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Electrical activity of subcortical areas in epilepsy
ELECTRICAL ACTIVITY OF SUBCORTICAL AREAS IN EPILEPSY 1 RoRrwr A. HAYNE, M . D . , Lou~s BrLINSON, M . D . a n d FREOrRIC A. G m n s , M . D . Dixon State Hospital and the University ot Illinois, Department o[ P.~ychiatry, and the Illinois Neuropsychiatric Institute, Chicago, Illinois In some cases of epilepsy, particularly those in which the clinical manifestations suggest a diencephalic lesion, the cortex m a y show no electroencephalographic abnormalities even during the seizure. In these cases it has been assumed that the seizures result from a discharging lesion in the depths of the brain. However, subcortical loci ol seizure activity have rarely been demonstrated in man. Penfield (15) has stated that the results of surgical procedure in epilepsy depend on the care with which patients are selected and studied prior to and at operation. Knowledge of the source and extent of seizure activity is a pre-requisite to neurosurgicai intervention and should be determined before a destructive procedure is carried out. Until the subcortex is explored there is no assurance that the chief focus in a n y given case is in the cortex. Some therapeutic failures are doubtless due to the surgical attack being directed at a secondary cortical rather than a p r i m a r y subcorticat focus. O n the other hand, some patients without evidence o~ a localized cortical discharge may have a subcortical focus that could be destroyed or [unctionally isolated. t The presentation by Dr. Gibbs was based upon research carried out in collaboration with Drs. Percival Bailey, Louis Belinson, John Green and Robert A. Hayne. The original reports of these studies are in the process of preparation, but we are fortunate to be able to include one in this symposium. This paper was the subject of a report before the Central Association of Electreencephalooraphers on October 25, 1947, and the Chicago Neurological Society on March 9, 1948. Financial aid for this study was obtained from the Miller Fund and from the Rockefeller Foundation.
MATERIAL AND METHOD If the activity of specific subcortical structures is to be recorded and, on the basis of data so obtained, lesions are to be made in the depths of the brain, it is necessary that a precise technique be available for guiding and localizing the electrodes. T o meet this requirement a H o r s l e y - C l a r k type of stereotaxic instrument was developed for man (fig. 1). From anatomical studies on
Fig. 1 Horsley-Clarke apparatus for man. three heads with brains fixed in situ at the time of autopsy, coordinate measurements were obtained. T h e s e showed that spacial relations between external landmarks and structures in the depths of the human brain are sufficiently constant to allow placement
[ 437 1
't38
ROBERT A. I-IAYNE, LOUIS BELINSON and FREDERIC A. (;IBBS
of a needle electrode in particular deep structures with a fair degree of accuracy. W i t h the stereotaxic instrument in place a properly placed burr hole was made and a needle electrode was inserted into the desired part of the brain. The procedure was carried out on 22 patients selected because they had severe, frequent and uncontrollable convulsions. In all cases the consents of the
was spontaneous and in others ~t was m duced with pentothal. Before the needle was withdrawn a pneumoencephalogram was obtained to provide means for checking the position of the needle (fig. 3). The classification of cases and the subcortical areas from which recordings were obtained are shown in table 1. In no case was the surgical removal or isolation of a
Fig. 2 Multi-electrode needle. The model shown here was made by A.M. Grass; it has I0 instead o[ 8 rings, patient and his parents or guardians were obtained. T h e needle electrode, which was constructed especially for this study, had the external diameter of a standard ventricular needle. As will be seen from figure 2, it is a multi-electrode needle 2.5 ram. in diameter made of eight silver rings 2 ram. in width separated by 2 ram. of insulatin 9 material. The risk of inserting this needle into the depths of the brain was believed to be no greater than that involved in ventriculog r a p h y or probin 9 for a tumor. This assumption was borne out by the results: in no case did the patient exhibit an untoward reaction to the procedure. ( T h e only significant discomfort was occasioned by the pneumoencephalography ). Subcortical as well as cortical electroencephalograms were registered with a Grass 6-channel electroencephalograph. Conventional leads from the scalp as well as the described leads from the depths o! the brain were used. Patients were studied both awake and asleep; in some cases sleep
Corroboration of encephalography.
Fi 9. 3 needle position by
pneumo-
E L E C T R I C A L A C T I V I T Y O F S U B C O R T I C A L A R E A S IN E P I L E P S Y TABLE
439
I
SUMMARY OF RESULTS
Case No.
Type o~ discharge from external electrodes
1.
Petit mal
2.
Petit mat
3.
Petit real
4.
Petit mal
5.
Petit mal
6.
Petit mal ,5 grand real
7.
Needle path
Discharge [tom depths
R. high parietal to inferior portion of L. thalamus R: high parietal to R. pulvinar R. high parietal to R. pulvinar R. high parietal to R. pulvinar R. high parietal to R. thalamus (insufficient air) R. lateral parietal to mesial temporo-occipital cortex
Absent pattern Absent pattern Absent pattern Absent pattern Absent pattern Absent except Grand leads
Petit mal (~ grand real
R. lateral parietal to inferior messial occipital cortex
Petit mal absent or inverted subcortex. Grand mal absent
8.
