Middle short gyrus of the insula implicated in speech production: intracerebral electric stimulation of patients with epilepsy.

International audiencePURPOSE: Different lines of evidence have suggested an involvement of the insular cortex in speech production. These have included results from lesion studies, functional imaging techniques, and electrical stimulation of the human insular cortex during invasive evaluation of epileptic patients. METHODS: We evaluated 25 patients who had drug refractory focal epilepsy with at least one electrode stereotactically implanted in the insular cortex. RESULTS: Eight responses to insular cortex electrical stimulation were reported by five patients as speech arrest (five responses) and a lowering of voice intensity (three responses). CONCLUSIONS: Data from this study implicate the middle short gyrus of the insula in the production of speech and show the importance of intrainsular electrode implantation during invasive pre-resection evaluation by stereo-electroencephalography (SEEG) when speech arrest occurs early in seizure semiology

Studying Network Mechanisms Using Intracranial Stimulation in Epileptic Patients

Patients suffering from focal drug-resistant epilepsy who are explored using intracranial electrodes allow to obtain data of exceptional value for studying brain dynamics in correlation with pathophysiological and cognitive processes. Direct electrical stimulation (DES) of cortical regions and axonal tracts in those patients elicits a number of very specific perceptual or behavioral responses, but also abnormal responses due to specific configurations of epileptic networks. Here, we review how anatomo-functional brain connectivity and epilepsy network mechanisms can be assessed from DES responses measured in patients. After a brief summary of mechanisms of action of brain electrical stimulation, we recall the conceptual framework for interpreting DES results in the context of brain connectivity and review how DES can be used for the characterization of functional networks, the identification of the seizure onset zone, the study of brain plasticity mechanisms, and the anticipation of epileptic seizures. This pool of exceptional data may be underexploited by fundamental research on brain connectivity and leaves much to be learned

: Seizure onset zone imaging

International audienceStereo-electroencephalography is used to localize the seizure onset zone and connected neuronal networks in surgical candidates suffering from intractable focal epilepsy. The concept of an epileptogenicity index has been proposed recently to represent the likelihood of various regions being part of the seizure onset zone. It quantifies low-voltage fast activity, the electrophysiological signature of seizure onset usually assessed visually by neurologists. Here, we revisit epileptogenicity in light of neuroimaging tools such as those provided in statistical parametric mapping software. Our goal is to propose a robust approach, allowing easy exploration of patients' brains in time and space. The procedure is based upon statistical parametric mapping, which is an established framework for comparing multi-dimensional image data that allows one to correct for inherent multiple comparisons. Statistics can also be performed at the group level, between seizures in the same patient or between patients suffering from the same type of epilepsy using normalization of brains to a common anatomic atlas. Results are obtained from three case studies (insular reflex epilepsy, cryptogenic frontal epilepsy and lesional occipital epilepsy) where tailored resection was performed, and from a group of 10 patients suffering from mesial temporal lobe epilepsy. They illustrate the basics of the technique and demonstrate its very good reproducibility and specificity. Most importantly, the proposed approach to the quantification of the seizure onset zone allows one to summarize complex signals in terms of a time-series of statistical parametric maps that can support clinical decisions. Quantitative neuroimaging of stereo-electroencephalographic features of seizures might thus help to provide better pre-surgical assessment of patients undergoing resective surgery

Category-Specific Visual Responses: An Intracranial Study Comparing Gamma, Beta, Alpha, and ERP Response Selectivity

