Intracerebral recordings of slow potentials in a contingent negative variation paradigm: an exploration in epileptic patients

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Electroencephalography and clinical Neurophysiology 95 (1995) 268-276

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Intracerebral recordings of slow potentials in a contingent negative variation paradigm: an exploration in epileptic patients M. Lamarche *, J. Louvel, P. Buser, I. Rektor 1 UnitO 1NSERM U 97 and Department of Neurosurgery, H@ital Ste Anne, 2 ter Rue d'Al~sia, 75014 Paris, France Accepted for publication: 23 May 1995

Abstract

While exploring epileptic patients with intracerebral multilead electrodes, we applied a forewarned reaction time task with two successive sound stimuli, a paradigm that is known to elicit a contingent negative variation (CNV). The second, imperative sound stimulus was followed by a hand or a foot movement. Eleven patients suffering drug-resistant partial epilepsies were tested. The slow potentials developing during the time between the two stimuli were usually not typical CNVs (sometimes comprising multiple successive components with distinct polarities). Such "CNV-like" potentials were obtained from two main cortical zones: a central one including premotor, motor, supplementary motor, postcentral and cingulate areas; and a temporal zone, mainly including the auditory cortex and its vicinity, and in some cases the amygdala. This restricted localization contrasted with the broader extent of the CNVs on the scalp. Intracerebral CNV-like events were obtained from both hemispheres, independent of the side of the performed movement. In some patients, readiness potentials (RPs) were also recorded for comparison and displayed a more restricted extent, being present only on the contralateral motor cortex and bilaterally in the supplementary motor areas. Our data suggest that the last part of the CNV cannot just be identified with the RP. Keywords: Intracerebral recording; Contingent negative variation; Epilepsy

1. Introduction

The contingent negative variation (CNV) is believed to be linked to different mental states and activities including level of vigilance, arousal, stress, attention, expectation, the will to elaborate a response, decisional performance, time estimation and preparation of a motor response (Timsit-Berthier 1984; Wei and Zheng 1987; Brunia 1988; Zappoli et al. 1991; see also Rockstroh et al. 1993 and review by McCallum and Curry 1993). It is generally now believed that the CNV is a composite phenomenon with two or more waves interposed between the potentials evoked by the two successive (warning and imperative) stimuli. More precisely, the earlier part is believed to be mainly linked to information processing subsequent to the warning stimulus, while the later part is related to motor

* Corresponding author. Tel.: 33 1 40789254; Fax: 33 1 45807293. 1 Present address: Clinic of Neurology, Masaryk University, Brno, Czech Republic.

preparation and the anticipation of the imperative stimulus. Although the late component can be recorded in the absence of any motor response (Ruchkin et al. 1986; Frost et al. 1988), it has been suggested by some authors (Griinewald et al. 1979; Brunia 1988) that the last part of the CNV shares key features with the readiness potential (RP), which develops prior to any self-paced voluntary movement (Kornhuber and Deecke 1964). Nevertheless one of the questions that remain open is whether this late component and the RP originate from the same generators (see e.g., Rohrbaugh and Gaillard 1983; Brunia 1987). In a series of pilot explorations on patients with intractable epileptic seizures, using a forewarned reaction time task (a more general designation used by several authors instead of " C N V paradigm," see e.g., B6cker et al. 1993), known to elicit a CNV in scalp recording of human subjects, we very soon realized that the recorded potentials from within the brain considerably differed from the conventional, scalp recorded, CNVs. We therefore decided to call these potentials " C N V - l i k e " slow potentials (SPs). The present paper describes a study to: (i) localize the structures from

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M. Lamarche et al. / Electroencephalography and clinical Neurophysiology 95 (1995) 268-276

which such SPs were recorded; (ii) relate the depth records to the scalp potentials; (iii) explore if possible the relationships between the " C N V - l i k e " potentials and the RPs obtained from the same cerebral sites, to assess whether the CNV late wave has generators different from those of the RP.

