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Objective: Postencephalitic epilepsy is often resistant to antiseizure medications, leading to evaluation for epilepsy surgery. Characterizing its localization carries implications for optimal surgical approach. We aimed to determine whether a prior history of encephalitis is associated with specific epileptogenic networks among patients with drug resistant epilepsy undergoing stereotactic EEG (SEEG)., Methods: We conducted a retrospective cohort study of drug resistant epilepsy, with and without a prior history of encephalitis. We analyzed SEEG recordings to identify patterns of seizure onset and organization. Seventeen patients with a history of encephalitis (of infectious etiology in two subjects) were identified from a database of patients undergoing SEEG and were compared to seventeen drug-resistant epilepsy controls without a history of encephalitis matched for confounding variables including pre-implantation hypotheses, epilepsy duration, age, and sex., Results: Independent bilateral seizures were noted in 65% of the postencephalitic epilepsy cohort. We identified four SEEG-ictal patterns in patients with a prior history of encephalitis: (1) anteromesial temporal onset (24%), (2) anteromesial temporal onset with early spread to the perisylvian region (29%), (3) perisylvian (59%) and (4) synchronized anteromesial temporal and perisylvian (29%) onsets. Patterns 3 and 4, with perisylvian involvement at onset, were unique to the encephalitis group (p = 0.0003 and 0.04 respectively) and exhibited a "patchwork" organization. None of the encephalitis patients vs 5/7 matched controls had Engel I outcome (p = 0.0048)., Conclusions: Postencephalitic epilepsies involve anteromesial temporal and perisylvian networks, often in a bilateral independent manner. Unique ictal patterns involving the perisylvian regions was identified in the encephalitis group, but not in the matched control group., Significance: These findings may reflect a selective vulnerability of the perisylvian regions to epilepsy resulting from encephalitis, significantly mitigating the chances of success with SEEG-guided temporal resections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Many analysis methods exist to extract graphs of functional connectivity from neuronal networks. Confidence in the results is limited because, (i) different methods give different results, (ii) parameter setting directly influences the final result, and (iii) systematic evaluation of the results is not always performed. Here, we introduce MULAN (MULtiple method ANalysis), which assumes an ensemble based approach combining multiple analysis methods and fuzzy logic to extract graphs with the most probable structure. In order to reduce the dependency on parameter settings, we determine the best set of parameters using a genetic algorithm on simulated datasets, whose temporal structure is similar to the experimental one. After a validation step, the selected set of parameters is used to analyze experimental data. The final step cross-validates experimental subsets of data and provides a direct estimate of the most likely graph and our confidence in the proposed connectivity. A systematic evaluation validates our strategy against empirical stereotactic electroencephalography (SEEG) and functional magnetic resonance imaging (fMRI) data., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Electrical brain stimulations (EBS) sometimes induce reminiscences, but it is largely unknown what type of memories they can trigger. We reviewed 80 years of literature on reminiscences induced by EBS and added our own database. We classified them according to modern conceptions of memory. We observed a surprisingly large variety of reminiscences covering all aspects of declarative memory. However, most were poorly detailed and only a few were episodic. This result does not support theories of a highly stable and detailed memory, as initially postulated, and still widely believed as true by the general public. Moreover, memory networks could only be activated by some of their nodes: 94.1% of EBS were temporal, although the parietal and frontal lobes, also involved in memory networks, were stimulated. The qualitative nature of memories largely depended on the site of stimulation: EBS to rhinal cortex mostly induced personal semantic reminiscences, while only hippocampal EBS induced episodic memories. This result supports the view that EBS can activate memory in predictable ways in humans., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The challenge in epilepsy surgery is to remove the epileptogenic zone without compromising postoperative function. Electrical stimulation (ES) was developed to identify with greater anatomical and physiological precision cortical structures essential to language and motor function. Because the language network is widely distributed in the left (dominant) hemisphere, and often varies among patients, brain mapping should delineate eloquent areas at the individual level. Although ES for language is commonly performed during a presurgical investigation, the procedure remains nonstandardized among centers, and differences between grids and intracerebral depth electrodes (stereoelectroencephalography) should be taken into account when comparing results from different series. Electrical simulation exerts a complex summation effect in a given volume of brain tissue; the net result may be difficult to predict because this depends on methodological and physiological factors as follows: stimulation parameters, type of electrodes used, tasks used, presence or not of an after-discharge. We discuss in the present article some methodological aspects of the stimulation procedure influencing functional mapping because it pertains in particular to language mapping. In stereoelectroencephalography, the other goal of ES is to trigger seizures. Because seizures develop in neural networks that are imperfectly sampled by intracerebral electrodes, spontaneous seizure recording is not always sufficient to properly localize the epileptogenic zone. The rationale for performing ES is based on the electrophysiological distinction between local/regional after-discharge and seizure networks. A different response to ES-induced seizures can be seen for supra- and infra-sylvian epilepsies. The procedures for triggering seizures and for functional mapping should be performed in conjunction to answer the fundamental question whether or not there is a spatio-temporal overlap between the epileptogenic and the functional network. The exploration of both networks through stimulation exemplifies the importance of anatomo-electro-clinical correlations in stereoelectroencephalography.

