F Dubeau

The National Institute of Neurology and Neurosurgery, Tlalpam, The Federal District, Mexico

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Publications (255)1411.3 Total impact

  • Dongmei An, François Dubeau, Jean Gotman
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    ABSTRACT: Objective To investigate whether specific frontal regions have a tendency to generate widespread bilateral synchronous discharges (WBSDs) and others focal spikes and to determine the regions most involved when WBSDs occur; to assess the relationships between the extent of electroencephalography (EEG) discharges and the extent of metabolic changes measured by EEG/functional magnetic resonance imaging (fMRI).Methods Thirty-seven patients with interictal epileptic discharges (IEDs) with frontocentral predominance underwent EEG/fMRI. Patients were divided into a Focal (20 patients) group with focal frontal spikes and a WBSD group (17 patients). Maps of hemodynamic responses related to IEDs were compared between the two groups.ResultsThe mean number ± SD of IEDs in the Focal group was 137.5 ± 38.1 and in the WBSD group, 73.5 ± 16.6 (p = 0.07). The volume of hemodynamic responses in the WBSD group was significantly larger than in the Focal group (mean, 243.3 ± 41.1 versus 114.8 ± 27.4 cm3, p = 0.01). Maximum hemodynamic responses occurred in both groups in the following regions: dorsolateral prefrontal, mesial prefrontal, cingulate, and supplementary motor cortices. Maxima in premotor and motor cortex, frontal operculum, frontopolar, and orbitofrontal regions were found only in the Focal group, and maxima in thalamus and caudate only occurred in the WBSD group. Thalamic responses were significantly more common in the WBSD group (14/17) than in the Focal group (7/20), p = 0.004. Deactivation in the default mode network was significantly more common in the WBSD group (14/17) than in the Focal group (10/20), p = 0.04.SignificanceThe spatial distribution and extent of blood oxygen level–dependent (BOLD) responses correlate well with electrophysiologic changes. Focal frontal spikes and WBSDs are not region specific in the frontal lobe, and the same frontal region can generate focal and generalized discharges. This suggests that widespread discharges reflect widespread epileptogenicity rather than a focal discharge located in a region favorable to spreading. The thalamus plays an important role in bilateral synchronization.
    Epilepsia 01/2015; · 4.58 Impact Factor
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    ABSTRACT: In humans, the knowledge of intracranial correlates of spindles is mainly gathered from noninvasive neurophysiologic and functional imaging studies which provide an indirect estimate of neuronal intracranial activity. This potential limitation can be overcome by intracranial electroencephalography used in presurgical epilepsy evaluation. We investigated the intracranial correlates of scalp spindles using combined scalp and intracerebral depth electrodes covering the frontal, parietal and temporal neocortex, and the scalp and intracranial correlates of hippocampal and insula spindles in 35 pre-surgical epilepsy patients. Spindles in the scalp were accompanied by widespread cortical increases in sigma band energy (10–16 Hz): the highest percentages were observed in the frontoparietal lateral and mesial cortex, whereas in temporal lateral and mesial structures only a low or no simultaneous increase was present. This intracranial involvement during scalp spindles showed no consistent pattern, and exhibited unexpectedly low synchrony across brain regions. Hippocampal spindles were shorter and spatially restricted with a low synchrony even within the temporal lobe. Similar results were found for the insula. We suggest that the generation of spindles is under a high local cortical influence contributing to the concept of sleep as a local phenomenon and challenging the notion of spindles as widespread synchronous oscillations.
    NeuroImage 10/2014; · 6.13 Impact Factor
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    ABSTRACT: Epilepsia partialis continua (EPC) is a life-threatening condition often caused by focal cortical dysplasia (FCD). Resection of the motor cortex is contemplated in the hope that the trade-off between a severe motor deficit and complete seizure control justifies the procedure.
