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Electroencephalography and cflnical Neurophysiology, 1991, 80:201-214 © 1991 Elsevier Scientific Publishers Ireland, Ltd. 0168-5597/91/$03.50 ADONIS 0168559791000770

EVOPOT 89201

Mapping study of somatosensory evoked potentials during selective spatial attention Luis Garcia-Larrea a, Hrlrne Bastuji b and Francois Maugui~re a,b CERMEP-Clinical Neurophysiology Laboratory, and b EEG Department, H~pital Neurologique, Lyon (France) (Accepted for publication: 18 July 1990)

Summary We have investigated the effects of selective spatial attention on early and middle-latency SEPs. Baseline control responses to electrical stimulation of 2 digits of the hand were recorded first in conditions of mental relaxation, in the absence of any cognitive task, to obtain truly 'neutral' responses uncontaminated by cognitive components. Then, during a 'task condition,' identical stimuli were applied to the same two fingers, but the subject's attention was driven towards the stimulated territory by the bias of mechanical taps delivered to the same digits. The earliest effect of directing attention towards the territory stimulated was a positive shift on contralateral somatosensory responses, with onset at 27.4+4 msec post stimulus. This SEP modification: (a) did not entail any change in the scalp distribution of components, as assessed by topographic mapping, and (b) was not present when attention was directed towards the hand contralateral to that receiving electrical stimuli. A second effect was represented by a parieto-central negativity in the 60-80 msec latency range; this feature could also be observed during contralaterally driven attention and was associated with topographical changes in SEP scalp distribution. Finally, a late centro-frontal negativity beginning at 90-100 msec (N140) appeared during ipsilateral attention, while P100 was not enhanced. Subcortical P14 and primary cortical N20 were not significantly affected by the tasks. We conclude that the 'early positive shift' is linked to the spatial aspects of selective attention and represents in part modulation of obligatory components (P25 through P45) existing in control SEPs; it probably corresponds with the deflections with similar polarity and time-course that have been described by others in response to somatosensory target stimuli. Conversely, 60-80 msec negative enhancement is less spatially selective and may represent non-specific arousal effects. The late negative component (N140) shares several features with the 'processing negativity' described in auditory paradigms and could represent the equivalent of this effect in the somatosensory system. Key words: Somatosensory evoked potentials; Selective spatial attention; Mapping

The neural mechanisms underlying selective attention in man are far from being elucidated. To explain improved task performance under attentional conditions one of the most conspicuous neuropsychological models implies the existence of sensory facilitation as a primary effect of attention (see Broadbent 1958; Posner and Presti 1987), while other theories invoke purely cognitive mechanisms, such as the change of detection criteria (Shaw 1984; Sperling 1984). Evoked potential (EP) investigations are relevant to this issue since they can provide information about the timing and duration of attention-related modulation of sensory processes. Moreover, compared to neuropsychological testing EPs have the advantage of providing quantitative information concerning not only the processing of attended stimuli, but also that of the rejected or unattended ones. Most data from current EP research support theories of sensory facilitation by attentional processes, but the question whether these effects occur at cortical or subcortical levels is not yet solved. EP studies in the audi-

Correspondence to: Luis Garcia-Larrea, CERMEP (Hrpital Neurologique), 59 Bd Pinel, 69003 Lyon (France).

tory and visual system have shown that attention induces early modifications of sensory responses. VEP enhancement related to attention has been reported with an onset latency of 80-90 msec (Eason 1981; Harter et al. 1982; Mangun et al. 1987). Also, in the auditory modality modifications of cortical EPs to attended stimuli have been consistently demonstrated with an onset latency of 50-60 msec (Hillyard et al. 1973; Nii~itiinen et al. 1978; Nii~itanen and Michie 1979; Hansen and Hillyard 1980), or even earlier in some recent reports (at about 30 msec post stimulus for Hillyard et al. 1987). The possibility of subcortical mechanisms for enhancement of attended, or rejection of unattended signals is supported by animal studies (Hernfindez-Pe6n 1966; Oatman 1971, 1976). In humans, although Lukas (1980, 1981) reported significant attentional effects on brain-stem auditory potentials (BAEPs), most investigators have consistently failed to obtain BAEP differences under selective attention tasks (Picton et al. 1971; Collet and Duclaux 1986; Hillyard et al. 1987; Gregory et al. 1989). A second, and also unsolved, issue concerns the nature of early attentional effects, since EP changes may reflect either modification of exogenous responses,

