Prospective multi-center study of an automatic online seizure detection system for epilepsy monitoring units.

OBJECTIVE: A method for automatic detection of epileptic seizures in long-term scalp-EEG recordings called EpiScan will be presented. EpiScan is used as alarm device to notify medical staff of epilepsy monitoring units (EMUs) in case of a seizure. METHODS: A prospective multi-center study was performed in three EMUs including 205 patients. A comparison between EpiScan and the Persyst seizure detector on the prospective data will be presented. In addition, the detection results of EpiScan on retrospective EEG data of 310 patients and the public available CHB-MIT dataset will be shown. RESULTS: A detection sensitivity of 81% was reached for unequivocal electrographic seizures with false alarm rate of only 7 per day. No statistical significant differences in the detection sensitivities could be found between the centers. The comparison to the Persyst seizure detector showed a lower false alarm rate of EpiScan but the difference was not of statistical significance. CONCLUSIONS: The automatic seizure detection method EpiScan showed high sensitivity and low false alarm rate in a prospective multi-center study on a large number of patients. SIGNIFICANCE: The application as seizure alarm device in EMUs becomes feasible and will raise the efficiency of video-EEG monitoring and the safety levels of patients.

EEG evidence of gender differences in a motor related CNV study.

In the present study gender differences related to the contingent negative variation (CNV) were investigated. A series of two acoustic stimuli was presented to participants across a wide age range. The first stimulus was consistent throughout the experiment whereas the second one was either a high frequency or a low frequency tone. One of them had to be answered by a button press (go condition) the other did not require any response (nogo condition). Between the first and the second tone there was a time period of two seconds in which the CNV appeared as a slow negative potential shift. Within this episode data were analysed with respect to gender differences. Statistical analysis revealed topographical differences between men and women in go conditions for both left and right index finger movements. Differences were found over frontal regions where women showed higher brain activity than men and over temporo-parietal regions where men produced higher brain activity than women. In order to explain the fact that only in "go" conditions significant gender differences occurred we introduce the phenomenon of implicit learning. Due to implicit learning assumed predictions related to S2 might have occurred from time to time. This is so, because a 50% chance for one of two different stimuli to occur leads to reasonable assumed predictions after two or more stimuli of a kind occurring in a series. The present data now provide evidence that if such assumed prediction or expectancy is directed towards an upcoming demand to act then brain activity is subject to gender differences. Further studies providing controlled sequences of "go" conditions versus "nogo" conditions have to be done to prove this idea true.

The effects of alteration of effector and side of movement on the contingent negative variation.

OBJECTIVE: The contingent negative variation (CNV) is a widespread electroencephalographic (EEG) potential that occurs during the interval between a warning stimulus and a subsequent imperative stimulus if a mental or motor response is required. The present study was designed to explore the impact of the previous trial on the CNV of the forthcoming trial, that is, how a previous movement affects brain activation preparing the next movement. Effects of alteration of finger (from index to middle, and vice versa) and hand (from left to right, and vice versa) were examined independently from each other. METHODS: CNV was recorded in 20 right-handed healthy subjects with electrodes placed at F7, F5, F3, F4, F6, F8, FC5, FC3, FC1, FC2, FC4, FC6, T7, C5, C3, C1, C2, C4, C6, T8, CP5, CP1, CP2, CP6, P7, P3, P4 and P8. In a visual/visual S1-choice paradigm, an earlier informative (S1) stimulus which instructed for side and finger of the following movement was followed 3 s later by an imperative (S2) stimulus providing the command to move. Subjects had to respond to each imperative stimulus with an appropriate button press made by brisk flexion movements with the index or middle finger of each hand. The CNV recorded in the interval between the informative and the imperative stimulus was analysed with respect to finger and hand of the present and the preceding movement. RESULTS/CONCLUSIONS: (1) A change of the side of movement is associated with a widespread increase of negativity contralateral to the currently prepared movement. (2) A change of finger is associated with a focal increase of negativity contralateral to the side of the current movement over temporoparietal and mid-parietal areas. (3) A change of finger results in a widespread increase of negativity over the left hemisphere.