Electromagnetic source localization in electroencephalography (EEG) and magnetoencephalography (MEG) allows finding the generators of transient interictal epileptiform discharges ('interictal spikes'). In intracerebral EEG (iEEG), oscillatory activity (above 30 Hz) has also been shown to be a marker of neuronal dysfunction. Still, the difference between networks involved in transient and oscillatory activities remains largely unknown. Our goal was thus to extract and compare the networks involved in interictal oscillations and spikes, and to compare the non-invasive results to those obtained directly within the brain. In five patients with both MEG and iEEG recordings, we computed correlation graphs across regions, for (1) interictal spikes and (2) epileptic oscillations around 30 Hz. We show that the corresponding networks can involve a widespread set of regions (average of 10 per patient), with only partial overlap (38 % of the total number of regions in MEG, 50 % in iEEG). The non-invasive results were concordant with intracerebral recordings (79 % for the spikes and 50 % for the oscillations). We compared our interictal results to iEEG ictal data. The regions labeled as seizure onset zone (SOZ) belonged to interictal networks in a large proportion of cases: 75 % (resp. 58 %) for spikes and 58 % (resp. 33 %) for oscillations in iEEG (resp. MEG). A subset of SOZ regions were detected by one type of discharges but not the other (25 % for spikes and 8 % for oscillations). Our study suggests that spike and oscillatory activities involve overlapping but distinct networks, and are complementary for presurgical mapping.

Ictal MEG recordings constitute rare data. The objective of this study was to evaluate ictal magnetic source localization (MSI), using two algorithms: linearly constrained minimum variance (LCMV), a beamforming technique and equivalent current dipole (ECD). Ictal MSI was studied in six patients. Three of them were undergoing post-operative re-evaluation. For all patients, results were validated by the stereoelectroencephalographic (SEEG) definition of the epileptogenic zone (EZ). EZ was quantified using the epileptogenicity index (EI) method, which accounts for both the propensity of a brain area to generate rapid discharges and the time for this area to become involved in the seizure. EI values range from 0 (no epileptogenicity) to 1 (maximal epileptogenicity). Levels of concordance between ictal MSI and EZ were determined as follows: A: ictal MSI localized the site whose value EI = 1, B: MSI localized a part of the EZ (not corresponding to the maximal value of EI = 1), C: a region could be identified on ictal MSI but not on SEEG, D: a region could be identified on SEEG but not on MSI, E: different regions were localized on MSI and SEEG. Ictal MEG pattern consisted of rhythmic activities between 10 and 20 Hz for all patients. For LCMV (first maxima), levels of concordance were A (two cases), B (two cases) and E (two cases). For ECD fitted on each time point separately (location characterized by the best goodness-of-fit value), levels of concordance were A (one case), B (one case), D (three cases) and E (one case). For ECD calculated for the whole time window, levels of concordance were A (two cases) and D (four cases). Source localization methods performed on rhythmic patterns can localize the EZ as validated by SEEG. In terms of concordance, LCMV was superior to ECD. In some cases, LCMV allows extraction of several maxima that could reflect ictal dynamics. In a medial temporal lobe epilepsy case, ictal MSI indicated an area of delayed propagation and was non-contributory to the presurgical assessment.

Posterior cortex epilepsies (PCE) are characterized by less satisfying postoperative results than temporal lobe epilepsies and are thus challenging for non-invasive presurgical investigations. The objective of this study was to evaluate the performance of magnetic source imaging (MSI) in PCE, validating the results by the SEEG (stereoelectroencephalography) definition of irritative and epileptogenic zones (IZ and EZ). Fourteen PCE surgery candidates were investigated using MSI and SEEG. LCMV (Linearly Constrained Minimum Variance) and MUSIC algorithms were used. IZ was quantified using a semi-automatic detection of interictal spikes. EZ was quantified using the epileptogenicity index (EI) method that accounts for both the propensity of a brain area to generate rapid discharges and the time for this area to get involved in the seizure. EI values range from 0 (no epileptogenicity) to 1 (maximal epileptogenicity). Levels of concordance between MSI and IZ, MSI and EZ were determined as follows: A = localized on MSI and SEEG for the site of value 1 (IZ and EZ quantification), B = localized on MSI and SEEG for a part of the IZ or a structure involved in the EZ (without the maximal value 1), C = localized on MSI and not SEEG, D = localized on SEEG and not MSI, E = localized on MSI and SEEG, discordant for site. Five PCE cases were characterized by focal IZ, nine by distributed IZ between several distant brain areas. MSI allowed to determinate IZ in 4/5 focal IZ cases. In case of distributed IZ, levels of concordance were A (2 cases), B (4 cases) and D (3 cases). In most distributed cases, MSI allowed to localize only a part of the IZ. Medial temporal involvement in the IZ was frequent (9/12 cases) and not evidenced by MSI. The brain area that demonstrated the maximal value of EI was shown by MSI in four out of five (80 %) focal IZ cases, in two out of nine (22 %) distributed cases. MSI results depend on IZ characteristics. A distributed IZ organization presents difficulties for MSI and highlights the need for further methodological approaches.