202

or the superimposition of genuine endogenous components, or both. Suggested criteria for accepting that attentional EP effects reflect only changes in exogenous components are that both wave shape and topography remain unchanged in attentive and non-attentive conditions (Hillyard 1986). However, in most published studies EPs under attention have been recorded with a few, if not only one, electrodes. Reports presenting detailed topographical studies of EPs obtained under attentional conditions are still exceptional (Desmedt et al. 1987; Desmedt and Tomberg, 1989). As compared with visual and auditory modalities, there have been relatively few reports of somatosensory evoked potentials (SEPs) under attentional tasks (Desmedt and Robertson 1977; Josiassen et al. 1982; Desmedt et al. 1983; Michie 1984; Michie et al. 1987; Papanicolau et al. 1989; Desmedt and Tomberg 1989). Most of them deal preferentially with responses to target detection, rather than with selective attention, thus rendering it difficult to disclose pure attentional effects from those linked to stimulus deviance. The earliest cognitive effect on SEPs was reported by Desmedt et al. (1983), who found a positive shift culminating at about 40 msec in parietal responses to target finger stimuli. Since this effect was observed only for targets it is difficult to ascertain which of stimulus deviance, rarity or attentional shift played the major role. Josiassen et al. (1982) described an amplitude enhancement of P45 in SEPs to targets, and also in responses to standard stimuli delivered to the adjacent finger; however, other investigators have not detected significant attentional effects in SEPs at earlier latencies than the N80 component (Michie et al. 1987) or even later (Papanicolau et al. 1989). The nature, and not only the timing, of SEP attentional changes is a subject of debate. Desmedt et al. (1983) qualified N60 in responses to targets as a 'cognitive' response, whereas Michie et al. (1987), on the basis of recording at 2 electrode sites only, considered enhanced N80 (N60 in other authors' nomenclature) as representing the modification of an exogenous component. In this study we recorded SEPs to electrical stimulation of fingers during a paradigm of selective spatial attention to address the questions of whether and how SEPs were modified when the attention of the subject was drawn towards the stimulated area. More precisely our purposes were: (a) to investigate the earliest latency at which significant effects of attention are detectable; (b) to assess whether the early changes of cortical SEPs previously reported for targets could also be observed in response to standard, non-target, stimuli presented in spatial locations to which attention is directed; and (c) to provide further insight into the nature, endogenous or exogenous, of attentional SEP changes by studying their topographical scalp distribution with multichannel SEP mapping.

L. GARCiA-LARREA ET AL.

Methods and subjects Experiments were performed on 11 young, healthy and fully informed unpaid volunteers aged 23-34 years. We obtained all records in a semi-darkened room, with the subject lying comfortably, eyes closed, on a wooden bed.

SEP stimulation and recording parameters Electrical 200/~sec square stimuli were delivered by a constant-current stimulator to the index and middle fingers of the left hand; stimulation intensity was adjusted at 3 times the sensory threshold. SEP mapping was performed in 9 subjects by means of 16 scalp electrodes attached to F7, F3, Fz, F4, F8, T3, C3, Cz, C4, T4, P3, Pz, P4, T6, O1 and 0 2 of the international 10-20 system. In the 2 other subjects a 4-channel montage (P4, C4, F4 and Fz) was used. Electrodes were Ag/AgC1 disks attached to the scalp with standard conductive paste. Impedance was kept below 3 k~2 in all cases. Reference was at the earlobe contralateral to the stimulus, with a ground electrode on the arm. Somatosensory evoked responses were amplified x 30,000 with an analog bandpass of 1-1500 Hz (3 dB down, 6 dB/octave), and digitized at 2 kHz for SEP mapping (bin width of 500/~sec). Analysis time was of 128 msec in all cases, with a prestimulus delay of 10 msec. A system for on-line artifact rejection was set up which eliminated from the average all responses exceeding + 80/~V. Two runs of 1000 stimuli were performed in each condition. SEP maps were computed using both linear interpolation from the 4 nearest neighbours and spline interpolation (Perrin et al. 1987).

Experimental procedure Each SEPs to least 2 subjects interval

recording session lasted between 2 and 3 h. upper limb stimulation were obtained under at experimental conditions in all subjects. In 2 the whole procedure was repeated at 6 month's in order to study the reproducibility of results. (a) Control SEPs ('no-task' condition). In the control condition, SEPs to 2 Hz electrical stimulation of the left index and middle fingers were recorded with the subject lying, eyes closed and relaxed, in a semi-darkened room. Stimulus intensity was set at 3 times the sensory threshold, a level usually entailing maximal amplitude of the first cortical SEP component (Lesser et al. 1979). Subjects were told to forget the stimulus and to tell themselves a pleasant story. (b) Task condition. This experiment, performed in all subjects, was designed to evaluate the effects of selective spatial attention directed to the fingers electrically stimulated for SEP recording. Standard SEPs to 2 Hz electrical finger stimulation were recorded exactly as in the control condition, but 10% probability cutaneous mechanical stimuli were con-

SEPs DURING SELECTIVESPATIALATTENTION currently applied over the same 2 digits. These latter were delivered manually in a pre-established, pseudorandom sequence by means of a gauze ball. The task consisted in counting silently, eyes closed, the mechanical stimuli. Responses to mechanical taps were not averaged, since they were used only to induce an attentional shift towards the electrically stimulated territory. Detection performances were checked at the end of each SEP run. (c) Complementary experiments. In order to differentiate between effects linked to selective spatial attention towards the stimulated fingers and those related to non-specific arousal effects induced by the cognitive task, we performed 2 further experiments in which mechanical taps were used to direct the subject's attention away from the territory stimulated for SEP recording. In 4 subjects SEPs to finger stimulation were recorded while the subject was involved in counting mechanical stimuli delivered to the contralateral hand; in 1 subject electrical and mechanical stimuli involved respectively the 2nd-3rd digits and the 5th digit of the same hand. All subjects underwent at least 2 SEP runs under each experimental condition in which they participated. The order of the different experiments was random, but one run of control SEPs was recorded first in all cases to get the subjects acquainted with electrical stimulation. All stimulus and recording parameters were kept constant across the different phases of the test, which differed from one another by the existence and location of a concomitant target only. Data reduction and statistical evaluation. SEPs to finger stimulation were compared between the control and task conditions. Amplitudes were measured (1) from baseline and (2) from onset of P14 at selected latencies corresponding to conspicuous peaks (P14, N20, P22, P27, N30, P45 and N60). The peak latency of N140 was in all cases beyond the end of our analysis time of 128 msec; amplitude comparisons were performed for this component at the last sampling point of the contralateral central electrode (C4). Significance of amplitude differences was computed using paired t tests. Furthermore, in order to evaluate amplitude differences in a whole SEP segment between 2 experimental conditions, series of 10-30 consecutive sample points were compared iteratively. In all these cases we applied Tukey's correction for repeated measures (Tukey et al. 1985; Mattson and Albee 1988). Finally, 'significance probability maps' were computed by performing sequential t tests on all sample points from all electrode sites (Duffy et al. 1981). Since we are aware of statistical limitations in applying repeated testing to 16 electrodes x 256 points, i.e., 4096 measures, the information obtained in that way was exclusively used for descriptive purposes (descriptive data analysis).

