The development of secondary epileptic discharges in the rhesus monkey after commissure section

473

Electroencephalography and Clinical Neurophysiology, 1974, 37:473 481 i" Elsevier Scientific Publishing Company. Amsterdam Printed in Tile Netherlands

THE

DEVELOPMENT

IN T H E

RHESUS

OF SECONDARY

MONKEY

AFTER

EPILEPTIC

COMMISSURE

DISCHARGES SECTION

V. NIE, J. J. MACCABE, G. ETTLINGER AND M. V. DRIVER lnslitute o/ P,vv('hialry. London SE5 8A F (Great Britaitt)

(Accepted for publication: May 10, 1974)

We have studied the development of secondary discharges in rhesus monkeys prepared with unilateral application of aluminium hydroxide to temporal or parietal cortex (Moffett et al. 1970: Gautrin et al. 1971). Nie et al. (1973) have discussed the incidence, time-course and other features of secondary discharges from temporal cortex in a majority of 33 monkeys. Our experience \~ith parietal implants is more limited: with, on average, a shorter period of observation and slightly different method of producing the primary focus, Moffett et al. (1970) failed to observe secondary discharges in any of their 6 monkeys. In the present work we reverted to parietal (as contrasted with temporal) epileptogenic implants in order to compare, after commissure section, the transmission of tactile information between the hemispheres in animals with or without discharging abnormalities. Here we report only EEG findings: for 4 monkeys with total commissure section and unilateral parietal epileptogenic implants ; for one similarly prepared animal in which a portion of the posterior body of the corpus callosum was intentionally spared ; and for 4 control animals with total commissure section but without epileptogenic implants. These 9 animals were the only ones to survive an outbreak of tuberculosis long enough to permit systematic study of their EEGs. To our surprise each of the 4 monkeys with total commissure section and parietal epileptogenic implants gave at some time evidence of independent contralateral epileptic discharges. METHOD Subjects

Nine immature rhesus monkeys (Macaca

mulatta) were randomly allocated for surgery: in 4 (Ep+TC1 to Ep+TC4) all commissures were divided and aluminium hydroxide was implanted on the left posterior parietal cortex: in one (Ep+PC) the same surgical procedures were followed except that about 5 mm of the posterior body of the corpus callosum was intentionally not divided; in another (Abl +TC) the commissures were completely divided but the left posterior parietal cortex was ablated from the region on which in other animals the epileptogenic agent was placed; in 3 controls TCI TC3 all commissures were divided. Two other animals are excluded from this report (although both showed independent secondary discharges in their EEGs): Ep+TC5 because of excessive associated brain damage; and Ep + PC2 because it was killed after only 4 monthly postoperative EEG recordings. Surgery In all animals, a large bilateral bone flap was turned on the right temporal muscle under barbiturate anaesthesia. The dura over the left hemisphere was reflected in a wide crescent, and (when it proved essential) some of the bridging vessels to the sagittal sinus were cut. Applying gentle retraction to both hemispheres the corpus callosum, psalterium, posterior commissure, massa intermedia of the thalamus and anterior commissure were divided with a fine-gauge sucker with the aid of a Zeiss operating microscope. Four celluloid caps, filled with boiled commercial aluminium hydroxide gel (Aludrox), were placed onto the left lateral posterior parietal-prestriate cortex anterior to the lunate sulcus but posterior to the anterior end of the intraparietal sulcus. The dura was carefully

v. NIE et al.

474 r e p o s i t i o n e d over the caps, b u t n o t sewn, a n d covered with gel-foam. T h e b o n e flap was tightly sewn and the skin closed. In a n i m a l Ep + PC, 5 m m of the posterior b o d y of the corpus callosum were left undivided. N o a l u m i n i u m hydroxide was i m p l a n t e d in a n i m a l A b l + T C : instead the left lateral posterior parietal prestriatecortexwas a b l a t e d (but spared in the sulci). A n i m a l s T C 1 TC3 were given a total c o m m i s s u r e section without f u r t h e r i n t e r v e n t i o n .