    Neurology 09/2014; · 8.30 Impact Factor
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    ABSTRACT: Objective Interictal high frequency oscillations (HFOs) in the 40–200 Hz range have been identified in scalp electroencephalography (EEG) recordings of patients with focal epilepsy. HFOs usually co-occur with interictal epileptiform discharges (IEDs), and are specific and accurate markers for the epileptic focus, but the brain regions involved when HFOs are generated are unknown. We investigated this question with combined EEG–functional magnetic resonance imaging (fMRI), measuring the blood oxygenation level–dependent (BOLD) signal, and examined HFOs in the gamma (40–80 Hz) and ripple (80–200 Hz) bands.Methods Twenty-eight consecutive patients with focal epilepsy who underwent HFO and EEG-fMRI studies were selected; six were excluded because of negative EEG-fMRI. The remaining 22 patients were divided into two equal groups (11 patients each) based on the frequency of co-occurrence of gamma or ripples with IEDs: low versus high gamma (LG/HG) and low versus high ripples (LR/HR).ResultsNo significant changes were found in the BOLD characteristics between the LG and HG groups. As a group, HR had a larger IED concordant BOLD cluster than the LR group, despite similar IED rates. In addition, the HR group had significantly more thalamic BOLD changes than the LR group (11/11 vs. 2/11). In HR, 5 of 11 patients had thalamic activation only, 4 of 11 had thalamic deactivation only, and 2 of 11 had activation and deactivation in different thalamic regions. In the LR group, 2 of 11 had thalamic activation. The lateralization of thalamic BOLD responses was concordant with the lateralization of cortical ripples in 12 of 13 patients.SignificanceScalp IEDs, when frequently accompanied by HFOs in the ripple but not in the gamma band, are associated with larger cortical metabolic responses and with thalamic involvement lateralized to the side of cortical ripples. We propose that a high rate of epileptic ripples is associated with a more active pathologic cortical-thalamocortical network.
    Epilepsia 08/2014; · 4.58 Impact Factor
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    ABSTRACT: Simultaneous recording of electroencephalography and functional magnetic resonance imaging (EEG-fMRI) has recently been applied for mapping the hemodynamic changes related to epileptic activity. The aim of this study is to compare the hemodynamic response function (HRF) to epileptic spikes in patients with focal cortical dysplasia (FCD) and those with hippocampal sclerosis (HS). In EEG-fMRI studies, the HRF represents the temporal evolution of blood oxygenation level-dependent signal changes. Several studies demonstrated that amplitude and latency of the HRF are variable in patients with epilepsy. However, the consistency of HRF parameters with underlying brain pathology is unknown. In this study, we examined 14 patients with FCD and 12 with unilateral HS selected from our EEG-fMRI database and compared the amplitude and latency of the HRF peak. We analyzed (1) HRFs in peak activation clusters, (2) HRFs in peak deactivation clusters, and (3) the maximum absolute responses within the EEG spike field, activation or deactivation. We found that the HRF peak amplitude in deactivation clusters was larger in the HS group than in the FCD when the deactivation occurred in default mode network (DMN) regions. This result suggests that spikes in patients with HS affect the DMN more strongly than those with FCD. However, if we focus on the maximum absolute t-value in the spike field, there is no significant difference between the two groups. The current study indicates that it is not necessary to use different HRF models for EEG-fMRI studies in patients with FCD and HS.
    Brain Topography 04/2014; · 2.52 Impact Factor
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    ABSTRACT: Introduction: Blood oxygenation level-dependent (BOLD) signal changes at the time of interictal epileptic discharges (IEDs) identify their associated vascular/hemodynamic responses. BOLD activations and deactivations can be found within the epileptogenic zone but also at a distance. Source imaging identifies electric (ESI) and magnetic (MSI) sources of IEDs, with the advantage of a higher temporal resolution. Therefore, the objective of our study was to evaluate the spatial concordance between ESI/MSI and BOLD responses for similar IEDs. Methods: Twenty-one patients with similar IEDs in simultaneous electroencephalogram/functional magnetic resonance imaging (EEG/fMRI) and in simultaneous EEG/magnetoencephalogram (MEG) recordings were studied. IEDs in EEG/fMRI acquisition were analyzed in an event-related paradigm within a general linear model (GLM). ESI/MSI of averaged IEDs was performed using the Maximum Entropy on the Mean. We assessed the spatial concordance between ESI/MSI and clusters of BOLD activations/deactivations with surface-based metrics. Results: ESI/MSI were concordant with one BOLD cluster for 20/21patients (concordance with activation: 14/21 patients, deactivation: 6/21 patients, no concordance: 1/21 patients; concordance with MSI only: 3/21, ESI only: 2/21). These BOLD clusters exhibited in 19/20 cases the most significant voxel. BOLD clusters that were spatially concordant with ESI/MSI were concordant with IEDs from invasive recordings in 8/11 patients (activations: 5/8, deactivations: 3/8). Conclusion: As the results of BOLD, ESI and MSI are often concordant, they reinforce our confidence in all of them. ESI and MSI confirm the most significant BOLD cluster within BOLD maps, emphasizing the importance of these clusters for the definition of the epileptic focus.