203 Topographical SEP studies were performed on grand-averages obtained from pooled data from all subjects. Previous to grand-averaging, responses were normalized in latency and amplitude. Amplitude normalization was accomplished by Z-transformation (Buschbaum et al. 1986) to avoid grand-averages being overinfluenced by subjects with larger amplitude SEPs. Latency normalization was performed to prevent artificial 'smoothing' due to different peak latencies in each subject (their heights ranging from 160 to 200 cm). This was accomplished by fixing the onset of subcortical P14 in every subject at the latency obtained in our shortest control (15 msec). Thus, traces from all other controls were shifted leftwards by eliminating several sampling points between the stimulation artifact and P14 onset. Pre-analysis delay was not affected by this manoeuvre.

Results

Electrical 2 Hz stimuli used to elicit SEPs were very easily neglected in both the control and task conditions. All subjects reported no difficulty in disregarding these stimuli when asked to concentrate on random light mechanical stimulation, irrespective of their location. This subjective report was consistent with the subjects' objective performance, which was excellent in all (with a maximum of 2% error in counting) and showed no difference across experiments. Under the experimental setting described as task condition (attention directed to the same territory where electrical shocks were being applied), 'attentive' SEPs demonstrated consistent changes when compared with control responses. The main effects of directing the subject's attention toward the electrically stimulated fingers were observed in contralateral traces and consisted in: (a) an early positive shift beginning at about 30 msec at P4 and C4; (b) a negative increase of parieto-central SEPs between 60 and 80 msec; and (c) a late negative deviation of centro-frontal responses beginning after 100 msec, which could not be completely studied because of our analysis time of 128 msec. These modifications are illustrated in Figs. 1 and 2, showing respectively the grand-average of all subjects and 2 individual examples. The far-field P14 and early cortical N20 were not significantly modified by task performing in our subjects: P14-N20 and onset-to-peak P14 amplitude remained stable in all experiments. Amplitude comparisons between control and task conditions for the main contralateral SEP components are given in Table I.

(a) The early positive shift This shift was observed in 10 out of 11 subjects. It appeared first at contralateral central and parietal electrodes, with an onset latency of 27.4 + 4 msec, but

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Fig. 1. Grand-average of contralateral parietal, central and frontal SEPs during the control and task conditions. Thicker lines correspond to SEPs recorded while attention was directed towards the stimulated hand. Traces obtained by subtraction of control from 'task' SEPs are shown under each pair of superimposed wave forms. P14, N20 and P22 were not significantly affected by the attentional task. A positive shift in attended traces appears at 27.4___4 msec. Its onset is earlier at central and parietal locations (middle and lower traces) but it lasts longer at F4 (upper traces). It became significant at 38 msec. A negative enhancement in the task SEPs is seen in parietal traces between 60 and 85 msec (lower traces, horizontally hatched area), while a progressive negativity of all contralateral attentive SEPs becomes evident from 100 msec (black dots in 'difference' wave forms). Negativity up in this and the next figures. Vertical bar, left of bottom trace: 2/tV.

culminated in the frontal regions where it lasted longer. In some subjects the central P22 was also concerned in the 'early positive shift' (see subject A in Fig. 2), but this was not constant and did not appear in grand-averages (Fig. 1). Although the onset of this effect occurred before 30 msec, its statistical significance (paired t test, corrected for multiple comparisons) was not achieved before approximately 40 msec (black dot in Fig. 1). Thus, P45 was the first somatosensory component to demonstrate significant amplitude differences between the task and control conditions.

The time onset of the early positive shift was remarkably reproducible across subjects, since it occurred between 25 and 31 msec in all of them but one, in whom no positive deviation was seen until 39 msec post stimulus. In contrast with this, the culmination and the end of this SEP change exhibited an important variability and could adopt 2 different pattei'ns; in 4 subjects, it was prominent at all of contralateral sites, and could last more than 60 msec (Fig. 2A), while in the 7 others its predominance was clearly frontal, being much smaller and short lasting at central and parietal electrodes (Fig.

205

SEPs DURING SELECTIVE SPATIAL ATTENTION TABLE I Peak amplitude (~zV) of SEP components during control and task conditions. Component

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-0.6 _+0.34 0.22+1.55 -1.07+0.7 0.59+0.75 1.29+0.7 -1.09_+0.73 -0.8 _+1.02 -0.98_+1.7

-0.98 0.88 -0.94 -1.05 -3.67 -0.67 1.68 2

0.18 0.2 0.16 0.16 0.002 ** 0.26 0.06 0.03 *

t o w a r d s the electrically s t i m u l a t e d fingers. In contrast, no significant e a r l y m o d i f i c a t i o n a p p e a r e d in SEPs when the s u b j e c t was c o u n t i n g m e c h a n i c a l stimuli delivered o u t s i d e the t e r r i t o r y electrically stimulated. This was verified either w h e n m e c h a n i c a l t a p s were c o n t r a l a t e r a l to the s t i m u l a t e d digits o r w h e n m e c h a n i c a l a n d electrical stimuli were a p p l i e d to different fingers of the s a m e hand. T h e s p a t i a l selectivity of the early positive shift is i l l u s t r a t e d b y Figs. 3 a n d 4.

