Non-cephalic reference recording of early somatosensory potentials to finger stimulation in adult or aging normal: differentiation of widespread N18 and contralateral N20 from the prerolandic p22 and N30 components

Electroencephalography and Clinical Neurophysiology, 1981, 52:553--570

553

Elsevier/North-Holland Scientific Publishers, Ltd.

NON-CEPHALIC R E F E R E N C E R E C O R D I N G OF E A R L Y SOMATOSENSORY P O T E N T I A L S TO F I N G E R STIMULATION IN A D U L T OR AGING NORMAL MAN: D I F F E R E N T I A T I O N OF WIDESPREAD N18 AND C O N T R A L A T E R A L N20 FROM THE P R E R O L A N D I C P22 AND N30 COMPONENTS 1 JOHN E. DESMEDT and GUY CHERON Brain Research Unit, University o f Brussels, 115 boulevard de Waterloo, Brussels 1000 (Belgium)

(Accepted for publication: October 1, 1981)

The recent surge of interest for early somatosensory evoked potential (SEP) c o m p o n e n t s is providing a wealth of clinically relevant data (e.g., Desmedt 1971; Noel and Desmedt 1975, 1980; Colon et al. 1977, 1978; E1Negamy and Sedgwick 1978; Anziska and Cracco 1980; Chiappa et al. 1980; Eisen and Odusote 1980; Small et al. 1980; Maugui~re et al. 1982) while raising new issues t hat call for special investigations. For example, the early negativities recorded from the posterior neck after median nerve stimulation (Liberson and Kim 1963; Matthews et al. 1974; Cracco and Cracco 1976; Hume and Cant 1978; Small et al. 1980; Desmedt and Cheron 1980a; Maugui~re and Courjon 1981) have recently been analysed with pre- and postvertebral electrode arrays whereby t he y could be resolved into an N l l c o m p o n e n t t ha t is propagated from spinal entry up the dorsal column, and an N13 c o m p o n e n t that is related to a fixed generator in the dorsal horn of the cervical spinal cord (Desmedt and Cheron 1981). On the other hand, there is still a problem with the p r o p e r evaluation of the early cortical responses. Most current studies have considered the

1 This research has been supported by grants from the Fonds de la Recherche Scientifique M6dicale and the Fonds National de la Recherche Scientifique, Belgium.

SEPs recorded from the parietal scalp while neglecting the SEP c o m p o n e n t s that can be picked up in f r o n t of the central sulcus. The latter present a distinct profile which undergoes dissociated changes with aging (Desmedt and Cheron 1980b). Moreover the early frontal c o m p o n e n t s P22 and N30 have now been shown to involve i n d e p e n d e n t cortical generators with a separate thalamocortical input since they persist in patients with postrolandic cortical lesions that eliminate the early parietal SEP c o m p o n e n t s (Maugui~re et al. 1982). T herefore the SEP studies in which a frontal electrode was c o n n e c t e d to grid 2 of the amplifiers as reference have been complicated by the unwanted interference of the frontal generators. A thorough examination of these problems requires that a non-cephalic electrode be c o n n e c t e d to grid 2 of the amplifiers whereby the subcortical far-field components P 9 - P l l - P 1 3 - P 1 4 have indeed been studied (Cracco and Cracco 1976; Anziska and Cracco 1980; Cracco et al. 1980; Desm e d t and Cheron 1980a; Grisolia and Wiederholt 1980; Wiederholt 1980). However, it is much less know n that the SEP c o m p o n e n t s following the P14 far-field display quite une x p e c t e d features with non-cephalic reference recording. One of these is an apparently bilateral distribution of the early SEP negativity (Kritchevsky and Wiederholt 1978) which would appear to conflict with the current interpretation of the N20 SEP compo-

0013-4649/81/0000--0000/$02.75 © 1981 Elsevier/North-Holland Scientific Publishers, Ltd.

554 n e n t as reflecting t h e c o n t r a l a t e r a l cortical ' p r i m a r y ' r e s p o n s e to m e d i a n n e r v e stimulation. T h e p r e s e n t p a p e r analyses t h e early SEP c o m p o n e n t s r e c o r d e d w i t h n o n - c e p h a l i c or w i t h e a r l o b e e l e c t r o d e s c o n n e c t e d to grid 2 as r e f e r e n c e and also t a c k l e s t h e issue o f individual variabilities of SEP c o m p o n e n t s in n o r m a l subjects. Such variabilities a n d t h e c o n s i s t e n t changes o c c u r r i n g w i t h n o r m a l aging have p r o v e n invaluable in the p r o p e r e v a l u a t i o n of genuine SEP c o m p o n e n t s (cf., D e s m e d t and C h e r o n 1 9 8 0 b ) . C o n s i s t e n t n e w f e a t u r e s have n o w b e e n disclosed, n a m e l y the o c c u r r e n c e o f a rather widespread N18 component that m u s t be distinguished f r o m the ' p r i m a r y ' c o n tralateral p o s t r o l a n d i c N 2 0 , and t h a t interacts with the p r e r o l a n d i c P22 a n d N 3 0 g e n e r a t o r s to p r o d u c e the t o p o g r a p h i c a l f e a t u r e s o f SEP wave f o r m s .