Petit mal ,9 grand mal
9.
Petit mal 6 grand real
R. high parietal to middle of R. thalamus R. high parietal to middle of R. thalamus R. high parietal to R. pulvinar R. high parietal to inferior portion of L. thalamus R. high frontal through head of caudate to white matter of orbito frontal cortex R. high parietal to R. nucleus medialis dorsalis thalami
Petit mal absent or inverted. Grand mal absent Petit real absent or inverted. Grand real inverted Both patterns absent or inverted
10.
Petit mal b variant
11. 12.
Petit mal ~ petit real variant Petit real variant
13.
Petit mal variant
14.
Petit real variant
15.
Ant. temp. spikes (psychom¢~or)
16.
or inverted wave-and-spike or inverted wave-and-spike or inverted wave-and-spike or inverted wave-and-spike or inverted wave-and-spike or inverted wave-and-spike from leads in deep cortex. mal discharges show in all in
Both patterns absent or inverted Absent or inverted
Absent or inverted
R. high frontal through caudate to putamen R. high parietal to R. nucleus medialis dorsalis thalami
Absent or inverted (i.e. positive spike) Absent or inverted (i.e. positive spike)
Ant. temp. spikes (psychomotor) Ant. temp. spikes (psychomotor)
R. high parietal to R. hypothalamus R. high parietal to left mid-brain
Absent or inverted ( i.e. positive spike) Absent or inverted (i.e. positive spike)
18.
Ant. temp. spikes (psychomotor)
R. high parietal to left medial posterior thalamus
19.
Ant. temp. spikes (psychomotor) Ant. temp. spikes (psychomotor)
R. high frontal to Island of Reil R. high frontal through caudate to R. lateral wall of 3rd ventricle.
Inverted spikes (i.e. positive). Independent grand mal discharges in outer subcortica! electrode Inverted (i.e. positive spikes) Absent or inverted (i.e. positive spikes)
21.
No seizure discharges
22.
No seizure discharges
R. lateral parietal to medial wall of R. lateral ventricle R. high frontal to R. putamen
17.
20.
Negative spikes in outermost subcortical electrode, Absent or inverted in depths Negative spikes in two outermost subcortical electrodes. Absent o r inverted in depths.
'H0
ROBERT A HAYNE, I,OLIlS BELINSON and FREDERIC A GIBBS
subcortical tocus attempted because in none was a purely subcortical focus found. REgUI.TS As previously observed in experimental animals (9 ]4), the electrical activity of the striatum and thalamus resembled in its general character that of the cortex. A close interrelation between the subcortical and cortical activity was usual. In most instances bursts of approximately 10 per second activity appeared in both superficial and deep leads at the same time, and fast activity appeared and disappeared in both more or less simultaneously, but 20 to 30 per sec. activity during the early phase of pentotha] anesthesia appeared first and was
from cortical leads usually showed also in subcortical leads, and conversely when seiz, ure discharges were seen in the subcortex they usually appeared on the cortex, However. in some cases entirely independent seizure activity was observable in the cortex and in the subcortex {fig. 5). In numerous instances isolated seizure discharges of the 3 per second wave-spike type. such as are characteristic of petit real epilepsy, were seen in the cortex with no corresponding discharge (and no preceding disturbance) in the thalamus or other subcorticat regions (fiq. 6), Isolated spikes were much more commonly observed from the cortex than from the subcortex. From deep in the cerebra] hemisphere the anterior temporal spike
L ANT T
R ANT T
RP
WHITE MATTER
R P WHITE MATTER ( D E E P E R )
R THAL
L PULVINAR
Fig. 4 Independent cortical and subcortical activity. Twent,~ to thirty per second activity characteristic of early pentothal anesthesia shows best in the most superficial of the subcortical leads. Reference electrode on botb ears.
most evident in the subcortical ring of the needle electrode (fig. 4). Such activity ,,,,,as least evident in those rings which were located in the central grey mass. At times the activity of cortical and subcortical structures was entirely independent. The same interdependence with occasional periods of independence occurred in both the sleeping and wakin 9 states. As with normal activity, so also with seizure activity, for seizure patterns derived
of psychomotor epilepsy either did not show or was positive in electrical sign when referred to a relatively inactive area (fig. 7). A reversal of phase was observed between cortical and subcortical seizure discharges (reference on a relatively inactive area): t h e wave-and-spike pattern appeared inverted in the subcortex, and spikes recorded as negative on the cortex appeared concomitantly as positive when picked up from the subcortex. In a few instances temporally relat-
ELECTRICAL ACTIVITY OF SUBCORTICAL AREAS IN EPILEPSY e d positive spikes occurred on the cortex with negative spikes in the subcortex. By moving the electrode it was found that the reversal of sign occurred, in the case of cortical negative spike activity, in or just beneath the cortex. T h e point of reversal was somewhat indeterminate: a point could
441
discharges had a positive spike component which was associated with a negative cortical spike. O n rare occasions subcortical positive spikes occurred independent of observed cortical spikes. In a few cases independent negative spikes were recorded from subcortical structures.
