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Target side and scalp topography of the somatosensory P300
468
Electroencephalography and clinical Neurophysiology, 88 (1993) 468-477 © 1993 Elsevier Scientific Publishers Ireland, Ltd. 0168-5597/93/$06.00
EEP 92113
Target side and scalp topography of the somatosensory P300 Philippe Bruyant, Luis Garcla-Larrea and Francois Maugui re Clinical Neurophysiology Unit, Research Lab. JE133, CERMEP, University Lyon I, 69003 Lyon (France)
(Accepted for publication: 27 April 1993)
Summary We recorded somatosensory P300 to target electrical shocks (10% probability) delivered to the left or right hand concurrently with non-target stimuli applied to the opposite hand. Target stimuli evoked a widely distributed P300, which was found to be double-peaked in 60% of the subjects investigated. The mean latencies of the "early" and "late" P300 peaks were respectively 302_+ 8 msec and 353 + 12 msec. Both components (but especially the earlier one) were consistently lateralized over the hemiscalp contralateral to the target stimuli, whichever the target side. Although on theoretical grounds P300 lateralization might depend upon the sustained attentional activation of the hemisphere contralateral to targets, this hypothesis was contradicted in one complementary experiment in which we dissociated the side receiving the P3-evoking, rare, stimuli from the side to which sustained attention was directed. Under these conditions the P3 evoked by rare, but ignored, shocks corresponded to the "early" peak of target P300 and was also predominant contralateral to the evoking stimulus, i.e., over the hemisphere not activated by sustained attention. Therefore the lateralization of the somatosensory P300, or at least that of its "early" component, is that of the hemisphere receiving the P3-evoking volley, and not that of the one involved in maintaining sustained attention. The P3 to rare-ignored shocks and the "early" P300 to targets had identical latencies; both are likely to reflect an automatic processing of deviant stimuli and thus belong to the family of "novelty P3s" (or "P3a"). Key words: P300; P3a; Somatosensory evoked potentials; Attention; Somatosensory; Event-related potentials; Topography
The P300 component of evoked potentials has been extensively studied since its first description in the auditory (Sutton et al. 1965) and somatosensory modalities (Desmedt et al. 1965). Although the P300 is now widely used in clinical situations where a cognitive impairment caused by dementia (Polich et al. 1986; Goodin 1990) or psychosis (Pfefferbaum et al. 1984, 1990) is suspected, neither the number nor the anatomical location of P300 generators is yet fully known. The bilateral, widespread distribution of this component over the scalp is consistent either with deep medial generators or with bilateral and simultaneously active cortical sources. Subcortical medial, mainly thalamic, activities with features similar to those of the P300 wave have been described in man (Yingling and Hosobuchi 1984; Katayama et al. 1985; Velasco et al. 1986); however, it has been recently shown that thalamic lesions do not affect the amplitude, but only the latency of P300 (Onofrj et al. 1992). This suggests that thalamic structures are not likely to be direct genera-
Correspondence to: Luis Garcla-Larrea, CERMEP, 59 Bd Pinel, 69003 Lyon (France). Tel.: (33) 72 33 00 07; Fax: (33) 78 53 31 12.
tors of the scalp-recorded P300, although they may participate as an intermediate relay in its genesis. Most studies converge on the conclusion that the scalp-recorded P300 reflects the activity of multiple bilateral neocortical and hippocampal generators (Vaughan and Ritter 1970; Simson et al. 1977; Courchesne 1978; Goff et al. 1978; Desmedt and Debecker 1979a,b; Wood et al. 1980; Pritchard 1981; McCarthy et al. 1982, 1989; Okada et al. 1983; Richer et al. 1983; Squires et al. 1983; Knight et al. 1989). This view is also supported by data from intracranial recording (Halgren et al. 1980; MacCarthy and Wood 1987; Smith et al. 1990) showing that bilateral cortical sources are simultaneously active in the latency range of the scalp P300. The question remains, however, as to whether it would be possible to activate preferentially the P300 generators of a single cerebral hemisphere. This seems to be the case when task performance depends on cognitive functions which are highly lateralized in the human brain; in such circumstances a lateralized P300 topography has been reported in both the visual and auditory modalities. For instance, in a face discrimination test, the P300 was found to predominate over the right hemiscalp (Small 1983), while in a verbal discrimination task it was observed that both auditory and visual P300 were
LATERALIZATION OF SOMATOSENSORY P300 lateralized toward the left hemiscalp (Friedman et al. 1975; Goodin et al. 1985). These experimental paradigms are based on the concept of functional hemispheric dominance, but there has hitherto been no available evidence that an asymmetry of the P300 potential could be related to the target side. For example, in a verbal discrimination task, the P300 was found lateralized toward the left hemisphere whatever the visual field wherein the target was presented to the subject (Nelson et al. 1990). In the auditory modality very few P300 studies have used monaural stimulation, and even under these conditions no scalp P300 asymmetries have been reported in relation to the target side (Perrault and Picton 1984; Knight et al. 1989). However, the bilateral cortical projections of the ascending auditory pathways entail simultaneous activation of both cortical reception areas even in the case of monaural stimulation, and therefore the auditory modality is not best adapted for investigating a target side-related P300 lateralization. In the visual system, hemifield stimulation allows to activate selectively a single hemisphere, but this requires sustained gaze fixation which is difficult to control in normal subjects and hardly obtainable in cognitively impaired patients. These difficulties can be easily overcome in the somatosensory modality, where lateralized stimuli (for example to one hand) are conveyed to contralateral sensory reception areas (Brodmann's areas 1, 2 and 3) exclusively, with no direct transcallosal connections between the two hand somatotopic areas (Killackey et al. 1983). The somatosensory system seems therefore particularly adapted to investigate whether there is a lateralized P300 topography when the task-relevant information is delivered to one hemisphere only. Most previous studies have failed to evidence any r i g h t / l e f t asymmetry of the somatosensory P300 (Desmedt and Debecker 1979a,b; Michie et al. 1987; Yamaguchi and Knight 1991a,b). However, some conflicting results have also been reported in favor of a lateralization of the somatosensory P300 on the scalp. Thus, a P300 predominance has been found on the hemiscalp ipsilateral to the target hand by Josiassen et al. (1982) while the P300 was lateralized on the hemiscalp opposite to targets in the study of Picton et al. (1984). A possible reason for these discrepancies is that the question of P300 scalp lateralization has never been addressed by mapping studies of cognitive SEPs exploring the distribution of potential fields on the whole scalp surface. Therefore, in this study we used topographical mapping of SEPs in order to detect whether consistent asymmetries of the P300 could be evidenced in relation to the side where target stimuli were delivered during a somatosensory discrimination task. By delivering these stimuli either to the right or the left side of the body, and by shifting the attention of the subject either
469 toward, or away from them, it was possible to study selectively the effects of target side on the scalp distribution of somatosensory P300.
Methods and subjects Experiments were carried out in 26 healthy, righthanded unpaid volunteers (14 females). Their age range was 22-33 years. Subjects lay comfortably with eyes closed on a wooden bed, in a quiet, semi-darkened room.
Stimulation Electrical 300/xsec square pulses were delivered to the index and middle fingers of both hands (with equal intensity) by means of a constant current stimulator. Stimulation intensity was fixed at 2.5-3 times the sensory threshold. The average stimulus rate was 0.8 Hz, affected with a variance coefficient of 10%.
Main experimentalparadigm The main experiment was carried out in 17 subjects, whose SEPs were recorded during a classical "oddball" paradigm: frequent stimuli (90% of the total number, i.e., about 180 stimuli) were delivered to the fingers of one hand, and among them were randomly interspersed rare stimuli (10%, i.e., about 20 stimuli) delivered to the other hand. The subjects were instructed to count the rare stimuli (targets) and to disregard the frequent ones. After each run, they were asked to give the number of counted targets and were informed about their performance. All subjects performed the task with an error rate less than 1%. At least 4 consecutive runs (two with left-sided targets and two with right-sided targets) were obtained in each subject. Target presentation began systematically on the left side.