    Human Brain Mapping 02/2014; · 6.92 Impact Factor
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    ABSTRACT: We describe two patients who showed snapping of the right hand fingers during invasive intracranial EEG evaluation for epilepsy surgery. We correlated the EEG changes with the finger-snapping movements in both patients to determine the underlying pathophysiology of this phenomenon. At the time of finger snapping, EEG spread from the supplementary motor area towards the temporal region was seen, suggesting involvement of these sites.
    Epilepsy & Behavior Case Reports. 01/2014; 2:108–111.
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    ABSTRACT: Simultaneous electroencephalography/functional magnetic resonance imaging (EEG/fMRI) recording can noninvasively map in the whole brain the hemodynamic response following an interictal epileptic discharge. EEG/fMRI is gaining interest as a presurgical evaluation tool. This study aims to determine how hemodynamic responses related to epileptic activity can help predict surgical outcome in patients considered for epilepsy surgery. Thirty-five consecutive patients with focal epilepsy who had significant hemodynamic responses and eventually surgical resection, were studied. The statistical map of hemodynamic responses were generated and coregistered to postoperative anatomic imaging. Patients were classified into four groups defined by the relative relationship between the location of the maximum hemodynamic response and the resection: group 1, fully concordant; group 2, partially concordant; group 3, partially discordant; and group 4, fully discordant. These findings were correlated with surgical outcome with at least 12-month follow-up. Ten patients in group 1 had the maximum t value (t-max) inside the resection; nine in group 2 had the t-max outside but close to the resection and the cluster with t-max overlapped the resection; five in group 3 had the t-max remote from resection, but with another less significant cluster in the resection; and 11 in group 4 had no response in the resection. The degree of concordance correlated largely with surgical outcome: a good surgical outcome (Engel's class I) was found in 7 of 10 patients of group 1, 4 of 9 of group 2, 3 of 5 of group 3, and only 1 of 11 of group 4. These results indicate that the partially concordant and partially discordant groups are best considered as inconclusive. In contrast, in the fully concordant and fully discordant groups, the sensitivity, specificity, positive predictive value, and negative predictive value were high, 87.5%, 76.9%, 70%, and 90.9%, respectively. This study demonstrates that hemodynamic responses related to epileptic activity can help delineate the epileptogenic region. Full concordance between maximum response and surgical resection is indicative of seizure freedom, whereas a resection leaving the maximum response intact is likely to lead to a poor outcome. EEG/fMRI is noninvasive but is limited to patients in whom interictal epileptic discharges can be recorded during the 60-90 min scan.
    Epilepsia 12/2013; 54(12):2184-94. · 4.58 Impact Factor
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    Piero Perucca, François Dubeau, Jean Gotman
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    ABSTRACT: The process by which the brain transitions into an epileptic seizure is unknown. In this study, we investigated whether the transition to seizure is associated with changes in brain dynamics detectable in the wideband EEG, and whether differences exist across underlying pathologies. Depth electrode ictal EEG recordings from 40 consecutive patients with pharmacoresistant lesional focal epilepsy were low-pass filtered at 500 Hz and sampled at 2,000 Hz. Predefined EEG sections were selected immediately before (immediate preictal), and 30 seconds before the earliest EEG sign suggestive of seizure activity (baseline). Spectral analysis, visual inspection and discrete wavelet transform were used to detect standard (delta, theta, alpha, beta and gamma) and high-frequency bands (ripples and fast ripples). At the group level, each EEG frequency band activity increased significantly from baseline to the immediate preictal section, mostly in a progressive manner and independently of any modification in the state of vigilance. Preictal increases in each frequency band activity were widespread, being observed in the seizure-onset zone and lesional tissue, as well as in remote regions. These changes occurred in all the investigated pathologies (mesial temporal atrophy/sclerosis, local/regional cortical atrophy, and malformations of cortical development), but were more pronounced in mesial temporal atrophy/sclerosis. Our findings indicate that a brain state change with distinctive features, in the form of unidirectional changes across the entire EEG bandwidth, occurs immediately prior to seizure onset. We postulate that these changes might reflect a facilitating state of the brain which enables a susceptible region to generate seizures.