Post-operative recovery All a n i m a l s gave variable evidence o f the effects o f b r a i n o e d e m a a n d / o r h y d r o c e p h a l u s d u r i n g the first 6 post-operative weeks. Summaries are given in T a b l e I. M o s t severely affected were : Ep + TC4, A b l + T C a n d TC3 ; least

affected were E p + T C 1 a n d E p + T C 2 . F o u r a n i m a l s ( E p + T C 1 , A b l + T C , TC1 a n d TC2) experienced right-sided epileptic c o n v u l s i o n s for 2 days, 1 day, 5 days a n d 1 day respectively within 7 days o f surgery. These were treated with E p a n u t i n , a n d with V a l i u m if the attacks were very severe. N o a n i m a l was observed to have left-sided or bilateral convulsions.

Anti-tuberculosis prophylaxis T w o a n i m a l s c o n t r a c t e d tuberculosis : a n i m a l E p + T C 1 was killed at 7 m o n t h s a n d E p + T C 3 at 6 m o n t h s after surgery, w i t h o u t a n y drug t r e a t m e n t . F o u r o f the r e m a i n i n g 7 a n i m a l s were placed o n t r e a t m e n t as indicated in T a b l e I. Isoniazid a n d P A S were a d m i n i s t e r e d as P a s i n a h D (12.5 m g isoniazid/day : P A S p r o p o r t i o n a t e l y )

TABLE I Summary of post-operative course and treatments Animals

Early post-operative recovery

Neurological signs at 6 weeks

EEG recordings (Months)

Ep+TCI

Rt. paresis from day 2; rt.sided epileptic seizures on day 4~5 : rt. paresis variable.

None: behaviour normal.

2- 7

Ep +TC2

Very mild ft. paresis on day 2 + 3 ; incoordination and failure to see day 35 38.

None: behaviournormal.

2 12

Ep+TC3

Almost uneventful till day 57 when vision defective for 6 days.

None till episode on day 57; persistentmild incoordination.

2 7

Ep+TC4

Almost uneventful till day 57 when acute gastric illness and rt. paresis.

Rt. paresispersistedwhilealive.

Ep + PC

Very mild rt. paresis persisting from day I.

Abl + TC

Pasinah (Months)

Rifadin (Months)

7 l0

7 12

1~ 5

0- 3

2 5

Very mild rt. paresis and rt. sensory defect.

1 7

l

4

3 7

Severert. paresis from evening day 1: rt.-sided seizures day 2: blind day 3.

Rt. paresis and visual defect persisted while alive.

2 10

7 10

9 t0

TC!

Rt.-sided seizures day 2 3; drowsy day 12 19: rt. paresis day 12 13.

Mild rt. paresis and visual defect persisted while alive.

1 12

TC2

Rt.-sided seizures day 2; rt. paresis from day 1; gastric disorder day 6.

Very mild ft. paresis persisting while alive.

2- 8

TC3

Severe rt. paresis on day 3; blind from day 4.

Rt. paresis and visual defect 1 - 5 persisted while alive.

All dates (weeks, months) are taken to the nearest whole number and calculated from the day of surgery.

475

EPILEPTIC DISCHARGES AFTER COMMISSURE SECTION

in the drinking water; rifampicin as Rifadin (45 mg/day) on bread.

Ver(/ication o/lesions a. Experimentalanimals. Animals Ep + TC 1 ~ were perfused ; their brains removed, embedded in celloidin and cut serially at 25 g through a single block extending from genu to the posterior commissure. The sections were stained for cells and for fibres. All commissures (i.e., callosum including genu and splenium, anterior commissure and posterior commissure) and the massa intermedia were found to have been divided in all 4 animals except for a few fibres of the anterior corpus callosum remaining in one section in animal Ep + TCI. There was damage to the ventral margin of the left cingular cortex in Ep + TC2. The left ventricular system and IIIrd ventricle were dilated in all 4 animals, the most severely affected being E p + T C 2 and E p + T C 4 . The dilatation was so gross in the latter animal that there was severe reduction of brain substance on the left, and also some reduction on the right in this animal (with ventricular dilatation). No other evidence of any right-sided abnormalities was found. b. Control animals. Animals E p + PC, Abl + TC and TC1 and TC3 were perfused. Their brains were removed and cut into blocks about 5 mm thick. The surgical intentions were achieved except : in Ep + PC there was slight damage to the head of the left caudate nucleus and, over a considerable anterio>posterior extent, to the left internal capsule: in Abl + T C a few strands remained intact in the genu (and there was widespread bilateral destruction of cortex due to a presumed head injury during transport, already noted when opening the dura at the time of surgery): in TC1 there was dilatation of the ventricular system on the left, and of the right temporal lobe, and some cortical destruction in the left side around the edge of the bone flap : and in TC3 there was evidence of very severe hydrocephalus (with grossly dilated ventricles, massive reduction of cortical substance on the left, but no obvious damage to the right parieto-occipital cortex) and of intra-ventricular haemorrhage.