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Subcortical grand mal discharge. is on both ears.)
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Fig. 5 (In the lower sets of records the reference electrode
be found just beneath the cortex where the spike sometimes appeared with the same siqn as the cortical spike and sometimes with the opposite sign. At other times the same subcorticai point gave spikes of reduced voltage or a complete absence of spikes. W h e n an isolated cortical spike or waveand-spike pattern appeared the spike was almost invariably negative with respect to an indifferent area. Almost all subcortical
DISCUSSION T h e spontaneous non-paroxysmal activity recorded from the thalamus and the striatum has no more and no less specificity of pattern or independence than does that recorded from different parts of the cortex. Six channel simultaneous recordings show that synchronous firing of cortical and subcortical structures is common and that a high degree of interdependence is the rule.
4~12
ROBERT A. HAYNE, LOHIS BEI,INSON and FREDERIC A. GIBBS "]'his does not mean thai s t r u c t u r a l o r g a n ization a n d function a r e w i t h o u t s i g n i f i c a n c e for the e l e c t r o e n c e p h a l o g r a p h e r or b e y o n d his ran qe of i n v e s t i g a t i o n , h m e a n s t h a t in such a c o m p l e x s y s t e m , with its s h i f t y p a c e m a k e r activity, artificial s i m p l i f i c a t i o n is e s s e n t i a l to c o m p r e h e n s i o n . O n e such sire-
It might be a s s u m e d t h a t r e g i o n s that a r e h i s t o l o g i c a l l y so d i f f e r e n t as the s t r i a t u m a n d the t h a l a m u s , a n d w h i c h s u b s e r v e such d i f f e r e n t functions, w o u l d h a v e e n t i r e l y different p a t t e r n s of e l e c t r i c a l activity, but t h e y do not. In these d e e p s t r u c t u r e s are seen the same familiar p a t t e r n s that a r e r e c o r d e d from PT
M H
5 } INT
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.h ~
~j ' ~ , ~ , ~
~,?
LF-RF
4-3)
I
i
,
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8-51
CORONA R A D . - INT. CAP
7-4)
INT CAP.- LAT. N
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5 - 2 ) INT C A P -
8 - t j CORON2, R A 0 - ME' D N
4"1 ) L A T , N
N
MED. N
~ I~IED~N
Fig. 6 Petit real discharge showing independently in scalp lead and not showing or appearing out of phase in thalamic leads. (In the upper set of records the reference electrode is on both ears.)
the cortex. Physiologically and anatomically disappointing though this may seem, it was to be expected, for in the cortex itself, with all its varied architectonics and functional diversification, there is no good correlation between spontaneous electrical pattern and specific elements of design.
plification is a lesion. Another is an /dentillable signal. In the present study spontaneous seizure discharges have been utilized as identifiable signals. Evidence has been presented by others (15, I0. 11) to show that the petit real type of discharge originates in the central grey
ELECTRICAL ACTIVITY OF SUBCORTICAL AREAS IN EPILEPSY masses. T h e present findings do not suggest a subcortical but a cortical origin for the three per second wave-and-spike of petit mal, because (a) the spike registers on the cortex as negative when referred to a relatively inactive area, (b) it can appear as an isolated and purely focal discharge in one cortical area and (c) no evidence was found that it is causatively related to tha]amic or other subcortical activity. PT
443
chosen as a reference. Even with bipolar leads in the depths of the brain, i.e. using interconnected rings on the needle electrode, the same reversal of sign occurred. This reversal of sign was noted by Dusser de Barenne and McCulloch in their work with seizure potentials produced by local application of strychnine (7, 8). T h e y concluded that negative swings and negative spikes express activity originating in the
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Fig. 7 Anterior temporal spike of psychomotor type showing in scalp lead and not showing or appearing out of phase in thalamic leads. T h e negativity of spikes on the cortex and their positivity in the subcortex might be assumed to be an artifact due to the use of a common reference electrode. However, it made no difference whether the ear, the nose or a relatively inactive scalp area was
area where the electrode is placed, with the nearest cell layers leading, whereas the positive swings with positive spikes indicate activity in more distant layers. T h e y point out that their interpretation is in accord with the findings and interpretations of
444
ROBERT A. HAYNE, LOUIS BELINSON and FREDERIC A. GIBBS
Bishop and collaborators (2, 3. 4. 5), of Marshall W o o l s e y and Bard (t2, 13) and of Adrian ( 1 ) Curtis' analysis of potentials conducted through the corpus callosum (6) also indicates that if an electrode is in the primary dischargin9 area it will be driven negative with respect to a distant "indifferent" electrode and positive if it is outside the primary dischar,qe area or beyond the activated fiber system. T h e fact that isolated neyative spikes were commonly found in the present study and isolated positive spikes exceeding]y rare, is in accord with Curtis' ,qeneral conclusion that the primary disturbance is negative. H e showed that, if an incominq volley from a fiber tract is picked up by a cortical electrode outside and beyond the fiber system conducting the volley, a positive potential is recorded, but this is usually followed by a secondary local response which appears as a negative disturbance. This local response can be increased by strychninization and decreased by the application of nembutal. Thus, a local response, even when secondarily initiated, is recorded as negative when referred to an indifferent area. T h e incoming fiber volley, however, is recorded as positive. From the fore,qoing it is possible to deduce a " l a w " which gives localizing value to electrical sign in electroencephaloqraphy: N e y t a t i v i t y indicates a local d i s t u r b a n c e : positivitq indicates a d i s t a n t d i s t u r b a n c e .
