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Midbrain and callosal influences on the spread of focal cortical epileptic activity
Brain Research, 85 (1975) 53-58 ~() Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands
53
Midbrain and callosal influences on the spread of focal cortical epileptic activity
MICHAEL L. WOODRUFF Department 0[" Psychology, Middlebury College, Middlebury, Vt. 05753 (U.S.A.)
(Accepted November 1lth, 1974)
Two important factors which influence the generalization of cortical focal epileptiform discharge are the anatomical pathways which connect the focus to other brain areas and the ongoing background electrical activity of the cortex. The integrity of the corpus callosum is known to be of primary importance for the propagation of focal epileptic activity fi'om the neocortex of one hemisphere to a contralateral homotopic point 5. However, it is possible that subcortical pathways participate in this propagation 4. In addition, subcortical structures, particularly mesencephalic reticular areas, probably influence epileptic discharge as well as normal EEG. Though the results of several studies indicate that lesions of the reticular formation which produce increased synchrony of cortical rhythms potentiate forebrain epileptic activity1, 8, other reports have indicated that lesions of the reticular formation will attenuate cortical seizure activity a. One goal of the present study was to gather more data on the effect of reticular lesions on cortical epileptic discharge. A second goal was to gather data concerning the pattern of propagation of unilateral cortical epileptic loci after callosal section either alone or in combination with lesions of the mesencephalic reticular formation. Twenty-eight male New Zealand albino rabbits weighing between 2.5 and 3.2 kg were randomly divided into 4 groups. Group N served as intact controls (n--6). Following anesthetization the subjects in this group were placed in a stereotaxic instrument and had openings bored bilaterally over the frontal cortex, sensorimotor cortex and the occipital cortex. Bipolar stainless steel electrodes insulated with Formvar except for the cross-sectional tip diameter (tip diameter 10 mil, tip separation 0.5 ram, resistance 45-50 k~2 in saline) were positioned epidurally through each of the openings. Stainless steel screws served as anchors and a lead from one of the screws was used as a ground. An additional opening was drilled unilaterally over sensorimotor cortex and a cannula, constructed after the method of Nadler 6, was lowered through this hole into the first layer of cortex. The cannula and leads from the electrodes were secured in an Amphenol receptacle which was cemented to the skull with dental acrylic. The scalp was closed around the acrylic with wound clips and Bicillin was given intramuscularly to prevent postoperative infections.
54 Rabbits in group RL (n -- 10) were prepared in a manner identical to group N, except that bilateral cathodal electrolytic lesions were made in the reticular formation at the level of the superior colliculi. Rabbits in group CS (n=-6) had the corpus callosum sectioned before implantation of electrodes using a modificatio, of the technique employed by Isaacson e t al. 4 in the rat. The final group of rabbits (group CR, n--=6) had the callosum sectioned as in group CS and received a lesion of the reticular formation as in group RE. Electrodes and cannula were then implanted as in group N. Following 21 days recovery, recordings were made from each subject on 2 occasions. The recording sessions were separated by 5 days, and each session lasted 5.5 h. On each recording day the rabbit was placed in a standard rabbit restraining box. After 15 min habituation, leads were attached to the rabbit's electrodes and signals from the electrodes were fed into a 6-channel polygraph (Grass Model 7). Low- and highfrequency cut-offs of 1 and 35 Hz were used. After the rabbit was connected to the polygraph an additional 5-min habituation period ensued. This was followed by a 30-rain period of baseline EEG recording. At the end of baseline recording a 27-gauge cannula replaced the stylet which was usually in the permanent cannula and a 1.0/~1 solution of 125 I.U. of sodium penicillin G was injected over 1 rain. The cannula was then removed, the stylet replaced and a 5-h recording session began. At the conclusion of the second recording session each animal was sacrificed with an overdose of pentobarbital and intracardially perfused with 0 . 