visual system" Neg,rophysioi. ofy and psychophysics. [;prinFr, Berlin, 1961: 36337Z Al~mv, O. J. and MUgAWA,J. Amy$daloid propallation to the brain stem (Electrophysiological study). Electro. encepb, olin. Neurophy,ffoL, 1960, 12: 333~343. AItANA-INIOU~, R., Rt~IS, D. J., NAQUI~T, R. and MAoouN, H. W. Propa~tion of amy~laloid seizures. Acta neutel, lat.~mer., 19S$, I: 109-122. I~UMO~XNB, G. Mi©roelectrode recordings from single cortical neurons in the normal statesnd during epileptic di~haq~. £1ectrocntwph. elln. Neurophy~i,~/., 1954, 6: 520-521.
229
Bazt~fft, F. Some .nroblems in ncurophysiolofy. Athlone Press, London, 19[;3, 79 p. C4tJJ~WILL, P. C. and D o ~ , A. C. The preparation of capillary microelectrodes. J. Physiol. (lend.), 1955, 128:31 P. D v . t ~ o , J. M. R. Evaluation of permanent implantation of electrodes within the brain. Electroenceph. clin. Neuruphysiol., 1955, 7: 637--644. FlmCDEL,W. and GLOOa,P. Comparison of electrographic effects of stimulation of the 4tmygdala and brain stem reti~lar formation in cats. Electroenceph. clin. Neurophysiol., 1954, 6: 389--402. GLOOR, P. The pattern of conduction of amygdaloid seizure discharp. Arch. Neurol. Psyehiat. (Chic.), 1957, 77: 247-258. JASPaR, H., P~KTUmET,B. and Ft~NIOIN, H. EEG and cortical electrograms in patients with temporal lobe seizures. Arch. Neurol, Psychiat. (Chic.), 1951, 6.$: 272-290. K~DA, B. R. Somato-motor, autonomic and electrocorticographic respons~ to electrical stimulation of "rhineacephalic" and other structures in primates, cat and dog. Acta physiol, sca,,ul., 1951, 24, Suppl. 83: 1-285. KOtKEOAM],H., KIMOTO,A. and Kmo, C. Studies on the amygdaioid nuclei and periamygdaloid cortex. Experiments on the influence of their stimulation upon motility of small intestine and blood pressure. Foils p~ychiat, ncurol. ]UP., 19[;3, 7: 87-108. Moauzzl, G. and MAt3OUN,H. W. Brain stem reticular formation and activation of the EEG. Eiectroenceph. clin. NeurophysioL, 1949, 1: 455-473. MOUNTCASTLE,V. B., DAVtH, P. W. and BeRMAt¢,A. L. Response properties of neurons of cat's somatic sensory cortex to peripheral stimuli. J. Neurophysiol., 1957, 20: 374-407. [;AfrO, Y., MAEKAWA,K., TAKENAKA,S. and KASAMAI~U, A. [;ingle cortical unit activity during EEG arousal glib Ann. Meet. Jap. EEG Sot., 19[;7, 95-98. [;TOLL,J., AIMONEMAMAN,C. and JASPER,H. H. Electrophysiological studies of subcortical connections of anterior temporal resion in cat. J. Neurophysiol., 1951, 14: 305-316. UMm, H. and KA&w,,B. g. Functional localization with. in the amy~aioid complex in the cat. Eleotroenceph. olin. Neurophysiol., 1960, 12: 1~20.
Reference: YAMAMOXO,S. Unit activity in temporal cortex during amygdaloid seizures in cats, Electroencep& olin. Neurophysiol., 1963, 18: 221-229.