    PLoS ONE 11/2013; 8(11):e80972. · 3.53 Impact Factor
  • Piero Perucca, François Dubeau, Jean Gotman
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    ABSTRACT: Because seizures originate from different pathological substrates, the question arises of whether distinct or similar mechanisms underlie seizure generation across different pathologies. Better defining intracranial electroencephalographic morphological patterns at seizure-onset could improve the understanding of such mechanisms. To this end, we investigated intracranial electroencephalographic seizure-onset patterns associated with different epileptogenic lesions, and defined high-frequency oscillation correlates of each pattern. We analysed representative seizure types from 33 consecutive patients with drug-resistant focal epilepsy and a structural magnetic resonance imaging lesion (11 mesial temporal sclerosis, nine focal cortical dysplasia, six cortical atrophy, three periventricular nodular heterotopia, three polymicrogyria, and one tuberous sclerosis complex) who underwent depth-electrode electroencephalographic recordings (500 Hz filter, 2000 Hz sampling rate). Patients were included only if seizures arose from contacts located in lesional/peri-lesional tissue, and if clinical manifestations followed the electrographic onset. Seizure-onset patterns were defined independently by two reviewers blinded to clinical information, and consensus was reached after discussion. For each seizure, pre-ictal and ictal sections were selected for high-frequency oscillation analysis. Seven seizure-onset patterns were identified across the 53 seizures sampled: low-voltage fast activity (43%); low-frequency high-amplitude periodic spikes (21%); sharp activity at ≤13 Hz (15%); spike-and-wave activity (9%); burst of high-amplitude polyspikes (6%); burst suppression (4%); and delta brush (4%). Each pattern occurred across several pathologies, except for periodic spikes, only observed with mesial temporal sclerosis, and delta brush, exclusive to focal cortical dysplasia. However, mesial temporal sclerosis was not always associated with periodic spikes nor focal cortical dysplasia with delta brush. Compared to other patterns, low-voltage fast activity was associated with a larger seizure-onset zone (P = 0.04). Four patterns, sharp activity at ≤13 Hz, low-voltage fast activity, spike-and-wave activity and periodic spikes, were also found in regions of seizure spread, with periodic spikes only emerging from mesial temporal sclerosis. Each of the seven patterns was accompanied by a significant increase in high-frequency oscillations upon seizure-onset. Overall, our data indicate that: (i) biologically-distinct epileptogenic lesions share intracranial electroencephalographic seizure-onset patterns, suggesting that different pathological substrates can affect similarly networks or mechanisms underlying seizure generation; (ii) certain pathologies are associated with intracranial electroencephalographic signatures at seizure-onset, e.g. periodic spikes which may reflect mechanisms specific to mesial temporal sclerosis; (iii) some seizure-onset patterns, including periodic spikes, can also be found in regions of spread, which cautions against relying on the morphology of the initial discharge to define the epileptogenic zone; and (iv) high-frequency oscillations increase at seizure-onset, independently of the pattern.