depths of the brain lead to the followin~t conclusions: 1. T h e cortex and sub-cortex in epileptic patients display comparable normal and abnormal activity. 2. Like the cortex, however, various areas of the sub-cortex may show entirely independent abnormal activity. 3. During the induction of pentathol anesthesia 20 to 30 per second activity appeared first and remained most prominent in outer subcortical leads and showed least in leads from the central 9rey mass. 4. Isolated seizure discharges from the cortex are common, whereas they are rare in the subcortex. T h e fact that they de occur is important, because they may account for therapeutic failure in some cases where a cortical focus is ablated. 5. N o case was found in which seizure discharges in or around the medial thalamus could be interpreted as initiating 3 per second w a v e - a n d - s p i k e discharges of the petit real type. 6. P r i m a r y and secondary cortical discharyes have a neqative sign when referred to a relatively indifferent area. An incoming volley from a distant area is registered as a positive disturbance if referred to an indifferent re,qion, 7. Electrical si,qn has localizing value in electroencephalography : N e g a t i v i t y indicates a local disturbance: positivity indicates a distant disturbance. REFERENCES
SUMMARY AND CONCLUSIONS T h e electrical activity of the cortex and subcortex were studied in 22 patients with epilepsy by means of scalp electrodes and a multi-electrode needle which was placed in the depths of the brain with the aid of a stereotaxic instrument. T h e instrument was designed for man and coordinate measurements were obtained by studies on brains fixed in situ. In the present operative series the position of the needle was checked by p n e u m o e n c e p h a l o q r a p h y at the end of the recording. Analysis of records from the scalp and
1, AORIAN, E. D. The spread of activity in the cerebral cortex. 1. Physiol., 1936, 88: 127-161. 2. BARTLE¥. S. H. and BISHOp, G. H. The cortical response to stimulation of the optic nerve in the rabbit. Amer. ]. Physiol., 1933, 10~: 159-172. 3. BISHOp. G. H. Cyclic chanqes in excitability of the optic pathway of the rabbit. Amer. ]. Physiol., 1933. 103: 213-224. 4. BISHOp, G. H. La th4orie des circuits locaux permet-elle de pr4voir la Iorme du potentiet d'action? Arch. lnternat. Physiol., 1937, 45: 273-297. 5. BISHOp, G. H. and O'LE^RY, ]. L. Components of the electrical response of the optic cortex of the rabbit. Amer, 1. PhysioL, 1936. 117: 292308. 6. CURTIS, H. J. An analysis o[ cortical potentials mediated by the corpus callosum. /. Neurophysiol,. 1940. 3: 414-422.
E L E C T R I C A L A C T I V I T Y O F S U B C O R T I C A L AREAS IN E P I L E P S Y 7. DHSSER DE BARENNE, J. G. and MCCULLOCH, W. S. Kritisches und Experimentelles zur Deutung zur Potentialschwankungen des Elektrocorticogramms. Z. ges; Neurol. Psychiat., 1938, 162: B15-824. 8. DUSSER DE BARENNE, ]. G. and McCuLLOCH, W. S. Factors for facilitation and extinction in the central nervous system. ]. Neurophysiol., 1939, 2: 319"355. 9. Ge,RARO, R. W., MARSHALL, W. H. and SAUL, L. ]. Electrical activity of the cat's brain. Arch. Neurol. Psychiat., Chicago, 1936, 36: 675-738. 10. HURSH, J. B. Origin o[ the spike and wave pattern of petit mal epilepsy. Arch. Neurol. Psychiat., Chicac3o, 1945, 53: 274-282. 11. JASPER, H. H. and DROOGLEEVER-FoRTUYN, J. Experimental studies on the functional anatomy
12.
13.
14.
15.