UNIT
ACTIVITY
IN TEMPORAL
AMYGDALOID
CORTEX
221
DURING
SEIZURES IN CATS
Stll~IRO YAMAMOTO, M.D. 1
Department of Neurology and Neurosurgery, McGiU University and Montreal Neurological Institute, Montreal (Canada) (Received for publication: July 12, 1962)
INTRODUCTION
One characteristic phenomenon in temporal Iol,e seizures is flattening or desynchronization of the EEG at the onset of an attack, and this can also be produced by direct stimulation of the exposed uncus in patients undergoing surgical treatment for seizures (Jasper et el. 19S1). Experimentnily a similar EEG flattening has been shown, following electrical stimulation of the amygdaloid nucleus in the cat (Feindel and Gloor 1954; Kaada 1951; Ursin and Kaada 1960). The physiological significance of this phenomenon remains unknown. It may represent activation desynchronization as in the so-cniled~''arousal'' response (Arana-Iniguez et el. 1955; Ursin and Keada 1960). On the other hand, the amnesia and impaired mental functions which characterize the clinical seizure would suggest that such EEG flattening might express depression or interference with certain highly integrated cerebral functions. In the present study the behavior ofindividual cortical cells during seizures induced by amygdaloid stimulation in the cat is analyzed with microelectrodes. METHODS
The experiments were carried out on 51 cats. Surgical procedures were performed under ether anesthesia, with procainization of wound margins and pressure points. The animals were then immobilized by intermittent injections of flaxedil (geUemine triethiodide) except in 3 cases in which the high-spinal transection was carried out. Respiration was maintained artificially. After the initial injection of flaxedil or the high-spinal transection, a dose of 4 mg/kg of pentothal 1~ t address: Department of Sugpry, School of Medicine, University of Kanazawa, Kanazawa (Japan).
(thiopental sodium) was injected intravenously every 20 rain up to 12-16 mg/kg in total amount. The administration of pentothal minimized the epileptic activity which tendeJ to develop in animals subjected to repeated stimulation of the amygdala or the continuous activation pattern of the brain waves which usually occurred in curarized animals. Two pairs of bipolar wire electrodes as described by Deigado (1955) were stereotaxically introduced into the amygdala and the ventral hippcgampus ipeilateral to the exposed cortex. The electrodes in the amygdala were used for stimulation and those in the hippocampus for recording of the propagated after-discharge, The electrical stimulus to the amygdala was usually an 8-10 V, 5-msec pulse at 40/see for a period of 3 sec. The acoustic stimulus was a click, which was obtained by applying a rectangular voltage pulse (0.2-1.0 msec duration) to an electromagnetic type earphone. This was attached to an ear bar of the stereotaxic apparatus ipsilateral to the exposed cortex. The electrocorticogntm was recorded through a pair of silver electrodes separated at the tip by 5 mm and imbedded in a cortical stabilizer made of lucite curved to fit the contour of the brain. An opening was made in the stabilizer between the imbedded electrodes for passage of the microelectrode. The microelectrodes were micropipettes drawn to less than I ~ external diameter at the tip and filled with 3 M KCI (Caldwell and Downing 1955). The micrcelectrode was mounted in a mechanical micrometer ~nd connected with the input of a cathode follower (RCA 6AU6 in triode connection). The indifferent ei¢chode was screwed into the frontal bone. Potentials picked up by gross- and microEleetroenetph. din. Nturophy$1ol., 1963D]$: 221-229
222
S. YAMAMOTO
electrodes were amplified by CR-coupled amplitiers (Tektronix) and recorded by means of a 4-beam cathode-ray oscilloscope and a Grass camera. Ink-writer tracings were obtained simultancously by means of a~z Offner Type T EEG apparatus. In all the following illustrations, the upper beam is used for the surface. EEG, the second beam for the microelectrode recording
A
the recorded spikes often showed variations in amplitude and shape during a long continuous recording. RESULTS A most marked EEG flattening induced by amygdaloid stimulation was usually observed in the medial ectosylvian cortex, particularly in the
•
I See
500#V
Fill. I Increased unit activityrecorded from auditory area. FlrJt trace, surfaceEEG. Sacor~dtrace, unit recordinll.Bottomtrace. EEG of hlppocempus.Four sectionsof record are continuous,Stimulation of emyfp~¼fs indicatedby stimulationartefact at end of first section. from the same cortical area (upward deflection representing neptivity), and the third beam for the EEG from the other portion of the cortex or for stimulation marks. Generally the time constant was 0.2 sac for the EEG and 0.005 sac for microelectrode recordin$. In the course of unitary recording, slight changes in amplitude or shape of spikes were often encountered. These were considered in most cases th~ result of movement of the microelec. trode (Mountcastle et aL 1957) induced by artificial respiration or change in blood pressure following amygdaloid stimulation (KMda 1951, Koikegami et aL 1953). The results of unitary recording treated in this report are limited to those obtained from well-isolated units, though
auditory area. This consisted of low-voltage highfrequency waves similar to the "EEG activation" pattern (Moruzzi and M u o u n 1949), In the somato-sensory cortex, on the other hand, the pattern was very often that of a continuous "arousal condition", which obscured the effect of amygdaloid stimulation. Therefore, microelec. trode recordings were mostly performed in the medial ectosylvian cortex, In only six animals the lower part of posterior ectosylv/an and sylvian corticies was studied, This area will be referred to hereafter as "temporal tip" (Stoil eta/. 1951). As seen in Fig. I and 2, the EEG activation in the medial ectosylvian cortex usually developed almost immediately after the start of amysdaloid stimulation and lasted for 20-50 sac. On the FJeemsmeeph.dt~. N~quop~sJol., 1963, 15:221-229
CORTICALUNITS DURING A]g[YGDALOIDSEIZURES
...... ......
