The cortical generators of the contingent negative variation in humans: a study with subdural electrodes

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Abstract

Contingent negative variations (CNVs) and Bereitschaftspotentials (BPs) were recorded from subdural electrodes implanted in 14 patients with intractable epilepsy. For recording CNVs, a Go/NoGo S2 choice reaction-time paradigm was employed. Two seconds after presentation of a low tone burst (S1), either a medium (S2m) or a high tone burst (S2h) was delivered at random. Patients were instructed to make middle finger extensions after S2m but not after S2h. For recording BPs, patients repeated self-paced middle finger extensions. BPs were recorded from the primary motor area (MI), the primary sensory area (SI) and the supplementary sensorimotor area (SSMA). CNVs showed a patchy distribution in the prefrontal area and SSMA for the early component and in the prefrontal area, MI, SI, temporal area, occipital area and SSMA for the late component. These results suggest that the CNV recorded from the scalp is the summation of multiple cortical potentials which have different origins and different functions. The cortical distribution of the late CNVs was different from that of BPs. Late CNVs are not equivalent to BPs and are not related to motor preparation alone. After S2, 3 kinds of potentials, probably related to decision making, somatosensory feedback and motor execution under specific conditions, respectively, were observed.

Introduction

The contingent negative variation (CNV) is a slow negative shift of EEG which is elicited between warning (S1) and imperative (S2) stimuli when motor response to S2 is required. Although numerous studies have been done since the first report by Walter et al. (1964), there is still controversy regarding the neuronal generators of the CNV and its relationship to Bereitschaftspotentials (BPs) which precede self-paced voluntary movements (Kornhuber and Deecke, 1965).

In scalp recordings, the CNV is widely distributed over the head with its highest amplitude at the frontal and central electrodes. Studies with intracranial recordings using invasive electrodes in animals and humans have stressed the role of the frontal lobe as a possible generator of CNV. Rebert (1972)recorded CNVs in a simple cued reaction-time paradigm in monkeys. CNVs were obtained from the motor and premotor cortices. The premotor responses were larger than those in the motor cortex. Hablitz (1973)reported that CNVs were obtained from many regions in the frontal lobe including the prefrontal, premotor and motor cortices. As far as invasive recordings of CNVs in humans are concerned, very few data have been available so far. By comparing potentials recorded from scalp electrodes with those from intracerebral and subdural electrodes in humans, Walter (1967)concluded that CNVs arose from many areas of the frontal cortex. However, as Rebert (1976)pointed out, in most of these studies including both human and animal experiments, recordings were made only from the midline regions. Systematic studies covering all cortical regions, including the mesial surface of the brain, have not been reported yet. Recent studies with magnetoencephalography (MEG) have provided useful pieces of information regarding the cortical generators of the CNV. Fenwick et al. (1993), by recording the contingent magnetic variation (CMV) with a Go/NoGo paradigm, showed that the CMV consisted of multiple generators not only in the frontal cortex but also in the temporal, parietal and occipital cortices. Elbert et al. (1994)also recorded CMVs with a Go/NoGo paradigm and concluded that the generators of the CMV were distributed in the motor, sensory and association cortices.

Another issue in debate is the relationship between the CNV, especially the late CNV, and the BP, a slow negative potential preceding self-paced voluntary movements. CNVs are divided into two components, namely the early and late CNV (Loveless and Sanford, 1974; Gaillard, 1976; Rohrbaugh et al., 1976). The early CNV persists for 1–1.5 s after S1, and is maximum at the frontal scalp. The late CNV, which is maximum at the central scalp, starts to develop about 1 s before S2. Rohrbaugh and Gaillard (1983)showed that when there was no motor response CNV waveforms could be well approximated by the long duration slow negative waves elicited by non-paired stimuli. Their finding indicated that CNV consists of early CNV alone when motor responses are not required and suggested that the late CNV is equivalent to the BP. On the other hand, several investigators showed that late CNVs could be obtained without motor responses (Cohen and Walter, 1966; Donchin et al., 1972; Klorman and Ryan, 1980; Ruchkin et al., 1986). These studies suggested that the late CNV is related not only to motor preparation but also to anticipation of the imperative stimuli and that late CNV is not equivalent to the BP. In good agreement with these observations, Ikeda et al. (1994)reported that BPs were abolished in some pathological states in humans in spite of persistent CNVs. However, whether the late CNV is primarily related to motor preparation or not is still an open question (Tecce and Cattanach, 1993).

In the present study, to identify the generators of the CNV in human cerebral cortex and to clarify the relationship between the late CNV and the BP, CNVs in a Go/NoGo S2 choice reaction-time paradigm and BPs with self-paced voluntary movements were recorded from subdural electrodes implanted in 14 patients with intractable epilepsy. Although the polarity of the slow EEG shift recorded in the present CNV paradigm was not always negative, the term `contingent negative variation' was still used in this article for the sake of convenience.

Section snippets

Materials

Fourteen patients (13–50 years old) with intractable epilepsy, who had invasive monitoring with chronically implanted subdural electrodes for presurgical evaluation, participated in this study. Informed consent was obtained from every subject following the procedures approved by the local Institutional Review Board. None of the patients showed impairment of motor function on neurological examination. Eight patients showed lesions in the MRI. The lesions were located in the right cingulate gyrus

Auditory evoked potential (AEP) (Fig. 1)

AEPs elicited by both S1 and S2 of the CNV paradigm had the same waveform and distribution for both stimuli. AEPs with a clear negative peak at about 100 ms after S1 or S2 were obtained from 40 electrodes located close to the Sylvian fissure in 3 patients who had a large subdural plate on the lateral convexity (Fig. 1A). Among them 17 electrodes were in the face motor area as shown by electric stimulation. This negative peak seemed to correspond to the N100 of the long latency AEP recorded with

Auditory evoked potential (AEP)

Although the neural origins of long latency components of AEP are still unknown, there are some studies indicating that intact temporal lobes are necessary for the generation of long latency AEPs. Long latency AEPs could not be recorded in patients with bilateral destruction of the temporal lobe (Woods et al., 1987). Vaughan and Ritter (1970)reported that components N100, P200 and N200 of the AEP recorded over the scalp have a phase reversal over the temporal lobe. Studies with MEG have shown

Acknowledgements

This study was partly supported by the Grants-in-Aid for Scientific Research 06404031, for International Scientific Research 07044258 and for Priority Scientific Research from the Japan Ministry of Education, Science and Culture for H.S.

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