Brain regions generating seizures in patients with refractory partial epilepsy are referred to as the epileptogenic zone (EZ). During a seizure, paroxysmal activity is not restricted to the EZ, but may recruit other brain regions and propagate activity through large brain networks, which comprise brain regions that are not necessarily epileptogenic. The identification of the EZ is crucial for candidates for neurosurgery and requires unambiguous criteria that evaluate the degree of epileptogenicity of brain regions. To obtain such criteria and investigate the mechanisms of seizure recruitment and propagation, we develop a mathematical framework of coupled neural populations, which can interact via signaling through a slow permittivity variable. The permittivity variable captures effects evolving on slow timescales, including extracellular ionic concentrations and energy metabolism, with time delays of up to seconds as observed clinically. Our analyses provide a set of indices quantifying the degree of epileptogenicity and predict conditions, under which seizures propagate to nonepileptogenic brain regions, explaining the responses to intracerebral electric stimulation in epileptogenic and nonepileptogenic areas. In conjunction, our results provide guidance in the presurgical evaluation of epileptogenicity based on electrographic signatures in intracerebral electroencephalograms., (Copyright © 2014 the authors 0270-6474/14/3415009-13$15.00/0.)

Electroencephalography (EEG), magnetoencephalography (MEG), and intracerebral stereotaxic EEG (SEEG) are the three neurophysiological recording techniques, which are thought to capture the same type of brain activity. Still, the relationships between non-invasive (EEG, MEG) and invasive (SEEG) signals remain to be further investigated. In early attempts at comparing SEEG with either EEG or MEG, the recordings were performed separately for each modality. However such an approach presents substantial limitations in terms of signal analysis. The goal of this technical note is to investigate the feasibility of simultaneously recording these three signal modalities (EEG, MEG and SEEG), and to provide strategies for analyzing this new kind of data. Intracerebral electrodes were implanted in a patient with intractable epilepsy for presurgical evaluation purposes. This patient was presented with a visual stimulation paradigm while the three types of signals were simultaneously recorded. The analysis started with a characterization of the MEG artifact caused by the SEEG equipment. Next, the average evoked activities were computed at the sensor level, and cortical source activations were estimated for both the EEG and MEG recordings; these were shown to be compatible with the spatiotemporal dynamics of the SEEG signals. In the average time-frequency domain, concordant patterns between the MEG/EEG and SEEG recordings were found below the 40 Hz level. Finally, a fine-grained coupling between the amplitudes of the three recording modalities was detected in the time domain, at the level of single evoked responses. Importantly, these correlations have shown a high level of spatial and temporal specificity. These findings provide a case for the ability of trimodal recordings (EEG, MEG, and SEEG) to reach a greater level of specificity in the investigation of brain signals and functions., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Epileptic networks involve complex relationships across several brain areas. Such networks have been shown on intracerebral EEG (stereotaxic EEG, SEEG), an invasive technique. Magnetoencephalography (MEG) is a noninvasive tool, which was recently proven to be efficient for localizing the generators of epileptiform discharges. However, despite the importance of characterizing non-invasively network aspects in partial epilepsies, only few studies have attempted to retrieve fine spatiotemporal dynamics of interictal discharges with MEG. Our goal was to assess the relevance of magnetoencephalography for detecting and characterizing the brain networks involved in interictal epileptic discharges. We propose here a semi-automatic method based on independent component analysis (ICA) and on co-occurrence of events across components. The method was evaluated in a series of seven patients by comparing its results with networks identified in SEEG. On both MEG and SEEG, we found that interictal discharges can involve remote regions which are acting in synchrony. More regions were identified in SEEG (38 in total) than in MEG (20). All MEG regions were confirmed by SEEG when an electrode was present in the vicinity. In all patients, at least one region could be identified as leading according to our criteria. A majority (71%) of MEG leaders were confirmed by SEEG. We have therefore shown that MEG measurements can extract a significant proportion of the networks visible in SEEG. This suggests that MEG can be a useful tool for defining noninvasively interictal epileptic networks, in terms of regions and patterns of connectivity, in search for a "primary irritative zone"., (Copyright © 2013 Wiley Periodicals, Inc.)