445
of petit mal epilepsy. Res. Publ. Ass. neru. ment. Dis., 1947, 26: 272-298. MARSHALL, W. H., WOOLSEY, C. N. and BARD. P. Cortical representation of tactile sensibility as indicated by cortical potentials, Science, 193"/. 85: 388-390. MARSHALL, W. H., WOOLSEY. C. N. and BARD, P. In MacLeod: Physiolooy in modern medicine. 8th ed, St. Louis, C. V. Mosby & Co., 1938: 168-173. MORISON. R, S,. FINLAY. K. H. and LOTHROP. GLADYS N. Spontaneous electrical activity of thalamus and other [orebrain structures. ]. Neurophysiol., 1943, 6: 243-254. PENVXELI), W. and ERICgSON, T. C.: Epilepsy and cerebral localization. Sprin,,jfield, Ill., Charless C. Thomas. 1941: x + 623 pp.
D I S C U S S I O N : E. A. SPIEGEl D r . S p i e g e l ' s d i s c u s s i o n of this p a p e r h a s b e e n p r e p a r e d for p u b l i c a t i o n as a s e p a r a t e
article, which will appear of this j o u r n a l .
in a n e a r l y issue
Re[erence: HAYNE, R. A.. BELINSON, L. and GIBBS. F. A. Electrical activity of subcortical areas in epilepsy. EEG Clin. Neurophysiol., 1949. 1: 437-445.
MATERIAL AND METHOD If the activity of specific subcortical structures is to be recorded and, on the basis of data so obtained, lesions are to be made in the depths of the brain, it is necessary that a precise technique be available for guiding and localizing the electrodes. T o meet this requirement a H o r s l e y - C l a r k type of stereotaxic instrument was developed for man (fig. 1). From anatomical studies on
Fig. 1 Horsley-Clarke apparatus for man. three heads with brains fixed in situ at the time of autopsy, coordinate measurements were obtained. T h e s e showed that spacial relations between external landmarks and structures in the depths of the human brain are sufficiently constant to allow placement
[ 437 1
't38
ROBERT A. I-IAYNE, LOUIS BELINSON and FREDERIC A. (;IBBS
of a needle electrode in particular deep structures with a fair degree of accuracy. W i t h the stereotaxic instrument in place a properly placed burr hole was made and a needle electrode was inserted into the desired part of the brain. The procedure was carried out on 22 patients selected because they had severe, frequent and uncontrollable convulsions. In all cases the consents of the
was spontaneous and in others ~t was m duced with pentothal. Before the needle was withdrawn a pneumoencephalogram was obtained to provide means for checking the position of the needle (fig. 3). The classification of cases and the subcortical areas from which recordings were obtained are shown in table 1. In no case was the surgical removal or isolation of a
Fig. 2 Multi-electrode needle. The model shown here was made by A.M. Grass; it has I0 instead o[ 8 rings, patient and his parents or guardians were obtained. T h e needle electrode, which was constructed especially for this study, had the external diameter of a standard ventricular needle. As will be seen from figure 2, it is a multi-electrode needle 2.5 ram. in diameter made of eight silver rings 2 ram. in width separated by 2 ram. of insulatin 9 material. The risk of inserting this needle into the depths of the brain was believed to be no greater than that involved in ventriculog r a p h y or probin 9 for a tumor. This assumption was borne out by the results: in no case did the patient exhibit an untoward reaction to the procedure. ( T h e only significant discomfort was occasioned by the pneumoencephalography ). Subcortical as well as cortical electroencephalograms were registered with a Grass 6-channel electroencephalograph. Conventional leads from the scalp as well as the described leads from the depths o! the brain were used. Patients were studied both awake and asleep; in some cases sleep
Corroboration of encephalography.
Fi 9. 3 needle position by
pneumo-
E L E C T R I C A L A C T I V I T Y O F S U B C O R T I C A L A R E A S IN E P I L E P S Y TABLE
439
I
SUMMARY OF RESULTS
Case No.
Type o~ discharge from external electrodes
1.
Petit mal
2.
Petit mat
3.
Petit real
4.
Petit mal
5.
Petit mal
6.
Petit mal ,5 grand real
7.
Needle path
Discharge [tom depths
R. high parietal to inferior portion of L. thalamus R: high parietal to R. pulvinar R. high parietal to R. pulvinar R. high parietal to R. pulvinar R. high parietal to R. thalamus (insufficient air) R. lateral parietal to mesial temporo-occipital cortex
Absent pattern Absent pattern Absent pattern Absent pattern Absent pattern Absent except Grand leads
Petit mal (~ grand real
R. lateral parietal to inferior messial occipital cortex
Petit mal absent or inverted subcortex. Grand mal absent
8.
Petit mal ,9 grand mal
9.
Petit mal 6 grand real
R. high parietal to middle of R. thalamus R. high parietal to middle of R. thalamus R. high parietal to R. pulvinar R. high parietal to inferior portion of L. thalamus R. high frontal through head of caudate to white matter of orbito frontal cortex R. high parietal to R. nucleus medialis dorsalis thalami
Petit mal absent or inverted. Grand mal absent Petit real absent or inverted. Grand real inverted Both patterns absent or inverted
10.
