Coupling between beta band and high frequency oscillations as a clinically useful biomarker for DBS.

Beta hypersynchrony was recently introduced into clinical practice in Parkinson's disease (PD) to identify the best stimulation contacts and for adaptive deep brain stimulation (aDBS) sensing. However, many other oscillopathies accompany the disease, and beta power sensing may not be optimal for all patients. The aim of this work was to study the potential clinical usefulness of beta power phase-amplitude coupling (PAC) with high frequency oscillations (HFOs). Subthalamic nucleus (STN) local field potentials (LFPs) from externalized DBS electrodes were recorded and analyzed in PD patients (n = 19). Beta power and HFOs were evaluated in a resting-state condition; PAC was then studied and compared with the electrode contact positions, structural connectivity, and medication state. Beta-HFO PAC (mainly in the 200-500 Hz range) was observed in all subjects. PAC was detectable more specifically in the motor part of the STN compared to beta power and HFOs. Moreover, the presence of PAC better corresponds to the stimulation setup based on the clinical effect. PAC is also sensitive to the laterality of symptoms and dopaminergic therapy, where the greater PAC cluster reflects the more affected side and medication "off" state. Coupling between beta power and HFOs is known to be a correlate of the PD "off" state. Beta-HFO PAC seems to be more sensitive than beta power itself and could be more helpful in the selection of the best clinical stimulation contact and probably also as a potential future input signal for aDBS.

Ultra-fast oscillation detection in EEG signal from deep-brain microelectrodes.

For the last decades, ripples 80-200Hz (R)and fast ripples 200-500Hz (FR) were intensively studied as biomarkers of the epileptogenic zone (EZ). Recently, Very fast ripples 500-1000Hz (VFR) and ultra-fast ripples 1000-2000Hz (UFR) recorded using standard clinical macro electrodes have been shown to be more specific for EZ. High-sampled microelectrode recordings can bring new insights into this phenomenon of high frequency, multiunit activity. Unfortunately, visual detection of such events is extremely time consuming and unreliable. Here we present a detector of ultra-fast oscillations (UFO, >1kHz). In an example of two patients, we detected 951 UFOs which were more frequent in epileptic (8.6/min) vs. non-epileptic hippocampus (1.3/min). Our detection method can serve as a tool for exploring extremely high frequency events from microelectrode recordings.

Thalamic oscillatory activity may predict response to deep brain stimulation of the anterior nuclei of the thalamus.

We hypothesized that local/regional properties of stimulated structure/circuitry contribute to the effect of deep brain stimulation (DBS). We analyzed intracerebral electroencephalographic (EEG) recordings from externalized DBS electrodes targeted bilaterally in the anterior nuclei of the thalamus (ANT) in 12 patients (six responders, six nonresponders) with more than 1 year of follow-up care. In the bipolar local field potentials of the EEG, spectral power (PW) and power spectral entropy (PSE) were calculated in the passbands 1-4, 4-8, 8-12, 12-20, 20-45, 65-80, 80-200 and 200-500 Hz. The most significant differences between responders and nonresponders were observed in the BRIDGE area (bipolar recordings with one contact within the ANT and the second contact in adjacent tissue). In responders, PW was significantly decreased in the frequency bands of 65-80, 80-200, and 200-500 Hz (p < .05); PSE was significantly increased in all frequency bands (p < .05) except for 200-500 Hz (p = .06). The local EEG characteristics of ANT recorded after implantation may play a significant role in DBS response prediction.

High frequency oscillations in epileptic and non-epileptic human hippocampus during a cognitive task.

Hippocampal high-frequency electrographic activity (HFOs) represents one of the major discoveries not only in epilepsy research but also in cognitive science over the past few decades. A fundamental challenge, however, has been the fact that physiological HFOs associated with normal brain function overlap in frequency with pathological HFOs. We investigated the impact of a cognitive task on HFOs with the aim of improving differentiation between epileptic and non-epileptic hippocampi in humans. Hippocampal activity was recorded with depth electrodes in 15 patients with focal epilepsy during a resting period and subsequently during a cognitive task. HFOs in ripple and fast ripple frequency ranges were evaluated in both conditions, and their rate, spectral entropy, relative amplitude and duration were compared in epileptic and non-epileptic hippocampi. The similarity of HFOs properties recorded at rest in epileptic and non-epileptic hippocampi suggests that they cannot be used alone to distinguish between hippocampi. However, both ripples and fast ripples were observed with higher rates, higher relative amplitudes and longer durations at rest as well as during a cognitive task in epileptic compared with non-epileptic hippocampi. Moreover, during a cognitive task, significant reductions of HFOs rates were found in epileptic hippocampi. These reductions were not observed in non-epileptic hippocampi. Our results indicate that although both hippocampi generate HFOs with similar features that probably reflect non-pathological phenomena, it is possible to differentiate between epileptic and non-epileptic hippocampi using a simple odd-ball task.

