Role of the forebrain commissure and hemispheric independence in photosensitive response of epileptic baboon, Papio papio

Electroencephalography and clinical Neurophysiology, 1988, 69:363-370

363

Elsevier Scientific Publishers Ireland, Ltd. EEG 02068

Role of the forebrain commissure and hemispheric independence in photosensitive response of epileptic baboon, Papiopapio Hiroshi Fukuda

2, A n n e

Valin, P h i l i p p e Bry+re, D a n i e l l e Riche, J u h n A. W a d a 3 a n d Robert Naquet

Laboratoire de Physiologie Nerveuse, C.N.R.S., 91198 Gif-sur- Yvette (France) (Accepted for publication: 22 July 1987)

Summary The effect of monocular intermittent light stimulation (ILS) of either hemivisual field (HVF) of the full visual field (FVF) was examined in Papio papio with or without forebrain bisection. ILS of the HVF or the FVF in non-bisected baboons produced bisymmetrical and bisynchronous spike and wave which was followed by a self-sustained seizure without EEG evidence of hemispheric independence. ILS of the FVF in bisected baboons also produced bilateral spike and wave and self-sustained seizures of a similar nature. With ILS of the HVF in bisected baboons, EEG seizures lateralized largely to the contralateral hemisphere and when the ILS of the HVF was switched to the other eye similarly lateralized spike and wave and a self-sustained seizure were produced in the other hemisphere. These findings suggest that (a) the forebrain commissure, most probably the corpus callosum (and possibly the hippocampal commissure), plays a major but not unique role in the bisynchronization and generalization of the ILS-induced spike and wave and the self-sustained seizures, and (b) each hemisphere possesses independent cerebral excitability to the ILS. Key words: Corpus callosum; Seizure generalization; Photosensitivity; Papio papio

In experimental models of primary generalized epilepsy, including feline penicillin spike and wave discharge and kindled, primarily generalized, convulsive seizures in Papio papio, the corpus callosum (CC) is the major, if not the exclusive,

1 Preliminary results of this study were presented at the joint 40th anniversary meeting of the American Electroencephalographic Society and the American Epilepsy Society, Seattle, WA, November, 1986. This work was supported by the Fondation pour la Recherche M&iicale, the Fondation de France (R.N.) and the Medical Research Council of Canada (J.A.W.). z Present address: Department of Neurosurgery, Asahikawa Medical College, 4-5-3-11 Nishikagura, 078-11 Asahikawa, Japan. Supported by a Fellowship of C.N.R.S. and Fondation pour la Recherche M~dicale. 3 On sabbatical leave from the Faculty of Medicine, University of British Columbia, Vancouver, B.C., Canada.

Correspondence to: Dr. R. Naquet, Laboratoire de Physiologic Nerveuse, C.N.R.S., 91198 Gif-sur-Yvette (France).

anatomical substratum for the bisynchronization and generalization of seizure. Thus, section of the CC abolished the bisynchrony of the spike and wave discharge in feline generalized penicillin epilepsy (Musgrave and Gloor 1980), and in amygdala (AM)-kindled rats (Mclntyre 1975; McCaughran et al. 1977, 1978), in AM-kindled cats (Wada and Sato 1975; Wada et al. 1982) and in AM-kindled primates (Wada et al. 1981; Wada and Mizoguchi 1984; Wada and Komai 1985), CC section modified a bilateral symmetrical seizure into a lateralized one. Section of the CC in the naturally photosensitive baboon reduced the degree of synchrony of spontaneous or intermittent light stimulation (ILS)-induced paroxysmal discharges (Naquet et al. 1972). In this last study, the baboon was stimulated binocularly with ILS of the full visual field (FVF). It is obvious that ILS of the FVF results in bilateral excitation of the visual pathway, while the ILS of the hemivisual field (HVF)

0013-4649/88/$03.50 © 1988 Elsevier Scientific Publishers Ireland, Ltd.

364

results in lateralized excitation. In the past, the effectiveness of monocular stimulation in reducing photosensitivity in photosensitive epilepsy has been suggested (Foster and Campos 1964). In more recent studies, HVF stimulation in photosensitive epilepsy led to lateralized activation of paroxysmal discharge, reflecting independent cerebral hemispheric excitability in photosensitive epilepsy (Soso et al. 1980; Binnie et al. 1981; Wilkins et al. 1981; Takahashi 1983, 1984; Darby et al. 1986). In this study, we examined the possible role played by the forebrain commissure, i.e., the corpus callosum (and the hippocampal commissure), in the genesis of the generalized discharges induced by ILS in photosensitive baboons, Papio papio, with or without forebrain bisection.