9 ~ saline followed by 10 7/o formalin. The brain was removed, embedded in celloidin and sectioned at 30/~m. Every fifth section was retained and stained with thionin. Examination of the histology from groups CS and CR verified that the corpus callosum had been completely sectioned in all animals. Five rabbits in group RL and two rabbits in group CR had substantially larger lesions than did the other animals in these groups. The larger lesions included much of the reticular formation at the level of the superior colliculus, as well as small portions of the red nucleus, lateral lemniscus, central gray and substantia nigra. The smaller lesions were restricted to the reticular formation with slight damage to the red nucleus and central gray. The centers of these lesions were located about 2 mm more dorsally than were the centers of the larger lesions, though there was considerable overlap between the ventral portion of these lesions and the dorsal extent of the larger lesions. The larger lesions also produced more damage in the rostrat-caudal dimension. The EEG records from rabbits in groups N and CS consisted of long periods of low voltage fast activity and intervening periods of slow waves and spindles resembling sleep. The baseline records of 9 rabbits with reticular lesions were similar to those in groups N and CS. Seven rabbits in groups CR and RL had a far greater number of spindles (Fig. 1). In these animals this pattern occurred about once every 30 sec. All rabbits demonstrating increased spindling were found to have larger reticular lesions. Baseline records taken during the second recording session did not differ from those taken during the first session. The following parameters of the interictal spike discharges were examined by
55 CS-,l RF
RF
~SM
RSM
RO
RO
LF
LF
LSM
LSM
L0
LO
RF '
RL-S
,
RO
,
~ ', ~,,,,
RF
CR'I
,
RO
LF
LSM
LSM
L0
I Fig. l. Sample baseline EEG from a normal control rabbit (N-5), an animal with a split corpus callosum (CS-3), one with a large reticular formation lesion (RL-8), and one with small reticular lesion (CR-I). Calibration: 1 sec, 150 ffV. RF and LF, right and left frontal cortex; RSM and LSM, right and left sensorimotor cortex; RO and LO, right and left occipital cortex. measurement of the EEG recordings; spike amplitude, spike frequency, time fi'om application of penicillin to the first spike discharge and the time from the first spike to the first ictal episode. Spike frequency was obtained by counting the number of spikes during 30-sec interictal periods 5, 30, 120, 210, and 3130 rain after the appearance of the first interictal spike. The amplitude of 1C0 spikes was measured with a mm ruler at approximately 5, 90, 180 and 280 rain after the appearance of the first spike. Statistical evaluation was made with t-tests and one-way analyses of variance. No significant differences were found either between day 1 and day 2 or among groups for any of the measures of interictal activity. Subjects in group RL that had large reticular lesions ( n - 5 ) were grouped separately and the statistical analysis repeated. No significant differences were found. The pattern of propagation between hemispheres of the interictal discharges was affected by callosal section, but not by reticular lesions. Interictal discharges propagated to the contralateral homotopic cortex in the animals in groups N and RL, but not in groups CS and CR.
56 TABLE I MEAN DURATION AND TIME BETWEEN DISCHARGES FOR THE FIRST 2 0 1CTAL EPISODES FOR EA('H (.~ROUP
Group N
CS
CR
RL
RLS
RLL
39.1 39.6
48,2 49,3
35.3 38.4
69.6 * 78,5*
194.5 196.3
214,9 231.6
169.3 180.9
293.4" 332.9"
Mean seizure discharge duration (sec)
Day 1 Day 2
34.0 38.2
34.9 36.7
Mean time between seizures (sec)
Day 1 Day 2
186.9 192.2
190.2 201.4
• indicates a statistically significant difference. Three parameters of the ictal seizure discharges were analyzed: the total number of seizures during each recording session, the duration of each seizure and the time between them. A one-way analysis of variance (ANOVA) revealed no differences among groups for the total number of ictal episodes during the two experimental sessions. The least number of ictal events was 20, the most was 37. Table I presents the mean duration of the seizures and the mean time between such episodes for each group, t-Tests for matched samples failed to reveal any differences in duration between day I and day 2. When the durations of the seizures on day 1 for groups N, RE, CR and CS were compared using a 2-way ANOVA no significant differences were obtained. When the rabbits with large reticular lesions within group RL were considered as a separate group (group RLL) and the 2-way A N O V A repeated, a significant main effect was found (P < 0.01), though no significant trials or lesion 7. trials interaction was found. The subgroup of rabbits with small reticular lesions did not differ statistically from groups N, C R and CS. A subsequent Dunn's multiple comparison test indicated that group RLL had significantly longer electrical seizures than did the other groups (P < 0.01), which did not statistically differ from each other. Analysis of the data from day 2 had the same