Material a n d m e t h o d s T h e d a t a were c o l l e c t e d f r o m 40 n o r m a l adults (20 m a l e s a n d 20 females) o f 2 0 - - 3 5 years (37 subjects b e t w e e n 20 and 25 years and 3 b e t w e e n 30 and 35 y e a r s ) , and 35 h e a l t h y o c t o g e n a r i a n s (17 m a l e s and 18 females) o f 8 0 - - 9 1 y e a r s ( m e a n age 84.6 ± 3.8 S.D.). A b o u t h a l f o f t h e subjects h a d b e e n used for a p r e v i o u s p a p e r in which the criteria f o r selection o f the older s u b j e c t s have b e e n discussed ( D e s m e d t a n d C h e r o n 1980b, p. 405). All subject~ w e r e in g o o d h e a l t h , free f r o m n e u r o l o g i c a l disease and n o n - a d d i c t e d to t o b a c c o or alcohol. No s u b j e c t h a d a n y evid e n c e or h i s t o r y o f t r a u m a t o u p p e r l i m b , n e c k or skull. T h e y h a d given i n f o r m e d consent and m a n y o f t h e m agreed to r e t u r n f o r r e p e a t SEP studies. Besides f r e e d o m f r o m disease, t h e criteria f o r s u b j e c t selection involved ability to fully relax in o r d e r to minimize m u s c l e or e y e b l i n k i n t e r f e r e n c e and g o o d yields in SEP averaging. T h e subjects laid c o m f o r t a b l y on a c o u c h in a soundp r o o f e d , electrically shielded and air-condit i o n e d r o o m at 24 ° C.

J.E. DESMEDT, G. CHERON T h e stimuli were square electrical pulses of 0.2 m s e c delivered t h r o u g h a pair o f B e c k m a n c u p e l e c t r o d e s t o the left m e d i a n nerve ( c a t h o d e p r o x i m a l ) j u s t a b o v e t h e wrist. T h e intensities c h e c k e d b y a c u r r e n t p r o b e were 3--7 m A ( a b o u t 3 t i m e s the subjective threshold) and elicited small t h u m b t w i t c h e s . In o t h e r runs the stimuli were delivered t h r o u g h silver rings to fingers II and I I I o f the left h a n d , also at a b o u t 3 t i m e s subjective threshold. When the t h u m b was also s t i m u l a t e d to increase the a f f e r e n t volley, its stimulus was d e l a y e d b y 0.5 m s e c to m a k e up for the shorter distance to the spinal c o r d (cf., D e b e c k e r and D e s m e d t 1964). T h e t i m e intervals b e t w e e n stimuli varied at r a n d o m b e t w e e n 0.5 and 1.0 sec, and the m e a n s t i m u l a t i o n rate n e v e r e x c e e d e d 2/sec. T h e left u p p e r l i m b was w a r m e d b y i n f r a r e d and its skin t e m p e r a t u r e was n o r m a l at 3 5 - - 3 6 . 5 ° C . Each e x p e r i m e n t i n c l u d e d several runs with 14 s i m u l t a n e o u s r e c o r d i n g s t h a t involved t w o 8-channel FM m a g n e t i c r e c o r d e r s , o p e r a t e d at 7 in./sec. Scalp, earlobes and p o s t e r i o r n e c k sites were r e c o r d e d f r o m with u n v a r n i s h e d stainless steel needles 0.2 m m d i a m e t e r . T h e n o n - c e p h a l i c r e f e r e n c e was a silver p l a t e on the d o r s u m o f the right h a n d . E l e c t r o d e i m p e d a n c e was m a i n t a i n e d u n d e r 3 0 0 0 ft. Differential a m p l i f i e r s with 10 M ~ i n p u t i m p e d a n c e were used. T h e overall b a n d p a s s e x t e n d e d f r o m 2.5 k H z to 0.5 Hz ( D e s m e d t et al. 1974). F o r each run 1024 or 2 0 4 8 s a m p l e s were averaged off-line with a N i c o l e t m o d e l 1074 c o m p u t e r ( 4 0 9 6 w o r d s o f 9 bits) a f t e r editing the F M - t a p e d d a t a to e x c l u d e blockings, excess E M G or o t h e r i n t e r f e r e n c e (cf., D e s m e d t 1 9 7 7 , f o r details o f m e t h o d s ) . T h e bin w i d t h was 80 or 160 psec and 1024 p o i n t s were used f o r each o f the 4 traces simultan e o u s l y averaged. All figures p r e s e n t original records, t h a t is u n s m o o t h e d traces d r a w n on p a p e r by the averaging c o m p u t e r t h r o u g h an X-Y p l o t t e r , to allow detailed s c r u t i n i z a t i o n o f the responses. Several writings o f the same t r a c e (with a 0.2 m m shift along the o r d i n a t e ) were used to o b t a i n a t h i c k e r line f o r identification purposes when two different records

SOMATOSENSORY N18-N20-P22-N30 COMPONENTS were superimposed. C o m p o n e n t profiles and latencies were consistent in repeat runs on any given subject. The SEP c o m p o n e n t s were labelled from the positive (P) or negative (N) polarity and their modal peak latency, as r e c o m m e n d e d by an international c o m m i t t e e (Donchin et al. 1977).

