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Cortically elicited spike-wave afterdischarges in thalamic neurons
Electroencephalography and Clinical Neurophysiology, 1976, 4 1 : 6 4 1 - - 6 4 4
641
© Elsevier Scientific Publishing Company, Amsterdam -- Printed in The Netherlands
Laboratory note CORTICALLY ELICITED SPIKE-WAVE A F T E R D I S C H A R G E S IN THALAMIC N E U R O N S * M. STERIADE, G. OAKSON and A. DIALLO
Laboratoire de Neurophysiologie, Ddpartement de Physiologie, Facultd de Mddecine, Universitd Laval, Quebec (Canada) (Accepted for publication: May 4, 1976)
Recent studies reported the occurrence of 3/sec spike-wave epileptic focal afterdischarges (ADs) in monkey's precentral motor cortex (Steriade 1974) and cat's somatosensory cortex (Steriade and Yossif 1974) following augmenting type incremental responses induced by 10/sec stimulation of specific thalamo-cortical pathways. The initially depth-negative "spike" component, with steep slope and fast development, was superimposed by high-frequency discharges of excitatory interneurons which were thought to set in motion inhibitory elements responsible for the development of the subsequent long-lasting, depth-positive wave (Steriade 1974). The high susceptibility of interneurons to develop 3/sec spike-wave seizures led to the assumption that generalization in petit-mal epilepsy may result from synchronization between different focal cortical interneuronal pools with subsequent involvement of long-axoned neurons and spread of activity to critical regions of the brain (Steriade 1974). This brief note reports that similar patterns of 3--4/sec spike-wave ADs may occur in lateralis posterior (LP) thalamic neurons when cortico-thalamic pathways are set in motion by stimulating the suprasylvian cortical areas 5 and 7.
* Supported by grants from the Medical Research Council of Canada (MT-3689) and the Ministate de l'Education du Gouvernement du Quebec (Subvention pour formation de chercheurs).
Methods Experiments were carried o u t on locally anesthetized, encdphale isold cats, paralyzed with gallamine triethiodide, under artificial respiration, with control of the expired CO2 at 3.8 ± 0.2%. Two rostro-caudal arrays of stimulating electrodes, each consisting of four wires de-insulated for 0.1 mm at their tips, were inserted in deep layers of medial and lateral parts of the crown of anterior suprasylvian areas 5 and 7, from where antidromic invasion and synaptic excitation of LP cells could be obtained. Stimulation was bipolar, between the corresponding wires of each (medial and lateral) array. In addition, coaxial stimulating electrodes were placed in the center median (CM) thalamic nucleus and in the mesencephalic reticular formation (RF), from where orthodromic responses of LP cells were elicited. Single units were extracellularly recorded simultaneously with focal slow waves by means of platinum blacked stainless-steel microelectrodes (1--2 pm, impedances of 2--8 M~t) inserted at A 8 to 9.5, L 4 to 5, D 6 to 3.5, i.e. in a thalamic region usually labelled LP, within which the rostral and dorsal part constitutes the lateralis intermedius (LI) nucleus. Unitary discharges and focal slow waves (bandwidth: 1-10,000 c/sec), pulses synchronous with testing stimuli and EEG waves from the surface of the contralateral cortical areas 5 and 7 were recorded on a multichannel magnetic tape and then analyzed for suitable episodes.