EEG recordin:ls Monthly scalp

EEG

recordings

(usually

starting at the second month after surgery) were taken according to the methods described by Moffett et al. (1970). 8 silver/silver chloride electrodes were attached with collodion to the scalp of the animal seated comfortably in a chair. Bipolar recordings were taken with a Devices Instruments Polygraph. Time constant was 0.3 sec for all paper recordings with a high frequency cut of 15!~; at 50 c/sec. These values apply to Fig. 2 and 3. In addition the EEG was on 3 occasions recorded on magnetic tape (TC = 0.03 sec: H F = 5 0 c:sec; Ampex SP300 recorder, FM, 7.5 ips): at 4 months after surgery for E p + T C 2 , at 6 months for E p + T C 3 and at 3 months for Ep + TC4. Care was taken to ensure that homologous left and right channels were recorded on tracks recorded by the same tape head. Fig. 4 6 are derived from this latter method of recording. The sweeps in these figures are triggered by selecting one trace, and setting a DC amplitude of selected polarity: ally voltage greater than the set amplitude will initiate the s~veep.

EEG c/assi[i'cation For quantitative analysis, the monthly EEG recordings were carefully re-examined by one of us (V.N.). EEG phenomena regarded as of epileptic significance took one of two forms: either spike loci as conventionally accepted, or transient rhythmic slow waves as seen in certain seizures. Runs of complex wave-forms (e.:l., spikewave) were not seen. Care was taken to exclude sharp transient wave-forms of the normal EEG such as the vertex waves seen in light sleep (animals were prevented from falling asleep but would frequently give the appearance of being drowsy). However, on occasions the distinction between abnormal potentially epileptogenic discharges and bursts of lateralized normal vertex phenomena was not always clear-cut (see EEG findings for TC1 and TC3). Counts were separately made of: (i) spikes seen in the primary hemisphere and forming part of a seizure originating in the primary hemisphere, where a seizure is defined as a run of discharges lasting at least 1 sec at a frequency of at least 4 discharges/sec (except in one case, see Fig. 1); (ii) spikes transmitted (i.e., without detectable time lag) during a seizure from the secondary to the pri-

v. NIE et al.

476 primary

....... ..................

primary

]

O

~

secondary

~

secondary

6

Ep+TCI

p.,ff/j'j'//~ 3

2 ~ooo

~oo

~o

~ ~

primary ~

~o

~oo

,~oo

secondary

,ooo

~oo

7

100

10

2

~o

~~

primary

4

1000

I00

1000

1000

I00

10

~o

~oo

~ooo

secondary

~/~///~f~~

10

Ep+TC2

./~//~////.~.

I 1

Ep+TC4

10

I00

lOOt)

Fig. 1. The incidence of different kinds of discharging abnormality during monthly EEG recordings in all animals with parietal epileptogenic lesions and total commissure section (Ep + TC 1 - Ep + TC4). Ordinates: m o n t h s after surgery. Abscissae: log average frequency per 10 min of record of each abnormality. Note that the criterion for seizure discharges is exceptional lbr animal Ep + TC 1 in which case it was a run, lasting at least 30 sec, at a frequency of at least 3 discharges/sec.

mary hemisphere; (iii) interictal primary spikes originating from the primary hemisphere; (iv) interictal spikes seen in leads from the primary hemisphere but probably transmitted from events originating in the secondary hemisphere; (v) spikes seen in the secondary hemisphere and forming part of a seizure originating in the second hemisphere; (vi) spikes transmitted during a seizure from the primary to the secondary hemisphere; (vii) interictal secondary spikes originating from the secondary hemisphere;and (viii) interictal spikes seen in the leads from the secondary hemisphere but probably transmitted from events originating in the primary hemisphere. Where an event is transmitted it may therefore have been counted twice: for instance on the primary side as a primary (i.e., independent)

interictal event (class iii) and on the secondary side as the secondary (i.e., transmitted) interictal event (class viii); or as a transmitted seizure discharge in the primary hemisphere (class ii) and an independent seizure discharge in the secondary hemisphere (class v). It should also be noted that independent status was assigned to discharges which appeared synchronously and with equal amplitude over both hemispheres, since it was not possible to ascertain the true site of origin of the discharge. RESULTS