Results In order to clarify the presentation, all SEP c o m p o n e n t s are given standard labels with the model peak latency for median nerve stimulation in a y o u n g subject of mean arm length: thus, the labels for the positive scalp far fields P9-P11-P13-P14, for the postcentral N20-P27P45 and for the precentral P22-N30 are used irrespective of the actual peak latency (which may be ab o u t 3 msec longer in the case of finger stimulation, for example). The records illustrated for each subject are from both sides of the scalp at a parietal site 70 m m from the midline and 30 mm behind Cz and at a frontal site 50 mm from midline and 61) mm in front of Cz (Fig. 1). The emphasis is on the inter-subject differences in those SEP features which were consistent in any given subject. With a non-cephalic reference on the right hand, the contralateral parietal SEP disclosed several inflections on the rising limb of N20, after the P14 far field (Fig. 1B). The first inflection also occurred ipsilaterally at the frontal (Fig. 1A) and earlobe electrodes (Fig. 1C). This p h e n o m e n o n differed from a mere return of the P14 positivity and we propose to designate it as the widespread N18 component (hatched). In this subject the N18 was fairly consistent in size and profile ipsilaterally. F o r lack of any ot her specific reason, we consider that it terminated or decreased at the time of onset of the frontal N30 (Fig. 1A). T h e N18 is t h o u g h t to be present at the contralateral electrodes where its interaction with postcentral N20 and precentral P22 generators resulted in typical wave forms. The onset of N20 could be estimated from the

555 divergence time of the contralateral trace from the ipsilateral (Fig. 1B) or after electronic subtraction of these two traces whereby the early far fields are removed and a fair a p p r o x i m a t i o n of the early 'primary' cortical negative response is directly displayed (Fig. 2D) (cf., Desmedt and Cheron 1980a, Fig. 10). A similar profile of N20 was seen with earlobe (instead of non-cephalic) reference (Fig. 2C), obviously because the N18, being roughly similar at earlobe and ipsilateral parietal electrodes, canceled out. In these traces the rising limb of N20 displayed a second inflection whose significance remained obscure. At the frontal electrodes recorded with non<:ephalic reference, the trace diverged downward contralaterally with the onset of the P22 (Fig. 1A). This was virtually absent ipsilaterally in this subject. Electronic subtraction of the two traces removed the early far fields and displayed a well-delineated P22 (Fig. 2A) which was rather similar to the one seen in the earlobe reference recording (Fig. 2B). The actual onset time of P22 may have to be negotiated, but a clear positive transition seemed to occur about 1 msec after the onset of the postcentral N20. The duration of P22 could only be surmised. It was taken to decrease or disappear as the frontal negativity N30 t o o k off: this was clearly indicated in the non-cephalic recording (Fig. 1A). Some N30 activity was usually present ipsilaterally, as indeed suggested by the added negativity at the same latency in the ipsilateral record (Fig. 1A). If so, the electronic subtraction of the two frontal traces underestimated the true size of the contralateral N30 (Fig. 2A), whereas the earlobe reference recording disclosed more appropriately a larger N30 (Fig. 2B) because the earlobe itself presented little 'N30' activity (Fig. 1C). In this subject, postcentral positivities were virtually absent with non-cephalic reference recording (Fig. 1B). A P27 appeared to be riding on a steady negativity and was revealed either by subtraction of the parietal traces (Fig. 2D) or by earlobe reference recording

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Fig. 1. Normal male subject of 34 years. Non-cephalic reference recording of SEP components recorded at the frontal scalp (A), at the parietal scalp (B) and at the earlobes (C). Negativity of the active electrode produces an upward movement of the trace in this and all subsequent figures. The traces from the contralateral side are presented by thicker lines (drawn by several writings of the computer) and are superimposed on the traces from the ipsilateral side. Electrode positions and traces are numbered from 1 to 4. The electric stimulus is delivered to the left fingers II and III. The far-field onset and the P9 and P14 far fields are well delineated. After P14, a first inflection on the negative-going traces indicates the onset of component N18 (vertical fine-dotted line) while the onset of the parietal N20 is indicated as corresponding to the divergence of the contralateral and ipsilateral parietal traces in B. The N18 p h e n o m e n o n is represented by hatched area which is arbitrarily terminated at the onset of the frontal N30 component (A). The N18 is present at all electrodes ipsilaterally, and is supposed to underlie the focal SEP components N20 (B) or P22 (A) on the contralateral side.

(Fig. 2C). Both manipulations indeed removed much of the N18 phenomenon and subsequent negativity. The onset time of P27 was well d e f i n e d a n d q u i t e d i f f e r e n t f r o m t h e o n s e t s o f t h e p r e c e n t r a l P 2 2 or N 3 0 . I t w a s

s u r p r i s i n g t h a t a large P 4 5 a p p e a r e d p r e c e n t r a l l y (Figs. 1 A a n d 2B) w h i l e n o n e was r e c o r d e d p o s t c e n t r a l l y (Fig. 2C,D). When comparing recordings from either e a r l o b e s , P 1 4 far f i e l d was l a r g e r c o n t r a l a t e r a l

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to the h a n d s t i m u l a t e d as previously described ( D e s m e d t and C h e r o n 1 9 8 0 a , Figs. 5 and 6) while the s u b s e q u e n t negativities were fairly similar (Figs. 1C and 3C). It is difficult to decide w h e t h e r the transient u p w a r d deviation at the c o n t r a l a t e r a l earlobe b e t w e e n a b o u t 18 and 24 msec related t o a slight increase o f either N 1 8 , or N 2 0 , or b o t h on t h a t side. The n e x t a d u l t subject also disclosed clear inflections o n the negative-going trace after the P 1 4 far field and the N 1 8 and N 2 0 c o m portents were easily d i f f e r e n t i a t e d (Fig. 3B).