result. In addition, the durations of the seizures of the animals in group CR with large lesions fell within the range of the subjects in group RLL, while the animals with small lesions fell within the normal range. The appearance of the electrical seizure activity was not altered by either the reticular lesions or the sections of the callosum. However, sections of the callosum, either alone or in combination with reticular lesions, changed the time course of propagation of the ictal electrographic seizures. The result of the callosal split was to delay the spread of the discharge to the contralateral cortex by many seconds. In fact, if the discharge was of short duration the contralateral cortex remained uninvolved, If the discharges were long enough the contratateral cortex would suddenly display seizure activity (Fig. 2) after a long delay. Previous research has established the importance of the corpus callosum lor the propagation of epileptiform discharge from the primary cortical site to the contralateral homotopic point 4,5,7. In agreement with these findings sectioning the corpus
57 LF
LO
CS-2
ISft
I ' ua~,~c
~~
~ , ~ . . . . . +~"v'~j
'M
{t~fl~,'i~
,~ " . ' . " ~ q '
"tel
.,IJJl,lr~
) .,j~),
4~,.i~, ,h, ,d,,l~.,,~.b,,, , Jl,,i,~41 ~,j~
........
Fig. 2. Propagation of a cortical seizure in a rabbit with a split corpus callosum. Calibration: 1 sec, 200 ffV. Labels are the same as in preceding figure. callosum in the rabbits used in the present study prevented the propagation of interictal discharge from the primary cortical site to the contralateral area. The propagation of ictal seizure discharge, on the other hand, was only slowed, not stopped. The important variable determining whether or not seizure activity was propagated appeared to be the duration of the seizure, if the ictal episode lasted for more than approximately 25 sec seizure began in the contralateral cortex (Fig. 2). Other authors have suggested that subcortical pathways may act as a secondary system for propagation of epileptiform discharge from a primary cortical focus to the contralateral homotopic point 4,7. Isaacson e t al. 4 used anesthetized preparations and observed only propagation patterns of single interictal spikes. Propagation from primary focus to contralateral secondary focus after callosal section was so slight that it could be detected only by computer averaging. Servit et a l Y also observed propagation from one hemisphere to the other after commissural section in the fi'og, but also dealt only with interictal events. The results of the present study indicate that the amount of propagation that can occur after section of the callosum is a function of the duration of the primary epileptic seizure. Epileptiform discharge can propagate quite well to contralateral cortical sites, at least in the lisencephalic brain of the rabbit, after the corpus callosum is split, if the discharge is an extended ictal episode.
58 An important point is that lesions of the reticular formation increased the duration of the electrical seizures only if the lesions produced some noticeable change in the EEG recordings made before the application of penicillin. Lesions that produced an increased amount of spindle-like activity in the baseline EEG were correlated with increased duration of ictal discharges. These lesions destroyed about one-half of the reticular formation at the level of the red nucleus. Wilder (personal communication) has found that lesions in this region of the cat's midbrain will produce cortical epileptiform discharges. As indicated above, there have been conflicting reports as to whether or not lesions of the reticular formation attenuate, potentiate, or have no effect upon epileptiform activity induced in telencephalic structures. The results of the present study suggest that reticular lesions that lead to spindle-like synchronous activity in the pre-seizure EEG will also lengthen seizure discharge while lesions which are too small to produce a detectable change in background EEG activity have no effect. Previous work by Woodruff et al. 8 indicated that lesions of the reticular core which lead in increased desynchrony in the hippocampal EEG significantly shorten focal ictal seizures in this structure. It is suggested, then, that the divergent effects of reticular lesions on telencephalic epileptiform activity which have been reported 1- 3,S may be explained in terms of the effects of these lesions on the ongoing background EEG rhythms of the forebrain. This research was supported in part by USPHS Training Grant MH-10320 to the Center for Neurobiological Sciences, University of Florida and N I M H Grant 16348-03 to R. L. Isaacson. The author is indebted to Drs. B. J. Wilder, R. L. Isaacson, F. A. King and C. Van Hartesveldt for their critical reading of initial versions of this manuscript.