269

potential (RP) using another classic protocol (Kornhuber and Deecke 1964) that we have used in a previous study specifically devoted to these potentials (Rektor et al. 1994). Each session took about 1 h. Recording from the depth electrodes usually began on the second day after implantation and was repeated as often as possible. 2.1. Protocols and recording procedures

2. Patients and methods Eleven patients suffering from drug-resistant partial epileptic seizures were investigated in this series (they will be designated herein nos. 1-11; see Table 1 for their main characteristics). Some of our patients were considered clinically " n o r m a l " since they had no sign of neurological deficits while others suffered from hemiparesis or hemiplegia (see Table 1). None of them showed any major overt cognitive deficit while performing in the warned RT task used, or in daily interaction. They were all under minimal antiepileptic therapy (sodium valproate, hydantoin, barbiturates, carbamazepine, vigabatrin, depending on the patient's symptomatology). All except patient 7, with right hemiparesis, and patient 9 were right-handed. To localize their epileptic foci, the patients were implanted with chronic depth, multilead electrodes introduced into sites corresponding to the clinical and electro-clinical characteristics of their seizures (Fig. 1). Three to 7 days after electrode implantation, patients underwent several sessions of stereo-electroencephalographic (SEEG) recording of their ongoing activity, as well as a variety of electrical stimulation, to provide information on the localization of the epileptic focus. Consent was obtained from each patient for the CNV and RP tests, about which they were amply informed. In each case, a forewarned RT protocol was used to obtain the CNV-like potentials (Walter et al. 1964). Some patients (5, 6, 7 and 11) were also tested for the readiness

Table 1 Clinical characteristics of studied patients Patient no. Sex Age (years) 1 M 26 2 F 27 3 F 26

The patient lay comfortably on a bed and was instructed to fixate a given point in the visual field. In the CNV paradigm, two successive acoustic stimuli were delivered through a loudspeaker: a first tone S1 (warning stimulus), followed after 1.5 or 3 sec by the imperative stimulus $2, which was a repetition of a similar tone. The subject was instructed to perform a unilateral movement of the hand or foot as rapidly as possible after $2 (pressing a switch) to interrupt the $2 sequence. Each auditory stimulus was a burst at 1000 Hz, 75 dB, lasting 100 msec; the repetition rate of the $2 sounds was 5 Hz. The successive trials with the S1-$2 sequences were delivered at random intervals around 10 sec ( 1 0 + 2 sec). Blocks of 30 trials were performed, with a fixed foreperiod (1.5 or 3 sec), and movement of the same limb. We did not systematically evaluate the reaction time, but no obvious interindividual differences were observed. In the RP paradigm, the instruction was to perform the movement at will ("self-pacing"), the movement being the same as in the CNV paradigm. The patient was asked to maintain intervals of at least 10 sec between successive movements, without counting or otherwise estimating the time. Naturally, in case of unilateral motor deficit, the requested movements were all performed with the " h e a l t h y " side. All recording from scalp electrodes or deep leads was performed against a binauricular reference. Scalp electrodes were Nihon Kohden cups. The depth electrodes

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normal normal normal/slight right tcmporo-parieto-occipital junction atrophy normal/left temporo-basal lesion left hemiparesis/left microcephaly right fronto-polar porencephaly normal/right parietal and fronto-polar porencephaly right hemiparesis/left lateral ventricular dilatation normal/right temporo-polar lesion normal/small left striatum and temporo-parieto-occipitaljunction atrophy normal/right gyrus parahippocampi gliosis left hemiplegia/right fronto-polar porencephaly

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M. Lamarche et al. / Electroencephalography and clinical Neurophysiology 95 (1995) 268-276