T h e c o n t r a l a t e r a l f r o n t a l electrode presented a t y p i c a l P 2 2 - N 3 0 - P 4 5 sequence, b u t the ipsilateral f r o n t s h o w e d definite P22 activity (Fig. 3A) in c o n t r a s t to the previous subject (Fig. 1A). T h e s u b t r a c t i o n o f the frontal traces thus t e n d e d to u n d e r e s t i m a t e the P22 (Fig. 4A). A t the c o n t r a l a t e r a l parietal elect r o d e , large P27 and P45 were seen, even with the n o n - c e p h a l i c r e f e r e n c e (Figs. 3B and 4C). These c o m p o n e n t s were virtually absent f r o m the ipsilateral trace so t h a t the s u b t r a c t i o n displayed quite p r o m i n e n t 'W' profiles (Fig. 4D).

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Fig. 3. Normal male subject of 35 years. Same presentation of non-cephalic reference recordings of SEP components at the frontal scalp (A), at the parietal scalp (B) and at the earlobes (C). The contralateral traces are presented with thicker line. The electric stimulus is delivered to the left median nerve at the wrist. The N18 component is indicated by hatching. The n e x t n o r m a l adult subject p r e s e n t e d characteristic P9, P l l and P14 far fields foll o w e d b y a clear inflection c o r r e s p o n d i n g to the o n s e t o f the w i d e s p r e a d N 1 8 (Fig. 5). The a m p l i t u d e o f N 1 8 was definitely smaller t h a n in previous subjects at all sites c o m p a r e d . M o r e o v e r the p r e r o l a n d i c P22 was quite large c o n t r a l a t e r a l l y and p r e s e n t with a smaller size ipsilaterally (Fig. 5A). In fact the traces at the f r o n t were r a t h e r similar on b o t h sides so t h a t their s u b t r a c t i o n resulted in very small deflexions (Fig. 6A) t h a t u n d e r e s t i m a t e d the true

size o f P22 and N30. These were b e t t e r disp l a y e d with earlobe reference recordings in w h i c h the P9 and N 1 8 effects virtually canceled o u t (Fig. 6B). T h e o n s e t of the parietal N 2 0 and P27 was clear in all m o n t a g e s (Figs. 5B and 6C,D). T h e P45 was p r e s e n t at the c o n t r a l a t e r a l parietal. Fig. 7 illustrates a n o r m a l adult in w h o m the N 1 8 was r a t h e r large while the prerolandic P22 was quite small. The frontal N 3 0 ' s were very large on b o t h sides f r o n t a l l y , b u t n o t at the ipsilateral parietal e l e c t r o d e (Fig. 7C).

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There was a steady negativity prolonging the N18. The onset of N20 was clearly indicated but its amplitude was small and it required good quality records to identify the N20 riding over the large N18 phenomenon (Fig. 7B). The subtraction displayed the N20 without ambiguity and also the P27 (Fig. 7D). If considered independently of the N18 and steady negativities identified in the ipsilateral trace, the contralateral trace would have been difficult to interpret correctly (Fig. 7B). In this subject subtraction of the frontal record yielded a spurious 'N14' (because the P14 far field was larger at the front, now used as a reference; see Desmedt and Cheron 1980a,

Fig. 9) and larger N2O and P27 (because the front reference connected to grid 2 of the amplifier picked up the P22 and N30) (Fig. 7E). The posterior neck trace identified the spinal entry time from the onset of N l l (Fig. 7F) which coincided with the onset of the P l l scalp far field (cf., Desmedt and Cheron 1980a, 1981). Fig. 8 illustrates another young adult with rather small N18 and a large P22 which appeared at the contralateral front only (A). The frontal N30 presented an earlier onset ipsilaterally, presumably because of the lack of competing P22 on that side in this experiment. The true onset of N30 was taken as

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indicated at the trough of P22 and onset of ipsilateral N30. The difference in onset latencies for N20 and P22 was rather important in this subject (Fig. 8C).

Comparison with healthy octogenarians Fig. 9 presents similar data for a female subject of 85 years who was selected as discussed before (Desmedt and Cheron 1980b) for lack of any interfering disease state. With non-cephalic reference large far-field potentials were recorded (Fig. 9A,B) and the onset of the spinal N l l at the posterior neck (Fig. 9D) matched the onset of the scalp-recorded

P l l far field. A feature of aging is the enhancement of the parietal SEP components N20, P27 and P45. The N18 was also present with the same profile and onset at the first upward inflection as in the young adults. The frontal negativity tended to be reduced in the older subjects. The present study on a larger number of subjects replicated the data of the previous paper (Desmedt and Cheron 1980b) to document the significant increase of the N20, P22, P27 and P45 SEP components and the decrease of the frontal N30 c o m p o n e n t (Table I). It was interesting to enquire whether

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Fig. 6. Same subject as in Fig. 5. Earlobe reference recordings (B,C) and subtraction of ipsilateral from contralateral records (A,D).

t h e d i f f e r e n c e s o f SEP w i t h aging were also p r e s e n t to t h e s a m e e x t e n t w h e n a n o n - c e p h a lic r e f e r e n c e e l e c t r o d e was used. W h e n m e a sured f r o m baseline, the c o n t r a l a t e r a l parietal n e g a t i v i t y ( w h i c h is s h o w n in t h e p r e s e n t p a p e r to include in f a c t t h e N 1 8 and N 2 0 c o m p o n e n t s ) was clearly larger in o c t o g e n a r ians (Table II). T h e d i f f e r e n c e was s u b s t a n t i a t e d by the N20 measures obtained after subtract i o n o f t h e ipsilateral parietal r e s p o n s e . By contrast the amplitude of the widespread N18 was n o t significantly d i f f e r e n t b e t w e e n t h e y o u n g adults a n d t h e h e a l t h y o c t o g e n a r i a n s