642
M. S T E R I A D E ET AL.
activity could be modulated from the cerebral cortex, CM thalamic nucleus and rostral RF. Only those units which generated action potentials without notches, unusually high rates of discharge or other signs of mechanical injury, and without changes in shape or amplitude over long (1--2 h) periods of recording, were retained for analysis. As known, spike
Results
The cortically elicited spike-wave ADs occurred in those LI or LP cells which discharged high-frequency (200--600/sec) spike bursts spontaneously and in response to synaptic volleys. This represented a group of 12 cells from a population of 111 neurons whose
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ls Fig. 1. D e v e l o p m e n t o f c o r t i c o - t h a l a m i c responses i n t o a self-sustained afterdiseharge. Six-shock (dots) trains to cortical area 7; recording in the ipsilateral LP thalamic nucleus. Below the five oscilloscopic traces (1--5), three (a--c) ink-written samples depict adequately amplified slow waves recorded in LP by the m i c r o e l e c t r o d e (upper trace) and surface E E G r h y t h m s from the contralateral anterior suprasylvian gyrus ( b o t t o m trace). Figures (1--4) on EEG recordings correspond to periods of stimulation indicated by the same figures on oscilloscopic traces and represent the 8th (1), the 16th (2), the 28th (3) and the last, 35th (4) cortical shock-train. Non-depicted periods of 5 sec separate EEG traces a--b, b--c and the two parts of trace c. The three spike-wave c o m p l e x e s indicated by arrows in the oscilloscopic trace 3 correspond to those indicated by arrows in the EEG trace c. Description and c o m m e n t s in text. In this and the following figure, positivity downwards.
S P I K E - W A V E ADs IN T H A L A M I C N E U R O N S
inactivation and partial discharges may occur within epileptic high-frequency barrages, due to excessive depolarization (see Fig. 6B in Steriade 1974 and Fig. 8 in Steriade and Yossif 1974). The occurrence of spike inactivation and fragmentation during self-sustained epileptic activity was attributed to a nondamaged cell provided that it appeared within a burst following a first full, unbroken discharge (Fig. 1). Low-rate (10/sec) cortical stimulation was used in order to detect subtle, progressive developments of thalamic responses leading finally to epileptic ADs. As a rule, trains of 5--6 shocks at 10/sec were delivered every 1.5--2 sec. The typical LP neuron depicted in Fig. 1 fired a burst of 250/sec discharges 15--20 msec after the last stimulus of the 10/sec shock train applied to area 7 (1). Beginning with the 12th train, the cell was regularly excited by cortical shocks and continued to exhibit a self-sustained activity, with rhythmic bursts at 5/sec, between cortical shocktrains (2). While at the onset of cortical stimulation the incremental responses, timelocked with each cortical shock, were localized in the ipsilateral LP nucleus, with develo p m e n t of rhythmic LP activity between cortical shock-trains both evoked and self-sustained activities spread to the homotopic region of the stimulated area 7 (compare inkwritten records a and b). At later stages of stimulation, the duration of the evoked neuronal bursts became longer, their frequency higher and spike inactivation was observed following the few first discharges (3). Correlatively, during the inter-stimuli periods, 4/sec spike-wave self-sustained activity occurved (arrows in 3), consisting of two (al-a2) negative slow waves lasting together about 60--70 msec, and a subsequent (b) longlasting (180 msec) positive shift. The neuronal spike burst was closely related to the depolarizing slow negative components and especially to the first one, while complete neuronal silence was seen during the positive wave. The last cortical shock-train (in 4) was followed by an epileptic AD, exhibiting simi-
643
lar patterns to those appearing during the inter-stimulation periods, lasting 5 sec, with a frequency of spike-wave complexes of 3.5/sec which finally slowed down to 2.5/sec. To emphasize the remarkable similarities of spike-wave epileptic patterns in different LI and LP thalamic neuronal pools, three other spike-wave ADs, following the same type of
1
b
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0.2 s f
j
B
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1 s
Fig. 2. Spike-wave p a t t e r n s o f cortically elicited thalamic afterdischarges. T h r e e d i f f e r e n t seizures, rec o r d e d in LI (A--B) a n d LP (C) t h a l a m i c nuclei, following r h y t h m i c s t i m u l a t i o n (five or six-shock trains, like in Fig. 1) of cortical areas 5 (B--C) a n d 7 (A). T h e seizures h a d f r e q u e n c i e s o f 3--4/sec a n d lasted 6 sec (A), 9 sec (B) a n d 14 sec (C). In C, b e l o w t h e t w o oscilloscopic traces, t h e i n k - w r i t t e n sample rep r e s e n t s a d e q u a t e l y amplified slow waves r e c o r d e d by t h e m i c r o e l e c t r o d e ( t h e t h r e e arrows r e p r e s e n t t h e t h r e e c o m p l e x e s in I ) a n d surface E E G waves f r o m t h e c o n t r a l a t e r a l cortical area 5. N o t e s t r i k i n g similarity b e t w e e n spike-wave ( a l - - a 2 - - b ) c o m p l e x e s in A--B a n d t h o s e in t h e p r e c e d i n g Fig. 1, 3.