    Brain 10/2013; · 10.23 Impact Factor
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    ABSTRACT: We aim to analyze the fast oscillations in the scalp EEG of focal epilepsy patients with low-to-high rates of interictal epileptiform discharges (IEDs), in order to determine how this neurophysiological feature influences fast oscillation occurrence and their significance as markers of the seizure onset zone (SOZ). Thirty-two patients were studied, subdivided in four categories based on IED frequency: groups A, B and C respectively with high, intermediate and low IED rate, and group D with no IED. Thirty minutes of slow-wave sleep EEG, low-pass filtered at 300Hz and sampled at 1000Hz, were reviewed. IEDs and fast oscillations (gamma activity, 40-80Hz; and ripples, >80Hz) were marked. Each channel was classified as inside or outside the irritative zone and the SOZ. We calculated the number and rates of IEDs and fast oscillation, their co-occurrence, their frequency in the irritative zone and SOZ, and the specificity, sensitivity and accuracy to determine the SOZ in the overall population and separately for each group. We analyzed 984 channels. Group A (high IED rate) showed the highest fast oscillation rate (gamma: 0.37±0.73; ripples: 0.17±0.26), followed by group B (gamma: 0.08±0.06; ripples: 0.07±0.05), group C (gamma: 0.06±0.06; ripples: 0.04±0.01), and finally group D, with very low values (gamma: 0.03±0; ripples: 0.03±0). IEDs co-occurred with gamma in 9.5% and with ripples in 3.2%; and gamma and ripples co-occurred with IEDs in 46.2% and 44.4%, respectively. The fast oscillations were more frequent inside than outside the irritative zone and the SOZ (p<0.001). Compared to the IEDs, the fast oscillations were less sensitive (sensitivity: IEDs 78%, gamma 66% and ripples 48%) but more specific (specificity: IEDs 50%, gamma 76% and ripples 83%) and accurate (accuracy: IEDs 54%, gamma 74% and ripples 77%) in identifying the SOZ; the same results were reproduced for the different groups separately. This study confirms that fast oscillations can be recorded from the scalp EEG. Gamma activity and ripples are more frequent in patients with frequent IEDs and, in general, inside the irritative zone. However, compared to IEDs, gamma and ripples are less sensitive but more specific and accurate in identifying the SOZ, and this remains in patients with low fast oscillation rates. These findings suggest that IEDs and fast oscillations could share some common neuronal network, but gamma activity and ripples are a better biomarker of epileptogenicity.
    Epilepsy research 08/2013; · 2.48 Impact Factor
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    ABSTRACT: Functional neuroimaging studies of epilepsy patients often show, at the time of epileptic activity, deactivation in default mode network (DMN) regions, which is hypothesized to reflect altered consciousness. We aimed to study the metabolic and electrophysiological correlates of these changes in the DMN regions. We studied six epilepsy patients that underwent scalp EEG-fMRI and later stereotaxic intracerebral EEG (SEEG) sampling regions of DMN (posterior cingulate cortex, Pre-cuneus, inferior parietal lobule, medial prefrontal cortex and dorsolateral frontal cortex) as well as non-DMN regions. SEEG recordings were subject to frequency analyses comparing sections with interictal epileptic discharges (IED) to IED-free baselines in the IED-generating region, DMN and non-DMN regions. EEG-fMRI and SEEG were obtained at rest. During IEDs, EEG-fMRI demonstrated deactivation in various DMN nodes in 5 of 6 patients, most frequently the pre-cuneus and inferior parietal lobule, and less frequently the other DMN nodes. SEEG analyses demonstrated decrease in gamma power (50-150 Hz), and increase in the power of lower frequencies (<30 Hz) at times of IEDs, in at least one DMN node in all patients. These changes were not apparent in the non-DMN regions. We demonstrate that, at the time of IEDs, DMN regions decrease their metabolic demand and undergo an EEG change consisting of decreased gamma and increased lower frequencies. These findings, specific to DMN regions, confirm in a pathological condition a direct relationship between DMN BOLD activity and EEG activity. They indicate that epileptic activity affects the DMN, and therefore may momentarily reduce the consciousness level and cognitive reserve.
    PLoS ONE 06/2013; 8(6):e68038. · 3.53 Impact Factor
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    ABSTRACT: In EEG-fMRI studies, BOLD responses related to interictal epileptic discharges (IEDs) are most often the expected positive response (activation) but sometimes a surprising negative response (deactivation). The significance of deactivation in the region of IED generation is uncertain. The aim of this study was to determine if BOLD deactivation was caused by specific IED characteristics. Among focal epilepsy patients who underwent 3T EEG-fMRI from 2006 to 2011, those with negative BOLD having a maximum t-value in the IED generating region were selected. As controls, subjects with maximum activation in the IED generating region were selected. We established the relationship between the type of response (activation/deactivation) and (1) presence of slow wave in the IEDs, (2) lobe of epileptic focus, (3) occurrence as isolated events or bursts, (4) spatial extent of the EEG discharge. Fifteen patients with deactivation and 15 with activation were included. The IEDs were accompanied by a slow wave in 87 % of patients whose primary BOLD was a deactivation and only in 33 % of patients with activation. In the deactivation group, the epileptic focus was more frequently in the posterior quadrant and involved larger cortical areas, whereas in the activation group it was more frequently temporal. IEDs were more frequently of long duration in the deactivation group. The main factor responsible for focal deactivations is the presence of a slow wave, which is the likely electrographic correlate of prolonged inhibition. This adds a link to the relationship between electrophysiological and BOLD activities.