Methods

Six male baboons, Papio papio, weighing 7.4-11.8 kg were used in this study. Only one of them was naturally photosensitive while the remaining five were not. Under pentobarbital (30 mg/kg) anaesthesia, 4 baboons underwent varying degrees of CC section according to the modified stereotaxic approach described by Magni et al. (1960). Briefly, 2 small burr holes were made along the midline anteriorly and posteriorly. Following minimal opening of the dura mater immediately lateral to the sagittal sinus, a cotton thread was passed through intracranially along the falx between the 2 dural slits by a flexible metal guide. Once this was accomplished, the thread was placed in the eye of the electrode cartier which was then introduced into the midline at the desired depth. Subsequently, the thread (which was now running between the 2 eyes of the stereotaxically placed needles) was pulled back and forth several times and then removed. Only, minimal and infrequent venous haemorrhage was noted. One month postoperatively, extra-dural electrodes were implanted bilaterally from frontal to occipital regions for the purpose of recording. In order to assure stable HVF stimulation, during each experimental session, the animals were intubated under ketamine (10 mg/kg i.m.), para-

H. F U K U D A ET AL.

lysed and maintained by repeated intravenous administration of diallyl-nortoxiferine bichlorhydrate under artificial ventilation. Subsequently, the animals were placed in a painless position. In order to obtain a reliable degree of photosensitivity, all the animals were given DL-allylglycine (120-200 mg/kg i.v.) 3 h prior to ILS. This was necessary since natural photosensitivity markedly diminishes when paralysis is induced (Mrnini et al. 1980). ILS was applied monocularly for HVF or FVF stimulation. Monocular HVF stimulation was accomplished by delivering ILS from 20 ° lateral to the vertical visual axis while briefly covering one eye as well as the nasal half of the other eye. For FVF stimulation, ILS was delivered monocularly with the other eye completely covered. In an attempt to induce a series of seizures, the intensities of the ILS were varied, with a minimal interval of 30 min, or the side of the eye being stimulated was changed. The experimental session lasted for 2-3 h and was repeated after a minimum 2 week interval. The stability of the results obtained was ensured by repeated replication of results in each animal over a period of 6-18 months. Following completion of the study, all the animals were deeply anaesthetised and their brains perfused with saline and 10% formalin. The extent of the midline section was verified by serial coronal sections. The reconstructed extent of the lesion is shown in Fig. 1.

Results

The results are summarized in Table I and Figs. 2 and 3. Details are given below. As indicated in Fig. 1, both PP-01 and PP-37 had an intact CC, while PP-05, PP-35 and PP-41 had the bulk of the CC (and the hippocampal commissure) bisected. PP-06 had only partial anterior bisection of the CC.

H) Non-bisectedbaboons (PP-O1 and PP-37) ILS produced bisymmetrical and bisynchronous spike and wave, polyspikes and waves which were followed by self-sustained generalized seizures regardless of whether it was delivered to the HVF or the FVF. The timing of ictal onset

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Results in PP-06 were identical to those of intact baboons as described above. In the other 3 baboons, ILS of the HVF, regardless of the side, always resulted in a largely lateralized EEG seizure involving the stimulated hemisphere. Not only the self-sustained seizure but also the polyspikes and waves which preceded the seizure were localized to one hemisphere. Similarly, the expected postictal electrographic events were also lateralized to the stimulated hemisphere (Fig. 3A and B). On the PAPIO PAPIO N°37

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1,50so¢ Fig. 2. Bisymmetrical and bisynchronousseizure induced by the ILS of HVF in non-bisected baboon. Note the bisymmetrical and bisynchronous polyspikes and waves, self-sustained seizure and bisymmetrical postictal electrical silence and slow wave burst.

366

H. FUKUDA ET AL.

other hand, ILS of the FVF resulted in a generalized bilateral EEG seizure which began with slightly different onset and ended with either the same timing of termination or with a certain asymmetry (Fig. 4). I1S of the FVF was found to be more effective than that of HVF in precipitating EEG seizures. This was shown by the fact that the quantity of DL-allylglycine required to induce a photosensitive response was much smaller for FVF stimulation than that required for HVF stimulation. Likewise, the onset of the seizure was much earlier when the FVF was stimulated in contrast to HVF stimulation (Table I).

conventional ILS of the FVF in intact or in bisected baboons under allylglycine is about 1 h if the maximum generalized EEG seizure is induced. However, when a largely lateralized self-sustained seizure was induced in one hemisphere by ILS of the HVF, the postictal refractory period of the contralateral hemisphere was significantly shorter than that expected following ILS of the FVF. Also, following the lateralized EEG seizure induced by ILS of the HVF, if the FVF was stimulated, a largely lateralized EEG seizure involving the previously unaffected hemisphere was readily produced within 20 min following a HVF-induced lateralized seizure.

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Fig. 3. A, B: lateralized seizure induced by the ILS of HVF in forebrain-bisected baboon. Note the largely lateralized polyspikes and waves, self-sustained seizure and postictal events in left hemisphere (A) and in right hemisphere (B), respectively.

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Discussion

TABLE I Latency and duration of seizure induced by ILS of HVF or FVF with different doses of aL-allylglycine in forebrainbisected baboon no. 35. Left VCx st

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VCx st = visual cortex stimulation; L = left; R = right.