~.3
5oo,,v
F~ 2
Activation of unit started from onset of arayl;daloid stimulation. Sporadic bunts of very hilh frequency ~ m seen durins ~ o f ~ ! f l ~ frequency, Indications are as in Fill. !.
•
"
|
.m
! $ec
Fill. 3 Continuous epilsptic unit discharp. First and second traces in each section of record are as in Fill. 1. Bottom tmoe in first sw--tion indicstes click stimuli at I/inc. On and off of amylldslotd stimulation am tndicsted by arrows in first and second sections. Unit was driven by click stimuli and responded to llmylldaloid stimulation with continuous oellular epikptic dischllrp during period of EEO activation. This was ee~'6pAaleIsold preparation without curarizatinn.
other hand, the propagated after-discharge in the hippocampus developed gradually and subsided in 3-7 sec. In only 3 animals, however, a gradual development of the EEG activation was found in the medial ectosyivian cortex (upper tracing
of Fig. 6). In all the records taken from the area of temporal tip, propagation of epileptic afterdischarge or theta.wave-like slow waves were seen during a period of 3-13 sec following amygdaloid stimulation, and the EEG activation ap£1¢clroenceph. din. Neurophyslol., 1963, 15:221-229
224
s. Y A ~ O r o
peared thereafter. In the case shown in Fig. 4, EEG recordings were made in the temporal tip (posterior ectosylvian gyrus) and the auditory area. In the cortex of temporal tip, slow waves which appeared during a period of 4 see after amygdaloid stimulation were considered to be a propa a typi
A. Spontaneous unit activity Effects of a m y ~ o i d s ~ t i o n on unit activity were classified into ~ categories. (a) Increase in frequency of the unit disdmrge. This was observed in 83 out of 146 units (56.8%). Fig. I illustrates one of the typical example~. The
2 SOO~uV
I $eo
Fig. 4 Delayed f~ilitation of unit activity. Ftnt trace, EEG of lower part or posterior ecto,ylvlan i~rus.
Second trace, unit recording from rome cortical am. Bottom trace, IEI~Gof auditory area. Re~ords at bottom of flluro were obtained 40 ~ after amy~aloid ,timu¼tion, lation of the amygdala. In the auditory area, on the other hand, fast waves (30 c/sec) developed immediately after stimulation. These were considered as EEG "activation" although their voltage was not suppressed.
I. Unit activity The activity of the units was analyzed during the EEG activation induced by amygdaloid stimulation: 116 in the medial ectosylvian cortex, and 30 in the temporal tip. They were distributed in the depths of O.4 to 2.4 a m , altho~tgh encountered most frequently at 0.7 to i.8 mm. The voltage of the re':orded spike discharges ranged from 200/~V to 10 mV; 65 per cent of them were initially positive, and the others initially negative.
stimulation, reaching its maximum in 2 xc, and returned to its previous level when the EEG activation was about to subside. Fig. 2 is a sample record from another unit in the same area of the same animal as in Fig. I. This unit started to be activated almost from the beginning of amylgdaIoid stimulation, with latency of approximately 30 reset, looking as though it was responding to each stimulation pulse. After the end of the stimulation this increased activity continued for more than 18 sec: at 2 and 5 sec after the end of the stimulation, there appeared two burst~ of high-frequency spike discharge preceded by highamplitude transient spikes. The latter mayprobably have been caused by movements and the corresponding bursts be due to injury of the unit.