    Brain Topography 06/2013; · 2.52 Impact Factor
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    ABSTRACT: Neurophysiological studies have reported functional network alterations in epilepsy, most consistently in the theta frequency band. Highly interconnected brain regions (so-called 'hubs') seem to be important in these epileptic networks. High frequency oscillations (HFOs) in intracranial EEG recordings are recently discovered biomarkers that can identify the epileptogenic area and are thought to result from altered neuronal interactions. We studied whether the epileptogenic zone (identified by HFOs and seizure onset zone) is associated with pathological hubs. Bilateral depth electrode recordings from the hippocampus and amygdala were available from twelve patients suspected of temporal lobe epilepsy. HFOs, classified as ripples (80-250Hz) and fast ripples (250-500Hz), and epileptiform spikes were marked for all patients in a five-minute epoch of slow-wave sleep. For each channel, we computed hub-measures from a period without epileptiform spikes and found that the epileptogenic zone was associated with a decreased hub-value in the theta frequency band. The amount of HFOs, especially fast ripples, was negatively correlated with the hub-value per channel. Results from post-hoc analyses of other frequency bands, particularly the broad- and gamma frequency band, pointed in the same direction as the results for the theta frequency band. These findings suggest a pathological functional 'isolation' of the epileptogenic zone in the interictal state.
    NeuroImage 06/2013; · 6.13 Impact Factor
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    ABSTRACT: OBJECTIVE: High frequency oscillations (HFOs) are brief electroencephalographic events associated with epileptic activity, and likely representing biological markers of the epileptogenic zone. HFOs are usually detected with intracranial EEG and detection is influenced by contact size. The size of commercially available intracerebral electrodes varies widely. This study assesses HFO detection rates from adjacent electrode contacts in human intracerebral recordings. METHODS: Intracerebral recordings were collected from 11 patients undergoing stereoelectroencephalographic investigation using hybrid depth electrodes containing adjacent large (0.8 or 5mm(2)) and small (0.2 or 0.3mm(2)) contacts. HFOs were marked manually during 5-min tracings in 131 pairs of adjacent large and small contacts. HFO rates per minute and mean event durations were compared between adjacent contacts. RESULTS: A minimal but statistically significant advantage in ripple detection was found in a subgroup of large contacts. Otherwise, HFO rates and mean event durations were not statistically different between groups. CONCLUSION: The size of clinical contacts within the studied range did not influence HFO detection in a clinically relevant manner. Larger contacts provide a minimal advantage for ripple detection. SIGNIFICANCE: Our findings suggest that commercially available intracerebral electrodes with contacts between 0.2 and 5mm(2) likely possess similar HFO detection abilities.
    Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 04/2013; · 3.12 Impact Factor
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    ABSTRACT: The majority of epilepsies are focal in origin, with seizures emanating from one brain region. Although focal epilepsies often arise from structural brain lesions, many affected individuals have normal brain imaging. The etiology is unknown in the majority of individuals, although genetic factors are increasingly recognized. Autosomal dominant familial focal epilepsy with variable foci (FFEVF) is notable because family members have seizures originating from different cortical regions. Using exome sequencing, we detected DEPDC5 mutations in two affected families. We subsequently identified mutations in five of six additional published large families with FFEVF. Study of families with focal epilepsy that were too small for conventional clinical diagnosis with FFEVF identified DEPDC5 mutations in approximately 12% of families (10/82). This high frequency establishes DEPDC5 mutations as a common cause of familial focal epilepsies. Shared homology with G protein signaling molecules and localization in human neurons suggest a role of DEPDC5 in neuronal signal transduction.