The effects of alteration of effector and side of movement on movement-related cortical potentials.

The amplitude of the movement-related cortical potential (MRCP) preceding self-paced voluntary movements is larger if subjects alter between flexions of two fingers compared with repetitive movements of the same finger. However, earlier studies were confined to alternating movements between limbs only and therefore could not differentiate effects of between-limbs from within-limb alteration. The present study was designed to examine effects of alteration of finger (from index to middle, and vice versa) and hand (from left to right, and vice versa) independently from each other. MRCPs were recorded in 20 right-handed healthy young subjects with electrodes placed at Fp1, Fp2, F7, F3, F4, F8, T7, C5, C3, C1, C2, C4, C6, T8, P7, P3, P4, P8, O1 and O2. Subjects made self-paced flexion movements with the index or middle finger of each hand by pressing one out of 4 response buttons. In the alternating conditions, subjects pressed two buttons in a strictly alternating fashion. Every finger was combined with every other finger, arriving at a total of 6 alternating conditions. In the 4 regular conditions, subjects pressed a particular button repetitively across trials. The results show the following: (1) MRCPs over contralateral sensorimotor areas are higher if subjects change the side of movement than if the movements are done with the same hand repeatedly. (2) MRCPs over lateral parietal areas are higher for ipsilateral than contralateral movements in the regular conditions but also increase contralaterally after a change of the side of movement. (3) Any change of side or finger is associated with a widespread increase of negativity over the left hemisphere.

Physiological evidence of gender differences in word recognition: a magnetoencephalographic (MEG) study.

Magnetic field recordings were made in order to describe brain processes during a word recognition experiment. We investigated 26 healthy young subjects (14 females) and focused on gender differences related to recognition performance and brain activity. From about 200 ms to 350 ms after word onset the event-related field (ERF) patterns differed significantly between women and men, although the mean recognition performances did not. Differences were due to different strengths of activation as well as due to the involvement of different neural structures as underlined with statistical analysis. We interpret that our physiological findings demonstrate that different mental strategies are used for correct word recognition in the brains of women and men as assessed with magnetoencephalography (MEG). Our data might be linked to previous findings about the hemispheric asymmetry in male subjects (left lateralized) compared to women in whom both hemispheres seem to be equally involved in word processing.

False recognition depends on depth of prior word processing: a magnetoencephalographic (MEG) study.

Brain activity was measured with a whole head magnetoencephalograph (MEG) during the test phases of word recognition experiments. Healthy young subjects had to discriminate between previously presented and new words. During prior study phases two different levels of word processing were provided according to two different kinds of instructions (shallow and deep encoding). Event-related fields (ERFs) associated with falsely recognized words (false alarms) were found to depend on the depth of processing during the prior study phase. False alarms elicited higher brain activity (as reflected by dipole strength) in case of prior deep encoding as compared to shallow encoding between 300 and 500 ms after stimulus onset at temporal brain areas. Between 500 and 700 ms we found evidence for differences in the involvement of neural structures related to both conditions of false alarms. Furthermore, the number of false alarms was found to depend on depth of processing. Shallow encoding led to a higher number of false alarms than deep encoding. All data are discussed as strong support for the ideas that a certain level of word processing is performed by a distinct set of neural systems and that the same neural systems which encode information are reactivated during the retrieval.

A medial to lateral shift in pre-movement cortical activity in hemi-Parkinson's disease.