Complementary experiment An additional experiment was carried out in 9 subjects, who were asked to count frequent (90%) stimuli delivered to one hand, and to disregard rare stimuli (10%) delivered to the opposite hand. The experimental protocol was otherwise the same as that described for the main experiment. The rare stimuli were delivered to the right hand in 5 subjects and to the left hand in 4 subjects. The rationale for this complementary study was to dissociate the side to which sustained attention was directed (target side) from the side where rare stimuli were delivered. This was done in order to assess independently the possible contributions of sustained attention and side of stimulation to EP lateralization.
Evoked potential (EP) recording Somatosensory evoked potentials (SEPs) were recorded by means of 19 electrodes fixed in a flexible
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helmet (ElectroCapTM), and attached to the scalp according to the international 10-20 system. A common reference electrode was fixed to the nose, and a prefrontal midline electrode was connected to the ground. Electrode impedances were kept below 3 kO. The vertical E O G was monitored by means of a right supraorbital electrode connected to the same reference as the scalp electrodes. EPs were amplified × 30,000 with an analog bandpass of 0.3-30 Hz (3 dB down, 12 d B / o c t a v e ) and digitized with a bin width of 4 msec. The analysis time was 1024 msec, with an 80 msec prestimulus delay. An automatic artifact rejection system excluded from the average all responses exceeding 80 tzV.
P300 was operationally defined as the positive peak in the 280-500 msec latency range, with amplitude exceeding 5/~V, which appeared selectively in response to rare stimuli and was reproducible in two consecutive series (see Fig. 1). When two distinct positive peaks meeting these criteria were recorded within this latency range, they were measured separately and labeled "early" and "late" P300 respectively. To assess P300 lateralization, baseline-to-peak amplitudes were measured over a transverse electrode array passing through the parietal regions (T5, P3, Pz, P4 and T6) where P300 was found to predominate. These voltages were normalized as a percentage of the measured amplitude at Pz (McCarthy and Wood 1985). Normalized amplitude data were used to compute 2-factor ANOVAs (target side × electrode site) followed by post hoc paired t tests (Table III).
Data processing Once checked that the two runs obtained in the same condition (right-hand target or left-hand target) were reproducible the average of both was used to compute latencies and amplitudes. Grand averages across all subjects were also obtained for illustration purposes, but statistical analyses were performed on data from individual subjects, and never from grand averaged EPs (Kraus and McGee 1988). Topographic maps were computed using linear interpolation from the 4 nearest neighbor electrodes.
Results
Main experiment Representative traces obtained from one subject are presented in Fig. 1, and grand-averaged responses and maps illustrated in Figs. 2 and 3. The P300 was found to be double-peaked in 10/17 subjects (59%) as shown
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Fig. 1. Evoked responses to target somatosensory stimuli delivered to the right hand in one subject. SEPs to two consecutive runs of 20 stimuli are superimposed to illustrate replicability of the wave forms. The "early" and "late" P300 subcomponents appear as two distinct and reproducible peaks (black dots) as was the case in 60% of the subjects. In the remaining cases, although only one peak could be clearly disclosed, the other subcomponent appeared as a notch on its ascending or descending slope.
LATERALIZATION OF SOMATOSENSORY P300
471
TABLE I
amplitudes of the two P300 peaks to left and right targets, as measured across the temporo-parietal electrode array. A 2-factor A N O V A (target side × electrode location) showed a main effect of electrode position on the amplitude of both early and late P300 peaks ( P = 0.0001, see Table III). There was no significant effect of target side on the overall amplitudes ( P > 0.05 for the first peak; P > 0.1 for the second peak), but a significant interaction was found between electrode position and target side ( P = 0.0001 and P = 0.036 respectively for the early and late peaks). Thus, although no difference was evidenced between right and left targets for the overall P300 amplitude (averaged across electrodes), the distribution of amplitudes over the parietal scalp was clearly dependent on the stimulated side. Whatever the stimulated side, post-hoe paired t tests between symmetrical electrodes showed significantly greater amplitudes contralateral to the target (Table IV). This was particularly obvious for the early P300 peak, for which both parietal and temporal electrodes recorded significantly higher activities over the
Mean latencies ( _+S.E.) of the "early" and "late" P300 peaks following right and left targets. Right target Left target
Early P300
Late P300
300.9 _+3.2 303.3 + 3.1
356.2 + 3.5 351.1 + 4.7
in the traces of Fig. 1. In the other 7 subjects, although only one dominant peak was seen in the selected latency range, the ascending or descending slope of the P300 deflection was encroached by an inflection or notch, reproducible on the two runs in all cases. The mean latencies ( + S.D.) of the two components (pooled for right and left targets) were respectively 302 + 8 msec and 353 + 12 msec, and in spite of wave form smoothing induced by across-subject averaging these two subcomponents could also be identified in grandaveraged traces, as shown in Figs. 2 and 3. Both peaks were consistently lateralized over the hemiscalp contralateral to the target side. This is summarized in Fig. 4 and Table II, which show the mean normalized
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Fig. 2. Grand average of somatosensory responses to right- and left-hand stimulation (upper and lower half of the figure respectively).For each hand and recording electrode the responses to target (black lines) and non-target stimuli (dotted lines) have been superimposed. The P3 positivitywas observed for target stimuli exclusively.Note that even supraorbital electrodes, when referenced to the nose as scalp electrodes, may pick up a sizeable P3 to targets.
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Fig. 3. Grand average of target SEPs obtained in 17 subjects (main experiment), in response to targets delivered to the right hand (upper part of the figure) or to the left hand (lower part). The two sequences of maps in the middle part illustrate the evolution of P300 topography for right-sided and left-sided targets (upper and lower rows respectively) in the time range 256-380 msec. Each map represents the average of 4 successive sample points (16 msec). Note that the P300 evoked by right targets predominates on the left hemiscalp, while left targets evoke a P300 lateralized to the right. Two separate components (early and late P300) can be discriminated in the grand-averaged P300 waves to right- or left-hand targets. Whatever the target side the early peak (302 msec) was more clearly lateralized than the late one (353 msec),
L A T E R A L I Z A T I O N O F S O M A T O S E N S O R Y P300
473
T A B L E II Mean normalized amplitudes ( + S.E.) of the "early" and "late" P300 peaks following right and left targets. Values are expressed in percentage of amplitude at Pz.
Early P300
Right target Left target Right target Left target
Late P300
T5
P3
Pz
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T6
70.9 + 5.9 60.0 + 5.1 79.1 + 4.6 72.8 _+4.1
95.0 + 2.9 85.9 + 3.3 97.0 + 3.0 95.5 _+2.7
100 100 100 100
81.8 ± 3.2 100.6 _+3.7 93.2 + 3.6 101.8 + 4.6
49.37 + 4.39 71.8 + 4.9 66.2 + 4.1 81.0 _+5.5
scalp contralateral to the target side. For the late P300, significant differences were observed only between temporal electrodes.
Complementary experiment In this experiment the rare stimuli, which were to be ignored by the subjects, elicited a positivity culminating at a mean latency of 296 + 27 msec. This peak was also lateralized on the hemisphere contralateral to the rare stimulation, whatever the stimulated side (Fig. 5). Nine subjects underwent this complementary experiment, and data from left-sided rare (n = 4) and right-sided rare stimuli (n = 5) were pooled together for statistical purposes, electrodes being labeled "ipsilateral" or "contralateral" to the rare-ignored stimulus. One-way A N O V A demonstrated a significant effect of electrode position on the amplitude of this positive peak ( F (4,
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Fig. 4. M e a n normalized amplitude ( + S . E . ) of P300 across the temporo-parietal axis. Values are expressed in percentage of the amplitude at Pz. Note that, although both the "early" and "late" P3 components were asymmetrically distributed, lateralization is more conspicuous for the "early" subcomponent.
8) = 24.1; P = 0.0001). Post-hoc paired t tests between symmetrical electrodes evidenced significantly larger amplitudes of this P300 on the side contralateral to the rare stimuli, relative to the ipsilateral scalp (t = 4.06, P = 0.004 for parietal electrodes; t = 5.03, P = 0.001 for temporal electrodes).