Multi-feature localization of epileptic foci from interictal, intracranial EEG.

OBJECTIVE: When considering all patients with focal drug-resistant epilepsy, as high as 40-50% of patients suffer seizure recurrence after surgery. To achieve seizure freedom without side effects, accurate localization of the epileptogenic tissue is crucial before its resection. We investigate an automated, fast, objective mapping process that uses only interictal data. METHODS: We propose a novel approach based on multiple iEEG features, which are used to train a support vector machine (SVM) model for classification of iEEG electrodes as normal or pathologic using 30 min of inter-ictal recording. RESULTS: The tissue under the iEEG electrodes, classified as epileptogenic, was removed in 17/18 excellent outcome patients and was not entirely resected in 8/10 poor outcome patients. The overall best result was achieved in a subset of 9 excellent outcome patients with the area under the receiver operating curve = 0.95. CONCLUSION: SVM models combining multiple iEEG features show better performance than algorithms using a single iEEG marker. Multiple iEEG and connectivity features in presurgical evaluation could improve epileptogenic tissue localization, which may improve surgical outcome and minimize risk of side effects. SIGNIFICANCE: In this study, promising results were achieved in localization of epileptogenic regions by SVM models that combine multiple features from 30 min of inter-ictal iEEG recordings.

Very high-frequency oscillations: Novel biomarkers of the epileptogenic zone.

OBJECTIVE: In the present study, we aimed to investigate depth electroencephalographic (EEG) recordings in a large cohort of patients with drug-resistant epilepsy and to focus on interictal very high-frequency oscillations (VHFOs) between 500Hz and 2kHz. We hypothesized that interictal VHFOs are more specific biomarkers for epileptogenic zone compared to traditional HFOs. METHODS: Forty patients with focal epilepsy who underwent presurgical stereo-EEG (SEEG) were included in the study. SEEG data were recorded with a sampling rate of 25kHz, and a 30-minute resting period was analyzed for each patient. Ten patients met selected criteria for analyses of correlations with surgical outcome: detection of interictal ripples (Rs), fast ripples (FRs), and VHFOs; resective surgery; and at least 1 year of postoperative follow-up. Using power envelope computation and visual inspection of power distribution matrixes, electrode contacts with HFOs and VHFOs were detected and analyzed. RESULTS: Interictal very fast ripples (VFRs; 500-1,000Hz) were detected in 23 of 40 patients and ultrafast ripples (UFRs; 1,000-2,000Hz) in almost half of investigated subjects (n = 19). VFRs and UFRs were observed only in patients with temporal lobe epilepsy and were recorded exclusively from mesiotemporal structures. The UFRs were more spatially restricted in the brain than lower-frequency HFOs. When compared to R oscillations, significantly better outcomes were observed in patients with a higher percentage of removed contacts containing FRs, VFRs, and UFRs. INTERPRETATION: Interictal VHFOs are relatively frequent abnormal phenomena in patients with epilepsy, and appear to be more specific biomarkers for epileptogenic zone when compared to traditional HFOs. Ann Neurol 2017;82:299-310.

Impact of cognitive stimulation on ripples within human epileptic and non-epileptic hippocampus.

BACKGROUND: Until now there has been no way of distinguishing between physiological and epileptic hippocampal ripples in intracranial recordings. In the present study we addressed this by investigating the effect of cognitive stimulation on interictal high frequency oscillations in the ripple range (80-250 Hz) within epileptic (EH) and non-epileptic hippocampus (NH). METHODS: We analyzed depth EEG recordings in 10 patients with intractable epilepsy, in whom hippocampal activity was recorded initially during quiet wakefulness and subsequently during a simple cognitive task. Using automated detection of ripples based on amplitude of the power envelope, we analyzed ripple rate (RR) in the cognitive and resting period, within EH and NH. RESULTS: Compared to quiet wakefulness we observed a significant reduction of RR during cognitive stimulation in EH, while it remained statistically marginal in NH. Further, we investigated the direct impact of cognitive stimuli on ripples (i.e. immediately post-stimulus), which showed a transient statistically significant suppression of ripples in the first second after stimuli onset in NH only. CONCLUSION: Our results point to a differential reactivity of ripples within EH and NH to cognitive stimulation.