(b) 6 0 - 8 0 msec negative shift A s e c o n d effect o b s e r v e d in c o n t r a l a t e r a l traces during a t t e n t i o n was a n e g a t i v i t y a p p e a r i n g b e t w e e n 60 a n d 80 msec, m a i n l y r e c o r d e d in p a r i e t o - c e n t r a l leads. This feature was less c o n s t a n t t h a n the early positive effect, b e i n g o b s e r v e d in 7 out of 11 subjects. It a p p e a r e d either as an e n h a n c e m e n t of N60, or as a ' h u m p ' over the N 6 0 ' s d e s c e n d i n g slope (Figs. 2B, 3 a n d 6). H o w ever, its scalp d i s t r i b u t i o n with a p a r i e t a l m a x i m u m d i d not c o i n c i d e with that of c o n t r o l N60, which was clearly f r o n t o - c e n t r a l in all subjects. This a t t e n t i o n - r e l a t e d p a r i e t o - c e n t r a l negativity app e a r s well d e f i n e d in the g r a n d - a v e r a g e (Fig. 1) a n d

* Difference significant at the 95% confidence level. * * Difference significant at the 99% confidence level.

2B). These i n t e r i n d i v i d u a l differences m a k e of g r a n d averages a difficult tool to d e a l with, since E P effects w h i c h are p r e s e n t i n m o s t individuals, b u t with different scalp p r e d o m i n a n c e , m a y be artificially s m o o t h e d , o r even ' a v e r a g e d o u t ' in p o o l e d data. T h e early positive shift in c o n t r a l a t e r a l SEPs was o b s e r v e d o n l y w h e n the subject's a t t e n t i o n was d i r e c t e d

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Fig. 2. Two individual examples of SEPs obtained during the task condition (thicker traces) superimposed on control responses. In A (male subject, aged 32 years) the attention-related positive shift (dotted) was prominent at all contralateral locations, and no enhancement of N60 was recorded. Conversely, the early positive shift was predominant on frontal traces in subject B (male, 33 years), while parietal, and to a lesser extent central, SEPs exhibited a negative enhancement in the 60-80 msec range under attention (black oblique arrow on lower right traces). Calibration mark (bottom right): 2 #V for subject A, 1 #V for subject B.

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Fig. 3. Contralateral parietal SEPs in one subject (male, 30 year old). All responses shown were obtained during the same recording session. The upper part of the figure shows responses obtained during the main task condition (attention directed towards the stimulated hand, thicker line) superimposed on control SEPs. Below the superimposition is represented the 'difference wave' obtained by subtracting control from task wave forms. In the lower part of the figure, SEPs obtained during the 'contralateral attentive' task (when attention was directed towards the hand contralateral to stimulation) also superimposed on control SEPs. The result of subtracting control from task wave forms is illustrated below the superimposed traces. When attention was focussed on the stimulated hand (upper traces) there was (A) an early positive shift between 25 and 45 msec (dotted in the figure), (B) a negative enhancement between 50 and 80 msec, immediately followed by (C) a late negative enhancement corresponding to the onset of N140. These different effects are labelled A, B and C respectively in the 'difference wave form.' When the attention of the subject was focussed on the hand contralateral to the electrical stimuli (lower traces) the early positive shift (A) completely disappeared, as well as the late enhancement of N140 (C). However, the negative enhancement from 55 to 80 msec persisted, suggesting that, conversely to what happens with the preceding and following effects, the spatial features of the task were not necessary for N60 enhancement to occur. Calibration at bottom right, 2/~V.

skims statistical significance ( P = 0.06) at the parietal electrode (Table I). Four subjects failed to exhibit a definite negativity within the 60-80 msec latency range; however, there was also in them a tendency for the early positive shift to abate during this time-segment when performing the attentional task. There was in fact an inverse relationship between the maximal amplitudes of the early positive shift and of the middle-latency negative deviation, suggesting that these 2 components reflect the existence of 2 different attentional effects overlapping in time (Fig. 5). The 60-80 msec negativity was observed not only when attention was directed towards the stimulated fingers, but also in experiments in which the subjects directed their attention towards mechanical stimuli ap-

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Fig. 4. Contralateral central records from one subject (female, 33 years old). All responses were obtained during the same recording session. Upper traces: responses obtained during the main task condition (attention towards the stimulated hand, thicker line) superimposed on baseline SEPs recorded in the absence of any cognitive task. The 'difference wave' calculated by subtraction of control from task wave forms is represented below the superimposed traces. Lower traces: responses obtained during the 'contralateral attentive' task (attention directed towards the band contralateral to stimulation, thicker trace) superimposed on control SEPs. Subtraction of control from task wave forms is illustrated by the bottom trace. During the main task SEPs showed a clear early positive shift beginning at 30 msec. This effect was maximal at the contralateral central electrode. represented in the figure. A negative shift at the end of the analysis time (onset of N140) was also observed (dotted), but there was no enhancement of N60 in this subject. When attention was directed towards the hand c o n t r a l a t e r a l to stimulation (lower traces) both the early positive shift and the late negativity were strongly attenuated and virtually disappeared. Calibration at bottom right, 2 ffV.