Eiecln~em',~p&din. Nemophysiol., 1963, IJ: 221-229
CORTICALUNrlB DURING AMYGDALOIDSEIZURES
However, the same phenomena as shown in Fig. 2 could be observed in 4 records taken from the same unit at lO-min intervals. Fig, 3 is a sample record of a single unit which responded to a click stimulus and was activated during the period of EEG activation with a continuous firing at a freq~ of over 300/see. This unit could be activated in the ~ w a y by a ~ n d amygdaloid
225
wave-like after-discharge. Thereafter there was an enhancement of unit activity which appeared to be associated with EEG activation, However, the appearance of propagated after-discharge in thi~ area was found to be not always associated with an arrest of the unit activity. Co) Decrease m frequency of the unit discharge. This was encountered in 23 out of 146 units
500~V
I See Fig. $ D~reaud unit activityfollowingamyldaloid stimulation.Indicationsare as in Fill. I. stimulation performed after a sufficiently Ions interval, It should be noted, however, that such a long lasting high.frequen~ u n i ~ discharge was e n c o u n ~ only in ent~plmle Do[J eats without curarization. Upon repeated amygdaloid stimulation, such animals tended to show an epileptic state characterized by continuous cortical seizure discharges, intense salivation, mastieatory movements, etc. In 11 units in the 8r¢~lpof"in¢reased"activ ity, it took for the activity to increase 1 see or longer after the end of amygdaloid stimulation. Five ofthese eleven units were found in the cortex of temporal tip. In this area, results were rather complicated, since the propagated after-discharge preceded a simple EEG activation. The record of Fig. 4 obtained from such region showed a blocking of unit activity during the propagated theta-
(15.8 ~). In the ease of Fig. $ the EEG activation started from the onset ofamygdaloid stimulation and continued about 20 sec during which period a decrease in unit activity was seen. In this type of neuron the unit activity could be depressed repeatedly by repeated stimulation, and a temporary arrest of unit discharge was seen during a period from I-9 see after stimulation. (c) No change infrequency of the unit discharfe. Forty out of 146 units (27.4%) did not modify their firing pattern either during or following amygdaloid stimulation c~pable ofeliciting EEG activation.
B. Evoked unit response The most common effect of amygdaloid stimulation on the neurons which responded to a click stimulus in the primary auditory area was Electroenccph. din. NGurophysiol., 1963, 13:221-229
226
$. YAMAMOTO
i See
500,V
Fis. 6 EfYectsof 8mygdaloid stimulation upon unit response to click stimuU. First trace, EEG of primary ~,uditory urea. Second trace, unit recording from nine cortical urea. Bottom trace, marks of click stimuli. Recordsobtained 50 se~ after umygclaloid stimulation are in bottom section of tSrure.
a decrease in the threshold and an increase in the spikes in response to the click were seen. In the number of spikes, while the amplitude of surface record or 2 see after amygdaloid stimulation evoked pote,~tial was always decreased. In the (Fig. 7, 2S), it can be seen that the evoked unit sample record shown in Fig. 6, sub-threshold A dO 88 click stimuli (80~ of threshold voltap) were applied at a frequency of 2/No. About 2 see after the end of amygdaloid stimulation, an EEG activation developed and the unit ~gan not only to respond to each click stimulus, but also to discharge spontaneously. These phenomena continued for about 50 see and returned to the pre. vious state when the EEG activation gradually subsided. A slight change in spike shape du~ng the recording in this ease seemed to be due to slight movements of the microeleetrode relative to brain tissues and the unit was considered to be the same. In the ease shown in Fig, 7, a sub- Effects of an~lldaloidstimulationupon o~ok~l sur/~ poten+.