Subthalamic nucleus involvement in executive functions with increased cognitive load: a subthalamic nucleus and anterior cingulate cortex depth recording study.

We studied the appearance of broadband oscillatory changes (ranging 2-45 Hz) induced by a cognitive task with two levels of complexity. The event-related de/synchronizations (ERD/S) in the subthalamic nucleus (STN) and in the anterior cingulate cortex (ACC) were evaluated in an executive function test. Four epilepsy surgery candidates with intracerebral electrodes implanted in the ACC and three Parkinson's disease patients with externalized deep brain stimulation electrodes implanted in the STN participated in the study. A Flanker test (FT) with visual stimuli (arrows) was performed. Subjects reacted to four types of stimuli presented on the monitor by pushing the right or left button: congruent arrows to the right or left side (simple task) and incongruent arrows to the right or left side (more difficult complex task). We explored the activation of STN and the activation of the ACC while processing the FT. Both conditions, i.e. congruent and incongruent, induced oscillatory changes in the ACC and also STN with significantly higher activation during incongruent trial. At variance with the ACC, in the STN not only the ERD beta but also the ERD alpha activity was significantly more activated by the incongruent condition. In line with our earlier studies, the STN appears to be involved in activities linked with increased cognitive load. The specificity and complexity of task-related activation of the STN might indicate the involvement of the STN in processes controlling human behaviour, e.g. in the selection and inhibition of competing alternatives.

On the time course of synchronization patterns of neuronal discharges in the human brain during cognitive tasks.

Using intracerebral EEG recordings in a large cohort of human subjects, we investigate the time course of neural cross-talk during a simple cognitive task. Our results show that human brain dynamics undergo a characteristic sequence of synchronization patterns across different frequency bands following a visual oddball stimulus. In particular, an initial global reorganization in the delta and theta bands (2-8 Hz) is followed by gamma (20-95 Hz) and then beta band (12-20 Hz) synchrony.

Intracerebrally recorded high frequency oscillations: simple visual assessment versus automated detection.

OBJECTIVE: We compared the possible contribution (in the detection of seizure onset zone - SOZ) of simple visual assessment of intracerebrally recorded high-frequency oscillations (HFO) with standard automated detection. METHODS: We analyzed stereo-EEG (SEEG) recordings from 20 patients with medically intractable partial seizures (10 temporal/10 extratemporal). Independently using simple visual assessment and automated detection of HFO, we identified the depth electrode contacts with maximum occurrences of ripples (R) and fast ripples (FR). The SOZ was determined by independent visual identification in standard SEEG recordings, and the congruence of results from visual versus automated HFO detection was compared. RESULTS: Automated detection of HFO correctly identified the SOZ in 14 (R)/10 (FR) out of 20 subjects; a simple visual assessment of SEEG recordings in the appropriate frequency ranges correctly identified the SOZ in 13 (R)/9 (FR) subjects. CONCLUSIONS: Simple visual assessment of SEEG traces and standard automated detection of HFO seem to contribute comparably to the identification of the SOZ in patients with focal epilepsies. When using macroelectrodes in neocortical extratemporal epilepsies, the SOZ might be better determined by the ripple range. SIGNIFICANCE: Standard automated detection of HFO enables the evaluation of HFO characteristics in whole data. This detection allows general purpose and objective evaluation, without any bias from the neurophysiologist's experiences and practice.

The executive functions in frontal and temporal lobes: a flanker task intracerebral recording study.

The occurrence of the local generators of P3-like potentials elicited by a noise-compatibility flanker test was used to study the processing of executive functions, particularly in the frontal and temporal cortices. The test performed with arrows comprised a simpler congruent and a more difficult incongruent task. The two tasks activated the attention and several particular executive functions, i.e., working memory, time perception, initiation, and motor control of executed task. The incongruent task increased demand on executive functions, and besides the functions common for both tasks, an inhibition of automatic responses, the reversal of incorrect response tendency, the internal ordering of the correct response, and the initiation of the target-induced correct response were involved. In seven epilepsy surgery candidates (four men and three women), ranging in age from 26 to 38 years, multicontact depth electrodes were implanted in 590 cortical sites. In the two tasks, the P3-like potential sources were displayed in the mesial temporal structures, the lateral temporal neocortex, the anterior and posterior cingulate, the orbitofrontal cortex, and dorsolateral prefrontal cortex. The P3-like potentials occurred more frequently with the incongruent than with congruent stimuli in all these areas. This more frequent occurrence of P3 sources elicited by the incongruent task appeared significant in temporal lateral neocortex and orbitofrontal cortex. The executive functions are processed in a widespread frontotemporal neurocognitive network. This study confirms the involvement of the temporal neocortex in the executive functions.