As indicated in Fig. 1 secondary (independent and transmitted) discharges were seen in the EEGs of the 4 E p + T C animals. Although in

477

EPILEPTIC DISCHARGES AFTER COMMISSURE SECTION

two recordings the frequency of secondary seizure discharges was exceptionally high, in most recordings the incidence of secondary interictal discharges was greater. In view of the commissure section, of special importance are two classes of discharges: secondary independent seizure and secondary independent interictal discharges (classes v and vii). Three of our Ep + TC animals showed both of these kinds of discharge, in one instance within 2 months of surgery but otherwise from the 4th month after surgery. In the fourth animal ( E p + T C 2 ) there was relatively little seizure activity in the primary hemisphere (and only transmitted seizure activity in the second hemisphere); but instead, there were secondary independent interictal discharges in 7 of 13 monthly recordings. Animai E p + P C showed primary but not secondary discharges in the EEG. No evidence o f discharging activity was seen over either hemisphere in the EEGs of Abl + T C . Spike discharges were seen over the vertex and independently over both hemispheres in EEGs taken from TC1 at 6, 7 and 10 months after surgery. However, this animal also showed some discharging activity over the vertex and the right hemisphere in the pre-operative EEGs. All EEGs taken from this animal after surgery contained an excess of slow rhythms over the left hemisphere in comparison with most of the other animals. In

one recording taken from animal TC2 at 7 months after surgery there were very occasional sharp waves, with maximal amplitude at the vertex but spreading unilaterally. No spike discharges were seen in the recordings taken from TC3. Fig. 2 is an EEG recording taken from animal Ep +TC2. Primary spikes are seen focally over the left parietal region with apparent transmission to the contralateral side. In addition, interictal spikes are seen over the secondary (right) hemisphere which are clearly independent (in time) of primary events. Fig. 3 is an EEG recording taken from animal E p + T C 4 and shows a clearly independent burst o f spikes over the secondary (right) hemisphere. This is later followed by a burst of low amplitude spikes seen over the primary (left) hemisphere but seemingly without an associated discharge contralaterally. Fig. 4-6 were taken from EEGs recorded on magnetic tape. Secondary events are seen in all three figures, clearly independent in Fig. 4 and 6, possibly independent in certain examples of Fig. 5. The bilaterally synchronous events of Fig. 4 and 5 are probably not transmitted : a latency of 5-15 msec would be expected, but was not observed (with faster sweep speeds). Presumably they reflect events either originating very near to the vertex or transmission of high-amplitude potentials from the primary to the secondary

3/'~'~'~",~i":( ~h,~'x~¢'\'~'~¢~';~'~: ~'~~'~'~/~':' ,~,~'~,'~-r~,~,~t 1 0 0 ].IVJ 1 S e c ,

4 ,~"~vi#!'~,?.~ ,~~,>.~,~,~h~h.',~'~F,~'~4~?'

~

r

~.A~.~¢..

Fig. 2. EEG recordingfrom animal Ep + TC2 taken at 11 months after surgery. Spikesare seen over the primary (left)hemisphere (3.4)with transmission to the secondary(right)side (1,2). Clearlyindependentdischargesare also seen on the secondary side.

478

V. NIE et

al.

100 llVJ 1

Fig. 3. EEG recording from animal E p + T C 4 taken at 1 month after surgery. Clearly independent spikes are seen over the secondary (right) hemisphere (1,2) in addition to primary events (3,4).

Fig. 4. Example of EEG recordings in animal E p + T C 2 taken at 4 months. Traces (upper to lower): Rt. Frontal Rt. Parietal; Rt. Parietal Rt. Occipital; L. Frontal L. Parietal; L. Parietal-L. Occipital. Time base: 200 msec, large div. Gains: adjusted, decreasing (in order from most gain) in traces 1, 2, 4 and 3. Trigger: trace 2. Three right-sided (i.e., secondary) discharges are followed (at 1800 msec) by a bilaterally synchronous event of greater amplitude on the left (i.e., primary) side.