Petit mal b variant
11. 12.
Petit mal ~ petit real variant Petit real variant
13.
Petit mal variant
14.
Petit real variant
15.
Ant. temp. spikes (psychom¢~or)
16.
or inverted wave-and-spike or inverted wave-and-spike or inverted wave-and-spike or inverted wave-and-spike or inverted wave-and-spike or inverted wave-and-spike from leads in deep cortex. mal discharges show in all in
Both patterns absent or inverted Absent or inverted
Absent or inverted
R. high frontal through caudate to putamen R. high parietal to R. nucleus medialis dorsalis thalami
Absent or inverted (i.e. positive spike) Absent or inverted (i.e. positive spike)
Ant. temp. spikes (psychomotor) Ant. temp. spikes (psychomotor)
R. high parietal to R. hypothalamus R. high parietal to left mid-brain
Absent or inverted ( i.e. positive spike) Absent or inverted (i.e. positive spike)
18.
Ant. temp. spikes (psychomotor)
R. high parietal to left medial posterior thalamus
19.
Ant. temp. spikes (psychomotor) Ant. temp. spikes (psychomotor)
R. high frontal to Island of Reil R. high frontal through caudate to R. lateral wall of 3rd ventricle.
Inverted spikes (i.e. positive). Independent grand mal discharges in outer subcortica! electrode Inverted (i.e. positive spikes) Absent or inverted (i.e. positive spikes)
21.
No seizure discharges
22.
No seizure discharges
R. lateral parietal to medial wall of R. lateral ventricle R. high frontal to R. putamen
17.
20.
Negative spikes in outermost subcortical electrode, Absent or inverted in depths Negative spikes in two outermost subcortical electrodes. Absent o r inverted in depths.
'H0
ROBERT A HAYNE, I,OLIlS BELINSON and FREDERIC A GIBBS
subcortical tocus attempted because in none was a purely subcortical focus found. REgUI.TS As previously observed in experimental animals (9 ]4), the electrical activity of the striatum and thalamus resembled in its general character that of the cortex. A close interrelation between the subcortical and cortical activity was usual. In most instances bursts of approximately 10 per second activity appeared in both superficial and deep leads at the same time, and fast activity appeared and disappeared in both more or less simultaneously, but 20 to 30 per sec. activity during the early phase of pentotha] anesthesia appeared first and was
from cortical leads usually showed also in subcortical leads, and conversely when seiz, ure discharges were seen in the subcortex they usually appeared on the cortex, However. in some cases entirely independent seizure activity was observable in the cortex and in the subcortex {fig. 5). In numerous instances isolated seizure discharges of the 3 per second wave-spike type. such as are characteristic of petit real epilepsy, were seen in the cortex with no corresponding discharge (and no preceding disturbance) in the thalamus or other subcorticat regions (fiq. 6), Isolated spikes were much more commonly observed from the cortex than from the subcortex. From deep in the cerebra] hemisphere the anterior temporal spike
L ANT T
R ANT T
RP
WHITE MATTER
R P WHITE MATTER ( D E E P E R )
R THAL
L PULVINAR
Fig. 4 Independent cortical and subcortical activity. Twent,~ to thirty per second activity characteristic of early pentothal anesthesia shows best in the most superficial of the subcortical leads. Reference electrode on botb ears.
most evident in the subcortical ring of the needle electrode (fig. 4). Such activity ,,,,,as least evident in those rings which were located in the central grey mass. At times the activity of cortical and subcortical structures was entirely independent. The same interdependence with occasional periods of independence occurred in both the sleeping and wakin 9 states. As with normal activity, so also with seizure activity, for seizure patterns derived
of psychomotor epilepsy either did not show or was positive in electrical sign when referred to a relatively inactive area (fig. 7). A reversal of phase was observed between cortical and subcortical seizure discharges (reference on a relatively inactive area): t h e wave-and-spike pattern appeared inverted in the subcortex, and spikes recorded as negative on the cortex appeared concomitantly as positive when picked up from the subcortex. In a few instances temporally relat-
ELECTRICAL ACTIVITY OF SUBCORTICAL AREAS IN EPILEPSY e d positive spikes occurred on the cortex with negative spikes in the subcortex. By moving the electrode it was found that the reversal of sign occurred, in the case of cortical negative spike activity, in or just beneath the cortex. T h e point of reversal was somewhat indeterminate: a point could
441
discharges had a positive spike component which was associated with a negative cortical spike. O n rare occasions subcortical positive spikes occurred independent of observed cortical spikes. In a few cases independent negative spikes were recorded from subcortical structures.