~ and unit response to click stimulL First truce maximal strength of click stimulation was used of each frame, surface poteatbd ;.n prima~ auditory area to evoke a unit response. After amygdaloid respondit~ to submuxima! click stimulus. ,~coad trlu:e, stimulation, a depression of the surface potential unit responsesfrom samecortk:l urea. A, control record. was seen. During this period ofdepre~ed surface 2,5, 5,5, 12,5,2USand 40S: records 2, 5, 12, 20und dOsee end of an~lldaloid stimulation. Signal or click evoked potential, a development of spontaneous after stimulus is indicated by upward smalldeflectionon time unit discharge and an increase in number of scale shown in frame of 1:5, Ebetroe~epb. din. NemW~yslol., 1963, 15:221-229
CORTICALUNITS DUgIIqG AMYGDALOIDMEIZURES
response seem-., to he maqked by a massive spontaneous unit discharge. In the next two x~-cords (5S and 123), there was an increase in number of spikes of unit response. Such an increased unit activity returned to the previous level about 40 sec after amygdaloid stimulation (40S). In only one case a decrease in the number of spikes of unit response was found to be associated with that of the surface evoked potential. In the unit shown in Fig. 8, the unit response of control record consisted of a group of eady sp~kes followed by long-latency discharge by about 140 msec. Four sec after amygdaloid stimulation, the long-latency discharge was abolished, and the number of early spikes decreased (Fig. 8, 4S). Return to the previous level was obtained 20 sec after stimulation (20S). A
4S
1RS
227
sponded to the maximal development of the propagated seizure discharge in the hippocampus. DISCUS|OH
The EEG activation during amygdaloid seizure in cats was considered by Arana-lniguez et al. (1955) as an EEG arousal through excitation of the reticular activating system. Ursin and Kaada (1960) also noted that the EEG activation occurred with behavioral "attention" and both could be produced by stimulation with stimulus strength insufficient to produce a seizure discharge at the site of stimulation in the amygdala. Patterns of unit activity obtain¢.~! from the temporal cortex of the cat in response to amygdaloid stimulation varied considerabt~ from cell to cell. A frequency increase of the .~lx)ntaneous s~)ikes was found in over 50~0 of units, while the remaining ones s h o ~ d no change in their activity, and only in about 15~ a decease in their firing frequency was observed. Also for the units responding to click stimuli, the most common change was "facilitation". A similar finding on the unit activity was also obtained from the somatosensory and visual cortices during EEG activation induced by peripheral or reticular stimulation (Akimoto et al. 1961; Saito et al. 1957). The unit activity in the present study indicates, however, that the cortical mechanisms during amygdaloid seizures are rather more complicated than those involved in a simple "arousal" reaction. The changes in pattern of cortical unit activity following amygdaloid stimulation is of a build-up type requiring a considerable latency, and an unusu.~lly high.frequency firin$ often develops. It has been noted that the propagation of seizure discharge from the amygdaloid region occurs through the septum and the head of,'.audate nucleus to the mesencephalon, with inclusion of the whole diencephalon, hypothalamus and thalamus (Ajmone Marsa~l and Stoll 1951; Andy and Mukawa 1960; Arana-lniguez et al. 1955; Gloor 1957; Stoll et al. 1951). A gredual development of change in unit activity following amygdaloid stimulation may be ~^plained by the delay of propagation of the seizure disct,trge from the amygdala to subcortical structures, since the period of the maximal change in unit activity was.found to be coincident with that of
NIE/Nm 10 met
|OOpV
FiJ. 8 I)~reese in both'~voked surface potential and unit dis.