Fig. 5. Example of EEG recording in animal Ep + TC3 taken at 6 months. Upper trace: Rt. Frontal Rt. Parietal. Lower trace: L. Frontal-L. Parietal. Time base: 200 msec/div. Gains: double for upper relative to lower trace: Trigger: upper trace. Synchronous right-and left-sided events are seen (e.,q., at 0 and 1600 msec) and also asynchronous events (e.#., a secondary spike alone at 200 msec) occur.

hemisphere by volume conduction (e.9., through the scalp).

dent" secondary discharges actually reflect events originating in the primary hemisphere but not seen in the scalp leads from that hemisphere. While conceding that all primary events are not observed in scalp leads we nonetheless believe the secondary independent events to reflect activity of the second hemisphere. Nie and Ettlinger (1974) have ablated primary temporal foci in 3 monkeys : in the one monkey secondary temporal discharges survived in the absence of any further primary discharges: in the second monkey some primary discharges survived but

DISCUSSION

The evidence for independent secondary discharges According to convention, we have used asynchrony of discharge, together with a greater amplitude on the second side, as evidence for the development of secondary foci in our 4 Ep + TC monkeys. It might be argued that our "indepen-

EPILEPTIC DISCHARGES AFTER COMMISSURE SECTION

I

f

Fig. 6. Example of EEG recording in animal Ep + TC4 taken at 3 months. Traces as for Fig. 4. Time base: 200 msec/div. Gains: equal. Trigger: upper trace• Only right-sided (i.e., secondary) spikes are seen in this example.

were probably less frequent than the surviving (rather sparse) secondary events.

The origins o[the independent discharyes 1. Damage to the second hemisphere. There is no evidence that the second hemisphere suffered greater damage as a result of surgery in the 4 E p + T C animals than in the remainder. Some damage is present in the second hemisphere in a proportion of animals, but approximately equal in distribution and extent. The most severe damage was in animal TC3. 2. Earl)' post-operative histoJ3', including seizures. Overall, the 4 E p + T C animals had a lower incidence of post-operative complications than did the other 5. In particular, only Ep + TC 1 suffered from right-sided convulsions (no animal suffered from left-sided or bilateral seizures). 3. Spread of aluminium hydroxide. In our experience of secondary discharges in temporal animals (Nie et al. 1973) we have never seen damage to the secondary cortex in histological preparations (whereas there can be severe damage to the primary cortex). Likewise, in the histological sections of animals E p + T C I 3 of the present experiment we have found no evidence for damage of any kind in the secondary cortex. The aluminium hydroxide is held in celluloid caps which are pressed against the pial surface by the bone flap which is tightly sewn; and the falx intervenes as an effective barrier between the hemispheres.

479

4. Anti-tuberculosis prophylaxis. Detailed consideration of Table I and of the post-operative time-course of secondary discharges indicated in Fig. 1 precludes the possibility that medication initiated the secondary discharges. For instance, 2 of the E p + T C animals had no medication whatsoever. Moreover, our dosages of isoniazid were about one fourth of the smallest dosage reported to have EEG effects by Meldrum et al. (1970). 5. Volume conduction. The absolute size of the monkey's head is much smaller than that of man, which increases the possibility of volume conduction (through the scalp, or possibly through the brain) from the primary to secondary hemisphere. Moreover, Torres (1972) has shown that electrical after-discharges, propagated by volume conduction from surrounding cortex into an isolated secondary focus, can generate an independent self-sustained after-discharge in the secondary focus. Nonetheless, this evidence is not relevant. In Torres" work the isolation was undertaken q/?er the secondary locus had been allowed to develop, whereas in our experiment the commissures were cut hq/'ore the epileptogenic implant was made (at one operation), so that there was no "sensitized" secondary focus to be reactivated from the primary focus. Also the spatial separation between the primary and secondary loci in our animals was much greater than in the work of Torres. 6. Total as compared with partial division q/ the corpus callosum. It might appear at first sight that the total division of the corpus callosum could itself have been responsible for the onset of the secondary focus. This view cannot, however, be sustained. In animal Abl + TC the commissures were as completely divided as in the 4 E p + T C monkeys. Nevertheless, this animal never gave evidence in the EEG of primary or secondary discharges. Monkey TC1 did show a contralateral focus at 6, 7 and 10 months after surgery. However, the pre-operative EEGs of TC 1 gave some indication of discharges prior to operation, and surgical intervention might therefore atypically have elicited spike discharges in this animal at a later stage. Animal TC2 also showed occasional discharges over both hemispheres, 7 months after surgery. However, the discharge rate was low in comparison with

v. NIE et al.