OBJECTIVE: Recent evidence suggests that cortical activity associated with voluntary movement is relatively shifted from medial to lateral premotor areas in Parkinson's disease. This shift occurs bilaterally even for unilateral responses. It is not clear whether the shift in processing reflects an overall change in movement strategy, thereby involving alternate cortical areas, or reflects a compensatory change whereby, given the appropriate conditions, less impaired cortical areas are able to provide a similar function in compensation for those areas which are more impaired. This issue was examined in patients with hemi-Parkinson's disease, in whom basal ganglia impairment is most pronounced in one hemisphere. METHODS: Fourteen patients with hemi-Parkinson's disease and 15 age-matched control subjects performed a Go/NoGo finger movement task and the contingent negative variation (CNV) was recorded from 21 scalp positions. RESULTS AND CONCLUSIONS: Maximal CNV amplitudes were found over central medial regions for control subjects, but were shifted more frontally for Parkinson's disease patients, reduced in amplitude over the midline and lateralized towards the side ipsilateral to the greatest basal ganglia impairment. This shift in cortical activity from medial to lateral areas in Parkinson's disease patients appears to reflect a compensatory mechanism operating predominantly on the side of greatest basal ganglia impairment.

Left temporal and temporoparietal brain activity depends on depth of word encoding: a magnetoencephalographic study in healthy young subjects.

Using a 143-channel whole-head magnetoencephalograph (MEG) we recorded the temporal changes of brain activity from 26 healthy young subjects (14 females) related to shallow perceptual and deep semantic word encoding. During subsequent recognition tests, the subjects had to recognize the previously encoded words which were interspersed with new words. The resulting mean memory performances across all subjects clearly mirrored the different levels of encoding. The grand averaged event-related fields (ERFs) associated with perceptual and semantic word encoding differed significantly between 200 and 550 ms after stimulus onset mainly over left superior temporal and left superior parietal sensors. Semantic encoding elicited higher brain activity than perceptual encoding. Source localization procedures revealed that neural populations of the left temporal and temporoparietal brain areas showed different activity strengths across the whole group of subjects depending on depth of word encoding. We suggest that the higher brain activity associated with deep encoding as compared to shallow encoding was due to the involvement of more neural systems during the processing of visually presented words. Deep encoding required more energy than shallow encoding but for all that led to a better memory performance.

Combining ictal surface-electroencephalography and seizure semiology improves patient lateralization in temporal lobe epilepsy.

PURPOSE: The study goal was to assess the concordance of ictal surface-EEG and seizure semiology data in lateralizing intractable temporal lobe epilepsy (TLE) and to examine the benefits of the combined use of these two methods. METHODS: We independently analyzed the ictal recordings and clinical symptoms associated with 262 seizures recorded in 59 TLE patients. Each seizure was lateralized on the basis of (i) its associated ictal surface-EEG pattern according to a predefined lateralization protocol and (ii) its associated ictal and postictal seizure semiology according to strictly defined clinical criteria. Individual patients were also lateralized based on these data. RESULTS: Ictal surface-EEG findings lateralized 62.6% of seizures and 64.4% of patients. Seizure semiology findings lateralized 46.2% of seizures and 78.0% of patients. There was a high degree of concordance between lateralizations based on these two methods, for both individual seizures and individual patients. Combination of the information from the two methods allowed for lateralization in a greater proportion of both seizures (79.8%) and patients (94.9%). Combined EEG-seizure lateralization was concordant with the side of operation in 33 of 34 patients who underwent successful surgery (Engel's surgical outcome class I/II). CONCLUSIONS: In TLE, there is a high agreement between the lateralization of individual seizures and patients, which is based on ictal surface-EEG findings and seizure semiology. Furthermore, combination of these two methods improves the lateralization of individual seizures and patients. Thus, standardized combined EEG-seizure analysis is a valuable noninvasive tool in the presurgical evaluation of TLE.

Dissociation of motor preparation from memory and attentional processes using movement-related cortical potentials.