The possible mechanisms underlying the photosensitive response of the epileptic baboon Papio papio have been discussed, so far, only on the basis of findings obtained by ILS of the FVF, resulting in bihemispheric excitation (Killam et al. 1967; Catier et al. 1970; Naquet et al. 1972, 1987). In a significant departure from the previous studies, we examined the effect of ILS given to the HVF in baboons with or without forebrain section. We found that ILS of the HVF precipitates the spike and wave and the self-sustained seizure confined to the stimulated hemisphere in the forebrain-bisected baboon. Therefore, it is likely that

368

H. FUKUDA ET AL.

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the major anatomical pathway responsible for the precipitation of seizures following ILS must reside within the forebrain hemisphere. To what extent the brain-stem structures participate in such a process remains to be clarified. The quantities of DL-allylglycine required for both elicitation of photosensitivity and for determining the onset of ILS-induced seizures were persistently less when ILS was applied to the FVF than when it was applied to the HVF. This differential effectiveness of the FVF as compared to the HVF, in terms of drug quantity or seizure latency may be related to the surface of the retina stimulated by ILS (Serbanescu et al. 1973). This would seem to be different from the results obtained in man without allylglycine (Wilkins et al.

1981). However, this suggests that in our experimental conditions interhemispheric interaction, probably through the corpus callosum, may facilitate the processes involved in the precipitation of ILS-induced seizures. This is consistent with our previous finding that bilateral resection of the visual cortex eliminates photosensitivity, while unilateral resection reduces the intensity of ILSinduced paroxysmal discharge (Wada et al. 1973). Likewise, bilateral rather than unilateral stimulation of the lateral geniculate body has been reported as more effective in triggering generalized spike and wave discharge in feline penicillin-induced generalized epilepsy (Quesney 1984). More direct evidence of the importance of bihemispheric facilitatory interaction in producing photosensitiv-

FOREBRAIN COMMISSURE AND HEMISPHERIC INDEPENDENCE IN Papio papio ity was suggested by the fact that unilateral G A B A infusion into the fronto-rolandic cortex is not very effective, while bilateral G A B A infusion eliminates ILS-induced seizures in baboons (Brailowsky et al. 1987). In our study, only the CC (and HC), among midline structures, were disconnected. When the F V F was stimulated in these bisected baboons, the obvious intensification of ILS-induced seizure was noted in terms of the amount of drug required or the latency of E E G seizures. This finding suggests that subcortical routes other than the CC (and HC) may participate in ~he mechanism of interhemispheric facilitatory interaction. The duration of the postictal refractory period following lateralized seizures induced by H V F stimulation was significantly shorter than that of generalized seizures induced by FVF stimulation, regardless of whether the animals were bisected or not. Similarly, following a lateralized seizure, excitability to ILS in the hemisphere contralateral to the one subjected to H V F stimulation remained largely unchanged. While these findings indicate the largely independent nature of hemispheric excitability to ILS, they also suggest that the CC (and HC) are the likely participants in the mechanism of postictal refractory period following temporal cortex kindled seizures in forebrain-bisected cats, as documented by Sato et al. (1982). The extent of bisection in this study (Fig, 1) suggests that the anterior 2 / 3 of the CC may be important in this regard. This assumption is consistent with the result of an amygdaloid kindling study involving baboons and monkeys with complete and partial commissural bisection (Wada et al. 1981; Wada and Mizoguchi 1984). The finding suggests that despite the obvious difference in the mechanisms of precipitating seizures, both amygdaloidkindled and ILS-induced generalized seizures may share a common anatomical pathway, probably involving the CC. Finally, when the FVF was stimulated monocularly in bisected baboons, periodically the ictal E E G onset was asymmetrical between the two hemispheres. In contrast, in these animals, ictal termination was not always asymmetrical but could be bisynchronous. Such a finding would suggest that the bisected portion of the forebrain commissure is not in any case critically involved

369

in the timing of the mechanism of seizure termination between the two hemispheres. The series of naturally photosensitive baboons used by Naquet et al. (1972) and some more recent experiments after retinal lesions (Fukuda et al., in prep.) presented asymmetrical termination of seizures. Recently, lateralized electrical stimulation of the locus coeruleus has been reported to suppress bihemispheric epileptic discharge ( N e u m a n 1986; Jimenez-Rivera et al. 1987). Therefore, different possibilities exist to explain the mechanism of generalized seizure termination (Gloor 1968, 1979). More study is needed for better understanding of the mechanism of the termination of the seizure and if it is an active one, the type of subcortical or brain-stem structure that may exert an inhibitory effect upon both hemispheres or unilaterally. The authors wish to acknowledge the valuable comments offered by Dr. M. Kiyosawa (Neuro-ophthalmology), Dr. S. Brallowsky and Dr. C. Mrnini.

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