480 Ep + TC 1 - Ep + TC4. Furthermore, discharges were only apparent on one occasion, 7 months after surgery, which is a much later time of onset of discharges in comparison with the E p + T C animals. In addition, the discharges were at maximum amplitude over the vertex so it was not entirely clear whether they were related to epilepsy or to a lateralized distribution of normal vertex activity (see EEG classification). Moreover (as mentioned under Subjects) another monkey ( E p + P C 2 ) was studied for only 4 months alter a partial (as distinct l¥om a total) division of the corpus callosum : this animal did develop independent secondary discharges. 7. Callosal /unctions. Eidelberg (1969)has discussed the conflicting evidence for both inhibitory and facilitatory influences of the callosal pathways. Mutani et al. (1972) have reported an increase in the abnormal discharges of both primary and secondary loci after callosal section in the cat. provided the callosum is divided in cats with acute bilateral loci. These latter authors suggest that inhibitory influences are conveyed through the callosum in the cat: callosal section then reduces this inhibition. Since callosal section in their experiments produced enhancement of abnormal discharges only in cats with pre-existing bilateral acute foci (but not in cats with unilateral foci) the inhibition was thought to originate in each focus, but not in normal cortex. However, no observations on the EEG of the contralateral hemisphere are reported in the animals with unilateral foci. We likewise have not observed any enhancement of the primao' focus in animals with commissure section compared with animals without commissure section. The role of the corpus callosum remains in doubt. 8. Other possible pathways. The spike discharges contralateral to the lesion would appear most probably to have been transmitted neuronally from the primary focus to the opposite side along the remaining structures connecting the two hemispheres. Since the anterior commissure, posterior commissure, psalterium and massa intermedia were also divided it may be supposed that the hypothalamus, subthalamus or midbrain are involved. Eidelberg (1969) in his experiments has proposed an extracallosal pathway between left and right sensori-motor cortex

by way of connections between each pyramidal tract and the opposite medial lemniscus. In addition, various slender commissures are present in these areas though in general, connecting as they do the deep and near midline grey structures, they appear to offer no more than a very indirect pathway from the cortex of one cerebral hemisphere to that of the other. Another possibility, though probably even more indirect, is offered by the reticular formation of the thalamic-midbrain region. This is to some extent topographically differentiated, as evidenced by the localized fronto-parietal activation produced by its stimulation under some conditions (French et al. 1952). It therefore appears to allow transmission of a localized cortico-reticular disturbance to homologous contralateral cortex. Such a route could be initially through the thalamus or, more directly, the internal capsule followed by crossing in the subthalamus, hypothalamus or possibly midbrain. It is difficult to accept, however, that such a multisynaptic pathway could transmit what is essentially an epileptic dysfunction to the opposite cortex without itself becoming the seat of abnormal function. In such a case it might be expected to induce runs of bilateral spike-wave phenomena, such as are provoked by electrical stimulation (Weir 1964), but which were not observed in these experiments. SUMMARY

Nine rhesus monkeys had total or partial division o f the forebrain commissures, of the massa intermedia of the thalamus, and of the posterior commissures. Subsequently, but at the same operation, in five of these animals celluloid caps containing aluminium hydroxide were placed unilaterally on posterior parietal cortex. Monthly EEG recordings were taken from all animals. All 5 monkeys with epileptogenic implants were found to show abnormal spike discharges over the primary hemisphere; in addition, transmitted discharges from the primary to the secondary hemisphere were noted in these animals. Four animals were unexpectedly found to have contralateral (i.e., secondary) EEG abnormalities (both ictal and interictal) which appeared to

481

EPILEPTIC DISCHARGES AFTER COMMISSURE SECTION

be independent in time of primary discharges. In all 4 of these monkeys the histological findings indicated complete division of the corpus callosum, anterior and posterior commissures, and of the massa intermedia. Possible mechanisms for the development of independent secondary discharging loci after commissure section were considered. Nonspecific surgical effects were thought unlikely to be implicated. Instead it seemed most likely that the discharges spread neuronally from the primary to the secondary hemisphere by way of certain remaining pathways. RESUME DEVELOPPEMENT