The relationship between epileptogenic lesions and the extension of epileptogenicity is a major challenge in presurgical evaluation of drug resistant epilepsies. In this study, we aimed at quantifying the epileptogenic properties of brain structures explored by depth electrodes in patients investigated by stereoelectroencephalography (SEEG) and suffering from focal drug-resistant epilepsy associated with cavernous angioma (CA). Epileptogenicity of the perilesional region and distant brain areas was calculated according to the "epileptogenicity index" (EI), a technique that allows mathematical quantification of rapid discharges at seizure onset taking into account the time at which the discharge occurs. Thirteen seizures from 6 patients were studied. Localization of the cavernoma was the frontal lobe (two cases), the temporal lobe (three cases) or the anterior insula (one case). Visual inspection of the ictal discharge showed that in the majority of cases (5/6) the perilesional region was either not involved or involved with other distant sites. Using EI quantification, complex patterns of epileptogenicity were observed in five patients. A large number of brain regions out of the lesional region disclosed higher values than the lesion site. Mean values in the perilesional region and in the extralesional sites were not significantly different (p=0.34). Complex organization of the epileptogenic zone may be found in drug-resistant CA associated epilepsy. Thus, this result should be borne in mind when patients with CA and drug resistant epilepsy are investigated. If there is a suspicion of a larger epileptogenic zone than the lesion, intra-cerebral exploration by SEEG may be required before surgery that may be guided by the definition of the EZ., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Recent theory of physiology of language suggests a dual stream dorsal/ventral organization of speech perception. Using intra-cerebral Event-related potentials (ERPs) during pre-surgical assessment of twelve drug-resistant epileptic patients, we aimed to single out electrophysiological patterns during both lexical-semantic and phonological monitoring tasks involving ventral and dorsal regions respectively. Phonological information processing predominantly occurred in the left supra-marginal gyrus (dorsal stream) and lexico-semantic information occurred in anterior/middle temporal and fusiform gyri (ventral stream). Similar latencies were identified in response to phonological and lexico-semantic tasks, suggesting parallel processing. Typical ERP components were strongly left lateralized since no evoked responses were recorded in homologous right structures. Finally, ERP patterns suggested the inferior frontal gyrus as the likely final common pathway of both dorsal and ventral streams. These results brought out detailed evidence of the spatial-temporal information processing in the dual pathways involved in speech perception., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We aimed at determining the lateralizing and localizing values of "hemiballic-like" ictal movements observed in some partial seizures. Among 20 patients disclosing ictal hyperkinetic features and explored by stereotactic-EEG (SEEG), this sign was observed in four patients. In these cases, hemiballic movement was ipsilateral to the ictal-onset zone and was associated with contralateral ictal dystonia. Noninvasive and subsequent invasive recording revealed seizure origin in the inferior parietal lobule or the parietal operculum in three patients and in the inferior prefrontal cortex in one., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

The possibility of recording changes in brain signals occurring before epileptic seizures is of considerable interest, both as markers for seizure anticipation and as a window into the mechanisms of seizure generation. Several studies have reported preictal changes on electrophysiological traces. More recently, observations have been made of changes occurring on haemodynamic signals before interictal events or before seizures, often without concurrent changes observed on electrophysiology. We present here a critical review of these findings, in optical imaging, SPECT and fMRI, followed by a discussion based on data from intracerebral EEG., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: Surgical treatment of focal epilepsy in patients with focal cortical dysplasia (FCD) is most successful if all epileptogenic tissue is resected. This may not be evident on structural magnetic resonance imaging (MRI), so intracranial electroencephalography (icEEG) is needed to delineate the seizure onset zone (SOZ). EEG-functional MRI (fMRI) can reveal interictal discharge (IED)-related hemodynamic changes in the irritative zone (IZ). We assessed the value of EEG-fMRI in patients with FCD-associated focal epilepsy by examining the relationship between IED-related hemodynamic changes, icEEG findings, and postoperative outcome., Methods: Twenty-three patients with FCD-associated focal epilepsy undergoing presurgical evaluation including icEEG underwent simultaneous EEG-fMRI at 3T. IED-related hemodynamic changes were modeled, and results were overlaid on coregistered T1-weighted MRI scans fused with computed tomography scans showing the intracranial electrodes. IED-related hemodynamic changes were compared with the SOZ on icEEG and postoperative outcome at 1 year., Results: Twelve of 23 patients had IEDs during recording, and 11 of 12 had significant IED-related hemodynamic changes. The fMRI results were concordant with the SOZ in 5 of 11 patients, all of whom had a solitary SOZ on icEEG. Four of 5 had >50% reduction in seizure frequency following resective surgery. The remaining 6 of 11 patients had widespread or discordant regions of IED-related fMRI signal change. Five of 6 had either a poor surgical outcome (<50% reduction in seizure frequency) or widespread SOZ precluding surgery., Interpretation: Comparison of EEG-fMRI with icEEG suggests that EEG-fMRI may provide useful additional information about the SOZ in FCD. Widely distributed discordant regions of IED-related hemodynamic change appear to be associated with a widespread SOZ and poor postsurgical outcome., (Copyright © 2011 American Neurological Association.)