(Table II). T h e transit t i m e s f r o m o n s e t o f N 2 0 to t h e o n s e t o f the o t h e r cortical SEP c o m p o n e n t s w e r e also r e - m e a s u r e d w i t h t h e n o t i o n t h a t an N 1 8 c o m p o n e n t was p r e s e n t u n d e r n e a t h t h e N 2 0 , and a larger n u m b e r of subjects considered. T h e r e is o n e n e w f e a t u r e in t h e s e upd a t e d m e a s u r e s , n a m e l y t h a t we c o n s i d e r e d n o w t h e P22 at the f r o n t a l e l e c t r o d e s a b o u t 60 m m in f r o n t of Cz in o r d e r to avoid t h e i n t e r f e r e n c e f r o m t h e p o s t c e n t r a l N20. T h e latter s o m e t i m e s d i f f u s e d to s o m e e x t e n t t o w a r d s t h e f r o n t ( a l t h o u g h w i t h smaller am-

562

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Fig. 7. Normal male subject of 25 years. Non-cephalic reference recordings of frontal (A) and parietal (B) electrodes. Electrical stimulation of left fingers II and III. C: superposition of the 4 traces displayed in A and B. D: subtraction of the ipsilateral parietal from the contralateral parietal record. E: subtraction of the contralateral frontal from the contralateral parietal record. F : posterior neck recording at C6.

plitude) and this e f f e c t was f o u n d to c o n t r i b u t e to u n d u l y d e l a y i n g the a p p a r e n t o n s e t o f the p r e r o l a n d i c P22. When measuring t h e P22 onset f u r t h e r in f r o n t , as we n o w r e c o m m e n d ,

Fig. 8. Normal male subject of 23 years. Non-cephalic reference recording of SEP of frontal (A) and parietal (B) electrodes. Electrical stimulation of [eft fingers II and III. C: superposition of the 4 traces displayed in A and B. D: subtraction of the ipsilateral parietal from the contralateral parietal record.

a s h o r t e r transit time was f o u n d for this comp o n e n t , n a m e l y 0.62 ± 0.7 msec (instead o f 2.5 _+ 1.1 msec in D e s m e d t and C h e r o n 1 9 8 0 b , Table III) for the y o u n g adults and 0.95 -+ 0.94 msec (instead o f 3.4 :t 0.8 msec in the same paper) for the octogenarians. T h e increase in transit time f r o m o n s e t of N 2 0 to

SOMATOSENSORY N18-N20-P22-N30 COMPONENTS

r

onset of P22 remained significant at P < 0.02 ( T a b l e I I I ) . T h e r e is also a s l i g h t c h a n g e in t h e mean transit time from onset of N20 to peak o f P 2 2 , w h i l e t h e o t h e r m e a s u r e s a r e in g o o d a g r e e m e n t w i t h t h e p r e v i o u s s t u d y . T h e reas o n s f o r m e a s u r i n g P 2 2 a t m o r e f r o n t a l electrodes will become clear from detailed SEP m a p s (in p r e p a r a t i o n ) .

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Time features o f N 1 8 and early SEP comporte n ts With non-cephalic reference recording, the characteristic pattern of the positive scalp farfield potentials P9, P l l , P13-P14 was re~orded in 38% of the subjects (Figs. 3 and 10A,B). Intersubject variations affected

B

m a i n l y t h e P l l ( a b s e n t in 3 2 % o f t h e s u b j e c t s ; Figs. 8 a n d 1 0 D ) o r t h e P 1 3 ( a b s e n t o r d o u b t f u l in 4 4 % ; F i g s . 3, 1 0 C a n d 1 1 A ) . I n some subjects the P13 was larger than P14 (Fig. 10D). The duration of P14 up to the onset of N18 (Fig. 11A) had a mean value of 1.66 ± 0.58 msec and P14 tended to be somewhat s h o r t e r w h e n it w a s p r e c e d e d b y a c l e a r P 1 3 ( s t i p p l e d a r e a in F i g . 1 1 D ) . T h e d u r a t i o n o f Pll was 1.56 +-0.77 msec (Fig. 11C). These durations of scalp far fields were significantly shorter at P < 0.001 than the duration of the spinal N13-P13 component (4.19-+ 0.64 m s e c ; F i g . l l E ) w h i c h w a s b e s t m e a s u r e d in

c

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Fig. 9. Healthy octogenarians female of 85 years. Non-cephalic reference recording of SEP of frontal

(A) and parietal (B) electrodes. Electrical stimulation of the left median nerve at wrist. C: subtraction of the ipsilateral parietal from the contralateral parietal record. D: posterior neck recording at C6.

TABLE I Voltage of SEP components recorded with earlobe reference (pV). Component

Young adults (n = 40)

Healthy octogenarians (n = 35)

Difference (%)

t test

N20 P27 P22 P45 N30

0.78 1.41 0.74 1.61 2.49

1.30 2.10 1.27 3.64 1.54

+67 +49 +71 +126 --38

P < P < P < P< P <

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_+ 0.4 + 1.0 _+ 0.7 + 1.2 _+ 1.0

0.001 0.02 0.02 0.001 0.02

564

J.E. DESMEDT, G. CHERON

TABLE II Voltage of early negative SEP components (pV). Component

Reference

Young adults

Healthy octogenarians

Difference (%)

t test

Contralateral parietal (N18 + N20)

Non-cephalic

0.98 -+ 0.2 (n = 17)

1.43 -+ 0.4 (n = 9)

+46

P < 0.001

N18 Ipsilateral parietal

Non~ephalic

0.58 -+ 0.2 (n = 17)

0.61 -+ 0.3 (n = 9)

+5

N20 Contralateral parietal

Ipsilateral parietal

0.54 + 0.1 (n = 17)

0.92 -+ 0.3 (n = 9)

+70

P < 0.001

N20 Contralateral parietal

Earlobe

0.78 -+ 0.4 (n = 40)

1.30 -+ 0.4 (n = 35)

+67

P < 0.001

P > 0.2

TABLE III Transit times from the onset of N20 to various components (msec) (mean + S.D.).