~arlM in response to click stimulus foliowins amy~aloid stimulation. Indications are m in Fig. 7. II, Relationship between EE6 activation, unit activity and propagated hippocamixt! seizure dis. dmrge The release of the unit activity from the effects, either fncilitatory or inhibitory, of the amygdaIoid stimulation, was found to occur almost coincidently with the return of the EEG activity to the resting pattern. This parallelism, however, was not absolute. The EEG activation usually developed almost sintuitaneou~ly with the onse~ of" amygdaloid stimulation. It was a consistent finding for the units characterized by increase of their firing frequency that the maximal effects would occur 2-5 sec after the ,nd of amygdaloid stimulation; this time approximately corre-
Electroenceph. din. Heurophyslol., 1903, 15:221-229
228
s. YAb[AMOTO
propagated seizure discharge occurring in the hippocampns. A similar but more prolonged pro~gation of discharge is assumed to exist in the brain stem (Andy and Mukawa 1960; AranaInigucL et al. 1955; Gloor 1957). These consideIations suggest that when the amygdala is stimulated with strong intensities, the cortex is affected ~rough two n~cchanisms; one is a mere arousal reaction which develops with a short latency after amygdaloid stimulation, the other being a profound subcortieal involvement which is affected by the propagated seizure discharge. A spread of amygdaloid seizures to the cerebral cortex in cats has been noted to be confined to the areas corresponding to the anterior temporal and insular cortices in primate (AranaIniguez eta/. 1955; Gloor 1957). The unit activity during the propagated aAer-discharge, epileptic or them-wave-like, obtained in the temporal tip area in the present study was quite variable, so that a definite conclusion regarding this problem was not obtained. Some of the instances of high-frequency firing observed in the present study could probably be interpreted as a sign of damaged neurons. Actually, in many eases, units were lost in a few seconds after amygdaloid stimulation and, in such cases, their activity was usually characteristic of injury discharge. This was most likely due to movement of the brain tissue with changes in the blood pressure resulting from amygdaloid stimu. l,~tion (Kaada 1951; Koikegami et al. 1953). Although for other units the high.frequency discharge also appeared sunestively similar to an injury discharge ~he ~bove described phenomena could be produced repeatedly in the same unit by repeated stimulation. Adischarge at over 300/ sac seems indeed to be a manifestation of cellular seizure discharge (Baumjartner 1954). If this interpretation is correct, it may be important to note that cellular "seizure" can occur in the cortex while the EEG shows a simple activation pattern during amygdaloid seizures. Under a state ofarousal reaction, a depression of ~-qr~hcepotentials evoked by click stimuli was noted by Bremer (1953). Most neurons in the primary auditory area which responded to click stimuli in the p~sent study reacted to amygdaloid stimulation with a decrease of the threshold and an increase in number of spikes, while the cur-
responding surface potentials were depressed. The phenomena of a decreased threshold and increased ~ring of the unit may explain some of the behavioral reaction (such as "attention") following amygdaloid stimulation. However, the development of an irregular spontaneous unit discharge or an excessively long.lasting unit response might provide some explanation for the phenomenon of confusion or other behavioral automatisms in the psychomotor seizures. It seems conceivable that automatic irrational behavior and amnesia which characterize amygdaloid seizures in man may be caused by inhibition or blocking of neuronal circuits in the ternporal neocortex. The results of the present study in the cat suggest, however, that "inhibition" has a relatively minor role in amygdaloid stimulation. A blockade of physiological function of the cortex due to hyperactivity of neurons seems a mo~c likely mechanism of the psychomotor seizure. SUMMARY !. Unit activity of the media; and posterior ectosylvian and posterior sylvian cortices following amygdaloid stimulation with activation of the cortical EEG was studied in 51 cats. 2. Stimulation of the amygdala could produce a cortical electrographtc effect consisting of a low voltage, fast and asynchronous activity having characteristics of the "arousal" pattern. This phenomenon was most marked in the medial ectosylvian cortex, i.e. the auditory area, in the eat immobilized by flaxedil or hiah4pinal tran. section. 3. During EEG activation which followed amygdaloid stimulation, an increase of the spontaneous unit activity was found in the l a r ~ t number of units O6,8Yo), the next one showing no change in activity (27.4~'0), and the units whose activity was depmmed were encountered with least frequency (!$.8Yo). 4, In most cases, the change in unit activity was maintained during the EEG activation. In