644 cortical stimulation as shown in Fig. 1, are illustrated in Fig. 2. The two negative (al--a2) slow c o m p o n e n t s (a2 being occasionally divided in two wavelets, arrows in Fig. 2, A and B) and the b positive wave lasted, like those in Fig. 1, 70 and 180 msec, respectively, and the neuronal spike potential emerged from the first (al) slow depolarizing c o m p o n e n t (in B and C).
M. STERIADE ET AL. posterior thalamic bursting neurons following incremental responses elicited by lO/sec shock-trains applied to the anterior suprasylvian cortex. The pattern of cortically elicited thalamic spike-wave complexes, with brief depolarizing components and a long-lasting hyperpolarizing wave, resembles that of previously described spike-wave seizures elicited in cortical interneurons following specific thalamo-cortical augmenting responses.
Discussion The thalamically elicited spike-wave ADs in cortical interneurons (Steriade 1974; Steriade and Yossif 1974) and the cortically induced spike-wave thalamic ADs in the present experiments share two important features. First, their pattern was uniformly characterized by an initial, brief depolarizing event (the "spike" in cortical ADs, the a f - a 2 components in the present thalamic recordings) superimposed by repetitive unit discharges, followed by a long-lasting positive wave reflecting extracellularly hyperpolarizing potentials in the neighboring pool of neurons. This " s y n m o r p h i s m " (Petsche 1972), defined by a pattern uniformity in various recorded points, is likely to be an essential characteristic of spike-wave seizures. Secondly, the observed spike-wave ADs followed incremental responses developed within specific thalamocortical and cortico-thalamic pathways. That the epileptic activity used, at least partially, the same neuronal circuitry as that of the evoked responses in late stages of stimulation was shown by resetting (Fig. 7 in Steriade and Yossif 1974) or complete disruption (present Fig. 1, 4) of self-sustained spike-wave complexes induced by testing volleys eliciting orthodromic responses. Summary Self-sustained, 3--4/sec spike-wave ADs were elicited in lateralis intermedius--lateralis
R6sum6 Post-ddcharges de pointe-onde d'origine corticale dans les neurones thalamiques Des post-d6charges de complexes pointeonde ~ 3--4/sec ont ~t6 obtenues dans des neurones des noyaux thalamiques LI et LP apr~s r~ponses du type augmentant 6voqu~es par des brefs trains de stimuli corticaux ~ 10/ sec appliqu6s sur les aires suprasylviennes ant6rieures. La morphologie des complexes thalamiques du type pointe-onde, avec des composantes d6polarisantes rapides et une onde hyperpolarisante de longue dur~e, rappelle celle des complexes pointe-onde d6crits ant~rieurement dans les interneurones du cortex moteur et somatosensoriel apr~s r~ponses augmentantes thalamo-corticales.
References Petsche, H. General discussion. In H. Petsche and M.A.B. Brazier (Eds.), Synchronization of EEG activity in epilepsies. Springer Verlag, New York, Wien, 1972: 428--430. Steriade, M. Interneuronal epileptic discharges related to spike-and-wave cortical seizures in behaving monkeys. Electroenceph. clin. Neurophysiol., 1974, 37: 247--263. Steriade, M. and Yossif, G. Spike-and-wave afterdischarges in cortical somatosensory neurons in cat. Electroenceph. clin. Neurophysiol., 1974, 37: 633--648.