Purpose: The determination of epileptogenic structures in partial epilepsy is crucial in the context of epilepsy surgery. In this study we have quantified the "epileptogenicity" of mesial temporal lobe structures (M), lateral neocortical regions (L), and extratemporal perisylvian structures (ET) in patients with temporal lobe epilepsy (TLE), in order to classify the brain networks involved in seizure generation., Methods: Thirty-four patients having TLE investigated by intracerebral recordings using stereotactic electroencephalography (EEG) (SEEG) were selected. Epileptogenicity of M, L, and ET structures was quantified according to the "epileptogenicity index" (EI), a new way to quantify rapid discharges at seizure onset, ranging from 0 (no epileptogenicity) to 1 (maximal epileptogenicity)., Results: Automatic clustering using EI values from M, L, and ET separated patients into four classes: mesial group (max EI in M), lateral group (max EI in L), mesiolateral group (high EI in both M and L) and temporoperisylvian group (TPS) (high values in ET). The median number of highly epileptogenic structures (defined by EI >0.3) was four, a result confirming that most TLE is organized as "epileptogenic networks." We found that the duration of epilepsy was correlated with the number of epileptogenic structures and that surgical prognosis was also related to the extent of the epileptogenicity in the brain., Conclusions: Several distinct epileptogenic networks are involved in seizure generation in TLE. Findings advocate for a progressive recruitment of epileptogenic structures in human brain with time., (Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.)

In many applications which make use of EEG to investigate brain functions, a central question is often to relate the recorded signals to the spatio-temporal organization of the underlying neuronal sources of activity. A modeling attempt to quantitatively investigate this imperfectly known relationship is reported. The proposed plausible model of EEG generation relies on an accurate representation of the neuronal sources of activity. It combines both an anatomically realistic description of the spatial features of the sources (convoluted dipole layer) and a physiologically relevant description of their temporal activities (coupled neuronal populations). The model was used in the particular context of epileptiform activity (interictal spikes) to interpret simultaneously generated scalp and intracerebral EEG. Its integrative properties allowed for the bridging between source-related parameters (spatial extent, location, synchronization) and the properties of resulting EEG signals (amplitude of spikes, amplitude gradient along intracerebral electrodes, topography over scalp electrodes). The sensitivity of both recording modalities to source-related parameters was also studied. The model confirmed that the cortical area involved in interictal spikes is rather large. Its relative location with respect to recording electrodes was found to strongly influence the properties of EEG signals as the source geometry is a critical parameter. The influence, on simulated signals, of the synchronization degree between neuronal populations within the epileptic source was also investigated. The model revealed that intracerebral EEG can reflect epileptic activities corresponding to weak synchronization between neuronal populations of the epileptic patch. These results, as well as the limitations of the model, are discussed.

Objective: Our aim was to investigate relationships between heterotopic and remote cortical structures at seizure initiation, in a patient with bilateral periventricular nodular heterotopias (BPNH) explored by intracerebral electrodes., Methods: Stereoelectroencephalography (SEEG) was performed in a man with BPNH and refractory epilepsy to investigate the hypothesis of right temporal lobe epilepsy and the possible involvement of heterotopic structures during seizures. SEEG signals were analyzed with quantification of functional coupling between different brain structures during seizures, using nonlinear regression. We have used Z-score transformation of correlation values to reflect the change from the preictal period. Relationships between BPNH and cortical structures were investigated using analysis of stimulation-induced potentials., Results: Three spontaneous seizures were recorded and analyzed. Signal analysis of interdependencies in two seizures demonstrated a large initial network involving both heterotopia and cortical structures. Stimulations of heterotopia induced responses in remote cortical structures., Conclusions: Distinct epileptogenic networks were identified, in which leader structures were either the heterotopic or the mesial temporal structures, with functional connections between heterotopic and cortical areas., Significance: These results confirm that a vast epileptogenic network, including heterotopic and cortical neurons, may be responsible for seizure generation in BPNH. This may explain certain surgical failures in this group.