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be found just beneath the cortex where the spike sometimes appeared with the same siqn as the cortical spike and sometimes with the opposite sign. At other times the same subcorticai point gave spikes of reduced voltage or a complete absence of spikes. W h e n an isolated cortical spike or waveand-spike pattern appeared the spike was almost invariably negative with respect to an indifferent area. Almost all subcortical
DISCUSSION T h e spontaneous non-paroxysmal activity recorded from the thalamus and the striatum has no more and no less specificity of pattern or independence than does that recorded from different parts of the cortex. Six channel simultaneous recordings show that synchronous firing of cortical and subcortical structures is common and that a high degree of interdependence is the rule.
4~12
ROBERT A. HAYNE, LOHIS BEI,INSON and FREDERIC A. GIBBS "]'his does not mean thai s t r u c t u r a l o r g a n ization a n d function a r e w i t h o u t s i g n i f i c a n c e for the e l e c t r o e n c e p h a l o g r a p h e r or b e y o n d his ran qe of i n v e s t i g a t i o n , h m e a n s t h a t in such a c o m p l e x s y s t e m , with its s h i f t y p a c e m a k e r activity, artificial s i m p l i f i c a t i o n is e s s e n t i a l to c o m p r e h e n s i o n . O n e such sire-
It might be a s s u m e d t h a t r e g i o n s that a r e h i s t o l o g i c a l l y so d i f f e r e n t as the s t r i a t u m a n d the t h a l a m u s , a n d w h i c h s u b s e r v e such d i f f e r e n t functions, w o u l d h a v e e n t i r e l y different p a t t e r n s of e l e c t r i c a l activity, but t h e y do not. In these d e e p s t r u c t u r e s are seen the same familiar p a t t e r n s that a r e r e c o r d e d from PT
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Fig. 6 Petit real discharge showing independently in scalp lead and not showing or appearing out of phase in thalamic leads. (In the upper set of records the reference electrode is on both ears.)
the cortex. Physiologically and anatomically disappointing though this may seem, it was to be expected, for in the cortex itself, with all its varied architectonics and functional diversification, there is no good correlation between spontaneous electrical pattern and specific elements of design.
plification is a lesion. Another is an /dentillable signal. In the present study spontaneous seizure discharges have been utilized as identifiable signals. Evidence has been presented by others (15, I0. 11) to show that the petit real type of discharge originates in the central grey
ELECTRICAL ACTIVITY OF SUBCORTICAL AREAS IN EPILEPSY masses. T h e present findings do not suggest a subcortical but a cortical origin for the three per second wave-and-spike of petit mal, because (a) the spike registers on the cortex as negative when referred to a relatively inactive area, (b) it can appear as an isolated and purely focal discharge in one cortical area and (c) no evidence was found that it is causatively related to tha]amic or other subcortical activity. PT
443
chosen as a reference. Even with bipolar leads in the depths of the brain, i.e. using interconnected rings on the needle electrode, the same reversal of sign occurred. This reversal of sign was noted by Dusser de Barenne and McCulloch in their work with seizure potentials produced by local application of strychnine (7, 8). T h e y concluded that negative swings and negative spikes express activity originating in the
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Fig. 7 Anterior temporal spike of psychomotor type showing in scalp lead and not showing or appearing out of phase in thalamic leads. T h e negativity of spikes on the cortex and their positivity in the subcortex might be assumed to be an artifact due to the use of a common reference electrode. However, it made no difference whether the ear, the nose or a relatively inactive scalp area was
area where the electrode is placed, with the nearest cell layers leading, whereas the positive swings with positive spikes indicate activity in more distant layers. T h e y point out that their interpretation is in accord with the findings and interpretations of
444
ROBERT A. HAYNE, LOUIS BELINSON and FREDERIC A. GIBBS
Bishop and collaborators (2, 3. 4. 5), of Marshall W o o l s e y and Bard (t2, 13) and of Adrian ( 1 ) Curtis' analysis of potentials conducted through the corpus callosum (6) also indicates that if an electrode is in the primary dischargin9 area it will be driven negative with respect to a distant "indifferent" electrode and positive if it is outside the primary dischar,qe area or beyond the activated fiber system. T h e fact that isolated neyative spikes were commonly found in the present study and isolated positive spikes exceeding]y rare, is in accord with Curtis' ,qeneral conclusion that the primary disturbance is negative. H e showed that, if an incominq volley from a fiber tract is picked up by a cortical electrode outside and beyond the fiber system conducting the volley, a positive potential is recorded, but this is usually followed by a secondary local response which appears as a negative disturbance. This local response can be increased by strychninization and decreased by the application of nembutal. Thus, a local response, even when secondarily initiated, is recorded as negative when referred to an indifferent area. T h e incoming fiber volley, however, is recorded as positive. From the fore,qoing it is possible to deduce a " l a w " which gives localizing value to electrical sign in electroencephaloqraphy: N e y t a t i v i t y indicates a local d i s t u r b a n c e : positivitq indicates a d i s t a n t d i s t u r b a n c e .