641
© Elsevier Scientific Publishing Company, Amsterdam -- Printed in The Netherlands
Laboratory note CORTICALLY ELICITED SPIKE-WAVE A F T E R D I S C H A R G E S IN THALAMIC N E U R O N S * M. STERIADE, G. OAKSON and A. DIALLO
Laboratoire de Neurophysiologie, Ddpartement de Physiologie, Facultd de Mddecine, Universitd Laval, Quebec (Canada) (Accepted for publication: May 4, 1976)
Recent studies reported the occurrence of 3/sec spike-wave epileptic focal afterdischarges (ADs) in monkey's precentral motor cortex (Steriade 1974) and cat's somatosensory cortex (Steriade and Yossif 1974) following augmenting type incremental responses induced by 10/sec stimulation of specific thalamo-cortical pathways. The initially depth-negative "spike" component, with steep slope and fast development, was superimposed by high-frequency discharges of excitatory interneurons which were thought to set in motion inhibitory elements responsible for the development of the subsequent long-lasting, depth-positive wave (Steriade 1974). The high susceptibility of interneurons to develop 3/sec spike-wave seizures led to the assumption that generalization in petit-mal epilepsy may result from synchronization between different focal cortical interneuronal pools with subsequent involvement of long-axoned neurons and spread of activity to critical regions of the brain (Steriade 1974). This brief note reports that similar patterns of 3--4/sec spike-wave ADs may occur in lateralis posterior (LP) thalamic neurons when cortico-thalamic pathways are set in motion by stimulating the suprasylvian cortical areas 5 and 7.
* Supported by grants from the Medical Research Council of Canada (MT-3689) and the Ministate de l'Education du Gouvernement du Quebec (Subvention pour formation de chercheurs).
Methods Experiments were carried o u t on locally anesthetized, encdphale isold cats, paralyzed with gallamine triethiodide, under artificial respiration, with control of the expired CO2 at 3.8 ± 0.2%. Two rostro-caudal arrays of stimulating electrodes, each consisting of four wires de-insulated for 0.1 mm at their tips, were inserted in deep layers of medial and lateral parts of the crown of anterior suprasylvian areas 5 and 7, from where antidromic invasion and synaptic excitation of LP cells could be obtained. Stimulation was bipolar, between the corresponding wires of each (medial and lateral) array. In addition, coaxial stimulating electrodes were placed in the center median (CM) thalamic nucleus and in the mesencephalic reticular formation (RF), from where orthodromic responses of LP cells were elicited. Single units were extracellularly recorded simultaneously with focal slow waves by means of platinum blacked stainless-steel microelectrodes (1--2 pm, impedances of 2--8 M~t) inserted at A 8 to 9.5, L 4 to 5, D 6 to 3.5, i.e. in a thalamic region usually labelled LP, within which the rostral and dorsal part constitutes the lateralis intermedius (LI) nucleus. Unitary discharges and focal slow waves (bandwidth: 1-10,000 c/sec), pulses synchronous with testing stimuli and EEG waves from the surface of the contralateral cortical areas 5 and 7 were recorded on a multichannel magnetic tape and then analyzed for suitable episodes.
642
M. S T E R I A D E ET AL.
activity could be modulated from the cerebral cortex, CM thalamic nucleus and rostral RF. Only those units which generated action potentials without notches, unusually high rates of discharge or other signs of mechanical injury, and without changes in shape or amplitude over long (1--2 h) periods of recording, were retained for analysis. As known, spike
Results
The cortically elicited spike-wave ADs occurred in those LI or LP cells which discharged high-frequency (200--600/sec) spike bursts spontaneously and in response to synaptic volleys. This represented a group of 12 cells from a population of 111 neurons whose
~[
;
,d
,I
~a
ir
a
¢
1
!