Magnetoencephalography (MEG) sensors are capable of recording the tiny magnetic activity from the brain. They can be constituted of either magnetometers or gradiometers that respectively record the magnetic field or its gradient. In this paper, we present a framework for constructing realistic MEG signals. This framework can be used to test different probe configurations and source localization algorithms. The methodology of generation of synthetic signals is presented, and synthetic signals are compared to real signals. Paroxysmal activity generated with this model and originating from a deep cerebral source is determined with two different localization algorithms. Preliminary results show that gradiometers even with a short baseline perform close to magnetometer and that the use of hybrid systems should be further investigated.

In human partial epilepsies and in experimental models of chronic and/or acute epilepsy, the role of inhibition and the relationship between the inhibition and excitation and epileptogenesis has long been questioned. Besides experimental methods carried out either in vitro (human or animal tissue) or in vivo (animals), pathophysiologic mechanisms can be approached by direct recording of brain electrical activity in human epilepsy. Indeed, in some clinical presurgical investigation methods like stereoelectroencephalography, intracerebral electrodes are used in patients suffering from drug resistant epilepsy to directly record paroxysmal activities with excellent temporal resolution (in the order of 1 millisecond). The study of neurophysiologic mechanisms underlying such depth-EEG activities is crucial to progress in the understanding of the interictal to ictal transition. In this study, the authors relate electrophysiologic patterns typically observed during the transition from interictal to ictal activity in human mesial temporal lobe epilepsy (MTLE) to mechanisms (at a neuronal population level) involved in seizure generation through a computational model of EEG activity. Intracerebral EEG signals recorded from hippocampus in five patients with MTLE during four periods (during interictal activity, just before seizure onset, during seizure onset, and during ictal activity) were used to identify the three main parameters of a model of hippocampus EEG activity (related to excitation, slow dendritic inhibition and fast somatic inhibition). The identification procedure used optimization algorithms to minimize a spectral distance between real and simulated signals. Results demonstrated that the model generates very realistic signals for automatically identified parameters. They also showed that the transition from interictal to ictal activity cannot be simply explained by an increase in excitation and a decrease in inhibition but rather by time-varying ensemble interactions between pyramidal cells and local interneurons projecting to either their dendritic or perisomatic region (with slow and fast GABAA kinetics). Particularly, during preonset activity, an increasing dendritic GABAergic inhibition compensates a gradually increasing excitation up to a brutal drop at seizure onset when faster oscillations (beta and low gamma band, 15 to 40 Hz) are observed. These faster oscillations are then explained by the model feedback loop between pyramidal cells and interneurons targeting their perisomatic region. These findings obtained from model identification in human temporal lobe epilepsy are in agreement with some results obtained experimentally, either on animal models of epilepsy or on the human epileptic tissue.

Low-voltage rapid discharges (or fast EEG ictal activity) constitute a characteristic electrophysiological pattern in focal seizures of human epilepsy. They are characterized by a decrease of signal voltage with a marked increase of signal frequency (typically beyond 25 Hz). They have long been observed in stereoelectroencephalographic (SEEG) signals recorded with intra-cerebral electrodes, generally occurring at seizure onset and simultaneously involving distinct brain regions. Spectral properties of rapid ictal discharges as well as spatial correlations measured between SEEG signals generated from distant sites before, during and after these discharges were studied. Cross-correlation estimates within typical EEG sub-bands and statistical tests performed in 10 patients suffering from partial epilepsy (frontal, temporal or fronto-temporal) reveal that SEEG signals are significantly de-correlated during the discharge period compared with periods that precede and follow this discharge. These results can be interpreted as a functional decoupling of distant brain sites at seizure onset followed by an abnormally high re-coupling when the seizure develops. They lead to the concept of 'disruption' that is complementary of that of 'activation' (revealed by significantly high correlations between signals recorded during seizures), both giving insights into our understanding of pathophysiological processes involved in human partial epilepsies as well as in the interpretation of clinical semiology.

One acoustic feature that plays an important role in pitch perception is frequency. Studies on the processing of frequency in the human and animal brain have shown that the auditory cortex is tonotopically organized: low frequencies are represented laterally whereas high frequencies are represented medially. To date, the study of the functional organization of the human auditory cortex in the processing of frequency has been limited to the use of either scalp-recorded auditory evoked potentials (AEPs), which have relatively poor spatial resolving power, or functional imagery techniques, which have poor temporal resolving power. The present study uses intracerebrally recorded AEPs to explore this topic in the primary and secondary auditory cortices of both hemispheres of the human brain. Recordings were carried out in 45 adult patients with drug-resistant partial seizures. In the right hemisphere, clear spectrally organized tonotopic maps were observed with distinct separations between different frequency-processing regions. AEPs for high frequencies were recorded medially, whereas AEPs for low frequencies were recorded laterally. In the left hemisphere, however, this tonotopic organization was less evident, with different regions involved in the processing of a range of frequencies. The hemisphere-related difference in the processing of tonal frequency is discussed in relation to pitch perception.