those units exhibiting facilitatory effect, their maximal firing frequency occurred in 2-5 sac after the end of amygdaloid stimulation, in rather close coincidence with the appearance of the propagated aSter-discharge in tt= hippoeampus. 5. Surface-evoked potentials in the primary Eteetvoencepb, din. Nm~u~stol,, 1~3, 1.5: 211-2~
CORTICAL UNITS DURING AMYGDALOIDSEIZURES auditory a r e a in response to d i c k stimuli were always depressed temporarily after amygdaloid stimulation, which however, tended to "facilit a t e " the unit response by decreasing its threshold to click stimuli and increasing the n u m b e r o f spikes. 6. Some neurons in the primary auditory area reacted to a m y g d a l o i d stimulation with very highfrequency firins, their pattern being suggestive o f cellular epileptic discharge during the period o f E E G activation. This m a y indicate a sub-epileptic state o f the cortex rather than a simple arousal reaction. I wish to exp~gss my ~inccre gratitude to Dr. H. H. Jasper for his guidanoe and help in preparing and carrying out this study. I am indebted to Dr. P. Gloor for his invaluable advice. My grateful thanks are also due to Dr. K. Iwama for helpful criticism of the manuscript. REFERENCES
AJMONE MAMAN, C. and STou., J. [;ubcortical connections of the temporal pole in relation to temporal lobe seizures. AreA. Neurol. Psychiat. (Chic.), 19[;1, 66. 669-686. Agtt,toxo, H., [;Afro, Y. and NAKAMURA,Y. Effects of arousal stimuli on evoked neuronal activities in cat's visual cortex. In R. JuNo and H. Koamtuua (Editors), Freiburg symlmslum on the visual system" Neg,rophysioi. ofy and psychophysics. [;prinFr, Berlin, 1961: 36337Z Al~mv, O. J. and MUgAWA,J. Amy$daloid propallation to the brain stem (Electrophysiological study). Electro. encepb, olin. Neurophy,ffoL, 1960, 12: 333~343. AItANA-INIOU~, R., Rt~IS, D. J., NAQUI~T, R. and MAoouN, H. W. Propa~tion of amy~laloid seizures. Acta neutel, lat.~mer., 19S$, I: 109-122. I~UMO~XNB, G. Mi©roelectrode recordings from single cortical neurons in the normal statesnd during epileptic di~haq~. £1ectrocntwph. elln. Neurophy~i,~/., 1954, 6: 520-521.
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Bazt~fft, F. Some .nroblems in ncurophysiolofy. Athlone Press, London, 19[;3, 79 p. C4tJJ~WILL, P. C. and D o ~ , A. C. The preparation of capillary microelectrodes. J. Physiol. (lend.), 1955, 128:31 P. D v . t ~ o , J. M. R. Evaluation of permanent implantation of electrodes within the brain. Electroenceph. clin. Neuruphysiol., 1955, 7: 637--644. FlmCDEL,W. and GLOOa,P. Comparison of electrographic effects of stimulation of the 4tmygdala and brain stem reti~lar formation in cats. Electroenceph. clin. Neurophysiol., 1954, 6: 389--402. GLOOR, P. The pattern of conduction of amygdaloid seizure discharp. Arch. Neurol. Psyehiat. (Chic.), 1957, 77: 247-258. JASPaR, H., P~KTUmET,B. and Ft~NIOIN, H. EEG and cortical electrograms in patients with temporal lobe seizures. Arch. Neurol, Psychiat. (Chic.), 1951, 6.$: 272-290. K~DA, B. R. Somato-motor, autonomic and electrocorticographic respons~ to electrical stimulation of "rhineacephalic" and other structures in primates, cat and dog. Acta physiol, sca,,ul., 1951, 24, Suppl. 83: 1-285. KOtKEOAM],H., KIMOTO,A. and Kmo, C. Studies on the amygdaioid nuclei and periamygdaloid cortex. Experiments on the influence of their stimulation upon motility of small intestine and blood pressure. Foils p~ychiat, ncurol. ]UP., 19[;3, 7: 87-108. Moauzzl, G. and MAt3OUN,H. W. Brain stem reticular formation and activation of the EEG. Eiectroenceph. clin. NeurophysioL, 1949, 1: 455-473. MOUNTCASTLE,V. B., DAVtH, P. W. and BeRMAt¢,A. L. Response properties of neurons of cat's somatic sensory cortex to peripheral stimuli. J. Neurophysiol., 1957, 20: 374-407. [;AfrO, Y., MAEKAWA,K., TAKENAKA,S. and KASAMAI~U, A. [;ingle cortical unit activity during EEG arousal glib Ann. Meet. Jap. EEG Sot., 19[;7, 95-98. [;TOLL,J., AIMONEMAMAN,C. and JASPER,H. H. Electrophysiological studies of subcortical connections of anterior temporal resion in cat. J. Neurophysiol., 1951, 14: 305-316. UMm, H. and KA&w,,B. g. Functional localization with. in the amy~aioid complex in the cat. Eleotroenceph. olin. Neurophysiol., 1960, 12: 1~20.
Reference: YAMAMOXO,S. Unit activity in temporal cortex during amygdaloid seizures in cats, Electroencep& olin. Neurophysiol., 1963, 18: 221-229.