Interictal high-frequency oscillations indicate seizure onset zone in patients with focal cortical dysplasia.

Interictal high-frequency oscillations (HFO) were recently identified in recordings from depth macroelectrodes in epileptic patients. StereoEEG (SEEG) recordings were analyzed in four patients with medically intractable partial seizures due to focal cortical dysplasia type IIA. Characteristics of HFO within seizure onset zone (SOZ), irritative zone, and remote brain areas were investigated. Whilst the rate of occurrence for ripples (80-200 Hz) was significantly higher in recordings from within than outside the SOZ, the rate of fast ripples (200-450 Hz) was less reliable index of SOZ. Interestingly, the mean powers across subjects were significantly higher within than outside the SOZ in both ripple and fast ripple frequency ranges. Our study demonstrates a capacity of interictal HFO to detect the SOZ in focal cortical dysplasias.

Neural correlates of affective picture processing--a depth ERP study.

Using functional neuroimaging techniques (PET and fMRI), various cortical, limbic, and paralimbic structures have been identified in the last decade as neural substrates of human emotion. In this study we used a novel approach (intracerebral recordings of event-related potentials) to add to our knowledge of specific brain regions involved in affective picture processing. Ten intractable epileptic patients undergoing pre-surgical depth electrode recording viewed pleasant, neutral, and unpleasant pictures and intracerebral event-related potentials (ERPs) were recorded. A total of 752 cortical and subcortical sites were investigated. Significant differences in ERPs to unpleasant as compared to neutral or pleasant pictures were frequently and consistently observed in recordings from various brain areas--the mesial temporal cortex (the amygdala, the hippocampus, the temporal pole), the lateral temporal cortex, the mesial prefrontal cortex (ACC and the medial frontal gyrus), and the lateral prefrontal cortex. Interestingly, the mean latencies of responses to emotional stimuli were somewhat shorter in the frontal lobe structures (with evidently earlier activation within lateral prefrontal areas when compared to mesial prefrontal cortex) and longer in the temporal lobe regions. These differences, however, were not significant. Additional clearly positive findings were observed in some rarely investigated regions--in the posterior parietal cortex, the precuneus, and the insula. An approximately equivalent number of positive findings was revealed in the left and right hemisphere structures. These results are in agreement with a multisystem model of human emotion, distributed far beyond the typical limbic system and substantially comprising lateral aspects of both frontal lobes as well.

Directional functional coupling of cerebral rhythms between anterior cingulate and dorsolateral prefrontal areas during rare stimuli: a directed transfer function analysis of human depth EEG signal.

What is the neural substrate of our capability to properly react to changes in the environment? It can be hypothesized that the anterior cingulate cortex (ACC) manages repetitive stimuli in routine conditions and alerts the dorsolateral prefrontal cortex (PFC) when stimulation unexpectedly changes. To provide evidence in favor of this hypothesis, intracerebral stereoelectroencephalographic (SEEG) data were recorded from the anterior cingulate and dorsolateral PFC of eight epileptic patients in a standard visual oddball task during presurgical monitoring. Two types of stimuli (200 ms duration) such as the letters O (frequent stimuli; 80% of probability) and X (rare stimuli) were presented in random order, with an interstimulus interval between 2 and 5 s. Subjects had to mentally count the rare (target) stimuli and to press a button with their dominant hand as quickly and accurately as possible. EEG frequency bands of interest were theta (4-8 Hz), alpha (8-12 Hz), beta (14-30 Hz), and gamma (30-45 Hz). The directionality of the information flux within the EEG rhythms was indexed by a directed transfer function (DTF). The results showed that compared with the frequent stimuli, the target stimuli induced a statistically significant increase of DTF values from the anterior cingulate to the dorsolateral PFC at the theta rhythms (P < 0.01). These results provide support to the hypothesis that ACC directly or indirectly affects the oscillatory activity of dorsolateral PFC by a selective frequency code under typical oddball conditions.