1 ANDY,O. J., ANDMUKAWA,J., Brain stem lesion effects on electrically induced seizures, Electroeneeph, clin. NeurophysioL, 11 (1959) 397. 2 DtCHTER, M. A., HERMAN,C. J., AnD SELZER,M., Silent cells during interictal discharges and seizures in hippocampal penicillin foci. Evidence for the role of extracellutar K + in the transition from the interictal state to seizures, Brain Research, 48 (1972) 173-183. 3 FREEDr~Ar~,D. A., ANDMOOSSY,J., Effect of mesencephatic lesion on the cortical electroconvulsant threshold, Neurology (Minneap.), 3 (1953) 714-720. 4 ISAACSON,R. L., SCHWARTZ,H., PERSOFF, N., AND P1NSON, L., The role of the corpus callosum in the establishment of areas of secondary epileptiform activity, Epilepsia, 12 (1971) 133-146. 5 MORRELL,F., Secondary epileptogenic lesions, Epilepsia, 1 (1960) 538-560. 6 NADLER, R. D., A simplified cannula system for implanting and injecting chemicals into the brains of small animals, Eleetroenceph. olin. Neurophysiol., 19 (1965) 312-313. 7 SERV1T,Z., STREJCKOVA,A., ANDVOLANSCHI,D., An epileptogenic focus in the frog telencephalon. Pathways of propagation of focal activity, Exp. NeuroL, 21 (1968) 383-396. 8 WOODRUFF,M. L., GAGE,F. H., ANDISAACSON,R. L., Changes in focal epileptic activity produced by brain stem sections in the rabbit, Electroenceph. elin. Neurophysiol., 35 (1973) 475-486.
53
Midbrain and callosal influences on the spread of focal cortical epileptic activity
MICHAEL L. WOODRUFF Department 0[" Psychology, Middlebury College, Middlebury, Vt. 05753 (U.S.A.)
(Accepted November 1lth, 1974)
Two important factors which influence the generalization of cortical focal epileptiform discharge are the anatomical pathways which connect the focus to other brain areas and the ongoing background electrical activity of the cortex. The integrity of the corpus callosum is known to be of primary importance for the propagation of focal epileptic activity fi'om the neocortex of one hemisphere to a contralateral homotopic point 5. However, it is possible that subcortical pathways participate in this propagation 4. In addition, subcortical structures, particularly mesencephalic reticular areas, probably influence epileptic discharge as well as normal EEG. Though the results of several studies indicate that lesions of the reticular formation which produce increased synchrony of cortical rhythms potentiate forebrain epileptic activity1, 8, other reports have indicated that lesions of the reticular formation will attenuate cortical seizure activity a. One goal of the present study was to gather more data on the effect of reticular lesions on cortical epileptic discharge. A second goal was to gather data concerning the pattern of propagation of unilateral cortical epileptic loci after callosal section either alone or in combination with lesions of the mesencephalic reticular formation. Twenty-eight male New Zealand albino rabbits weighing between 2.5 and 3.2 kg were randomly divided into 4 groups. Group N served as intact controls (n--6). Following anesthetization the subjects in this group were placed in a stereotaxic instrument and had openings bored bilaterally over the frontal cortex, sensorimotor cortex and the occipital cortex. Bipolar stainless steel electrodes insulated with Formvar except for the cross-sectional tip diameter (tip diameter 10 mil, tip separation 0.5 ram, resistance 45-50 k~2 in saline) were positioned epidurally through each of the openings. Stainless steel screws served as anchors and a lead from one of the screws was used as a ground. An additional opening was drilled unilaterally over sensorimotor cortex and a cannula, constructed after the method of Nadler 6, was lowered through this hole into the first layer of cortex. The cannula and leads from the electrodes were secured in an Amphenol receptacle which was cemented to the skull with dental acrylic. The scalp was closed around the acrylic with wound clips and Bicillin was given intramuscularly to prevent postoperative infections.