Discussion
In this study somatosensory target stimuli delivered to one hand during a counting-oddball paradigm elicited a lateralized P300 which predominated on the hemiscalp contralateral to the target. The somatosensory P300 was made up of two overlapping subcomponents manifested by the presence of two separate peaks within the 250-400 msec range, as described by Barrett et al. (1987). Scalp lateralization, although significant for both peaks, was more conspicuous for the earlier of the two (mean latency 302 msec) whereas it was significant only in the temporal region for the second peak (353 msec). This asymmetry is consistent with the notion of multiple bilateral sources contributing to scalp P300 and suggests that it is possible to activate preferentially the P300 generators located in one hemisphere. A number of previous studies have failed to provide evidence of a somatosensory P300 lateralization related to target side (Desmedt and Debecker 1979a,b; Michie et al. 1987; Desmedt 1989; Yamaguchi and Knight 1991a,b). However, the P300 latencies reported in the earlier studies always exceeded 330 msec and therefore were likely to correspond to those of our "late" P300 exclusively. In our study the late P300 peak was far less lateralized than the early component and showed symmetrical amplitude when measured at electrodes close to the midline ( P 3 / P 4 or C3/C4). Significant amplitude differences appeared, however, when temporal electrode measurements were also considered (Fig. 3 and Table IV). Such lateral measurements were not included in other studies, which might explain in part the differences between our conclusions and theirs. The choice of a linked-earlobes reference may have also contributed to obscure a possible P300 asymmetry in previous work, since this reference is known to reduce interhemispheric amplitude differences (Nufiez
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P. BRUYANT ET AL.
TABLE III Two-factor analysis of variance (target side × electrode) on normalized amplitude of the early and late P300 peaks. "Early" P300 df F test Target side (A) 1 3.1 Electrode(B) 4 41.4 AB 4 8.3
P
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df F
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test value 1.8 0.183 24.2 0.0001 2.6 0.0361
1981). We purposely chose a nose reference (Simson et al. 1977; Stapleton et al. 1987) which eliminates this drawback and has been shown to be electrically inactive with regard to the P300 (Goodin et al. 1985). Finally, the counting task performed by our subjects was devoid of any motor activity, thus avoiding the topographic uncertainties linked to the superimposition of a negative "readiness potential" contralateral to the responding hand, which occurs whenever a motor response must follow target detection and may distort P300 topography (Barrett et al. 1987). An asymmetry of the P300 scalp distribution has previously been demonstrated during tasks supported by hemispheric specialization (Friedman et al. 1975; Small 1983; Goodin et al. 1985). In our paradigm, some effects of hemispheric specialization could not be a priori ruled out, for there is some evidence that the right hemisphere is preferentially involved in tactile attention (Meador et al. 1988), while the left hemisphere is engaged by counting tasks in right-handed subjects (Pascual-Leone et al. 1991). However, such task-dependent effects cannot account for the P300 asymmetry in our subjects since, although the task was identical for targets delivered to the right or to the left hands, the P300 consistently predominated contralateral to the target side. The physiological lateralization of P300 may be relevant for clinical studies using this potential, since l e f t / r i g h t P300 asymmetries have been described as possible electrophysiological markers in a variety of pathological conditions, including schizophrenia (Faux et al. 1990) and focal cortical lesions (Yamaguchi and Knight 1991b). Overlooking the physiological asymmetry of somatosensory P300 in normals may obviously entail erroneous interpretations in patients, and therefore a detailed evaluation of its scalp distribution, including recording at far lateral electrodes, seems mandatory when obtaining normative data for clinical use. The scalp asymmetry observed for the late P300 peak, limited to far temporal sites, makes it tempting to establish some connection with the reports of P300 asymmetries observed either after hippocampectomy (McCarthy et al. 1989), or in schizophrenic patients with atrophy of the temporal lobe (Faux et al. 1990; McCarley et al. 1993), since P300 asymmetry was in
these cases also restricted to the temporal electrodes. Indeed, bilateral temporal lobe generators whose activities would be reflected only by recording over the lateral scalp could account for these observations, and in our experimental conditions activation of a temporal source contralateral to the target side would also be plausible. However, at this point no firm conclusion can be reached on this issue since the scalp asymmetry of our late P300 peak could also result merely from a spatio-temporal overlap with the early P300 peak, which we found to be highly lateralized. One hypothesis to explain the scalp P300 lateralization stems from the "hemispheric activation" model (see Kinsbourne 1977; Heilman 1979) whereby sustained attention towards one half of the extra- or intrapersonal space "activates" the opposite hemisphere. In agreement with this model, SEP studies have consistently shown an enhancement of early contralateral potentials when attention is directed toward the stimulated hand (Josiassen et al. 1982; Desmedt et al. 1983; Garcia-Larrea et al. 1991). In our study tonically maintained attention toward the target hand could theoretically have induced a predominant activation of the P300 generators in the opposite (activated) hemisphere. However, the even concept of hemispheric "activation," as a mechanism underlying sustained lateralized attention, cannot be modality-specific since the main clinical evidence supporting it is the observation of a polymodal sensory neglect toward stimuli delivered in the half of the space contralateral to a thalamic or cortical lesion. Consequently, if hemispheric "activation" were the main factor accounting for P300 asymmetry in the somatosensory modality, such an asymmetry should also be observed whenever attention is tonically directed to one hemispace, independently of the sensory modality. However, no asymmetry of the auditory P300 has hitherto been reported in response to monaural targets (Picton and Hillyard 1974; Perrault and Picton 1984; Knight et al. 1989) thus suggesting that lateralized attention per se does not produce any contralateral hemisphere predominance of P300.
TABLE IV Comparisons of normalized amplitudes at homologous electrodes (T5 vs. T6 and P3 vs. P4). Values are t values of 2-tailed paired t tests. The early P300 is significantlygreater at parietal and temporal electrodes contralateral to the target side when compared to homologous ipsilateral electrodes. A significant difference has been obtained only between temporal electrodes for the late P300.
Right target Left target
Early P300 T5 vs. T6 4.598 * * - 2.282 *
• P < 0.05; ** P < 0.01.
P3 vs. P4 3.217 * * - 3.088 * *
Late P300 T5 vs. T6 P3 vs. P4 2.456 * 0.839 - 2.459 * - 1.704
L A T E R A L I Z A T I O N O F S O M A T O S E N S O R Y P300
475
The somatosensory system, with no direct transcallosal connections between the hand areas in 3b (Killackey et al. 1983), is particularly appropriate for assessing whether lateralized sustained attention can cause a shift of P300 distribution on the scalp surface. Indeed, this system offers the possibility to dissociate the hemisphere tonically "activated" by attention from that receiving rare (but ignored) P3-evoking stimuli. This dissociation was achieved in our complementary experiment where subjects were asked to count frequent (90%) stimuli delivered to one hand (and consequently to focus tonically their attention toward this side), while rare non-target shocks were applied to the fingers on the opposite side (Fig. 5). Under this condition, the P300 potential evoked by rare-ignored stimuli peaked with a latency similar to that of the early P300 to rare-target stimuli and was clearly lateralized on the half of the scalp opposite to stimulation, i.e., over the
"non-activated" hemisphere. Therefore, the lateralization of the somatosensory P300, and particularly of its "early" component, seems to depend on the hemisphere which receives the P3-evoking stimulus and not on the one involved in maintaining sustained attention. The positivity evoked in our subjects by rare, unattended stimuli in the complementary experiment is likely to belong to the family of "novelty P3s," which may be isolated in response to rare unattended, taskirrelevant stimuli in the auditory, visual and somatosensory modalities (Courchesne et al. 1975; Squires et al. 1975; Yamaguchi and Knight 1991a,b). Whatever the sensory modality, these positivities are commonly labeled "P3a" and are thought to reflect an automatic attentional shift toward a deviant stimulus (Squires et al. 1975; Ford et al. 1976; Yamaguchi and Knight 1991a,b). The latency of this novelty-P3 was in our subjects coincident with that of the "early" peak of
stai d attention: right side re sts lus: left hand lguV Sustained attention: Rare stimtlus: right
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Fig. 5. Traces and m a p s corresponding to the "complementary experiment," in which the side of the body receiving sustained attention was contralateral to the one receiving the rare stimuli (see text). Traces from temporal (T5, T6), parietal (P3, P4) and central (C3, C4) electrodes are superimposed. In the upper half of the figure traces and maps correspond to grand-averaged SEPs to rare stimuli delivered to the left hand while sustained attention was directed toward the right side. T h e reciprocal is shown in the lower half of the figure (rare stimulus to right hand, sustained attention to the left side). The P3 recorded in response to rare-ignored stimuli was single peaked, culminated in average at 296 msec and was lateralized always toward the hemiscalp contralateral to the rare stimulation, even if tonic sustained attention was directed away from that side.