We explored the degree to which the duration of acoustic cues contributes to the respective involvement of the two hemispheres in the perception of speech. To this end, we recorded the reaction time needed to identify monaurally presented natural French plosives with varying VOT values. The results show that a right-ear advantage is significant only when the phonetic boundary is close to the release burst, i.e., when the identification of the two successive acoustical events (the onset of voicing and the release from closure) needed to perceive a phoneme as voiced or voiceless requires rapid information processing. These results are consistent with the recent hypothesis that the left hemisphere is superior in the processing of rapidly changing acoustical information., (Copyright 2000 Academic Press.)

Objective: We investigated the relative participation of each cerebral hemisphere during a lateralized task that can be performed by a single hemisphere. While our companion article ( Clarke et al. 1999) focused on visual and motor event-related potentials (ERPs) recorded from occipital and peri-Rolandic sites, the present article is concerned with ERP correlates of intermediate stages of information processing from remaining cerebral regions., Methods: Intracranial ERPs were recorded from temporal, parietal and frontal lobe sites in 13 patients with intractable epilepsy while they performed a lateralized visual oddball task., Results: Visually-responsive N2 and/or P3 effects were recorded from medial temporal and supramarginal sites that appear to reflect activity along ventral and dorsal visual streams, respectively. Likewise, certain prefrontal sites, that are probably involved in working memory, were also visually-responsive. The majority of sites exhibiting N2, P3 and/or slow wave components, however, were unaffected by lateralized visual field or response hand effects. Target-evoked P3-like components were most frequently recorded from medial temporal and prefrontal sites. Post-response slow wave components were pervasive, and polarity reversals were present in the insula/operculum region, apparently reflecting somatosensory activity from SII., Conclusions: The general absence of lateralized ERP effects despite lateralized stimulus input and response output suggests the importance of interhemispheric integration over hemispheric independence in the processing of this type of task.

Recordings directly within the brain can establish local evoked potential generation without the ambiguities always associated with extracranial electromagnetic measures. Depth recordings have found that sensory stimuli activate primary cortex and then material-specific encoders. Sensory-specific areas remain active for long periods, but by about 200 ms are joined by activation in widespread brain systems. One system is related to the orientation of attention. It is centered in paralimbic and attentional frontoparietocingular cortex, and associated with the P3a. A second system associated with P3b envelopes cognitive contextual integration. It engages the ventral temporofrontal event-encoding cortices (inferotemporal, perirhinal, and ventrolateral prefrontal), association cortices (superior temporal sulcal and posterior parietal), and the hippocampus. Thus, even in simple tasks, activation is widespread but concentrated in particular multilobar systems. With this information, the late cognitive potentials can be used to monitor the probable location, timing and intensity of brain activation during cognitive tasks.

Purpose: Single photon emission computed tomography (SPECT) is used as an adjunctive method in preoperative localization of epileptic foci. In temporal lobe epilepsy (TLE), interictal hypoperfusion is observed in 60-70% of cases. Correlation with ictal EEG changes is observed in approximately 50-60% of cases. Relationships with interictal EEG have been studied less. We compared interictal SPECT data obtained in 20 patients with their interictal intracerebral electrical activity recorded by depth electrodes to evaluate a potential relationship., Methods: We studied 20 sequential patients whose clinical, surface, and depth EEG data indicated seizure originating in the temporal lobe and who had interictal [99mTc]hexamethylpropylene amine oxime (HMPAO)-SPECT stereo-EEG (SEEG). Intracerebral electrodes were placed according to the patient's profile. The interictal extent of epileptiform activity allowed delineation of the irritative zone. Interictal spike frequency was also analyzed semiquantitatively. Visual and numerical SPECT analysis was performed blind to SEEG data., Results: Interictal hypoperfusion was observed in 16 patients, involving the epileptogenic temporal lobe in 14. Except for 1 patient who manifested lateral temporal hypoperfusion corresponding to a mass lesion, two distinctive patterns of hypoperfusion were noted: (a) mesial hypoperfusion (5 patients), and (b) global temporal hypoperfusion (8 patients). In 8 patients, hypoperfusion had also extended into the adjacent cortex. Temporal mesial hypoperfusion was associated with spiking limited to the mesial structures, whereas global temporal hypoperfusion or hypoperfusion extending beyond the temporal lobe was associated with a similar topographic pattern of spikes., Conclusions: Comparison between SPECT and SEEG data collected in the interictal phase indicated that the extent of the hypoperfused area correlated topographically with that of the underlying irritative zone.