3
0.1 s
,
ls Fig. 1. D e v e l o p m e n t o f c o r t i c o - t h a l a m i c responses i n t o a self-sustained afterdiseharge. Six-shock (dots) trains to cortical area 7; recording in the ipsilateral LP thalamic nucleus. Below the five oscilloscopic traces (1--5), three (a--c) ink-written samples depict adequately amplified slow waves recorded in LP by the m i c r o e l e c t r o d e (upper trace) and surface E E G r h y t h m s from the contralateral anterior suprasylvian gyrus ( b o t t o m trace). Figures (1--4) on EEG recordings correspond to periods of stimulation indicated by the same figures on oscilloscopic traces and represent the 8th (1), the 16th (2), the 28th (3) and the last, 35th (4) cortical shock-train. Non-depicted periods of 5 sec separate EEG traces a--b, b--c and the two parts of trace c. The three spike-wave c o m p l e x e s indicated by arrows in the oscilloscopic trace 3 correspond to those indicated by arrows in the EEG trace c. Description and c o m m e n t s in text. In this and the following figure, positivity downwards.
S P I K E - W A V E ADs IN T H A L A M I C N E U R O N S
inactivation and partial discharges may occur within epileptic high-frequency barrages, due to excessive depolarization (see Fig. 6B in Steriade 1974 and Fig. 8 in Steriade and Yossif 1974). The occurrence of spike inactivation and fragmentation during self-sustained epileptic activity was attributed to a nondamaged cell provided that it appeared within a burst following a first full, unbroken discharge (Fig. 1). Low-rate (10/sec) cortical stimulation was used in order to detect subtle, progressive developments of thalamic responses leading finally to epileptic ADs. As a rule, trains of 5--6 shocks at 10/sec were delivered every 1.5--2 sec. The typical LP neuron depicted in Fig. 1 fired a burst of 250/sec discharges 15--20 msec after the last stimulus of the 10/sec shock train applied to area 7 (1). Beginning with the 12th train, the cell was regularly excited by cortical shocks and continued to exhibit a self-sustained activity, with rhythmic bursts at 5/sec, between cortical shocktrains (2). While at the onset of cortical stimulation the incremental responses, timelocked with each cortical shock, were localized in the ipsilateral LP nucleus, with develo p m e n t of rhythmic LP activity between cortical shock-trains both evoked and self-sustained activities spread to the homotopic region of the stimulated area 7 (compare inkwritten records a and b). At later stages of stimulation, the duration of the evoked neuronal bursts became longer, their frequency higher and spike inactivation was observed following the few first discharges (3). Correlatively, during the inter-stimuli periods, 4/sec spike-wave self-sustained activity occurved (arrows in 3), consisting of two (al-a2) negative slow waves lasting together about 60--70 msec, and a subsequent (b) longlasting (180 msec) positive shift. The neuronal spike burst was closely related to the depolarizing slow negative components and especially to the first one, while complete neuronal silence was seen during the positive wave. The last cortical shock-train (in 4) was followed by an epileptic AD, exhibiting simi-
643
lar patterns to those appearing during the inter-stimulation periods, lasting 5 sec, with a frequency of spike-wave complexes of 3.5/sec which finally slowed down to 2.5/sec. To emphasize the remarkable similarities of spike-wave epileptic patterns in different LI and LP thalamic neuronal pools, three other spike-wave ADs, following the same type of
1
b
"
0.2 s f
j
B
£
1 s
Fig. 2. Spike-wave p a t t e r n s o f cortically elicited thalamic afterdischarges. T h r e e d i f f e r e n t seizures, rec o r d e d in LI (A--B) a n d LP (C) t h a l a m i c nuclei, following r h y t h m i c s t i m u l a t i o n (five or six-shock trains, like in Fig. 1) of cortical areas 5 (B--C) a n d 7 (A). T h e seizures h a d f r e q u e n c i e s o f 3--4/sec a n d lasted 6 sec (A), 9 sec (B) a n d 14 sec (C). In C, b e l o w t h e t w o oscilloscopic traces, t h e i n k - w r i t t e n sample rep r e s e n t s a d e q u a t e l y amplified slow waves r e c o r d e d by t h e m i c r o e l e c t r o d e ( t h e t h r e e arrows r e p r e s e n t t h e t h r e e c o m p l e x e s in I ) a n d surface E E G waves f r o m t h e c o n t r a l a t e r a l cortical area 5. N o t e s t r i k i n g similarity b e t w e e n spike-wave ( a l - - a 2 - - b ) c o m p l e x e s in A--B a n d t h o s e in t h e p r e c e d i n g Fig. 1, 3.