Modifications of cognitive and motor tasks affect the occurrence of event-related potentials in the human cortex.

This study concerns the question of how task modification affects the frequency occurrence of event-related potentials (ERP) inside the active cortical areas. In 13 candidates for epilepsy surgery, 156 sites in the temporal (74), frontal (73), and parietal (9) cortices were recorded by means of depth and subdural electrodes. Four modifications of the somatosensory evoked P3-like potentials were performed; (i) an oddball paradigm with silent counting of target stimuli (P3c); (ii) an oddball paradigm with a hand movement in response to target stimuli (P3m); (iii) an S1-S2 paradigm, ERP in the P300 time window after the S2 stimulus, with silent counting of target stimuli (S2c), and (iv) an S1-S2 paradigm with a hand movement in response to target stimuli (S2m). In comparing the oddball paradigms with the S1-S2 (contingent negative variation, CNV) paradigms, four regions emerge that are significantly linked with the oddball P3; the prefrontal cortex, the cingulate, the amygdalo-hippocampal complex, and the lateral temporal cortex. A prominent role of the cingulate and the fronto-orbital cortex in the cognitive processing of movement was supported when tasks with identical cognitive loads but different required responses were compared. Even relatively simple cognitive tasks activate many cortical regions. The investigated areas were activated in all tests; however, small regions in each field were active or inactive in relation to the nature of the task. The study indicates a variable and task-dependent internal organization of a highly complex and widely distributed system of active cortical areas.

Combined event-related fMRI and intracerebral ERP study of an auditory oddball task.

Event-related fMRI (efMRI) has been repeatedly used to seek the neural sources of endogenous event-related potentials (ERP). However, significant discrepancies exist between the efMRI data and the results of previously published intracranial ERP studies of oddball task. To evaluate the capacity of efMRI to define the sources of the P3 component of ERP within the human brain, both efMRI and intracerebral ERP recordings were performed in eight patients with intractable epilepsy (five males and three females) during their preoperative invasive video-EEG monitoring. An identical auditory oddball task with frequent and target stimuli was completed in two sessions. A total of 606 intracerebral sites were electrophysiologically investigated by means of depth electrodes. In accordance with the finding of multiple intracerebral generators of P3 potential, the target stimuli evoked MRI signal increase in multiple brain regions. However, regions with evident hemodynamic and electrophysiological responses overlapped only partially. P3 generators were always found within hemodynamic-active sites, if these sites were investigated by means of depth electrodes. On the other hand, unequivocal local sources of P3 potential were apparently also located outside the regions with a significant hemodynamic response (typically in mesiotemporal regions). Both methods should thus be viewed as mutually complementary in investigations of the spatial distribution of cortical and subcortical activation during oddball task.

Cognitive- and movement-related potentials recorded in the human basal ganglia.

Sources of potentials evoked by cognitive processing of sensory and motor activities were studied in 9 epilepsy surgery candidates with electrodes implanted in the basal ganglia (BG), mostly in the putamen. Several contacts were also located in the pallidum and the caudate. The recorded potentials were related to a variety of cognitive and motor activities (attentional, decisional, time estimation, sensory processing, motor preparation, and so on). In five different tests, we recorded P3-like potentials evoked by auditory and visual stimuli and sustained potential shifts in the Bereitschaftspotential and Contingent Negative Variation protocols. All of the studied potentials were generated in the BG. They were recorded from all over the putamen. Various potentials on the same lead or nearby contacts were recorded. A functional topography in the BG was not displayed. We presume that the cognitive processes we studied were produced in clusters of neurons that are organized in the basal ganglia differently than the known functional organization, e.g., of motor functions. The basal ganglia, specifically the striatum, may play an integrative role in cognitive information processing, in motor as well as in nonmotor tasks. This role seems to be nonspecific in terms of stimulus modality and in terms of the cognitive context of the task.

Cognitive potentials in the basal ganglia-frontocortical circuits. An intracerebral recording study.