476 t h e t a r g e t P300, a n d t h u s w e m a y a s s u m e t h a t this e a r l y p e a k also c o r r e s p o n d s to a P 3 a ( B a r r e t t et al. 1987). I f this a s s u m p t i o n is c o r r e c t o u r f i n d i n g s w o u l d s u g g e s t t h a t , in t h e s o m a t o s e n s o r y m o d a l i t y , t h e a u t o m a t i c p r o c e s s i n g o f s e n s o r y s t i m u l i i n d e x e d by t h e P3a is c o n t r o l l e d m a i n l y by t h e h e m i s p h e r e r e c e i v i n g t h e p e r i p h e r a l i n p u t , e v e n t h o u g h t h e full p r o c e s s i n g o f i n f o r m a t i o n ( i n c l u d i n g t a r g e t i d e n t i f i c a t i o n ) is o b v i o u s l y n o t r e s t r i c t e d to this h e m i s p h e r e .
References Barrett, G., Neshige, R. and Shibasaki, H. Human auditory and somatosensory evoked potentials: effects of response condition and age. Electroenceph. clin. Neurophysiol., 1987, 66: 409-419. Courchesne, E. Changes in P3 waves with event repetition: long-term effects on scalp distribution and amplitude. Electroenceph. clin. Neurophysiol., 1978, 45: 754-766. Courchesne, E., Hillyard, S.A. and Galambos, R. Stimulus novelty, task relevance and the visual evoked potential in man. Electroenceph. clin. Neurophysiol., 1975, 39: 131-143. Desmedt, J.E. Topographic mapping of generators of somatosensory evoked potentials. In: K. Maurer (Ed.), Topographic Brain Mapping of EEG and Evoked Potentials. Springer, Berlin, 1989: 76-89. Desmedt, J.E. and Debecker, J. Wave form and neural mechanism of the decision P350 elicited without pre-stimulus CNV or readiness potential in random sequences of near threshold auditory clicks and fingers stimuli. Electroenceph. clin. Neurophysiol., 1979a, 47: 648-670. Desmedt, J.E. and Debecker, J. Slow potential shifts and decision P350 interactions in tasks with random sequences of nearthreshold clicks and finger stimuli delivered at regular intervals. Electroenceph. clin. Neurophysiol., 1979b, 47: 671-679. Desmedt, J.E., Debecker, J. and Manil, J. Mise en 6vidence d'un signe 61ectrique c6r6bral associ6 ~ la d&ection par le sujet d'un stimulus sensoriel tactile. Bull. Acad. Roy. M6d. Belg., 1965, 5: 887-936. Desmedt, J.E., Nguyen, T.H. and Bourguet, M. The cognitive P40, N60 and P100 components of somatosensory evoked potentials and the earliest electrical signs of sensory processing in man. Electroenceph. clin. Neurophysiol., 1983, 56: 272-282. Faux, S.F., Shenton, M.E., McCarley, R.W., Nestor, P.G., Marcy, B. and Ludwig, A. Preservation of P300 event-related potential topographic asymmetries in schizophrenia with use of either linked-ear or nose reference sites. Electroenceph. clin. Neurophysiol., 1990, 75: 378-391. Ford, J.M., Roth, W.T. and Kopell, B.S. Auditory evoked potentials to inpredictable shifts in pitch. Psychophysiology, 1976, 13: 32-39. Friedman, D., Simson, R., Ritter, W. and Rapin, I. Cortical evoked potentials elicited by real speech words and human sounds. Electroenceph. clin. Neurophysiol., 1975, 38: 13-19. Garcla-Larrea, L., Bastuji, H. and Mauguibre, F. Mapping study of somatosensory evoked potentials during selective spatial attention. Electroenceph. clin. Neurophysiol., 1991, 80: 201-214. Goff, W.R., Allison, T. and Vaughan, Jr., H.G. The functional neuroanatomy of event-related potentials. In: E. Callaway, P. Tueting and S. Koslw (Eds.), Event-Related Brain Potentials in Man. Academic Press, New York, 1978: 349-411. Goodin, D.S. Clinical utility of long-latency "cognitive" event-related potentials (P3): the pros. Electroenceph. clin. Neurophysiol., 1990, 76: 2-5. Goodin, D.S., Waltz, D.A. and Aminoff, M.J. Task-dependent hemi-
P. BRUYANT ET AL. sphere asymmetries of the visual evoked potential. Neurology, 1985, 35: 378-384. Halgren, E., Squires, N.K., Wilson, C.L., Rohrbaugh, J.R., Babb, T.L. and Crandall, P.H. Endogenous potentials generated in the human hippocampal formation and amygdala by infrequent events. Science, 1980, 210: 803-805. Heilman, K.M. Neglect and related disorders. In: K.M. Heilman and E. Valenstein (Eds.), Clinical Neuropsychology. Oxford University Press, New York, 1979: 268-307. Josiassen, R.C., Shagass, C., Roemer, R.A., Ercegovac, D.V. and Straumanis, J.J. Psychophysiol., 1982, 19: 146-159. Katayama, Y., Tsukiyama, T. and Tsubokawa, T. Thalamic negativity associated with the endogenous late positivity component of cerebral evoked potentials (P300): recordings using discriminative aversing conditioning in humans and cats. Brain Res. Bull., 1985, 14: 223-226. Killackey, H.P., Gould, III, H.J., Cusik, C., Pons, T.P. and Kaas, J.H. The relation of corpus callosum connections to architectonic fields and and body surface maps in sensorimotor cortex of new and old world monkeys. J. Comp. Neur01., 1983, 219: 384-419. Kinsbourne, H. Hemi-neglect and hemisphere rivalry. In: E.A. Weinstein and R.P. Friedland (Eds.), Advances in Neurology, Vol. 18. Raven Press, New York, 1977: 41-49. Knight, R.T., Scabini, D., Woods, D.L. and Clayworth, C.C. Contributions of temporal-parietal junction to the human auditory P3. Brain Res., 1989, 502: 109-116. Kraus, N. and McGee, T. Color imaging of the human middle latency response. Ear Hear., 1988, 9: 159-167. McCarley, R.W., Shenton, M.E., O'Donnell, B.F., Faux, S.F., Kikinis, R., Nestor, P.G. and Jolesz, F.A. Auditory P300 abnormalities and left posterior superior temporal gyrus volume reduction in schizophrenia. Arch. Gen. Psychiat., 1993, 50: 190-197. McCarthy, G. and Wood, C.C. Scalp distributions of event-related potentials: an ambiguity associated with analysis of variance models. Electroenceph. clin. Neurophysiol., 1985, 62: 203-208. McCarthy, G. and Wood, C.C. Intracranial recordings and endogenous ERPs in humans. Electroenceph. clin. Neurophysiol., 1987, Suppl. 39: 331-337. McCarthy, G., Wood, C.C., Allison, R., Goff, W.R., Williamson, P.D. and Spencer, D.D. Intracranial recordings of event-related potentials in humans engaged in cognitive tasks. Soc. Neurosci. Abst., 1982, 8: 976. McCarthy, G., Wood, C.C., Williamson, P.D. and Spencer, D.D. Task-dependent field potentials in human hippocampal formation. J. Neurosci., 1989, 9: 4253-4268. Meador, K.J., Loring, D.W., Lee, G.P., Brooks, B.S., Thompson, E.E., Thompson, W.O. and Heilman, K.M. Right cerebral specialization for tactile attention as evidenced by intracarotid sodium amytal. Neurology, 1988, 38: 1763-1766. Michie, P.T., Bearpark, H.M., Crawford, J.M. and Glue, L.C.T. The effects of spatial selective attention on the somatosensory eventrelated potential. Psychophysiology, 1987, 24: 449-463. Nelson, C.A., Collins, P.F. and Torres, F. The lateralization of langauge comprehension using event-related potentials. Brain Cogn., 1990, 14: 92-112. Nufiez, P.L. Electric Fields of the Brain: the Neurophysics of Electroencephalography. Oxford University Press, New York, 1981. Okada, Y.C., Kaufman, L. and Williamson, S.J. The hippocampal formation as a source of the slow endogenous potentials. Electroenceph, clin. Neurophysiol., 1983, 55: 417-426. Onofrj, M., Curatola, L., Malatesta, G., Colamartino, P., Bazzano, S., Nobilio, D. and Ferracci, F. Delayed P3 event-related potentials (ERPs) in thalamic hemorrhage. Electroenceph. clin. Neurophysiol., 1992, 83: 52-61. Pascual-Leone, A., Gates, J.R. and Dhuna, A. Induction of speech arrest and counting errors with rapid-rate transcranial magnetic stimulation. Neurology, 1991, 41: 697-702.