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Fig. 5. Graph illustrating the relationship between the amplitudes of the 'early positive shift' and of the N60 enhancement during attention. Values obtained at electrode C4. Each dot represents 1 subject participating in this study. Subjects exhibiting the greater positive shifts tended to show no N60 enhancement, whereas the 7 subjects with enhanced N60 had smaller positive shifts. This behaviour suggests that both features represent different attentional effects overlapping in time. Correlation coefficient for the regression line is r = 0.64, P < 0.01.

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plied contralateral to the electrical ones (Fig. 3). In fact, in some subjects the 60-80 msec negativity was even greater during this latter condition, and in one case the negative shift appeared only during contralateral attention, when the early positive shift was no longer present. Although inconstant across subjects, this middlelatency negative enhancement proved to be remarkably reproducible over time in 2 subjects in whom the experimental conditions were reproduced at 6 months' intervals (Fig. 6).

(c) Late negativity (N140) This deviation between SEPs obtained during control and task conditions was recorded from 90 msec to the end of the analysis time. It was evident in all contralateral leads, with a clear m a x i m u m over the central regions (Fig. 1). It appeared in 7 of 11 subjects during the 'same territory' attentive condition, but in none of the 4 subjects in whom attention was directed contralaterally to the stimulated fingers (Figs. 3 and 4). The onset latency and scalp distribution of this attentional effect were similar to those of the N140 component, but our analysis time of 128 msec only allowed for a partial study of it; particularly its peak latency could not be ascertained in any of the subjects.

(d) SEP topography Maps of grand-averages under control and task conditions are provided in Figs. 7 and 8. In spite of the early effects described above no topographic variations were observed between control and attentive SEPs during the first 50 msec of the response. Thus N20, P22, P27, N30 and P45 showed their usual, well-delineated,

voltage distributions which remained unchanged during the counting task (Fig. 7). In order to study the scalp distribution of voltage differences between the experimental conditions we computed 'difference m a p s ' by subtraction of control SEPs from those obtained when attention was directed towards the stimulated fingers. Difference maps at peak latencies of SEP components are displayed in Fig. 8, along with the control and 'attentive' maps which they are derived from. The early positive shift during attention was represented in maps by a deeper red colour and broadening of the positivity in the scalp region corresponding to the P45, and to a lesser extent to the P27. In 'difference maps' the region first affected by the voltage difference is centred on C4. Scalp topographies were different for control and 'attentive' SEPs at N60 peak latency (see Fig. 7, 58-68 msec and Fig. 8, 65 msec). When N60 waned in control SEPs a parietal negativity still persisted in SEPs under attention, which corresponds to the parietal negative shift observed between 60 and 80 msec in traces recorded during the task condition (see Section (b) of Results and Fig. 1, bottom traces). As a result of this persisting negativity, the N60 m a x i m u m was displaced backwards, and delayed, in attentive SEP traces and maps. Parietal negativity between 60 and 80 msec was accompanied by persisting, or even increased, positivity in ipsilateral frontal and central regions and gave a roughly bipolar aspect to SEP maps within this time range. This aspect was even more obvious on difference maps (Fig. 8, 65 msec) where a dipole-like configuration of voltage differences clearly appears, with the isoelectric line grossly overlapping the scalp projection of the central sulcus. Topographic differences between control and attentive SEPs increased towards the end of our analysis time. F r o m 100 msec post-stimulus control maps were dominated by a broad positivity (P100) maximal at posterior and midline electrodes, whereas in maps obtained during the counting task the contralateral regions were occupied by a strong negativity maximal at C4. This corresponded to the late negative enhancement (N140) observed in SEPs during the task condition (see Fig. 1). Difference maps at the end of the analysis time show a broad negativity centred over the contralateral centro-frontal scalp.

Discussion In designing our experimental paradigms we tried to overcome some methodological biases that commonly burden EP cognitive studies. When responses to control and target stimuli are averaged during the same runs, as in classical attentional paradigms (Hillyard et al. 1973; Michie et al. 1987), control EPs are likely to be 'contaminated' by cognitive effects, arising for example from

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changes in vigilance due to the test demands. To avoid such arousal effects on control responses we compared SEPs under attentive conditions with true control SEPs, obtained in the absence of any cognitive demand. This approach has recently been validated as a satisfactory method to avoid cognitive contamination of control somatosensory responses (Desmedt and Tomberg 1989). Moreover, in some reports responses to both targets and standards delivered to the same cutaneous territory were averaged in the same session (Michie 1984; Michie et al. 1987), thus making necessary the introduction of differences in stimulus intensity to allow for target recognition, with the inconvenience that stimulus intensity is by itself a source of amplitude variation in both early and middle-latency SEPs (Lesser et al. 1979; Bastuji et al. 1989). In our paradigm the intensity of electrical stimuli triggering SEP averaging was kept constant in all conditions. Mechanical taps (responses to which were not averaged) were chosen as a simple method to direct the subjects attention towards different body regions. When we wanted to drive attention towards the electrically stimulated fingers we applied mechanical stimuli to this same territory. Conversely, mechanical taps were applied distant to the electrical shocks when we wanted attention to be directed away from these latter. One can assume that an equivalent level of tonic arousal is requested to perform both tasks, while the spatial drive of attention is clearly different. By combining these two paradigms in the same subjects the SEP changes linked to arousal and to selective spatial attention can be dissociated. Electrical stimuli were delivered at a relatively high rate (2 Hz) during all experiments, and this prevented any temptation to count them. Indeed, most subjects declared that they completely forgot about the electrical pulses during the test, to rediscover their existence only after having completed the counting of mechanical stimuli. Mechanical stimuli, even if not averaged, probably elicited SEPs which could theoretically interfere with responses to electrical shocks; in particular, a P300 to mechanical taps probably occurred. However, since mechanical taps were applied randomly and were not time-locked with averaging sweeps this interference was

209

unlikely in our case. Moreover, we recorded in one subject several runs in which electrical pulse intensity was set to zero, and mechanical stimuli applied and counted as in the task condition. This resulted in an essentially flat average.