54 Rabbits in group RL (n -- 10) were prepared in a manner identical to group N, except that bilateral cathodal electrolytic lesions were made in the reticular formation at the level of the superior colliculi. Rabbits in group CS (n=-6) had the corpus callosum sectioned before implantation of electrodes using a modificatio, of the technique employed by Isaacson e t al. 4 in the rat. The final group of rabbits (group CR, n--=6) had the callosum sectioned as in group CS and received a lesion of the reticular formation as in group RE. Electrodes and cannula were then implanted as in group N. Following 21 days recovery, recordings were made from each subject on 2 occasions. The recording sessions were separated by 5 days, and each session lasted 5.5 h. On each recording day the rabbit was placed in a standard rabbit restraining box. After 15 min habituation, leads were attached to the rabbit's electrodes and signals from the electrodes were fed into a 6-channel polygraph (Grass Model 7). Low- and highfrequency cut-offs of 1 and 35 Hz were used. After the rabbit was connected to the polygraph an additional 5-min habituation period ensued. This was followed by a 30-rain period of baseline EEG recording. At the end of baseline recording a 27-gauge cannula replaced the stylet which was usually in the permanent cannula and a 1.0/~1 solution of 125 I.U. of sodium penicillin G was injected over 1 rain. The cannula was then removed, the stylet replaced and a 5-h recording session began. At the conclusion of the second recording session each animal was sacrificed with an overdose of pentobarbital and intracardially perfused with 0 . 9 ~ saline followed by 10 7/o formalin. The brain was removed, embedded in celloidin and sectioned at 30/~m. Every fifth section was retained and stained with thionin. Examination of the histology from groups CS and CR verified that the corpus callosum had been completely sectioned in all animals. Five rabbits in group RL and two rabbits in group CR had substantially larger lesions than did the other animals in these groups. The larger lesions included much of the reticular formation at the level of the superior colliculus, as well as small portions of the red nucleus, lateral lemniscus, central gray and substantia nigra. The smaller lesions were restricted to the reticular formation with slight damage to the red nucleus and central gray. The centers of these lesions were located about 2 mm more dorsally than were the centers of the larger lesions, though there was considerable overlap between the ventral portion of these lesions and the dorsal extent of the larger lesions. The larger lesions also produced more damage in the rostrat-caudal dimension. The EEG records from rabbits in groups N and CS consisted of long periods of low voltage fast activity and intervening periods of slow waves and spindles resembling sleep. The baseline records of 9 rabbits with reticular lesions were similar to those in groups N and CS. Seven rabbits in groups CR and RL had a far greater number of spindles (Fig. 1). In these animals this pattern occurred about once every 30 sec. All rabbits demonstrating increased spindling were found to have larger reticular lesions. Baseline records taken during the second recording session did not differ from those taken during the first session. The following parameters of the interictal spike discharges were examined by
55 CS-,l RF
RF
~SM
RSM
RO
RO
LF
LF
LSM
LSM
L0
LO
RF '
RL-S
,
RO
,
~ ', ~,,,,
RF
CR'I
,
RO
LF
LSM
LSM
L0
I Fig. l. Sample baseline EEG from a normal control rabbit (N-5), an animal with a split corpus callosum (CS-3), one with a large reticular formation lesion (RL-8), and one with small reticular lesion (CR-I). Calibration: 1 sec, 150 ffV. RF and LF, right and left frontal cortex; RSM and LSM, right and left sensorimotor cortex; RO and LO, right and left occipital cortex. measurement of the EEG recordings; spike amplitude, spike frequency, time fi'om application of penicillin to the first spike discharge and the time from the first spike to the first ictal episode. Spike frequency was obtained by counting the number of spikes during 30-sec interictal periods 5, 30, 120, 210, and 3130 rain after the appearance of the first interictal spike. The amplitude of 1C0 spikes was measured with a mm ruler at approximately 5, 90, 180 and 280 rain after the appearance of the first spike. Statistical evaluation was made with t-tests and one-way analyses of variance. No significant differences were found either between day 1 and day 2 or among groups for any of the measures of interictal activity. Subjects in group RL that had large reticular lesions ( n - 5 ) were grouped separately and the statistical analysis repeated. No significant differences were found. The pattern of propagation between hemispheres of the interictal discharges was affected by callosal section, but not by reticular lesions. Interictal discharges propagated to the contralateral homotopic cortex in the animals in groups N and RL, but not in groups CS and CR.