The EEG activity preceding self-paced voluntary movements (movement-related cortical potential, MRCP) is smaller if subjects make the same movement each time (regular task) compared with when different movements are made each time (random task). To test whether extra activity in the random task is due to increased motor preparation needed to switch between different movements, or to memory/attentional processes needed to select movements randomly, we compared regular and random movements with an additional alternating task. This alternating task required subjects to make different movements each time as in the random task, but since the task was very simple, the memory/attentional load was similar to that in the regular task. The MRCP was equally large over motor areas in both random and alternating tasks, suggesting that the extra activity over sensorimotor areas reflected processes involved in motor preparation rather than memory/attention. We speculate that, in the regular task, some part of the instructions for the previous movement remains intact, reducing the amount of preparation needed for the next repetition. Thus the MRCP is smaller than in the alternating and random tasks. Although the MRCPs in alternating and random tasks were similar over the motor areas, the random task had more activity than the alternating task in contralateral frontal areas. This part of the MRCP may therefore be related to memory/attentional processes required to randomize the sequence of movements. We conclude that the MRCP contains dissociable components related to motor preparation and memory/attention.

Electrophysiological, neuropsychological and clinical findings in multiple sclerosis patients receiving interferon beta-1b: a 1-year follow-up.

We assessed serial event-related potentials (ERPs) as well as neuropsychological and clinical test findings in a group of multiple sclerosis (MS) patients (n = 14) treated with interferon beta-1b (INF-beta-1b) compared to normal controls (n = 14). All investigations were done within 1 week before INF-beta-1b therapy was started and 12 months later. An auditory oddball paradigm was employed. No significant differences in the N100, P200, N200 or P300 latencies between patients and control group were found, but 3 out of 14 MS patients developed abnormal P300 latencies (more than 2 standard errors from the mean) after 1 year of INF-beta-1b therapy. This was not reflected by the respective neurological impairment as assessed by the Expanded Disability Status Scale score. ERPs might be a useful tool in clinical studies in order to evaluate drug effects on cognition, but for a final statement, the analysis of ERPs in a larger group of patients is required.

High resolution spatiotemporal analysis of the contingent negative variation in simple or complex motor tasks and a non-motor task.

OBJECTIVES: Since the characteristics of the Bereitschaftspotential (BP) - voluntary movement paradigm of internally-driven movements - have been established recently by our group using high resolution DC-EEG techniques, it was of great interest to apply similar techniques to the other slow brain potential--contingent negative variation (CNV) of externally-cued movements--with the same motor tasks using the same subjects. METHODS: The CNV for simple bimanual sequential movements (task 1), complex bimanual sequential movements (task 2) and a non-motor condition (task 3) was recorded on the scalp using a 64 channel DC-EEG in 16 healthy subjects, and the data were analyzed with high resolution spatiotemporal statistics and current source density (CSD). RESULTS: (1) The CNV was distributed over frontal, frontocentral, central and centroparietal regions; a negative potential was found at the frontal pole and a positive potential was found over occipital regions. (2) CNV amplitudes were higher for task 2 than for task 1, and there was no late CNV for task 3. (3) A high resolution spatiotemporal analysis revealed that during the early CNV component, statistical differences existed between the motor tasks (tasks 1 and 2) and the non-motor task (task 3), which occurred at frontocentral, central, centroparietal, parietal and parieto-occipital regions. During the late CNV component, additional significant differences were found not only between the motor tasks and the non-motor task but also between motor task 1 and task 2 at frontocentral, central and centroparietal regions. (4) Comparison of the CNV between the frontomesial cortex (situated over the supplementary/cingulate areas, SCMA) and both lateral pre-central areas (situated over the primary motor areas, MIs) showed that there was no statistically significant difference between the two cortical motor areas except for the early CNV. (5) Comparison of the CNV between the 3 tasks over the cortical motor areas showed that there were significant differences between the motor tasks and the non-motor task regarding the auditory evoked potential (AEP) and the early CNV component, and between all 3 tasks in the late CNV, the visual evoked potential (VEP(2)) and the N-P component. (6) The ranges and the densities of the CSD maps were larger and higher for complex than for simple tasks. The current sinks of the AEP and the early CNV were located at Fz, the late CNV at FCz and surrounding regions. As to be expected, current sources of the VEPs were located at the occipital lobes. The CNV was a current sink (negative) except for the VEP's main component which was a current source (positive). CONCLUSIONS: (1) The CNV topography over the scalp varied with the complexity of motor tasks and between motor and non-motor conditions. (2) The origin of the early CNV may rest in the frontal lobes, while the late CNV may stem from more extensive cortical areas including SCMA, MIs, etc. (3) The late CNV component is not identical with the BP.