LATERALIZATION OF SOMATOSENSORY P300 Perrault, N. and Picton, T.W. Event-related potentials recorded from the scalp and nasopharynx. II. N2, P3 and slow wave. Electroenceph. clin. Neuropbysiol., 1984, 59: 261-278. Pfefferbaum, A., Wenegrat, B.G., Ford, J.M., Roth, W.T. and Kopell, B.S. Clinical application of the P3 component of the event-related potentials. If. Dementia, depression and schizophrenia. Electroenceph. clin. Neurophysiol., 1984, 59: 104-124. Pfefferbaum, A., Ford, J.M. and Kraemer, H.C. Clinical utility of long-latency "cognitive" event-related potentials (P3): the cons. Electroenceph. clin. Neurophysiol., 1990, 76: 6-12. Picton, T.W. and Hillyard, S.A. Human auditory evoked potentials. If. Effects of attention. Electroenceph. clin. Neurophysiol., 1974, 36: 191-199. Picton, T.W., Stuss, D.T., Champagne, S.C. and Nelson, R.F. The effects of age on human event-related potentials. Psychophysiology, 1984, 21: 312-325. Polich, J. Bifurcated P300 peaks: P3a and P3b revisited. J. Clin. Neurophysiol., 1988, 5: 287-294. Polich, J., Ehlers, C.L., Otis, S., Mandell, A.J. and Bloom, F.E. P300 latency reflects the degree of cognitive decline in dementing illness. Electroenceph. clin. Neurophysiol., 1986, 63: 138-144. Pritchard, W.S. Psychophysiology of P300. Psychol. Bull., 1981, 89: 506-540. Richer, F., Johnson, R.A. and Beatty, J. Sources of late components of the brain magnetic responses. Neurosci. Abst., 1983, 9: 656. Simson, R., Vaughan, Jr., H.G. and Ritter, W. The scalp topography of potentials in auditory and visual discrimination tasks. Electroenceph, clin. Neurophysiol., 1977, 42: 528-535. Small, M. Asymmetrical evoked potentials in response to face stimuli. Cortex, 1983, 19: 441-450. Smith, M.E., Halgren, E., Sokolik, M., Baudena, P., Musolino, A., Liegeois-Chauvel, C. and Chauvel, P. The intracranial topography of the P3 event-related potential elicited during auditory oddball. Electroenceph. clin. Neurophysiol., 1990, 76: 235-248.
477 Stapleton, J.M., Halgren, E. and Moreno, K.A. Endogenous potentials after anterior temporal lobectomy. Neuropsychologia, 1987, 25: 549-557. Squires, N.K., Squires, K.C. and Hillyard, S.A. Two varieties of long-latency positive waves evoked by unpredictable auditory stimuli in man. Electroenceph. clin. Neurophysiol., 1975, 38: 387-401. Squires, N.K., Halgren, E., Wilson, C. and Crandall, P. Human endogenous limbic potentials: cross-modality and depth/surface comparisons in epileptic subjects. In: A.W.K. Galliard and W. Ritter (Eds.), Tutorials in ERP Research: Endogenous Components. Elsevier/North-Holland, Amsterdam, 1983: 217-232. Sutton, S., Braren, M., Zubin, J. and John, E.R. Evoked potential correlates of stimulus uncertainty. Science, 1965, 150: 1187-1188. Vaughan, Jr., H.G. and Ritter, W. The sources of auditory evoked responses recorded from the human scalp. Electroenceph. clin. Neurophysiol., 1970, 28: 360-367. Velasco, M., Velasco, F., Velasco, A.L., Almanza, X. and Olivera, A. Subcortical correlates of the P300 potential complex in man to auditory stimuli. Electroenceph. clin. Neurophysiol., 1986, 64: 199-210. Wood, C.C., Allison, T., Goff, W.R., Williamson, P.D. and Spencer, D.B. On the neural origin of P300 in man. In: H.H. Kornhuber and L. Deecke (Eds.), Motivation, Motor and Sensory Processes of the Brain. Progr. Brain Res., Vol. 54. Elsevier, Amsterdam, 1980: 51-56. Yamaguchi, S. and Knight, R.T. P300 generation by novel somatosensory stimuli. Electroenceph. clin. Neurophysiol., 1991a, 78: 50-55. Yamaguchi, S. and Knight, R.T. Anterior and posterior association cortex contributions to the somatosensory P300. J. Neurosci., 1991b, 11: 2039-2054. Yingling, C.D. and Hosobuschi, Y. A subcortical correlate of P300 in man. Electroenceph. clin. Neurophysiol., 1984, 59: 72-76.
Electroencephalography and clinical Neurophysiology, 88 (1993) 468-477 © 1993 Elsevier Scientific Publishers Ireland, Ltd. 0168-5597/93/$06.00
EEP 92113
Target side and scalp topography of the somatosensory P300 Philippe Bruyant, Luis Garcla-Larrea and Francois Maugui re Clinical Neurophysiology Unit, Research Lab. JE133, CERMEP, University Lyon I, 69003 Lyon (France)
(Accepted for publication: 27 April 1993)
Summary We recorded somatosensory P300 to target electrical shocks (10% probability) delivered to the left or right hand concurrently with non-target stimuli applied to the opposite hand. Target stimuli evoked a widely distributed P300, which was found to be double-peaked in 60% of the subjects investigated. The mean latencies of the "early" and "late" P300 peaks were respectively 302_+ 8 msec and 353 + 12 msec. Both components (but especially the earlier one) were consistently lateralized over the hemiscalp contralateral to the target stimuli, whichever the target side. Although on theoretical grounds P300 lateralization might depend upon the sustained attentional activation of the hemisphere contralateral to targets, this hypothesis was contradicted in one complementary experiment in which we dissociated the side receiving the P3-evoking, rare, stimuli from the side to which sustained attention was directed. Under these conditions the P3 evoked by rare, but ignored, shocks corresponded to the "early" peak of target P300 and was also predominant contralateral to the evoking stimulus, i.e., over the hemisphere not activated by sustained attention. Therefore the lateralization of the somatosensory P300, or at least that of its "early" component, is that of the hemisphere receiving the P3-evoking volley, and not that of the one involved in maintaining sustained attention. The P3 to rare-ignored shocks and the "early" P300 to targets had identical latencies; both are likely to reflect an automatic processing of deviant stimuli and thus belong to the family of "novelty P3s" (or "P3a"). Key words: P300; P3a; Somatosensory evoked potentials; Attention; Somatosensory; Event-related potentials; Topography
The P300 component of evoked potentials has been extensively studied since its first description in the auditory (Sutton et al. 1965) and somatosensory modalities (Desmedt et al. 1965). Although the P300 is now widely used in clinical situations where a cognitive impairment caused by dementia (Polich et al. 1986; Goodin 1990) or psychosis (Pfefferbaum et al. 1984, 1990) is suspected, neither the number nor the anatomical location of P300 generators is yet fully known. The bilateral, widespread distribution of this component over the scalp is consistent either with deep medial generators or with bilateral and simultaneously active cortical sources. Subcortical medial, mainly thalamic, activities with features similar to those of the P300 wave have been described in man (Yingling and Hosobuchi 1984; Katayama et al. 1985; Velasco et al. 1986); however, it has been recently shown that thalamic lesions do not affect the amplitude, but only the latency of P300 (Onofrj et al. 1992). This suggests that thalamic structures are not likely to be direct genera-
Correspondence to: Luis Garcla-Larrea, CERMEP, 59 Bd Pinel, 69003 Lyon (France). Tel.: (33) 72 33 00 07; Fax: (33) 78 53 31 12.