Early SEP changes ( < 50 msec) Selective attention toward the electrically stimulated fingers during the counting task did not modify latency, amplitude or topographical distribution of cortical components N20 or P22, or of subcortical P14. These resuits, also reported for SEPs to target stimuli by Desmedt et al. (1983), do not support the notion of a 'subcortical gating' of peripheral inputs during selective attention (Hern~ndez-Pern 1966; Oatman 1971, 1976), at least for the somatosensory system. So far, only Lukas (1980, 1981) has reported the existence of significant changes in subcortical EPs during attentional tasks in the auditory modality, but these results have not been replicated by others (Picton et al. 1971; Collet and Duclaux 1986; Hillyard et al. 1987; Gregory et al. 1989). Hence, evidence from electrophysiological studies does not point to subcortical gating as a relevant mechanism for directed attention in man. Such a mechanism might, however, exist but be too subtle to be detected by conventional electrophysiological methods. The first effect of selective spatial attention was represented by a positive shift of contralateral traces entailing significant amplitude increase of P45. While Josiassen et al. (1982) also reported an enhancement of P45 in SEPs to standards which were delivered to the finger adjacent to targets, more recent reports have failed to obtain any significant effect on early SEPs ( < 50 msec) during selective attentional tasks (Michie 1984; Michie et al. 1987). This may have been partly due to the system bandpass and sampling rate used in these studies (low-pass cut-off at 30 Hz and bin width of 5 msec) which did not permit, as the authors stated, an accurate study of early SEP components. Papanicolau et al. (1989) also reported the absence of any short-latency SEP effect during an experimental paradigm similar to ours, in which a continuous, nonaveraged mechanical stimulus was applied to the stimulated hand. Methodological considerations may also apply to explain their negative results since only 100

Fig. 7. Grand-averages of responses from the 9 subjects who underwent topographic SEP mapping. Maps are consecutive between 20 and 112 msec post stimulus, each frame representing the average of 3-3.5 msec of analysis time. The left half of the figure corresponds to control SEPs, while maps on the right side were recorded during the task condition (attention directed towards the stimulated hand). From 20 to 30 msec grand-averaged maps are identical in control and task conditions. The contralateral positivities P27 and P45 are significantly enhanced in task SEP maps, but the overall topography of these components remains unchanged. From 50 msec onward topographical differences appear which are mainly characterized by: (1) a backward displacement of the contralateral negativity at 60-70 msec in task SEPs (last frame in 3rd row), with increasing simultaneous positivity over the left hemiscalp (ipsilateral to stimulation), and (2) the progressive development of a central negativity with onset at 90 msec. This negativity is only present at lateral electrodes in control SEPs, but dominates the contralateral scalp on maps obtained under selective attention (maps obtained from 100 to 120 msec, bottom row).

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L. GARCIA-LARREA ET AL.

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SEPs DURING SELECTIVE SPATIAL ATTENTION responses were averaged per run, which did not allow a good resolution of early SEP c o m p o n e n t s (see D e s m e d t et al. 1974). However, even u n d e r these unfavourable conditions their Fig. 1 shows a small e n h a n c e m e n t of P45 in SEPs to standards delivered close to targets. A positive shift in contralateral early SEPs, with very similar time-course and characteristics to the one described in this paper, was consistently obtained by Desmedt et al. (1983) and more recently by D e s m e d t and T o m b e r g (1989) in response to target stimuli that were identified and counted by the subjects. T h e y reported this effect to begin at a latency of 2 5 - 3 0 msec and to reach its m a x i m u m at 40 msec in parietal leads, and labelled it accordingly 'cognitive P40.' O u r results demonstrate that this early positive shift is also recorded in SEPs to non-targets, provided that they are delivered to an area to which the subject's attention is drawn. D e s m e d t and T o m b e r g (1989) also reported a 'cognitive P40' effect in SEPs to non-targets during a ' L i e ' experiment in which subjects were told to attend targets to one digit, but in fact received only an h o m o geneous set of standard stimuli. As in our case, statistical significance of this early effect was not achieved until about 40 msec post stimulus. O n the basis of polarity, circumstances of appearance and time-course characteristics we believe that both their 'cognitive P40' and our 'early positive shift' m a y be considered one and the same effect, in direct relationship to the attentional resources put by the subject on the stimulated territory. Even though all our subjects were repeatedly asked to remain relaxed during the experiments (or to stop them altogether if they felt unable to do so), it can be argued that involuntary contraction of the h a n d towards which attention was directed m a y have been responsible for some of the early effects observed in SEPs. Indeed, several investigators have shown the existence of early SEP modifications associated with voluntary contraction of limb muscles (Cohen and Starr 1985; Cheron and Borenstein 1987), but these changes include a marked suppression of P22, which remained stable in our subjects, and especially a decrease of P27, which was actually increased in our records because of the positive shift that began slightly earlier. O n the other hand, the study of Cheron and Borenstein (1987)