Single photon emission tomography (SPET) imaging holds promise for localization of the site of extratemporal seizures, but limited data currently exist; in particular, correlations with stereo-electroencephalography (S-EEG) have not been made. Ten patients aged 14-44 years (mean 25 years) with a proven frontal or central epilepsy by S-EEG and post-surgical follow-up were studied retrospectively: 7 patients had frontal cortectomy and one patient had a callosotomy for bifrontal epilepsy. All patients underwent clinical, inter-ictal and ictal video-EEG, computed tomography scan and/or magnetic resonance imaging, SPET and S-EEG examinations. SPET was performed inter-ictally, while on usual epileptic medications, using 99Tcm-HMPAO (n = 4) or 123I-IMP (n = 6) as the perfusion tracer. The SPET images were evaluated independently by two observers, blind to any data other than the diagnosis of frontral or central epilepsy. Localization of inter-ictal SPET hypoperfusion was compared with the epileptogenic (EZ), irritative (IZ) and lesional (LZ) zones, as defined by S-EEG. Six patients showed structural frontal abnormalities. One patient had normal SPET and one had a contralateral hypoperfusion. Therefore, concordance of sides was found in 8 of 10 patients (including one with bilateral SPET and S-EEG abnormalities). The hypoperfusion was equal to or larger than the EZ + IZ + LZ in 6 patients (5 had a frontal lesion). SPET hypoperfusion was smaller than the EZ in one patient, and different from the EZ, IZ and LZ in two patients. Although this was a retrospective study, it provides qualitative data regarding the significance of inter-ictal SPET abnormalities in frontal or central epilepsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Purpose: We recorded with intracerebral electrodes the onset of limbic seizures in patients with mesial temporal lobe epilepsy (MTLE) to identify the dynamic interactions between the hippocampus (HIP), amygdala (AMY) and entorhinal cortex (EC). Method: Interactions were quantified by analyzing the interdependencies between stereo-electroencephalographic (SEEG) signals using a nonlinear cross-correlation method. Seizures from 12 patients were analyzed by identifying three periods of interest: (i) the rapid discharge that occurs at seizure onset (“during rapid discharge”, DRD period); (ii) the time interval that precedes this rapid discharge (“before rapid discharge”, BRD period); and the time that follows the rapid discharge (“after rapid discharge”, ARD period). The transition from interictal to ictal discharge was classified into: (i) “type 1 transition” in which the emergence of pre-ictal spiking was followed by a rapid discharge; and (ii) “type 2 transition” that was associated with rapid discharge onset without prior spiking. Results: In both types of transition the BRD period was characterized by significant cross-correlation values indicating strong interactions among mesial temporal structures as compared to those seen during background activity. Interactions between HIP and EC were predominant in 10 of 12 patients (83%). Interactions between EC and AMY were observed in 6 of 12 cases (50%) and between AMY and HIP in 7 of 12 cases (58%). Analysis of coupling directionality indicated that most of the couplings were driven either by HIP (six patients) or by the EC (four patients). The DRD period was characterized by a significant decrease of cross-correlation values. In addition, type 1 transition was characterized by interactions that uniformly involved the three structures, while type 2 transition was associated with interactions between EC and HIP. Finally, analysis of coupling direction demonstrated that the HIP was always the leader in type 1 transition whereas in type 2 the EC was most often the leading structure. Conclusions: This study demonstrates that pre-ictal synchronization between mesial structures is the initial event for seizures starting in the mesial temporal region. [Copyright &y& Elsevier]

Objective: Our main goal was to evaluate the accuracy of an original non-supervised spatio-temporal magnetoencephalography (MEG) localization method used to characterize interictal spikes generators.Methods: MEG and stereotactic intracerebral recordings (stereo-electro-encephalographic exploration, SEEG) data were analyzed independently in 4 patients. MEG localizations were performed with and without anatomical constraints.Results: We analyzed 1326 interictal spikes recorded using MEG. For each patient, 2–3 typical source patterns were described. These source configurations were compared with SEEG. SEEG findings and MEG spatio-temporal localization results were remarkably coherent in our 4 patients. Most of the MEG patterns were similar to interictal SEEG patterns from a spatio-temporal point of view.Conclusions: We were able to evaluate the usefulness of our non-invasive localization method. This approach described correctly the part of the epileptogenic network involved in the generation of interictal events. Our results demonstrate the potential of MEG in the non-invasive spatio-temporal characterization of generators of interictal spikes. [Copyright &y& Elsevier]