Onset of P22 Peak of P22 Peak of P27 Onset of N30 PeakofN30 Peak of P45

Young adults (n = 40)

Healthy octogenarians (n = 35)

Difference (%)

t test

0.62 4.3 8.0 4.9 11.0 24.2

0.95 6.0 10.0 7.3 15.1 29.5

+53 +39 +25 +49 +37 +22

P > P< P > P< P< P<

+ 0.7 -+1.4 + 2.9 -+1.0 +2.7 -+ 2.6

_+0.94 -+1.4 + 3.0 +1.2 -+6.1 -+ 3.8

TABLE IV Mean transit times from spinal entry estimated as onset of neck N l l or scalp P l l (mean-+S.D. in (msec). To To To To To

onset of P13-P14 scalp far fields peak of P14 scalp far field onset of scalp N18 onset of parietal N20 onset of prerolandic P22

Mean interval from onset of P13-P14 far fields to peak of P14 Mean interval from peak of P14 far field to onset of scalp N18

1.75 3.71 4.74 6.4 7.02

_+0.30 + 0.55 + 0.27 _+0.45 _+0.51

1.96 -+ 0.27

0.1 0.02 0.1 0.001 0.02 0.01

1 9 8 1 ) . E v i d e n c e s u g g e s t s t h a t t h e a f f e r e n t volley arrives at the t h a l a m u s at a m e a n of a b o u t 3.71 + 0.58 msec after spinal entry, thus at a b o u t t h e p e a k o f t h e P 1 4 scalp far field. T h e o n s e t o f t h e w i d e s p r e a d N 1 8 is o n l y 1.03-+ 0.31 msec thereafter, while the onset of the p a r i e t a l N 2 0 is 2 . 6 9 _+ 0 . 4 2 m s e c t h e r e a f t e r (Table IV).

Discussion

1.03 + 0.27

prevertebral (oesophageal) recordings and which was r e c e n t l y s h o w n to be related to a f i x e d g e n e r a t o r in t h e d o r s a l h o r n ( D e s m e d t and Cheron 1981, 1982). Table IV provides a replication and update based o n 40 n o r m a l adults for the transit times along the central somatosensory pathw a y (cf., D e s m e d t a n d C h e r o n 1 9 8 0 a , b ,

T h i s p a p e r r e p l i c a t e s a n d e x t e n d s several points recently made about the functional o r g a n i z a t i o n of the s o m a t o s e n s o r y system in m a n a n d its c h a n g e s w i t h n o r m a l a g i n g (Desm e d t and C h e r o n 1 9 8 0 a , b , 1981). It e m p h a sizes t h e s h a r p a n d c o n s i s t e n t d i f f e r e n c e s r e c o r d e d in f r o n t or b e h i n d the central sulcus contralateral to the hand stimulated (Desmedt and Cheron 1980b; Papakostopoulos and

SOMATOSENSORY N18-N20-P22-N30 COMPONENTS

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Fig. 10. E x a m p l e s o f d i f f e r e n t p a t t e r n s o f positive scalp far-field p o t e n t i a l s r e c o r d e d w i t h a noncephalic r e f e r e n c e in n o r m a l y o u n g adults. Electrical s t i m u l a t i o n o f the left m e d i a n nerve at wrist. The active e l e c t r o d e is placed at the c o n t r a l a t e r a l parietal scalp (A,B,C,) and at m i d f r o n t Fz (D). The o n s e t of the N18 is i n d i c a t e d in all traces, as well as the o n s e t o f N20 (A--C) or P22 (D). A: female o f 23 years. B:

565

Crow 1980). In addition, the use of noncephalic reference recording helped resolve current issues about the early SEP negativities through the demonstration that an N18 phen o m e n o n with widespread scalp distribution must be distinguished from the cortical N20 SEP c o m p o n e n t which is restricted to the contralateral parietal region. SEP components disclose a number of consistent features varying within a reasonably restricted range .(Tables I--III), but they also present intriguing intersubject variabilities that have confused a number of questions and that have certainly not been given adequate consideration, at least in published reports. We think that both the intersubject variabilities and the changes associated with normal aging offer considerable opportunities for a more realistic evaluation of the genuine SEP components (Desmedt and Cheron 1980b). Clinical applications of SEPs are to be upgraded through such detailed information in order to better identify the characteristic changes associated with specific disease conditions. Su bcortical SE P cornponents With non-cephalic reference recording, all scalp and neck electrodes record first a positive P9 far-field potential that is related to action potential volley of peripheral nerve fibres near the entrance into the brachial plexus. The spinal N l l recorded at the posterior neck is related to the ascending volley in dorsal column and its onset, coinciding with that of the scalp-recorded P l l far field (Figs. 7 and 9), corresponds to the arrival of the peripheral nerve volley at the spinal cord C6-C7 segments (Desmedt and Cheron 1980a, 1981). N l l is eliminated as well as the subsequent SEP components by spinal root avulsion in brachial plexus lesions (Anziska and Cracco 1980). The onset of the P13-P14 scalp farfield potential is t h o u g h t to correspond to the

male o f 22 years. C: male o f 22 years. D: female of 20 years.