High resolution DC-EEG mapping of the Bereitschaftspotential preceding simple or complex bimanual sequential finger movement.

The present set of experiments investigated the Bereitschaftspotential (BP) preceding voluntary bimanual sequential simple (task 1) and complex movements (task 2) in supplementary/cingulate and primary motor areas (SCMA, MIs) using 64-channel direct current electroencephalography analysis in 16 right-handed healthy subjects. The results showed that: (1) onset times of BPs preceding the two tasks were significantly earlier at Cz than at C3 and C4, (2) the complex task induced significantly larger amplitudes than the simple task over the SCMA 1.1 s before EMG onset (BPI period), over the SCMA and both MIs for the BP2 period, extending from the SCMA and MIs to all frontocentral, central, centroparietal, and frontal areas during the motor potential period, (3) task difference prior to 0.96 s mainly appeared in the SCMA rather than in either MI, (4) the BP had a significantly larger amplitude in the SCMA than in the MIs, the differences being asymmetric between the left and the right hemisphere motor areas, and (5) the sinks of BP current source density (CSD) preceding the two tasks were found in the frontocentral midline; and the regions and intensities of CSD maps were larger and stronger in task 2 than they were in task I at the same times of the epoch. The results suggested that: (1) the SCMA and MIs participate in bimanual sequential simple or complex movements, (2) the SCMA appears to not only serve as a trigger command for voluntary movement but also seems to design the different motor modes, (3) the amplitude, duration, onset time, CSD region, and intensity of BP all increase with the level of complexity of the movement, (4) the greater the complexity of the action, the earlier the preparation and the larger the extent of activated neuronal populations in the SCMA, (5) activation of the SCMA occurred prior to that of the MI, and (6) the activation suggests an asymmetry between left and right MIs in simultaneous bilateral finger movement, but this asymmetry seems to be less pronounced for complex movements.

Magnetoencephalography in focal epilepsy.

The introduction of whole-head magnetoencephalographic (MEG) systems facilitating simultaneous recording from the entire brain surface has led to a major breakthrough in the MEG evaluation of epilepsy patients. MEG localizations estimates of the interictal spike zone showed excellent agreement with invasive electrical recordings and were useful to clarify the spatial relationship of the irritative zone and structural lesions. MEG appears to be especially useful for study of patients with neocortical epilepsy, and helped to guide the placement of subdural grid electrodes in patients with nonlesional epilepsies. MEG could differentiate between patients with mesial and lateral temporal seizure onset. Spike propagation in the temporal lobe and the spatio-temporal organization of the interictal spike complex could be studied noninvasively. MEG was useful to delineate essential brain regions before surgical procedures adjacent to the central fissure. MEG appears to be more sensitive than scalp EEG for detection of epileptic discharges arising from the lateral neocortex, whereas only highly synchronized discharges arising from mesial temporal structures could be recorded. A major limitation of MEG has been the recording of seizures because long-term recordings cannot be performed on a routine basis with the available technology. Because MEG and EEG yield both complementary and confirmatory information, combined MEG-EEG recordings in conjunction with advanced source modeling techniques should improve the noninvasive evaluation of epilepsy patients and further reduce the need for invasive procedures.