tors of the scalp-recorded P300, although they may participate as an intermediate relay in its genesis. Most studies converge on the conclusion that the scalp-recorded P300 reflects the activity of multiple bilateral neocortical and hippocampal generators (Vaughan and Ritter 1970; Simson et al. 1977; Courchesne 1978; Goff et al. 1978; Desmedt and Debecker 1979a,b; Wood et al. 1980; Pritchard 1981; McCarthy et al. 1982, 1989; Okada et al. 1983; Richer et al. 1983; Squires et al. 1983; Knight et al. 1989). This view is also supported by data from intracranial recording (Halgren et al. 1980; MacCarthy and Wood 1987; Smith et al. 1990) showing that bilateral cortical sources are simultaneously active in the latency range of the scalp P300. The question remains, however, as to whether it would be possible to activate preferentially the P300 generators of a single cerebral hemisphere. This seems to be the case when task performance depends on cognitive functions which are highly lateralized in the human brain; in such circumstances a lateralized P300 topography has been reported in both the visual and auditory modalities. For instance, in a face discrimination test, the P300 was found to predominate over the right hemiscalp (Small 1983), while in a verbal discrimination task it was observed that both auditory and visual P300 were
LATERALIZATION OF SOMATOSENSORY P300 lateralized toward the left hemiscalp (Friedman et al. 1975; Goodin et al. 1985). These experimental paradigms are based on the concept of functional hemispheric dominance, but there has hitherto been no available evidence that an asymmetry of the P300 potential could be related to the target side. For example, in a verbal discrimination task, the P300 was found lateralized toward the left hemisphere whatever the visual field wherein the target was presented to the subject (Nelson et al. 1990). In the auditory modality very few P300 studies have used monaural stimulation, and even under these conditions no scalp P300 asymmetries have been reported in relation to the target side (Perrault and Picton 1984; Knight et al. 1989). However, the bilateral cortical projections of the ascending auditory pathways entail simultaneous activation of both cortical reception areas even in the case of monaural stimulation, and therefore the auditory modality is not best adapted for investigating a target side-related P300 lateralization. In the visual system, hemifield stimulation allows to activate selectively a single hemisphere, but this requires sustained gaze fixation which is difficult to control in normal subjects and hardly obtainable in cognitively impaired patients. These difficulties can be easily overcome in the somatosensory modality, where lateralized stimuli (for example to one hand) are conveyed to contralateral sensory reception areas (Brodmann's areas 1, 2 and 3) exclusively, with no direct transcallosal connections between the two hand somatotopic areas (Killackey et al. 1983). The somatosensory system seems therefore particularly adapted to investigate whether there is a lateralized P300 topography when the task-relevant information is delivered to one hemisphere only. Most previous studies have failed to evidence any r i g h t / l e f t asymmetry of the somatosensory P300 (Desmedt and Debecker 1979a,b; Michie et al. 1987; Yamaguchi and Knight 1991a,b). However, some conflicting results have also been reported in favor of a lateralization of the somatosensory P300 on the scalp. Thus, a P300 predominance has been found on the hemiscalp ipsilateral to the target hand by Josiassen et al. (1982) while the P300 was lateralized on the hemiscalp opposite to targets in the study of Picton et al. (1984). A possible reason for these discrepancies is that the question of P300 scalp lateralization has never been addressed by mapping studies of cognitive SEPs exploring the distribution of potential fields on the whole scalp surface. Therefore, in this study we used topographical mapping of SEPs in order to detect whether consistent asymmetries of the P300 could be evidenced in relation to the side where target stimuli were delivered during a somatosensory discrimination task. By delivering these stimuli either to the right or the left side of the body, and by shifting the attention of the subject either
469 toward, or away from them, it was possible to study selectively the effects of target side on the scalp distribution of somatosensory P300.
Methods and subjects Experiments were carried out in 26 healthy, righthanded unpaid volunteers (14 females). Their age range was 22-33 years. Subjects lay comfortably with eyes closed on a wooden bed, in a quiet, semi-darkened room.
Stimulation Electrical 300/xsec square pulses were delivered to the index and middle fingers of both hands (with equal intensity) by means of a constant current stimulator. Stimulation intensity was fixed at 2.5-3 times the sensory threshold. The average stimulus rate was 0.8 Hz, affected with a variance coefficient of 10%.
Main experimentalparadigm The main experiment was carried out in 17 subjects, whose SEPs were recorded during a classical "oddball" paradigm: frequent stimuli (90% of the total number, i.e., about 180 stimuli) were delivered to the fingers of one hand, and among them were randomly interspersed rare stimuli (10%, i.e., about 20 stimuli) delivered to the other hand. The subjects were instructed to count the rare stimuli (targets) and to disregard the frequent ones. After each run, they were asked to give the number of counted targets and were informed about their performance. All subjects performed the task with an error rate less than 1%. At least 4 consecutive runs (two with left-sided targets and two with right-sided targets) were obtained in each subject. Target presentation began systematically on the left side.
Complementary experiment An additional experiment was carried out in 9 subjects, who were asked to count frequent (90%) stimuli delivered to one hand, and to disregard rare stimuli (10%) delivered to the opposite hand. The experimental protocol was otherwise the same as that described for the main experiment. The rare stimuli were delivered to the right hand in 5 subjects and to the left hand in 4 subjects. The rationale for this complementary study was to dissociate the side to which sustained attention was directed (target side) from the side where rare stimuli were delivered. This was done in order to assess independently the possible contributions of sustained attention and side of stimulation to EP lateralization.
Evoked potential (EP) recording Somatosensory evoked potentials (SEPs) were recorded by means of 19 electrodes fixed in a flexible
470
P. B R U Y A N T E T AL.
helmet (ElectroCapTM), and attached to the scalp according to the international 10-20 system. A common reference electrode was fixed to the nose, and a prefrontal midline electrode was connected to the ground. Electrode impedances were kept below 3 kO. The vertical E O G was monitored by means of a right supraorbital electrode connected to the same reference as the scalp electrodes. EPs were amplified × 30,000 with an analog bandpass of 0.3-30 Hz (3 dB down, 12 d B / o c t a v e ) and digitized with a bin width of 4 msec. The analysis time was 1024 msec, with an 80 msec prestimulus delay. An automatic artifact rejection system excluded from the average all responses exceeding 80 tzV.
P300 was operationally defined as the positive peak in the 280-500 msec latency range, with amplitude exceeding 5/~V, which appeared selectively in response to rare stimuli and was reproducible in two consecutive series (see Fig. 1). When two distinct positive peaks meeting these criteria were recorded within this latency range, they were measured separately and labeled "early" and "late" P300 respectively. To assess P300 lateralization, baseline-to-peak amplitudes were measured over a transverse electrode array passing through the parietal regions (T5, P3, Pz, P4 and T6) where P300 was found to predominate. These voltages were normalized as a percentage of the measured amplitude at Pz (McCarthy and Wood 1985). Normalized amplitude data were used to compute 2-factor ANOVAs (target side × electrode site) followed by post hoc paired t tests (Table III).