566

J.E. DESMEDT, G. CHERON

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Fig. 11. Duration of far-field potentials and of the spinal P13-N13 component. A,B: non-cephalic reference recordings of SEP to median nerve stimulation in a young adult subject. A: earlobe derivation showing far fields PP, P l l and P14 (no P13 can be clearly identified in this experiment). The duration of P14 is taken from its onset to the onset of the N18 component. B: prevertebral (oesophageal) recording from the level of C5 showing after the P9 nerve far field a spinal root action potential, then a small negativity N l l from the dorsal column, and the P13 wave whose duration is indicated. The graphs C to E present pooled data in different adult subjects for the duration of the spinal P13 (C), of the scalp or earlobe recorded P14 (dotted area corresponds to P14 when preceded by clear P13 while the white area corresponds to P14 when P13 is apparently lacking) (D), and of the scalp

Pll(E). a c t i v a t i o n o f t h e a s c e n d i n g v o l l e y in t h e m e dial lemniscus since its timing at a mean of 1 . 7 5 -+ 0 . 3 0 m s e c a f t e r s p i n a l e n t r y ( T a b l e I V ) corresponds fairly well with the dorsal column conduction time (70 mm at 58.5 m/sec, t h a t is 1 . 2 m s e c ) p l u s a s y n a p t i c d e l a y o f 0 . 3 - 0.5 msec for the synapses between dorsal column axons and cuneate neurones (Desmedt and Cheron 1980a). S i n c e t h e l a r g e r a x o n s in t h e m e d i a l l e m n i s cus have a diameter of 8--9 pm, this corres p o n d s t o a c o n d u c t i o n v e l o c i t y o f a b o u t 36 m/sec if the conversion factor of 4.5 m/sec/ p m a p p l i e s ( s e e D i s c u s s i o n in D e s m e d t a n d

Cheron 1980a). With a conduction distance of a b o u t 7 0 m m in m e d i a l l e m n i s c a l a x o n s , t h e c o n d u c t i o n t i m e c a n b e c a l c u l a t e d as 7 0 : 36 = 1.94 msec. Such data would be rough estimates which we consider valid +10--20%. I n a n y c a s e t h i s v a l u e is r e m a r k a b l y c l o s e t o t h e m e a n t i m e f r o m o n s e t o f t h e s c a l p farfield P13-P14 up to the peak of the P14 (Table IV). Therefore we interpret the P13-P14 f a r f i e l d ( w h i c h is n o t r e c o r d e d b e l o w f o r a m e n m a g n u m ) as a v o l u m e - c o n d u c t e d p o t e n tial related to the summation of the travelling a c t i v i t y in m e d i a l l e m n i s c u s : t h e f a r - f i e l d o n set corresponds to the activation of the caudal

SOMATOSENSORY N18-N20-P22-N30 COMPONENTS lemniscal fibres while its peak at P14 reflects the arrival of the fastest lemniscal action potentials at the thalamus. These data show internal consistency and t h e y exclude the possibility that P14 could be generated at or above the thalamus (Desmedt and Cheron 1980a). This interpretation is actually supported by clinical evidence t ha t the P14 far field is preserved in patients with a thalamic vascular lesion that eliminates all subsequent SEP activity (Nakanishi et al. 1978; Maugui~re and Courjon 1981). We can now consider the transit time from the arrival at the thalamus to the onset of the N18 which has a mean value of 1.03 ± 0.31 msec (Table IV). Since a synaptic delay of no less than 0.3 msec must be allowed for in thalamus between the lemniscal axons and the ventrobasal neurones, this would only leave a b o ut 0.74 msec for c o n d u c t i o n along the nerve fibres that elicit the N18. This rules out N18 being generated at the cor t e x for the thalamocortical c o n d u c t i o n distance is about 60 mm and, with only 0.74 msec available, the c o n d u c t i o n velocity would have the unreasonably high value of 81 m/sec. A n o t h e r argument for denying a cortical origin to N18 is its widespread occurrence all over the scalp: this seems to preclude any specific regional or areal generator that would be consistent with the known an atom y of somatosensory connections (Jones and Powell 1969; Jones 1981). This N18 p r oba bl y reflects subcortical activities such as delayed potentials in the thalamus itself, or action potentials in the lower part of the thalamocortical axons. The observation that N18 presents a sizeable amplitude on the ipsilateral scalp also invites questions since the thalamocortical radiation potentials are elicited only from the hemithalamus contralateral to the side stimulated (Albe-Fessard et al. 1963; Ohye et al. 1972). A n o t h e r intriguing point is the negative sign o f N18 since all ot her far-field potentials present a positive deflexion, as indeed to be expected for volume c o n d u c t i o n b e y o n d the structure generating the nerve volley ( L o r e n t e