    Nature Genetics 03/2013; · 29.65 Impact Factor
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    ABSTRACT: PURPOSE: Removal of areas generating high-frequency oscillations (HFOs) recorded from the intracerebral electroencephalography (iEEG) of patients with medically intractable epilepsy has been found to be correlated with improved surgical outcome. However, whether differences exist according to the type of epilepsy is largely unknown. We performed a comparative assessment of the impact of removing HFO-generating tissue on surgical outcome between temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE). We also assessed the relationship between the extent of surgical resection and surgical outcome. METHODS: We studied 30 patients with drug-resistant focal epilepsy, 21 with TLE and 9 with ETLE. Two thirds of the patients were included in a previous report and for these, clinical and imaging data were updated and follow-up was extended. All patients underwent iEEG investigations (500 Hz high-pass filter and 2,000 Hz sampling rate), surgical resection, and postoperative magnetic resonance imaging (MRI). HFOs (ripples, 80-250 Hz; fast ripples, >250 Hz) were identified visually on a 5-10 min interictal iEEG sample. HFO rates inside versus outside the seizure-onset zone (SOZ), in resected versus nonresected tissue, and their association with surgical outcome (ILAE classification) were assessed in the entire cohort, and in the TLE and ETLE subgroups. We also tested the correlation of resected brain hippocampal and amygdala volumes (as measured on postoperative MRIs) with surgical outcome. KEY FINDINGS: HFO rates were significantly higher inside the SOZ than outside in the entire cohort and TLE subgroup, but not in the ETLE subgroup. In all groups, HFO rates did not differ significantly between resected and nonresected tissue. Surgical outcome was better when higher HFO rates were included in the surgical resection in the entire cohort and TLE subgroup, but not in the ETLE subgroup. Resected brain hippocampal and amygdala volumes were not correlated with surgical outcome. SIGNIFICANCE: In TLE, removal of HFO-generating areas may lead to improved surgical outcome. Less consistent findings emerge from ETLE, but these may be related to sample size limitations of this study. Size of resection, a factor that was ignored and that could have affected results of earlier studies did not influence results.
    Epilepsia 01/2013; · 4.58 Impact Factor
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    ABSTRACT: Purpose:  To assess the extent of brain involvement during focal epileptic activity, we studied patterns of cortical and subcortical metabolic changes coinciding with interictal epileptic discharges (IEDs) using group analysis of simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) scans in patients with focal epilepsy. Methods:  We selected patients with temporal lobe epilepsy (TLE, n = 32), frontal lobe epilepsy (FLE, n = 14), and posterior quadrant epilepsy (PQE, n = 20) from our 3 Tesla EEG-fMRI database. We applied group analysis upon the blood oxygen-level dependent (BOLD) response associated with focal IEDs. Key Findings:  Patients with TLE and FLE showed activations and deactivations, whereas in PQE only deactivations occurred. In TLE and FLE, the largest activation was in the mid-cingulate gyri bilaterally. In FLE, activations were also found in the ipsilateral frontal operculum, thalamus, and internal capsule, and in the contralateral cerebellum, whereas in TLE, we found additional activations in the ipsilateral mesial and neocortical temporal regions, insula, and cerebellar cortex. All three groups showed deactivations in default mode network regions, the most widespread being in the TLE group, and less in PQE and FLE. Significance:  These results indicate that different epileptic syndromes result in unique and widespread networks related to focal IEDs. Default mode regions are deactivated in response to focal discharges in all three groups with syndrome specific pattern. We conclude that focal IEDs are associated with specific networks of widespread metabolic changes that may cause more substantial disturbance to brain function than might be appreciated from the focal nature of the scalp EEG discharges.