211 did not disclose any change in P45, while this c o m p o nent was the single most affected in our subjects. Finally, SEP changes linked to muscle activity have been observed for strong contractions such as fist clenching, which was never the case in our experiments. Therefore, we conclude that h a n d muscle contraction cannot account for the early SEP changes observed in our records, which are more likely to be considered as attention related. A second issue regarding this early effect is whether it m a y be viewed as directly related to spatial attention (i.e., to attention directed selectively to a definite region of the b o d y space) or to a non-specific attentional drive, related for instance to an 'arousal effect' induced by the experimental conditions. We observed the early positive shift only when electrical and mechanical stimuli were delivered to the same territory. This was checked by applying mechanical targets to the h a n d contralateral to electrical stimuli, or to the 5th digit of the same hand. In all these cases the overall attentional and arousal effects, as evaluated by the subjective appreciation of the subjects and by the level of performance, were the same as in the main task condition, but the early positive shift of SEPs was absent or strongly reduced (Figs. 3 and 4). This is consistent with the findings reported by D e s m e d t et al. (1983), who noted in a single individual the absence of early SEP changes to standard stimuli delivered to digits, when targets were applied to the ipsilateral forearm, near the elbow. Spatial selectivity of the early positive shift is also consistent with recent results of D e s m e d t and T o m b e r g (1989) who f o u n d no early attentional effect ( < 50 msec) on digital SEPs to non-targets delivered to the same h a n d as target stimuli (but to different fingers). Thus, directing attention towards the stimulated territory seems a conditio sine qua non in order to obtain significant effects on SEPs in the 2 5 - 5 0 msec range. This favours the hypothesis of a spatially selective attentional drive, rather than tonically increased arousal, to explain the 'early positive shift' during attention-dem a n d i n g experiments. This effect could be related to a differential processing of all stimuli, be they targets or standards, c o m i n g by a preselected channel. F r o m this the possibility follows of what could be called a ' s o m a -

Fig. 8. Grand-average of responses from the 9 subjects who underwent topographic SEP recording. Maps were obtained at selected latencies corresponding to well individualized components. Maps on the same row correspond to the same latency. Left column: maps recorded with the subject relaxed, in the absence of ~my demanding cognitive task. Middle column: responses obtained when the subjects focussed their attention on the stimulated hand. Right column: "difference maps' computed by means of a point-by-point subtraction of control from attentive responses. Amplitude scales at the right of each row correspond to difference maps; for the two left columns it must by multiplied by 2. No significant differences between control and attentive maps were seen either for N20/P20, or for P22 or N30. Components P27 and P45 were more positive in maps recorded under the attentive conditions, but there were no gross changes in their voltage distribution: the topography of voltage differences at 30 and 43 msec corresponds well with that of P27 and P45 components respectively. Conversely, N60 topography was distorted on attentive maps; the corresponding 'difference map' shows a dipole-like voltage distribution in which the isopotential line grossly overlaps the scalp projection of the central sulcus. Finally, the widespread P100 in control SEPs is overcome in attentive maps by a growing negativity culminating beyond the end of the analysis time. Scalp distribution of voltage differences shows a contralateral, centro-frontal distribution consistent with that of N140.

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totopy of attention,' with priming of any input coming from a predetermined region of the body space. The minimal surface of this privileged region on which attention can be selectively focused is probably linked to the density of sensory innervation and central representation, and it seems that, at least in the upper limb, this area could be as small as a few square centimetres. It is of course not surprising that a similar effect could be observed in response to targets (Desmedt et al. 1983; Desmedt and Tomberg 1989) since in that case attention was consciously and obligatorily directed towards the territory they came from. In spite of these early changes no difference in SEP topography could be demonstrated during the first 50 msec of the response. Regarding P45, which was the single component most affected by this positive shift, its distribution was centred on the scalp central regions in control and attentive SEPs, and only a broader extension of the corresponding positivity, as well as greater absolute voltages, differentiated task from control responses (Fig. 8). These findings suggest that early changes in SEPs during attentional tasks do not reflect the activation of different generators from those already active under control conditions; otherwise differences in the overall potential distribution should have been observed. According to this, we decided not to describe this early effect with a label that might suggest the existence of a new EP component and preferred the more neutral and descriptive term of 'early positive shift.' The mechanisms underlying these early SEP attentional changes could imply a kind of facilitation of incoming inputs by the same neural networks processing them in basal conditions: a sort of gating effect on exogenous SEPs whose activity would be quantitatively modulated by the attentional state. In that context it is noteworthy that the scalp distribution of the 'cognitive P40' to target stimuli is also similar to that obtained for control SEPs (Desmedt et al. 1987; Desmedt and Tomberg 1989). Since the hypothesis of a peripheral or brain-stem gating (Hernhndez-Pern 1966; Lukas 1980) is not supported either by the stability of P14 and N20 during our attention task, or by the results of Desmedt et al. (1983) and Desmedt and Tomberg (1989), it follows that this early SEP modulation should take place at the cortical level, perhaps by the bias of sustained, reverberating thalamo-cortical loops (Skinner and Yingling 1977; Landry and Dykes 1985). Indeed, in mammals the existence of cortical cells responding differently to the same physical stimulus has been demonstrated, which enhance their response when behavioural significance of the stimulus is high (Hyv~irinen et al. 1980; Haenny et al. 1984; Moran and Desimone 1985). Using positron emission tomography (PET) Meyer et al. (1989) have also reported that attention directed towards a vibrotactile stimulus induces an increase of human cerebral

L. GARCIA-LARREA ET AL.

blood flow (CBF) in the somatosensory cortex; this is consistent with our finding of SEP modulation beginning as early as 27 msec in our subjects.