Data processing Once checked that the two runs obtained in the same condition (right-hand target or left-hand target) were reproducible the average of both was used to compute latencies and amplitudes. Grand averages across all subjects were also obtained for illustration purposes, but statistical analyses were performed on data from individual subjects, and never from grand averaged EPs (Kraus and McGee 1988). Topographic maps were computed using linear interpolation from the 4 nearest neighbor electrodes.
Results
Main experiment Representative traces obtained from one subject are presented in Fig. 1, and grand-averaged responses and maps illustrated in Figs. 2 and 3. The P300 was found to be double-peaked in 10/17 subjects (59%) as shown
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Fig. 1. Evoked responses to target somatosensory stimuli delivered to the right hand in one subject. SEPs to two consecutive runs of 20 stimuli are superimposed to illustrate replicability of the wave forms. The "early" and "late" P300 subcomponents appear as two distinct and reproducible peaks (black dots) as was the case in 60% of the subjects. In the remaining cases, although only one peak could be clearly disclosed, the other subcomponent appeared as a notch on its ascending or descending slope.
LATERALIZATION OF SOMATOSENSORY P300
471
TABLE I
amplitudes of the two P300 peaks to left and right targets, as measured across the temporo-parietal electrode array. A 2-factor A N O V A (target side × electrode location) showed a main effect of electrode position on the amplitude of both early and late P300 peaks ( P = 0.0001, see Table III). There was no significant effect of target side on the overall amplitudes ( P > 0.05 for the first peak; P > 0.1 for the second peak), but a significant interaction was found between electrode position and target side ( P = 0.0001 and P = 0.036 respectively for the early and late peaks). Thus, although no difference was evidenced between right and left targets for the overall P300 amplitude (averaged across electrodes), the distribution of amplitudes over the parietal scalp was clearly dependent on the stimulated side. Whatever the stimulated side, post-hoe paired t tests between symmetrical electrodes showed significantly greater amplitudes contralateral to the target (Table IV). This was particularly obvious for the early P300 peak, for which both parietal and temporal electrodes recorded significantly higher activities over the
Mean latencies ( _+S.E.) of the "early" and "late" P300 peaks following right and left targets. Right target Left target
Early P300
Late P300
300.9 _+3.2 303.3 + 3.1
356.2 + 3.5 351.1 + 4.7
in the traces of Fig. 1. In the other 7 subjects, although only one dominant peak was seen in the selected latency range, the ascending or descending slope of the P300 deflection was encroached by an inflection or notch, reproducible on the two runs in all cases. The mean latencies ( + S.D.) of the two components (pooled for right and left targets) were respectively 302 + 8 msec and 353 + 12 msec, and in spite of wave form smoothing induced by across-subject averaging these two subcomponents could also be identified in grandaveraged traces, as shown in Figs. 2 and 3. Both peaks were consistently lateralized over the hemiscalp contralateral to the target side. This is summarized in Fig. 4 and Table II, which show the mean normalized
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472
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Fig. 3. Grand average of target SEPs obtained in 17 subjects (main experiment), in response to targets delivered to the right hand (upper part of the figure) or to the left hand (lower part). The two sequences of maps in the middle part illustrate the evolution of P300 topography for right-sided and left-sided targets (upper and lower rows respectively) in the time range 256-380 msec. Each map represents the average of 4 successive sample points (16 msec). Note that the P300 evoked by right targets predominates on the left hemiscalp, while left targets evoke a P300 lateralized to the right. Two separate components (early and late P300) can be discriminated in the grand-averaged P300 waves to right- or left-hand targets. Whatever the target side the early peak (302 msec) was more clearly lateralized than the late one (353 msec),
L A T E R A L I Z A T I O N O F S O M A T O S E N S O R Y P300
473
T A B L E II Mean normalized amplitudes ( + S.E.) of the "early" and "late" P300 peaks following right and left targets. Values are expressed in percentage of amplitude at Pz.
Early P300
Right target Left target Right target Left target
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T6
70.9 + 5.9 60.0 + 5.1 79.1 + 4.6 72.8 _+4.1
95.0 + 2.9 85.9 + 3.3 97.0 + 3.0 95.5 _+2.7
100 100 100 100
81.8 ± 3.2 100.6 _+3.7 93.2 + 3.6 101.8 + 4.6
49.37 + 4.39 71.8 + 4.9 66.2 + 4.1 81.0 _+5.5
scalp contralateral to the target side. For the late P300, significant differences were observed only between temporal electrodes.
Complementary experiment In this experiment the rare stimuli, which were to be ignored by the subjects, elicited a positivity culminating at a mean latency of 296 + 27 msec. This peak was also lateralized on the hemisphere contralateral to the rare stimulation, whatever the stimulated side (Fig. 5). Nine subjects underwent this complementary experiment, and data from left-sided rare (n = 4) and right-sided rare stimuli (n = 5) were pooled together for statistical purposes, electrodes being labeled "ipsilateral" or "contralateral" to the rare-ignored stimulus. One-way A N O V A demonstrated a significant effect of electrode position on the amplitude of this positive peak ( F (4,
] 'Early' P300
"IO
E
t10
10
1oo: oo: 80
O0 go
70"
70
60
60
50. 40
80
50 left t a r g e t T5 P3 Pz P4 T6
I 'Late'P300 nN
IiO
80 E 70
50
left t a r g e t TS P3 Pz P4 T6
40
I
~
1oo go
60
"T'SP'3 P'z P~ r~
right t a r g e t . . . . . .
TS P3 Pz P4 T6
:110 '100 "gO 80 70 60 50
Fig. 4. M e a n normalized amplitude ( + S . E . ) of P300 across the temporo-parietal axis. Values are expressed in percentage of the amplitude at Pz. Note that, although both the "early" and "late" P3 components were asymmetrically distributed, lateralization is more conspicuous for the "early" subcomponent.
8) = 24.1; P = 0.0001). Post-hoc paired t tests between symmetrical electrodes evidenced significantly larger amplitudes of this P300 on the side contralateral to the rare stimuli, relative to the ipsilateral scalp (t = 4.06, P = 0.004 for parietal electrodes; t = 5.03, P = 0.001 for temporal electrodes).
Discussion
In this study somatosensory target stimuli delivered to one hand during a counting-oddball paradigm elicited a lateralized P300 which predominated on the hemiscalp contralateral to the target. The somatosensory P300 was made up of two overlapping subcomponents manifested by the presence of two separate peaks within the 250-400 msec range, as described by Barrett et al. (1987). Scalp lateralization, although significant for both peaks, was more conspicuous for the earlier of the two (mean latency 302 msec) whereas it was significant only in the temporal region for the second peak (353 msec). This asymmetry is consistent with the notion of multiple bilateral sources contributing to scalp P300 and suggests that it is possible to activate preferentially the P300 generators located in one hemisphere. A number of previous studies have failed to provide evidence of a somatosensory P300 lateralization related to target side (Desmedt and Debecker 1979a,b; Michie et al. 1987; Desmedt 1989; Yamaguchi and Knight 1991a,b). However, the P300 latencies reported in the earlier studies always exceeded 330 msec and therefore were likely to correspond to those of our "late" P300 exclusively. In our study the late P300 peak was far less lateralized than the early component and showed symmetrical amplitude when measured at electrodes close to the midline ( P 3 / P 4 or C3/C4). Significant amplitude differences appeared, however, when temporal electrode measurements were also considered (Fig. 3 and Table IV). Such lateral measurements were not included in other studies, which might explain in part the differences between our conclusions and theirs. The choice of a linked-earlobes reference may have also contributed to obscure a possible P300 asymmetry in previous work, since this reference is known to reduce interhemispheric amplitude differences (Nufiez