    Epilepsia 06/2012; 53(9):1618-27. · 4.58 Impact Factor
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    ABSTRACT: In mesial temporal lobe epilepsy (MTLE) the epileptogenic area is confined to the mesial temporal lobe, but other cortical and subcortical areas are also affected and cognitive and psychiatric impairments are usually documented. Functional connectivity methods are based on the correlation of the blood oxygen level dependent (BOLD) signal between brain regions, which exhibit consistent and reproducible functional networks from resting state data. The aim of this study is to compare functional connectivity of patients with MTLE during the interictal period with healthy subjects. We hypothesize that patients show reduced functional connectivity compared to controls, the interest being to determine which regions show this reduction. We selected electroencephalography-functional magnetic resonance imaging (EEG-fMRI) resting state data without EEG spikes from 16 patients with right and 7 patients with left MTLE. EEG-fMRI resting state data of 23 healthy subjects matched for age, sex, and manual preference were selected as controls. Four volumes of interest in the left and right amygdalae and hippocampi (LA, RA, LH, and RH) were manually segmented in the anatomic MRI of each subject. The averaged BOLD time course within each volume of interest was used to detect brain regions with BOLD signal correlated with it. Group differences between patients and controls were estimated. In patients with right MTLE, group difference functional connectivity maps (RMTLE - controls) showed for RA and RH decreased connectivity with the brain areas of the default mode network (DMN), the ventromesial limbic prefrontal regions, and contralateral mesial temporal structures; and for LA and LH, decreased connectivity with DMN and contralateral hippocampus. Additional decreased connectivity was found between LA and pons and between LH and ventromesial limbic prefrontal structures. In patients with left MTLE, functional connectivity maps (LMTLE - controls) showed for LA and LH decreased connectivity with DMN, contralateral hippocampus, and bilateral ventromesial limbic prefrontal regions; no change in connectivity was detected for RA; and for RH, there was decreased connectivity with DMN, bilateral ventromesial limbic prefrontal regions, and contralateral amygdala and hippocampus. In unilateral MTLE, amygdala and hippocampus on the affected and to a lesser extent on the healthy side are less connected, and are also less connected with the dopaminergic mesolimbic and the DMNs. Changes in functional connectivity between mesial temporal lobe structures and these structures may explain cognitive and psychiatric impairments often found in patients with MTLE.
    Epilepsia 05/2012; 53(6):1013-23. · 4.58 Impact Factor
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    Francesca Pittau, François Dubeau, Jean Gotman
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    ABSTRACT: To evaluate the clinical relevance of EEG/fMRI in patients with focal epilepsy, by assessing the information it adds to the scalp EEG in the definition of the epileptic focus. Forty-three patients with focal epilepsy were studied with EEG/fMRI using a 3-T scanner. Blood oxygen level-dependent (BOLD) signal changes related to interictal epileptic discharges (IEDs) were classified as concordant or not concordant with the scalp EEG spike field and as contributory if the BOLD signal provided additional information to the scalp EEG about the epileptic focus or not contributory if it did not. We considered patients having intracerebral EEG or a focal lesion on MRI as having independent validation. Thirty-three patients had at least 3 IEDs during the EEG/fMRI acquisition (active EEG), and all had a BOLD response. In 29 of 33 (88%) patients, the BOLD response was concordant, and in 21 of 33 (64%) patients, the BOLD response was contributory. Fourteen patients had an independent validation: in 12 of these 14, the BOLD responses were validated and in 2 they were invalidated. A BOLD response was present in all patients with active EEG, and more specific localization of the epileptic focus was gained from EEG/fMRI in half of the patients who were scanned, when compared with scalp EEG alone. This study demonstrates that EEG/fMRI, in the context of a clinical practice, may contribute to the localization of the interictal epileptic generator in patients with focal epilepsy.
    Neurology 04/2012; 78(19):1479-87. · 8.30 Impact Factor

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Institutions

  • 2013–2014
    • The National Institute of Neurology and Neurosurgery
      Tlalpam, The Federal District, Mexico
    • University of Florence
      Florens, Tuscany, Italy
  • 1989–2014
    • McGill University
      • • Department of Neurology and Neurosurgery
      • • McConnell Brain Imaging Centre
      Montréal, Quebec, Canada
  • 2012
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
  • 2006–2008
    • University of Birmingham
      • School of Psychology
      Birmingham, ENG, United Kingdom
    • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
      San Paulo, São Paulo, Brazil
    • Montreal Heart Institute
      Montréal, Quebec, Canada
  • 1999–2006
    • University of Campinas
      • Faculty of Medical Sciences
      Conceição de Campinas, São Paulo, Brazil
  • 2005
    • University of Zurich
      • Division of Neuropsychology
      Zürich, ZH, Switzerland
  • 2000
    • University of Innsbruck
      Innsbruck, Tyrol, Austria
  • 1997
    • Wayne State University
      • Department of Neurology
      Detroit, MI, United States