The specificity of neural responses to visual objects is a major topic in visual neuroscience. In humans, functional magnetic resonance imaging (fMRI) studies have identified several regions of the occipital and temporal lobe that appear specific to faces, letter strings, scenes, or tools. Direct electrophysiological recordings in the visual cortical areas of epileptic patients have largely confirmed this modular organization, using either single-neuron peri-stimulus time-histogram or intracerebral event-related potentials (iERP). In parallel, a new research stream has emerged using high-frequency gamma-band activity (50–150 Hz) (GBR) and low-frequency alpha/beta activity (8–24 Hz) (ABR) to map functional networks in humans. An obvious question is now whether the functional organization of the visual cortex revealed by fMRI, ERP, GBR, and ABR coincide. We used direct intracerebral recordings in 18 epileptic patients to directly compare GBR, ABR, and ERP elicited by the presentation of seven major visual object categories (faces, scenes, houses, consonants, pseudowords, tools, and animals), in relation to previous fMRI studies. Remarkably both GBR and iERP showed strong category-specificity that was in many cases sufficient to infer stimulus object category from the neural response at single-trial level. However, we also found a strong discrepancy between the selectivity of GBR, ABR, and ERP with less than 10% of spatial overlap between sites eliciting the same category-specificity. Overall, we found that selective neural responses to visual objects were broadly distributed in the brain with a prominent spatial cluster located in the posterior temporal cortex. Moreover, the different neural markers (GBR, ABR, and iERP) that elicit selectivity toward specific visual object categories present little spatial overlap suggesting that the information content of each marker can uniquely characterize high-level visual information in the brain

Exploring the Electrophysiological Correlates of the Default-Mode Network with Intracerebral EEG

While functional imaging studies allow for a precise spatial characterization of resting state networks, their neural correlates and thereby their fine-scale temporal dynamics remain elusive. A full understanding of the mechanisms at play requires input from electrophysiological studies. Here, we discuss human and non-human primate electrophysiological data that explore the neural correlates of the default-mode network. Beyond the promising findings obtained with non-invasive approaches, emerging evidence suggests that invasive recordings in humans will be crucial in order to elucidate the neural correlates of the brain's default-mode function. In particular, we contend that stereotactic-electroencephalography, which consists of implanting multiple depth electrodes for pre-surgical evaluation in drug-resistant epilepsy, is particularly suited for this endeavor. We support this view by providing rare data from depth recordings in human posterior cingulate cortex and medial prefrontal cortex that show transient neural deactivation during task-engagement

A Blueprint for Real-Time Functional Mapping via Human Intracranial Recordings

International audienceBACKGROUND: The surgical treatment of patients with intractable epilepsy is preceded by a pre-surgical evaluation period during which intracranial EEG recordings are performed to identify the epileptogenic network and provide a functional map of eloquent cerebral areas that need to be spared to minimize the risk of post-operative deficits. A growing body of research based on such invasive recordings indicates that cortical oscillations at various frequencies, especially in the gamma range (40 to 150 Hz), can provide efficient markers of task-related neural network activity. PRINCIPAL FINDINGS: Here we introduce a novel real-time investigation framework for mapping human brain functions based on online visualization of the spectral power of the ongoing intracranial activity. The results obtained with the first two implanted epilepsy patients who used the proposed online system illustrate its feasibility and utility both for clinical applications, as a complementary tool to electrical stimulation for presurgical mapping purposes, and for basic research, as an exploratory tool used to detect correlations between behavior and oscillatory power modulations. Furthermore, our findings suggest a putative role for high gamma oscillations in higher-order auditory processing involved in speech and music perception. CONCLUSION/SIGNIFICANCE: The proposed real-time setup is a promising tool for presurgical mapping, the investigation of functional brain dynamics, and possibly for neurofeedback training and brain computer interfaces

Cartographies d épileptogénicité évaluées en SEEG : apport des oscillations hautes fréquences (60-100Hz) ictales dans la définition de la zone de début de crise