depths of the brain lead to the followin~t conclusions: 1. T h e cortex and sub-cortex in epileptic patients display comparable normal and abnormal activity. 2. Like the cortex, however, various areas of the sub-cortex may show entirely independent abnormal activity. 3. During the induction of pentathol anesthesia 20 to 30 per second activity appeared first and remained most prominent in outer subcortical leads and showed least in leads from the central 9rey mass. 4. Isolated seizure discharges from the cortex are common, whereas they are rare in the subcortex. T h e fact that they de occur is important, because they may account for therapeutic failure in some cases where a cortical focus is ablated. 5. N o case was found in which seizure discharges in or around the medial thalamus could be interpreted as initiating 3 per second w a v e - a n d - s p i k e discharges of the petit real type. 6. P r i m a r y and secondary cortical discharyes have a neqative sign when referred to a relatively indifferent area. An incoming volley from a distant area is registered as a positive disturbance if referred to an indifferent re,qion, 7. Electrical si,qn has localizing value in electroencephalography : N e g a t i v i t y indicates a local disturbance: positivity indicates a distant disturbance. REFERENCES
SUMMARY AND CONCLUSIONS T h e electrical activity of the cortex and subcortex were studied in 22 patients with epilepsy by means of scalp electrodes and a multi-electrode needle which was placed in the depths of the brain with the aid of a stereotaxic instrument. T h e instrument was designed for man and coordinate measurements were obtained by studies on brains fixed in situ. In the present operative series the position of the needle was checked by p n e u m o e n c e p h a l o q r a p h y at the end of the recording. Analysis of records from the scalp and
1, AORIAN, E. D. The spread of activity in the cerebral cortex. 1. Physiol., 1936, 88: 127-161. 2. BARTLE¥. S. H. and BISHOp, G. H. The cortical response to stimulation of the optic nerve in the rabbit. Amer. ]. Physiol., 1933, 10~: 159-172. 3. BISHOp. G. H. Cyclic chanqes in excitability of the optic pathway of the rabbit. Amer. ]. Physiol., 1933. 103: 213-224. 4. BISHOp, G. H. La th4orie des circuits locaux permet-elle de pr4voir la Iorme du potentiet d'action? Arch. lnternat. Physiol., 1937, 45: 273-297. 5. BISHOp, G. H. and O'LE^RY, ]. L. Components of the electrical response of the optic cortex of the rabbit. Amer, 1. PhysioL, 1936. 117: 292308. 6. CURTIS, H. J. An analysis o[ cortical potentials mediated by the corpus callosum. /. Neurophysiol,. 1940. 3: 414-422.
E L E C T R I C A L A C T I V I T Y O F S U B C O R T I C A L AREAS IN E P I L E P S Y 7. DHSSER DE BARENNE, J. G. and MCCULLOCH, W. S. Kritisches und Experimentelles zur Deutung zur Potentialschwankungen des Elektrocorticogramms. Z. ges; Neurol. Psychiat., 1938, 162: B15-824. 8. DUSSER DE BARENNE, ]. G. and McCuLLOCH, W. S. Factors for facilitation and extinction in the central nervous system. ]. Neurophysiol., 1939, 2: 319"355. 9. Ge,RARO, R. W., MARSHALL, W. H. and SAUL, L. ]. Electrical activity of the cat's brain. Arch. Neurol. Psychiat., Chicago, 1936, 36: 675-738. 10. HURSH, J. B. Origin o[ the spike and wave pattern of petit mal epilepsy. Arch. Neurol. Psychiat., Chicac3o, 1945, 53: 274-282. 11. JASPER, H. H. and DROOGLEEVER-FoRTUYN, J. Experimental studies on the functional anatomy
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of petit mal epilepsy. Res. Publ. Ass. neru. ment. Dis., 1947, 26: 272-298. MARSHALL, W. H., WOOLSEY, C. N. and BARD. P. Cortical representation of tactile sensibility as indicated by cortical potentials, Science, 193"/. 85: 388-390. MARSHALL, W. H., WOOLSEY. C. N. and BARD, P. In MacLeod: Physiolooy in modern medicine. 8th ed, St. Louis, C. V. Mosby & Co., 1938: 168-173. MORISON. R, S,. FINLAY. K. H. and LOTHROP. GLADYS N. Spontaneous electrical activity of thalamus and other [orebrain structures. ]. Neurophysiol., 1943, 6: 243-254. PENVXELI), W. and ERICgSON, T. C.: Epilepsy and cerebral localization. Sprin,,jfield, Ill., Charless C. Thomas. 1941: x + 623 pp.
D I S C U S S I O N : E. A. SPIEGEl D r . S p i e g e l ' s d i s c u s s i o n of this p a p e r h a s b e e n p r e p a r e d for p u b l i c a t i o n as a s e p a r a t e
article, which will appear of this j o u r n a l .
in a n e a r l y issue
Re[erence: HAYNE, R. A.. BELINSON, L. and GIBBS. F. A. Electrical activity of subcortical areas in epilepsy. EEG Clin. Neurophysiol., 1949. 1: 437-445.