Modulation of spatial orientation processing by mental imagery instructions: a MEG study of representational momentum.

Under appropriate conditions, an observer's memory for the final position of an abruptly halted moving object is distorted in the direction of the represented motion. This phenomenon is called "representational momentum" (RM). We examined the effect of mental imagery instructions on the modulation of spatial orientation processing by testing for RM under conditions of picture versus body rotation perception and imagination. Behavioral data were gathered via classical reaction time and error measurements, whereas brain activity was recorded with the help of magnetoencephalography (MEG). Due to the so-called inverse problem and to signal complexity, results were described at the signal level rather than with the source location modeling. Brain magnetic field strength and spatial distribution, as well as latency of P200m evoked fields were used as neurocognitive markers. A task was devised where a subject examined a rotating sea horizon as seen from a virtual boat in order to extrapolate either the picture motion or the body motion relative to the picture while the latter disappeared temporarily until a test-view was displayed as a final orientation candidate. Results suggest that perceptual interpretation and extrapolation of visual motion in the roll plane capitalize on the fronto-parietal cortical networks involving working memory processes. Extrapolation of the rotational dynamics of sea horizon revealed a RM effect simulating the role of gravity in rotational equilibrium. Modulation of the P200m component reflected spatial orientation processing and a non-voluntary detection of an incongruity between displayed and expected final orientations given the implied motion. Neuromagnetic properties of anticipatory (Contingent Magnetic Variation) and evoked (P200m) brain magnetic fields suggest, respectively, differential allocation of attentional resources by mental imagery instructions (picture vs. body tilt), and a communality of neural structures (in the right centro-parietal region) for the control of both RM and mental rotation processes. Finally, the RM of the body motion is less prone to forward shifts than that of picture motion evidencing an internalization of the implied mass of the virtual body of the observer.

Neuromagnetic recordings in temporal lobe epilepsy.

The introduction of whole-head magnetoencephalography (MEG) systems facilitating simultaneous recording from the entire brain surface has established MEG as a clinically feasible method for the evaluation of patients with temporal lobe epilepsy (TLE). In mesial TLE, two types of MEG spike dipoles could be identified: an anterior vertical and an anterior horizontal dipole. Dipole orientations can be used to attribute spike activity to temporal lobe subcompartments. Whereas the anterior vertical dipole is compatible with epileptic activity in the mediobasal temporal lobe, the anterior horizontal dipole can be explained by epileptic activity of the temporal tip cortex. In nonlesional TLE, medial and lateral vertical dipoles were found which could distinguish between medial and lateral temporal seizure onset zones as evidenced from invasive recordings. In lesional TLE, MEG could clarify the spatial relationship of the structural lesion to the irritative zone. Evaluation of patients with persistent seizures after epilepsy surgery may represent another clinical important application of MEG because magnetic fields are less influenced than electric fields by the prior operation. Simultaneous MEG and invasive EEG recordings indicate that epileptic activity restricted to mesial temporal structures cannot reliably be detected on MEG and that an extended cortical area of at least 6 to 8 cm2 involving also the basal temporal lobe is necessary to produce a reproducible MEG signal. In lateral neocortical TLE MEG seems to be more sensitive than scalp-EEG which further underlines the potential role of MEG for the study of nonlesional TLE. Whole-head MEG therefore can be regarded as a valuable and clinically relevant noninvasive method for the evaluation of patients with TLE.

Supplementary motor area activation preceding voluntary movement is detectable with a whole-scalp magnetoencephalography system.