Les oscillations hautes fréquences (HFO) étudiées en stéréo-électroencéphalographie (SEEG) chez les patients présentant une épilepsie partielle pharmaco-résistante, semblent être le témoin de l épileptogénèse et reflètent assez fidèlement, par leur topographie, la seizure onset zone (SOZ). Récemment, notre équipe a fait état d une nouvelle méthode de cartographie de la SOZ basée sur l augmentation de puissance des HFO60-100 (HFO de fréquence comprise entre 60 et 100 Hz). Cette méthode, qui permet d établir une cartographie des réseaux neuronaux impliqués dans l initiation de la crise, a été appliquée à tous les patients implantés en SEEG entre 2009 et 2011 au CHU de Grenoble, qui avaient présenté au moins une crise épileptique spontanée. 21 patients ont ainsi été étudiés, de SOZ majoritairement néocorticale. La puissance ictale des HFO60-100 a été quantifiée pour chaque crise, puis des cartographies statistiques ont été utilisées pour représenter les régions corticales présentant une activation significative des HFO60-100 au début de la crise, comparativement aux HFO60-100 intercritiques. Pour tous les patients étudiés, une activation critique significative des HFO60-100 a été démontrée, quelle que soit la topographie de la SOZ, indépendamment de la présence d une lésion épileptogène. La topographie des HFO60-100 activées au début des crises semble corrélée à celle de la SOZ. Pour 11 des patients opérés, le pronostic chirurgical s avérait d autant plus favorable que la résection réalisée contenait les régions cérébrales présentant une activation significative des HFO60-100 ictales.High gamma oscillations (HFO, >60 Hz) at seizure onset are strongly associated to epileptogenesis, and their localising value for the seizure onset zone (SOZ) has been underlined using quantitative measures such as the epileptogenicity index. In particular, we recently reported a new method that produces images of epileptogenicity based on the detection of significant increase of HFO at seizure onset in stereotactic coordinates derived from patient s MRI (magnetic resonance imaging). Here, we applied the same analysis to 21 consecutive patients who underwent stereo-electroencephalography (SEEG) recordings between 2009 and 2011, and in whom at least one spontaneous seizure was recorded. Power of HFO ranging from 60 to 100Hz band (ictalHFO60-100) was quantified at onset for each seizure, and statistical parametric maps were used to represent the cortex areas displaying significant ictalHFO60-100 when compared to an interictal baseline. Analysis was performed at the patient level per seizure, with a group analysis for every patient. All patients presented a significant epileptogenicity map at seizure onset, whatever seizure onset location or histological lesion they had. IctalHFO60-100 map was highly reproducible over seizures per patient, and most significant ictalHFO60-100 had the same localisation as epileptogenic lesions. For 11 patients who underwent a 3DT1 MRI in the post-operative period, the removal of cortex areas displaying ictalHFO60-100 was associated to a better outcome. Epileptogenicity map is useful to evaluate the SOZ in the pre-surgical period. This new tool associated to SEEG might help to improve the surgical outcome of medically-intractable epilepsies.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

ANR Tecsan 07 - Epimouv Livrable 1-2-3 Partie CHU Caractérisation de la sémiologie motrice des crises épileptiques dans une unité d'épileptologie. Second système d'acquisition en clinique Logiciel de caractérisation des crises et Rapport d'évaluation.

Ce rapport décrits les 3 livrables réalisés par le CHU au terme du projet Epimouv. Il décrit le travail réalisé par le CHU et l'analyse des données réalisée pour classer les manifestations motrices au cours des crises. A partir de ces classifications, un algorithme pour détecter les crises les plus fréquentes et les plus problématiques, les crises tonico-cloniques secondairement généralisées est proposé et évalué. Une représentation de l'évolution stéréotypiques des classes de manifestations motrices au cours du temps est aussi proposée en fonction des pathologies

Preictal short-term plasticity induced by intracerebral 1 Hz stimulation.

International audienceShort-term changes of intrinsic properties of neural networks play a critical role in brain dynamics. In that context, epilepsy is a typical pathology where the fast transition between interictal and ictal states is probably associated to intrinsic modifications of underlying networks. In this study, we focused on the correlates of plastic neural mechanisms in the intracerebral electroencephalogram (iEEG). Data were obtained during 1 Hz electrical stimulation in twenty patients suffering from temporal lobe epilepsy and implanted with intracerebral electrodes for clinical evaluation before resective surgery. First, we developed a procedure of analysis for localisation of the seizure onset zone based on brain excitability and plasticity defined as the average, and as the first-order (linear) modulation respectively, of the standard deviation of iEEG responses over stimulations. Our results suggest that the candidate epileptic focus is particularly prone to exhibiting short-term plasticity. Second, we used Dynamic Causal Modelling (DCM) to model explicitly short-term plasticity as a fast modulation of synaptic efficacies in either intrinsic or extrinsic connections to the focus. We found the two types of modulation both likely. Third, we used DCM to study the fast modulation of synaptic connectivity of long-range connections in neuronal networks restricted to the temporal lobe. Using DCM, we were able to estimate which structures expressed a strong modulatory input to the epileptic focus. Such early changes in interregional connectivity might be important for the initiation of electrically-induced seizures. They may also reflect some aspects of the pathogenesis of epilepsy in those patients