We studied cognitive functions related to processing sensory and motor activities in the basal ganglia (BG), specifically in the putamen and in cortical structures forming the BG-frontocortical circuits. Intracerebral recordings were made from 160 brain sites in 32 epilepsy surgery candidates. We studied P3-like potentials in five different tests evoked by auditory and visual stimuli, and two sustained potentials that are related to cognitive activities linked with movement preparation: BP (Bereitschaftspotential) and CNV (contingent negative variation). We compared the presence of a potential with a phase reversal or an amplitude gradient to the absence of a generator. All of the studied cognitive potentials were generated in the BG; the occurrence in frontal cortical areas was more selective. The frequency of all but one potential was significantly higher in the BG than in the prefrontal and in the cingulate cortices. The P3-like potentials elicited in the oddball paradigm were also more frequent in the BG than in the motor/premotor cortex, while the occurrence of potentials elicited in motor tasks (BP, CNV, and P3-like potentials in the CNV paradigm) in the motor cortex did not significantly differ from the occurrence in the BG. The processing of motor tasks fits with the model by Alexander et al. of segregated information processing in the motor loop. A variable and task-dependent internal organisation is more probable in cognitive sensory information processing. Cognitive potentials were recorded from all over the putamen. The BG may play an integrative role in cognitive information processing.

The impact of motor activity on intracerebral ERPs: P3 latency variability in modified auditory odd-ball paradigms involving a motor task.

The P3 wave of event-related potentials was recorded with intracranial electrodes in 24 epileptic patients during the pre-surgical evaluation of epilepsy surgery. Three different cognitive auditory paradigms were used: (1) odd-ball paradigm with no output required (PGI) where patients had simply to recognize target tones, (2) odd-ball with motor response (PGII), where patients had to press a button in response to target tones, and (3) odd-ball with both counting task and motor response (PGIII), where patients had to recognize target tones, press a button in response to them, and count their number. The occurrence of P3 potential, its latency and amplitude, and the dependence of P3 latency on the task complexity were calculated. Identifiable P3 potentials in all the three paradigms were recorded from locations in mesial cortex (18 locations mesial temporal, eight locations mesial frontal, two locations mesial parietal) and lateral sites (eight sites lateral temporal, five lateral frontal, and two lateral parietal). P3 latency values ranged from 257 to 320 ms in all explored cortical areas when PGI was used; they significantly increased or decreased during PGII and PGIII, depending on the task and structure explored. In the mesial temporal cortex, the changes of P3 latency between paradigms were minimal. In the mesial parietal cortex, there was significant P3 delay in both PGII and PGIII relative to PGI. In the mesial frontal cortex, there was a significant latency decrease in PGII, and practically identical mean latency in PGI and PGIII. In all lateral cortices (temporal, frontal and parietal), there was always a P3 latency increase in PGII and PGIII relative to PGI, the most significant results being observed in the parietal and frontal lateral areas. The results support the multi-generator theory of P3. Prolongation of the mean P3 latency in lateral frontal and parietal cortices when the paradigm involved the execution of a motor task might reflect specific gating in this area during active movements, while the absence of modification in the temporal lobe may reflect minimal involvement of this region in motor planning or processing. The prolongation of mean P3 latency in practically all lateral structures in PGIII suggests that most cortical areas were involved in the cognitive functions needed for this test. The finding of reduction and subsequent prolongation of P3 latency in the mesial frontal cortex might reflect the unique specialization of this area and its specific involvement in motor processing.

Intracerebral somatosensory event-related potentials: effect of response type (button pressing versus mental counting) on P3-like potentials within the human brain.

OBJECTIVE: To assess the contribution of different anatomical brain sites to the genesis of P3 phenomena with respect to button pressing versus mental counting tasks. METHODS: Eight intractable epileptic patients undergoing depth electrode recordings prior to their surgery participated in the study. A total of 546 cerebral sites were recorded. A standard somatosensory oddball paradigm was used. The experiment was carried out in two sessions, differing in the requested responses to targets. The averaged responses in both tasks were compared. RESULTS: After targets, two kinds of P3-like potentials were observed within different cortical sites. Task-non-specific P3 potentials were seen for both types of responses to targets. The mean amplitude of these task-non-specific P3 potentials was significantly higher in the button pressing task. The intracerebral generators of this somatosensory P3 did not differ from the known generators of auditory and visual P3s. Task-specific P3-like potentials were found much less frequently. Button pressing unequivocally generated additional P3-like potentials in the premotor cortical sites. Mental counting repeatedly evoked additional P3-like waveforms in the left-side middle and inferior temporal gyri. CONCLUSIONS: In addition to multiple intracerebral P3 generators that reflect target detection processing, other task-specific P3-like potential generators can be found in the human brain. Their activity may affect the topography and precise parameters of scalp P3 potential.