DE

DECHARGES

EPILEPTIQUES

SECONDAIRES CHEZ MACACA M{!LA TTA APRES SECTION COMM1SSURALE

Neuf macaques (Macaca mulatta) ont subi section totale ou partielle des commissures tdlencephaliques, de la m a s s a i n t e r m e d i a du thalamus et de la commissure postdrieure. Au cours de la meme op&ation, 5 animaux ont requ, implantee unilatdralement sur le cortex parietal posterieur, une capsule de celluloide contenant de l'alumine. Des enregistrements EEG de tous les animaux ont 6t6 effectues chaque mois. Les 5 animaux avec implants 6pileptogenes ont presente des ddcharges anormale de pointes, sur l'hemisphdre primaire; par surcroit, des ddcharges transmises de l'hemisphere primaire vers l'hemisphere oppose ont 6t6 observees. Quatre animaux ont 6t6 trouves porteurs d'anomalies EEG contralaterales (secondaires), ictales et interictales, chronologiquement inddpendantes des ddcharges primaires. Chez ces 4 animaux, les donnees histologiques ont confirme que les sections du corps calleux, des commissures antdrieure et postdrieure et de la m a s s a m t e r m e d i a avaient et6 completes. On discute des mecanismes susceptibles d'expliquer le developpement de foyers secondaires inddpendants apres les commissurotomies effectuees. Des effets non spdcifiques li6s ~, l'intervention chirurgicale sont pratiquement ~ exclure.

En revanche, il est probable que l'extension des dacharges du foyer primaire vers l'hamisphere oppose s'effectue par certains trajets neuronaux non inclus dans les commissurotomies. We are grateful to the M.R.C. who supported one of us (V.N.) and defrayed the costs of this work; to Dr. M. C. Smith ~ h o supervised the histological preparation of four brains; to Dr. S. J. Strich who examined the remaining three brains with us; and to our colleagues M.H. and R.C.E. who helped in the surgery and post-operative care of s o m e of the monkeys. REFERENCES EIDEt,m:R¢;, E. Callosal and non-callosal connections between the sensory-motor cortex in cat and monkey. Eleclroe~w~7~h, c/in. Neurophysiol., 1969, 26:557 564. FRI-;N('I-t. J. B., VAN AMERONGEN, F. K. and MA(;OUN, H. W. An activating system in the brain stem of the monkc\ Arch. Neurol. f~svchiat. (Chic.), 1952, 6 8 : 5 7 7 590. GAUIRIN, D.. F['xTON, G. and ETTLINGER, G. Aluminium hydroxide implants on the infero-temporal cortex of the monkey: their mode of influencing visual discrimination performance. Exp. Neurol., 1971, 33:459 474. MELt)RUM, B. S., BALZANO, E., GADEA, M. and NAQUET, R. Photic and drug-induced epilepsy in the baboon (Papio papio): the effects of isoniazid, thiosemicarbazide, pyridoxine and amino-oxyacetic acid. Electroenceph. din. Neurophysiol., 1970, 29: 333- 347. MOFt:ETq. A. M.. DRIVI-;R. M. V., ST. JOHN-LOE, P. and ETTLINGER, G. Tactile discrimination performance in the monkey: the effect of unilateral posterior parietal discharging lesions. Cortex, 1970, 6 : 6 8 86. MUTANI, R., BERGAMINI, L., EARIELI,O, R. and QUATTROCOLO, G. An experimental investigation of the m e c h a n i s m s of interaction of asymmetrical acute epileptic foci. Epilepsia (Amst.), 1972, 13:597 608. NIE, V. and ETTLINGER, G. Ablation of the primary inferotemporal epileptogenic focus in rhesus monkeys with independent secondary spike discharges. Brain Res.. 1974,69:149 152. NIE. V.. UPTOY. A. anti l t i~ IN¢;ER. G. Behavioral impairment in the monkey folI,,,a ing implantation of aluminum hydroxide on the tempolal cortex: the role of cortical destruction. Evp. Neurol., 1973, 40:632 651. TORRES, F. Epileptic sensitization : spontaneous and induced activity of unsensitized and sensitized acutely isolated cerebral cortex. Epileps& (Amst.), 1972, 13:582 596. WHR, B. Spikes-wave from stimulation of reticular core. Arch. Neurol. ((77ic.). 1964, 11:209 218.