Despite the fact that the knowledge about the structure and the function of the supplementary motor area (SMA) is steadily increasing, the role of the SMA in the human brain, e.g., the contribution of the SMA to the Bereitschaftspotential, still remains unclear and controversial. The goal of this study was to contribute further to this discussion by taking advantage of the increased spatial information of a whole-scalp magnetoencephalography (MEG) system enabling us to record the magnetic equivalent of the Bereitschaftspotential 1, the Bereitschaftsfeld 1 (BF 1) or readiness field 1. Five subjects performed a complex, and one subject a simple, finger-tapping task. It was possible to record the BF 1 for all subjects. The first appearance of the BF 1 was in the range of -1.9 to -1.7 s prior to movement onset, except for the subject performing the simple task (-1 s). Analysis of the development of the magnetic field distribution and the channel waveforms showed the beginning of the Bereitschaftsfeld 2 (BF 2) or readiness field 2 at about -0.5 s prior to movement onset. In the time range of BF 1, dipole source analysis localized the source in the SMA only, whereas dipole source analysis containing also the time range of BF 2 resulted in dipole models, including dipoles in the primary motor area. In summary, with a whole-head MEG system, it was possible for the first time to detect SMA activity in healthy subjects with MEG.

Reduced activation of midline frontal areas in human elderly subjects: a contingent negative variation study.

Contingent negative variation (CNV) was recorded from electrodes F7, F3, Fz, F4, F8, T7, C3, Cz, C4, T8, P7, P3, Pz, P4 and P8 in 19 young (mean age: 23 years) and 15 elderly (mean age: 66 years) healthy right-handed subjects, using a S2-choice paradigm. Young subjects showed early peak negativity shortly after the warning stimulus over mid-frontal areas, whereas for the remaining electrodes the negativity increased continuously. The amplitude of the early CNV was selectively reduced in elderly subjects over midline but not lateral frontal areas. We conclude that the activation of frontal midline areas as pre-supplementary motor area or anterior cingulate might be impaired in higher age.

False recognition in a verbal memory task: an event-related potential study.

Brain potentials were recorded from 15 healthy young subjects during the performance of a word recognition task. During the study phase, subjects had to intentionally memorise a series of words. These words were presented again together with the same number of new words in a following test phase where the instruction was to discriminate between repeated words and new words. We compared event-related potentials (ERPs) evoked by correctly identified repeated words (hits) and ERPs evoked by incorrectly classified new words (false alarms). Although both types of words were thought to be repeated the ERPs indicated differences between these two conditions starting at about 450 ms after the stimulus onset. These differences were mostly pronounced over frontal scalp locations but occurred also over parietal scalp locations (false alarms produced significantly more negative going ERPs than hits). We interpret that frontal and parietal brain areas show greater activation during false recognition because of a more intensive search for item representations.

Bilateral subthalamic nucleus stimulation improves frontal cortex function in Parkinson's disease. An electrophysiological study of the contingent negative variation.

Parkinson's disease involves impaired activation of frontal cortical areas, including the supplementary motor area and prefrontal cortex, resulting from impaired thalamocortical output of the basal ganglia. Electrophysiologically, such impaired cortical activation may be seen as a reduced amplitude of the contingent negative variation (CNV), a slow negative potential shift reflecting cognitive processes associated with the preparation and/or anticipation of a response. Surgical interventions aimed at increasing basal ganglia-thalamic outflow to the cortex, such as electrical stimulation of the subthalamic nucleus with chronically implanted electrodes, have been shown to be effective in improving the clinical symptoms of Parkinson's disease. This study examined changes in cortical activity, as reflected in the CNV, associated with bilateral subthalamic nucleus stimulation in Parkinson's disease. The CNV was recorded from 10 patients with Parkinson's disease when on and off bilateral subthalamic nucleus stimulation, and was compared with the CNV of 10 healthy control subjects. Without subthalamic nucleus stimulation, Parkinson's disease patients showed reduced CNV amplitudes over the frontal and frontocentral regions compared with control subjects. With bilateral subthalamic nucleus stimulation, however, CNV amplitudes over the frontal and frontocentral regions were significantly increased. Results therefore suggest that impaired cortical functioning in Parkinson's disease, particularly within the frontal and premotor areas, is improved by subthalamic nucleus stimulation.