56 TABLE I MEAN DURATION AND TIME BETWEEN DISCHARGES FOR THE FIRST 2 0 1CTAL EPISODES FOR EA('H (.~ROUP
Group N
CS
CR
RL
RLS
RLL
39.1 39.6
48,2 49,3
35.3 38.4
69.6 * 78,5*
194.5 196.3
214,9 231.6
169.3 180.9
293.4" 332.9"
Mean seizure discharge duration (sec)
Day 1 Day 2
34.0 38.2
34.9 36.7
Mean time between seizures (sec)
Day 1 Day 2
186.9 192.2
190.2 201.4
• indicates a statistically significant difference. Three parameters of the ictal seizure discharges were analyzed: the total number of seizures during each recording session, the duration of each seizure and the time between them. A one-way analysis of variance (ANOVA) revealed no differences among groups for the total number of ictal episodes during the two experimental sessions. The least number of ictal events was 20, the most was 37. Table I presents the mean duration of the seizures and the mean time between such episodes for each group, t-Tests for matched samples failed to reveal any differences in duration between day I and day 2. When the durations of the seizures on day 1 for groups N, RE, CR and CS were compared using a 2-way ANOVA no significant differences were obtained. When the rabbits with large reticular lesions within group RL were considered as a separate group (group RLL) and the 2-way A N O V A repeated, a significant main effect was found (P < 0.01), though no significant trials or lesion 7. trials interaction was found. The subgroup of rabbits with small reticular lesions did not differ statistically from groups N, C R and CS. A subsequent Dunn's multiple comparison test indicated that group RLL had significantly longer electrical seizures than did the other groups (P < 0.01), which did not statistically differ from each other. Analysis of the data from day 2 had the same result. In addition, the durations of the seizures of the animals in group CR with large lesions fell within the range of the subjects in group RLL, while the animals with small lesions fell within the normal range. The appearance of the electrical seizure activity was not altered by either the reticular lesions or the sections of the callosum. However, sections of the callosum, either alone or in combination with reticular lesions, changed the time course of propagation of the ictal electrographic seizures. The result of the callosal split was to delay the spread of the discharge to the contralateral cortex by many seconds. In fact, if the discharge was of short duration the contralateral cortex remained uninvolved, If the discharges were long enough the contratateral cortex would suddenly display seizure activity (Fig. 2) after a long delay. Previous research has established the importance of the corpus callosum lor the propagation of epileptiform discharge from the primary cortical site to the contralateral homotopic point 4,5,7. In agreement with these findings sectioning the corpus
57 LF
LO
CS-2
ISft
I ' ua~,~c
~~
~ , ~ . . . . . +~"v'~j
'M
{t~fl~,'i~
,~ " . ' . " ~ q '
"tel
.,IJJl,lr~
) .,j~),
4~,.i~, ,h, ,d,,l~.,,~.b,,, , Jl,,i,~41 ~,j~
........