644 cortical stimulation as shown in Fig. 1, are illustrated in Fig. 2. The two negative (al--a2) slow c o m p o n e n t s (a2 being occasionally divided in two wavelets, arrows in Fig. 2, A and B) and the b positive wave lasted, like those in Fig. 1, 70 and 180 msec, respectively, and the neuronal spike potential emerged from the first (al) slow depolarizing c o m p o n e n t (in B and C).
M. STERIADE ET AL. posterior thalamic bursting neurons following incremental responses elicited by lO/sec shock-trains applied to the anterior suprasylvian cortex. The pattern of cortically elicited thalamic spike-wave complexes, with brief depolarizing components and a long-lasting hyperpolarizing wave, resembles that of previously described spike-wave seizures elicited in cortical interneurons following specific thalamo-cortical augmenting responses.
Discussion The thalamically elicited spike-wave ADs in cortical interneurons (Steriade 1974; Steriade and Yossif 1974) and the cortically induced spike-wave thalamic ADs in the present experiments share two important features. First, their pattern was uniformly characterized by an initial, brief depolarizing event (the "spike" in cortical ADs, the a f - a 2 components in the present thalamic recordings) superimposed by repetitive unit discharges, followed by a long-lasting positive wave reflecting extracellularly hyperpolarizing potentials in the neighboring pool of neurons. This " s y n m o r p h i s m " (Petsche 1972), defined by a pattern uniformity in various recorded points, is likely to be an essential characteristic of spike-wave seizures. Secondly, the observed spike-wave ADs followed incremental responses developed within specific thalamocortical and cortico-thalamic pathways. That the epileptic activity used, at least partially, the same neuronal circuitry as that of the evoked responses in late stages of stimulation was shown by resetting (Fig. 7 in Steriade and Yossif 1974) or complete disruption (present Fig. 1, 4) of self-sustained spike-wave complexes induced by testing volleys eliciting orthodromic responses. Summary Self-sustained, 3--4/sec spike-wave ADs were elicited in lateralis intermedius--lateralis
R6sum6 Post-ddcharges de pointe-onde d'origine corticale dans les neurones thalamiques Des post-d6charges de complexes pointeonde ~ 3--4/sec ont ~t6 obtenues dans des neurones des noyaux thalamiques LI et LP apr~s r~ponses du type augmentant 6voqu~es par des brefs trains de stimuli corticaux ~ 10/ sec appliqu6s sur les aires suprasylviennes ant6rieures. La morphologie des complexes thalamiques du type pointe-onde, avec des composantes d6polarisantes rapides et une onde hyperpolarisante de longue dur~e, rappelle celle des complexes pointe-onde d6crits ant~rieurement dans les interneurones du cortex moteur et somatosensoriel apr~s r~ponses augmentantes thalamo-corticales.
References Petsche, H. General discussion. In H. Petsche and M.A.B. Brazier (Eds.), Synchronization of EEG activity in epilepsies. Springer Verlag, New York, Wien, 1972: 428--430. Steriade, M. Interneuronal epileptic discharges related to spike-and-wave cortical seizures in behaving monkeys. Electroenceph. clin. Neurophysiol., 1974, 37: 247--263. Steriade, M. and Yossif, G. Spike-and-wave afterdischarges in cortical somatosensory neurons in cat. Electroenceph. clin. Neurophysiol., 1974, 37: 633--648.