Middle-latency changes (60-80 msec) As compared with control responses, contralateral central and parietal SEPs obtained during the task condition exhibited a tendency to become more negative between 60 and 80 msec. These middle-latency changes were less constant than those described as the 'early positive shift' since they appeared in 7 out of 11 subjects; in those cases a negative shift in SEPs under attention appeared mainly as a 'hump' on the descending slope of N60 (see Figs. 1, 2B, 3 and 6). The features of this negative trend were quite different from those of early changes, especially in that it was possible to obtain similar effects when the subject's attention was drawn to the hand opposite to the electrically stimulated fingers (Fig. 3). This indicates that, contrary to the early positive shift, selective spatial attention is not a necessary condition for this effect to develop. Such a modification is thus probably not directly related to the spatial components of attention, but more likely to be a non-selective arousal effect induced by the experimental conditions, and could correspond to the 'task performance' arousal components in N~i~it~inen's classification (1987). Middle-latency SEP cognitive changes appear inconstantly in previous literature: Desmedt et al. (1983) described an 'N60' cognitive effect in SEPs to target stimuli, but this effect was not found in later studies by the same team, also involving SEP responses to targets (Desmedt and Tomberg 1989). Michie et al. (1987) reported the enhancement of a negative potential at 80 msec in SEPs to attended, non-target, stimuli delivered to one hand. However, this effect only appeared when 'attended standards' were weaker than targets, but not if they were stronger. Hence, it is likely that differences in the level of the attentional demands may influence the development of a weaker or stronger negativity in the 60-80 msec range. In our case, we could not relate the appearance of this parieto-central negativity to the subjective difficulty of the task, since all subjects performed equally well. It is, however, conceivable that the subject 'commitment' in the experiment (desire for a good result) might explain in part this feature, perhaps through the bias of increased arousal. Spectral analysis of background E E G could help in future experiments to assess the tonic level of vigilance during this kind of cognitive experiment. In this time range, task SEPs began to differ in topography from control responses, suggesting the possibility that some supplementary generators could be simultaneously active. It is of course tempting to consider middle-latency attentional effects not only as a mere enhancement of exogenous N60, but as the result

SEPs DURING SELECTIVE SPATIAL ATTENTION

of superimposition of an endogenous potential responsible for the dipole-like configuration in 'difference maps' (Fig. 8). However, if a change of amplitude without topographic modifications, as observed for the early positive shift, does represent a strong argument against the existence of endogenous generators, the reverse is not true, since differential attenuation or enhancement of overlapping bioelectrical signals may induce topographic changes without the intervention of any new neural source (Achim and Richer 1988). Hence, the possibility that an apparently genuine 'endogenous component' is due to overlapping changes in exogenous responses cannot be ruled out by our records.

Late attentional changes The late negativity seen in task SEPs during the 'same-territory' attentive condition was considered to be N140, a component described in 1977 by Desmedt and Robertson. N140 is know to be enhanced in SEPs to target stimuli (Desmedt and Robertson 1977) as well as in response to standards delivered during 'oddball' paradigms, especially if targets and non-targets are applied to the same hand (Josiassen et al. 1982; Desmedt and Tomberg 1989; Papanicolau et al. 1989). In our subjects the very early phases of N140 development were very similar in control and task SEPs (see Fig. 7, 90-100 msec) and it was only later than it acquired predominance in SEPs recorded during the task condition (Fig. 7, frames from 100 to 120 msec). This component was clearly enhanced when attention was drawn towards the stimulated hand, but not, or very little, during the 'contralateral attentive' condition, when the attentional drive was directed towards the hand opposite to stimulation (Figs. 3 and 4). Josiassen et al. (1982) and Desmedt and Tomberg (1989) also found N140 to be greater for stimuli delivered to the same hand as targets than for shocks applied to the contralateral hand. These features are quite reminiscent of those observed for the 'processing negativity' in the auditory modality, since the processing negativity is known to be larger in response to a particular stimulus the more similar it is to the attended target (N~t~tt~nen 1985). Stimulus 'similarity' was in our case dependent on spatial topography, while in auditory experiments similitude is rather a matter of frequency content. However, units responding to contiguous frequencies are also spatially contiguous from the periphery to the cortex (see Pickles 1982). Thus, it could be proposed that both somatosensory N140 and auditory 'processing negativity' increase with the spatial concordance in the neural structures activated by the stimulus received and the stimulus expected. Accordingly, their maximal amplitude is in both cases obtained in response to targets (N~i~t~inen 1985; Desmedt and Tomberg 1989). In SEPs to targets the P100 potential is known to occur more conspicuously than the N140 (Desmedt and

213

Robertson 1977; Josiassen et al. 1982; Desmedt et al. 1983). Conversely, in our experimental paradigm, which involved SEPs to attended non-target stimuli only, the relative enhancement of N140 was much more prominent than that of P100. It may be suggested that the cognitive selection of a target among a series of attended stimuli occurs in the latency range of P100-N140, and that enhanced N140 with unchanged P100 might be a characteristic feature of the responses to attended, but non-target inputs. The relative importance of P100 and N140 components could then be seen as indexing the output of a selection process, whose ultimate goal would be the extraction, amongst a series of stimuli already privileged by attention, of the one to be considered as ' the target.'

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