(diameter 0.8 mm) had 5-15 leads, each 2 mm long, 1.3 mm apart. These electrodes were placed according to Talairach's stereotaxic coordinate system (Talairach et al. 1967; Talairach et Tournoux 1988). Post hoc NMR pictures were not systematically obtained. The electrode positions were largely determined from functional information provided by the SEEG staff, who systematically carried out electrical stimulation: single shocks were used to characterize the primary motor area and repetitive shocks to characterize the supplementary motor area (SMA) (Penfield and Welch 1951; Talairach and Bancaud 1965) and possibly other areas. Further details on the SEEG methodology and on stimulation have been described elsewhere (see e.g., Talairach et al. 1967). Surface electromyograms (EMGs) were recorded with a pair of cup electrodes placed on the skin over the flexor digitorum communis or the medial part of the calf muscles. Data acquisition and averaging were performed using a Nihon Kohden Neuropack 4 set with a band-pass for cortical recording between 0.01 Hz and 500 Hz (sampling frequency 2000 Hz). Through on-line monitoring, tracings with artifacts (such as eye movements, erratic general movements of the patient, saturating DC shift of the trace, etc.) could be rejected. In both conditions, the analysis window was 5 sec. In the CNV paradigm, averaging was started 500 msec before the S1 stimulus and in the RP, it was triggered by the EMG, covering a period from 3.5 sec before the movement to 1.5 sec after it. For each intracranial record, 30 trials were averaged for CNVs (after rejecting records with artifacts). The number of trials for RPs was slightly higher (40) since their amplitude was usually smaller. The CNV and RP records were then considered for their various features: polarity, duration and slope. The absolute values of the amplitudes were not taken into consideration, since small differences in intracerebral recording distances from a given source could cause large amplitude variations (Gloor 1987). The emphasis was placed on situation-dependent amplitude changes in the same lead. Since the objective of the depth explorations was to delimit the epileptic focus in each case, the electrode placements were determined on the basis of the clinical and EEG information gathered during prelimininary examination of the patient. To delimit the ictal zone as precisely as possible, some recording electrodes (or at least some leads) needed to be localized outside the limits of the pathological zone. Consequently, data were gathered on the presence or absence of a CNV at a number of presumably healthy brain sites. The aim was to characterize as precisely as possible the recorded slow potential shifts. These potentials were very slow shifts from the baseline during the foreperiod; they were either negative (as on the scalp), positive or often polyphasic. When an activity was detected resembling a CNV we could sometimes measure its slope. We chose to consider as a CNV-like activity any such slow potential

developing between the two stimuli, rising or falling from the baseline, with a slope above ___10 /xV/sec to reach a plateau. A large potential sometimes accompanied the movement itself; in this paper we shall not consider the issues associated with this type of potential.

3. Results 3.1. CNVs and RPs on the scalp

The study was focused on intracerebral records. Nevertheless, to determine whether our patients could be compared to the general population, we also routinely took scalp records of CNVs and RPs prior to implantation. CNVs were recorded in all patients at Cz (vertex), Pz and Fz. More laterally, scalp CNVs were also obtained from above the motor (C3 and C4) and the parietal cortex (P3 and P4). In all cases these CNVs were indistinguishable from those described in the literature (Timsit-Berthier 1984; Brunia 1988). The same holds true for the scalp RPs. 3.2. Cortical localization o f CNV-like slow potentials (SPs)

The overall positions of the recording electrodes is illustrated in Fig. 1: all electrodes that recorded an SP were pooled (filled circles), whichever movement was tested. They were mostly recorded from two cerebral regions: the central areas in all 3 patients where those potentials were sought (5, 6 and 7), including the motor and premotor cortex, the postcentral parietal cortex, the supplementary motor area and the underlying part of the cingulate gyrus. In 7 patients, records were obtained from the temporal lobe including the amygdala: out of 4 patients who were explored close to the auditory area (as indicated by the presence of large amplitude auditory evoked potentials, see below), 3 displayed an SP (patients 2, 4 and 8). Two of the 7 patients showed an SP in the amygdala (1 and 4). No slow potentials were recorded from the middle temporal gyrus (1, 2, 3, 4 and 10) or from other structures, including the hippocampus and hippocampal gyrus. All responsive sites were tested with movement of both hands; patients 5 and 7 were tested for hand and foot movements. 3.3. Polarity and shape o f the intracerebral SPs