474
P. BRUYANT ET AL.
TABLE III Two-factor analysis of variance (target side × electrode) on normalized amplitude of the early and late P300 peaks. "Early" P300 df F test Target side (A) 1 3.1 Electrode(B) 4 41.4 AB 4 8.3
P
value
"Late"P300
df F
Target 0.081 side (A) 1 0.0001 Electrode(B) 4 0.0001 AB 4
P
test value 1.8 0.183 24.2 0.0001 2.6 0.0361
1981). We purposely chose a nose reference (Simson et al. 1977; Stapleton et al. 1987) which eliminates this drawback and has been shown to be electrically inactive with regard to the P300 (Goodin et al. 1985). Finally, the counting task performed by our subjects was devoid of any motor activity, thus avoiding the topographic uncertainties linked to the superimposition of a negative "readiness potential" contralateral to the responding hand, which occurs whenever a motor response must follow target detection and may distort P300 topography (Barrett et al. 1987). An asymmetry of the P300 scalp distribution has previously been demonstrated during tasks supported by hemispheric specialization (Friedman et al. 1975; Small 1983; Goodin et al. 1985). In our paradigm, some effects of hemispheric specialization could not be a priori ruled out, for there is some evidence that the right hemisphere is preferentially involved in tactile attention (Meador et al. 1988), while the left hemisphere is engaged by counting tasks in right-handed subjects (Pascual-Leone et al. 1991). However, such task-dependent effects cannot account for the P300 asymmetry in our subjects since, although the task was identical for targets delivered to the right or to the left hands, the P300 consistently predominated contralateral to the target side. The physiological lateralization of P300 may be relevant for clinical studies using this potential, since l e f t / r i g h t P300 asymmetries have been described as possible electrophysiological markers in a variety of pathological conditions, including schizophrenia (Faux et al. 1990) and focal cortical lesions (Yamaguchi and Knight 1991b). Overlooking the physiological asymmetry of somatosensory P300 in normals may obviously entail erroneous interpretations in patients, and therefore a detailed evaluation of its scalp distribution, including recording at far lateral electrodes, seems mandatory when obtaining normative data for clinical use. The scalp asymmetry observed for the late P300 peak, limited to far temporal sites, makes it tempting to establish some connection with the reports of P300 asymmetries observed either after hippocampectomy (McCarthy et al. 1989), or in schizophrenic patients with atrophy of the temporal lobe (Faux et al. 1990; McCarley et al. 1993), since P300 asymmetry was in
these cases also restricted to the temporal electrodes. Indeed, bilateral temporal lobe generators whose activities would be reflected only by recording over the lateral scalp could account for these observations, and in our experimental conditions activation of a temporal source contralateral to the target side would also be plausible. However, at this point no firm conclusion can be reached on this issue since the scalp asymmetry of our late P300 peak could also result merely from a spatio-temporal overlap with the early P300 peak, which we found to be highly lateralized. One hypothesis to explain the scalp P300 lateralization stems from the "hemispheric activation" model (see Kinsbourne 1977; Heilman 1979) whereby sustained attention towards one half of the extra- or intrapersonal space "activates" the opposite hemisphere. In agreement with this model, SEP studies have consistently shown an enhancement of early contralateral potentials when attention is directed toward the stimulated hand (Josiassen et al. 1982; Desmedt et al. 1983; Garcia-Larrea et al. 1991). In our study tonically maintained attention toward the target hand could theoretically have induced a predominant activation of the P300 generators in the opposite (activated) hemisphere. However, the even concept of hemispheric "activation," as a mechanism underlying sustained lateralized attention, cannot be modality-specific since the main clinical evidence supporting it is the observation of a polymodal sensory neglect toward stimuli delivered in the half of the space contralateral to a thalamic or cortical lesion. Consequently, if hemispheric "activation" were the main factor accounting for P300 asymmetry in the somatosensory modality, such an asymmetry should also be observed whenever attention is tonically directed to one hemispace, independently of the sensory modality. However, no asymmetry of the auditory P300 has hitherto been reported in response to monaural targets (Picton and Hillyard 1974; Perrault and Picton 1984; Knight et al. 1989) thus suggesting that lateralized attention per se does not produce any contralateral hemisphere predominance of P300.
TABLE IV Comparisons of normalized amplitudes at homologous electrodes (T5 vs. T6 and P3 vs. P4). Values are t values of 2-tailed paired t tests. The early P300 is significantlygreater at parietal and temporal electrodes contralateral to the target side when compared to homologous ipsilateral electrodes. A significant difference has been obtained only between temporal electrodes for the late P300.
Right target Left target
Early P300 T5 vs. T6 4.598 * * - 2.282 *
• P < 0.05; ** P < 0.01.
P3 vs. P4 3.217 * * - 3.088 * *
Late P300 T5 vs. T6 P3 vs. P4 2.456 * 0.839 - 2.459 * - 1.704
L A T E R A L I Z A T I O N O F S O M A T O S E N S O R Y P300
475
The somatosensory system, with no direct transcallosal connections between the hand areas in 3b (Killackey et al. 1983), is particularly appropriate for assessing whether lateralized sustained attention can cause a shift of P300 distribution on the scalp surface. Indeed, this system offers the possibility to dissociate the hemisphere tonically "activated" by attention from that receiving rare (but ignored) P3-evoking stimuli. This dissociation was achieved in our complementary experiment where subjects were asked to count frequent (90%) stimuli delivered to one hand (and consequently to focus tonically their attention toward this side), while rare non-target shocks were applied to the fingers on the opposite side (Fig. 5). Under this condition, the P300 potential evoked by rare-ignored stimuli peaked with a latency similar to that of the early P300 to rare-target stimuli and was clearly lateralized on the half of the scalp opposite to stimulation, i.e., over the
"non-activated" hemisphere. Therefore, the lateralization of the somatosensory P300, and particularly of its "early" component, seems to depend on the hemisphere which receives the P3-evoking stimulus and not on the one involved in maintaining sustained attention. The positivity evoked in our subjects by rare, unattended stimuli in the complementary experiment is likely to belong to the family of "novelty P3s," which may be isolated in response to rare unattended, taskirrelevant stimuli in the auditory, visual and somatosensory modalities (Courchesne et al. 1975; Squires et al. 1975; Yamaguchi and Knight 1991a,b). Whatever the sensory modality, these positivities are commonly labeled "P3a" and are thought to reflect an automatic attentional shift toward a deviant stimulus (Squires et al. 1975; Ford et al. 1976; Yamaguchi and Knight 1991a,b). The latency of this novelty-P3 was in our subjects coincident with that of the "early" peak of
stai d attention: right side re sts lus: left hand lguV Sustained attention: Rare stimtlus: right
_
1
side Y
92@ms
Fig. 5. Traces and m a p s corresponding to the "complementary experiment," in which the side of the body receiving sustained attention was contralateral to the one receiving the rare stimuli (see text). Traces from temporal (T5, T6), parietal (P3, P4) and central (C3, C4) electrodes are superimposed. In the upper half of the figure traces and maps correspond to grand-averaged SEPs to rare stimuli delivered to the left hand while sustained attention was directed toward the right side. T h e reciprocal is shown in the lower half of the figure (rare stimulus to right hand, sustained attention to the left side). The P3 recorded in response to rare-ignored stimuli was single peaked, culminated in average at 296 msec and was lateralized always toward the hemiscalp contralateral to the rare stimulation, even if tonic sustained attention was directed away from that side.
476 t h e t a r g e t P300, a n d t h u s w e m a y a s s u m e t h a t this e a r l y p e a k also c o r r e s p o n d s to a P 3 a ( B a r r e t t et al. 1987). I f this a s s u m p t i o n is c o r r e c t o u r f i n d i n g s w o u l d s u g g e s t t h a t , in t h e s o m a t o s e n s o r y m o d a l i t y , t h e a u t o m a t i c p r o c e s s i n g o f s e n s o r y s t i m u l i i n d e x e d by t h e P3a is c o n t r o l l e d m a i n l y by t h e h e m i s p h e r e r e c e i v i n g t h e p e r i p h e r a l i n p u t , e v e n t h o u g h t h e full p r o c e s s i n g o f i n f o r m a t i o n ( i n c l u d i n g t a r g e t i d e n t i f i c a t i o n ) is o b v i o u s l y n o t r e s t r i c t e d to this h e m i s p h e r e .
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