567 de N5 1947; Arezzo et al. 1981). The disclosure of widespread N18 negativity appears to resolve at least in part the issue raised by Kritchevsky and Wiederholt (1978) who studied SEP with non-cephalic reference recording and found that there is no clear difference between the parietal derivations on the two sides of the head. We propose that, at the ipsilateral electrodes, a sizeable N18 is recorded with non-cephalic reference that must be distinguished from the contralateral N18 + N20. Measurements presented in Table II clarify this problem, as do also the figures illustrating the intersubject variations of these negativities. In all cases it was obvious that a surplus negativity (N20) was present at the contralateral parietal cortex. In view of its restricted location behind the central sulcus, this N20 must represent the earlier ('primary') cortical response in the projection areas 3--1--2 of somatosensory cort ex (cf., Desmedt and Cheron 1980a,b). N20 is large and of longer duration in normal new born babies (Desmedt and Manil 1970) and it shows a remarkable increase (not present for N18) during normal aging (Table II). N20 can also be recorded with a ihigh amplitude of several microvolts by electrodes placed directly on the postcentral gyrus (Domino et al. 1965; Papakostopoulos and Crow 1980). T he present data also replicate and emphasize that the ipsilateral parietal cortex does n o t generate a specific early response similar to N20, in addition to the widespread N18. The lack of ipsilateral early SEP c o m p o n e n t s for stimulation of distal upper limb was docum e n t e d by Desmedt and Robert son (1977) and confirmed since (Desmedt and Cheron 1980a,b). This has probably to do with the lack of callosal connections for the primary receiving areas representing the distal limb (Joihes and Powell 1969; Pandya and Vignolo 1969; Karol and Pandya 1971). T he cortical SEP c o m p o n e n t P22 described by Cheron and Desmedt (1980b) has been further delineated in the present data. Due to blurring of contours of regional potentials,

568 the postcentral N20 contributes to some delay in the recorded onset of the prerolandic P22 when the latter is recorded at a bout the level of Cz. This interference of potential fields is no longer present at m o r e frontal positions (60 mm in f r o n t of Cz) that were used here (cf., Cheron and Desmedt in preparation). It was thus possible to re-estimate the transit times and amplitude for P22 in a larger series of subjects (Tables I and II). We find that there is a rather short interval between the onset of N20 and P22, namely 0.62 msec. This finding supports the view that P22 is related to a separate generator (Papakostopoulos and Crow 1980; Desmedt and Cheron 1980b, 1982) and c a nnot be reduced to a simple mirror image (phase reversal) of N20. While there are i m p o r t a n t cortico-cortical connections from parietal areas 2 and 5 to precentral areas 4 and 6 (Jones and Powell 1969; Jones et al. 1978; Jones 1981), it now appears that P22 must be generated by separate thalamocortical connections because the interval between onset of N20 and P22 is rather short. Decisive evidence for this view comes from recent results of Maugui~re et al. (1982) showing that the prerolandic P22 and N30 c o m p o n e n t s persist in patients with a parietal lesion that eliminates the N20-P27P45 co mp o n en ts . The present study also confirms that SEP c o m p o n e n t s are generally larger and be t t e r delineated in the healthy old subjects than in the y o u n g adults. For example a clear 'W' pattern with clear P27 and P45 c o m p o n e n t s after the N20 at the contralateral parietal cor t e x was recorded in 47% of the young adults, but in 83% o f the octogenarians.

Summary Prerolandic and parietal SEPs to electrical stimulation of fingers or median nerve were studied with non-cephalic reference in 40 normal y o u n g adults and in 35 healthy octogenarians. Limb temperatures were 36--37°C.

J.E. DESMEDT, G. CHERON Intersubject variations of SEP c o m p o n e n t s were analysed. A new widespread c o m p o n e n t N18 was identified and shown to be generated below the cortex. This N18 is about the only early c o m p o n e n t recorded at the parietal ipsilateral region after the positive far-field potentials P9, P l l and P13-P14. Transit times along the central somatosensory pathway were replicated and discussed as well as other evidence about the sequential activation of the various neural structures involved. The N20 potential representing the earliest cortical response is recorded from the contralateral parietal region, but is absent ipsilaterally. The prerolandic potential is related to distinct generators and is elicited by a separate thalamocortical pathway rather than by corticocortical connections from areas 2 and 5 in parietal cortex. The changes associated with normal aging have been confirmed and extended.

R6sum6 Enregistrement avec rdfdrence non-cgphalique des potentiels somesthdsiques prdcoces ddclenchds par la stimulation des doigts chez l'adulte ou le sujet dgd normal: diffdrenciation de la composante diffuse N18 et de la composante contralatdrale N 2 0 des composantes prdrolandiques P22 and N30 Les potentiels 6voqu6s somesth6siques (PES) f r o n t a u x et pari6taux ~ la stimulation des doigts ou du nerf m~dian ont 6t6 6tudi6s avec l'utilisation d'une r6f6rence non-c6phalique chez 40 sujets adultes n o r m a u x et chez 35 octog6naires en bonne sant6. La temp6rature du m em bre stimul6 6tait de 36 ~ 38°C. Les variations interindividuelles des composantes PES ont 6t6 ana]ys6es. Une nouvelle c o m p o s a n t e diffuse N18 a 6t6 identifi6e (origine sous-corticale) et diff6renci6e du N20 contralat6ral. Aucune com posant e pr6coce ~ part le N18 n'a 6t6 observ6e ipsilat6ralement apr6s les potentiels de champ 61oign6 P9, P l l et P13-P14. Les temps de transit le long de la

SOMATOSENSORY N18-N20-P22-N30 COMPONENTS v o l e s o m e s t h ~ s i q u e o n t 4t4 c o n f i r m 4 s e t disc u t & s u r u n p l u s g r a n d n o m b r e d e s u j e t s . Les c o m p o s a n t e s p r ~ r o l a n d i q u e s o n t ~t4 m i s e s e n r e l a t i o n avec des g d n 4 r a t e u r s c o r t i c a u x dist i n c t s q u i s o n t activ4s p a r u n e v o l e t h a l a m o c o r t i c a l e s4par~e. Les m o d i f i c a t i o n s des P E S li5es au v i e i l l i s s e m e n t n o r m a l o n t 4t~ c o n firm~es et & e n d u e s .

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