Fig. 2. Propagation of a cortical seizure in a rabbit with a split corpus callosum. Calibration: 1 sec, 200 ffV. Labels are the same as in preceding figure. callosum in the rabbits used in the present study prevented the propagation of interictal discharge from the primary cortical site to the contralateral area. The propagation of ictal seizure discharge, on the other hand, was only slowed, not stopped. The important variable determining whether or not seizure activity was propagated appeared to be the duration of the seizure, if the ictal episode lasted for more than approximately 25 sec seizure began in the contralateral cortex (Fig. 2). Other authors have suggested that subcortical pathways may act as a secondary system for propagation of epileptiform discharge from a primary cortical focus to the contralateral homotopic point 4,7. Isaacson e t al. 4 used anesthetized preparations and observed only propagation patterns of single interictal spikes. Propagation from primary focus to contralateral secondary focus after callosal section was so slight that it could be detected only by computer averaging. Servit et a l Y also observed propagation from one hemisphere to the other after commissural section in the fi'og, but also dealt only with interictal events. The results of the present study indicate that the amount of propagation that can occur after section of the callosum is a function of the duration of the primary epileptic seizure. Epileptiform discharge can propagate quite well to contralateral cortical sites, at least in the lisencephalic brain of the rabbit, after the corpus callosum is split, if the discharge is an extended ictal episode.
58 An important point is that lesions of the reticular formation increased the duration of the electrical seizures only if the lesions produced some noticeable change in the EEG recordings made before the application of penicillin. Lesions that produced an increased amount of spindle-like activity in the baseline EEG were correlated with increased duration of ictal discharges. These lesions destroyed about one-half of the reticular formation at the level of the red nucleus. Wilder (personal communication) has found that lesions in this region of the cat's midbrain will produce cortical epileptiform discharges. As indicated above, there have been conflicting reports as to whether or not lesions of the reticular formation attenuate, potentiate, or have no effect upon epileptiform activity induced in telencephalic structures. The results of the present study suggest that reticular lesions that lead to spindle-like synchronous activity in the pre-seizure EEG will also lengthen seizure discharge while lesions which are too small to produce a detectable change in background EEG activity have no effect. Previous work by Woodruff et al. 8 indicated that lesions of the reticular core which lead in increased desynchrony in the hippocampal EEG significantly shorten focal ictal seizures in this structure. It is suggested, then, that the divergent effects of reticular lesions on telencephalic epileptiform activity which have been reported 1- 3,S may be explained in terms of the effects of these lesions on the ongoing background EEG rhythms of the forebrain. This research was supported in part by USPHS Training Grant MH-10320 to the Center for Neurobiological Sciences, University of Florida and N I M H Grant 16348-03 to R. L. Isaacson. The author is indebted to Drs. B. J. Wilder, R. L. Isaacson, F. A. King and C. Van Hartesveldt for their critical reading of initial versions of this manuscript.
1 ANDY,O. J., ANDMUKAWA,J., Brain stem lesion effects on electrically induced seizures, Electroeneeph, clin. NeurophysioL, 11 (1959) 397. 2 DtCHTER, M. A., HERMAN,C. J., AnD SELZER,M., Silent cells during interictal discharges and seizures in hippocampal penicillin foci. Evidence for the role of extracellutar K + in the transition from the interictal state to seizures, Brain Research, 48 (1972) 173-183. 3 FREEDr~Ar~,D. A., ANDMOOSSY,J., Effect of mesencephatic lesion on the cortical electroconvulsant threshold, Neurology (Minneap.), 3 (1953) 714-720. 4 ISAACSON,R. L., SCHWARTZ,H., PERSOFF, N., AND P1NSON, L., The role of the corpus callosum in the establishment of areas of secondary epileptiform activity, Epilepsia, 12 (1971) 133-146. 5 MORRELL,F., Secondary epileptogenic lesions, Epilepsia, 1 (1960) 538-560. 6 NADLER, R. D., A simplified cannula system for implanting and injecting chemicals into the brains of small animals, Eleetroenceph. olin. Neurophysiol., 19 (1965) 312-313. 7 SERV1T,Z., STREJCKOVA,A., ANDVOLANSCHI,D., An epileptogenic focus in the frog telencephalon. Pathways of propagation of focal activity, Exp. NeuroL, 21 (1968) 383-396. 8 WOODRUFF,M. L., GAGE,F. H., ANDISAACSON,R. L., Changes in focal epileptic activity produced by brain stem sections in the rabbit, Electroenceph. elin. Neurophysiol., 35 (1973) 475-486.