Whereas scalp recorded CNVs were always negative when recorded "monopolarly," the morphology of the intracerebrally recorded CNV-like potentials varied considerably between patients and between recording sites. In general they were bilateral, not depending on the side of the moving limb for their shape (see, e.g., patient 5, Fig. 2). The only exception was patient 7 whose SP in the motor cortex was only eontralateral, presumably due to his severe brain lesion. A difference was sometimes noticed between CNV-like potentials with a short foreperiod (1.5

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SPs were recorded from the superior temporal cortex in patients 2, 4 and 8. In patient 2 (Fig. 4) the SP was recorded from 3 successive leads in the vicinity of the auditory cortex, as assessed by the large amplitudes of the evoked potentials to the signals (see below). On the most superficial lead (H5) it showed a purely negative slope, while the two deeper leads (H3 and H1) showed a biphasic form, with an initial positive part. In contrast the SPs in the amygdala were positive (patients 1 and 4, not illustrated). 3.6. Comparisons between cortical and deeply recorded potentials

l Z/ Fig. 1. Overall topographical distribution of the recording electrodes in the explored patients. Each circle indicates the point of entry of a multilead depth electrode approaching from the lateral surface (top panel) and mostly extending to the mesial surface (bottom panel). Numbers indicate the patients (from 1 to 11, see Table 1). Filled circles indicate presence of a CNV-like SP, empty circles, absence of CNV-like SP. All electrodes, either right or left, were positioned in the same scheme (left convexity, right mesial surface), according to the standard Talairach's stereotaxic coordinate system (Talairach et al. 1967).

sec) vs. those with a longer period (3 sec). In the latter case, at least two distinct components could be separated, but their variability from patient to patient prevented systematic analysis. Moreover, there were numerous cases where a CNV-like potential was observed with a short foreperiod and none with a long one. 3.4. Central areas We shall first describe two illustrative examples (Figs. 2 and 3). In patient 5 both hands and both feet were tested and all recorded SPs in the central area were negative (Fig. 2). In the foot primary motor cortex (QI-1) the SP with foot movement appeared as a regularly increasing negativity; in both SMAs (electrodes M'I-1 and MI-1, Fig. 2) SPs were recorded with both hand and foot movements; they consisted of a first shift from the baseline followed by a plateau. In patient 6 the SPs in the left SMA, tested for the

As stated in the Introduction, the slow potentials recorded in the CNV paradigm were of variable shape, preventing any very systematic classification. For example, in patient 6 (Fig. 3), we recorded a complex potential with a first positive shift, followed by a slowly increasing negative potential (slope 50 /,~V/sec), resembling a CNV, from the most mesiai lead located in the SMA (M'I-1). More lateral leads (M'l-3), presumably recording from the white matter, detected the early positivity but not the late potential. Patient 5 (Fig. 2) displayed potentials whose shape was close to that of the scalp CNV. Recording was performed from both SMAs (M'I-1 left and MI-1 right), for left and right hand and foot movements, using the 1.5 and 3 sec paradigms. All in all, slowly increasing negativities of variable amplitudes (slope < or = 50 /~V/sec) were observed for all movements, most of them ending up as a plateau, but none of them displaying the final increase, typical of scalp records. In the right SMA (MI-1), notice that the potentials were of smaller amplitude, presumably because of the adjacent, right-sided porencephaly in this patient. In the same patient, slowly increasing potentials were recorded from the foot area on the right side (QI-1) for movements of both feet (at least in 3 out of 4 cases with slopes of about 30 /~V/sec). A troublesome case is depicted in Fig. 4. Recording was carried out from an electrode (H) located in the vicinity of Heschl's gyrus, as indicated by the large amplitude evoked field responses to the auditory stimuli. Surprisingly, the most superficial lead (H5) displayed an almost typical CNV, resembling those recorded from the scalp. With the deeper leads however (H3 and H1), which were nevertheless very close to the

M. Lamarche et al. /Electroencephalography and clinical Neurophysiology 95 (1995) 268-276

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