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Objective Non-rapid eye movement (NREM) sleep is supposed to play a key role in long-term memory consolidation transferring information from hippocampus to neocortex. However, sleep also activates epileptic activities in medial temporal regions. This study investigated whether interictal hippocampal spikes during sleep would impair long-term memory consolidation. Method We prospectively measured visual and verbal memory performance in 20 patients with epilepsy investigated with stereoelectroencephalography (SEEG) at immediate, 30-minute, and 1-week delays, and studied the correlations between interictal hippocampal spike frequency during waking and the first cycle of NREM sleep and memory performance, taking into account the number of seizures occurring during the consolidation period and other possible confounding factors, such as age and epilepsy duration. Results Retention of verbal memory over 1 week was negatively correlated with hippocampal spike frequency during sleep, whereas no significant correlation was found with hippocampal interictal spikes during waking. No significant result was found for visual memory. Regression tree analysis showed that the number of seizures was the first factor that impaired the verbal memory retention between 30 minutes and 1 week. When the number of seizures was below 5, spike frequency during sleep higher than 13 minutes was associated with impaired memory retention over 1 week. Interpretation Our results show that activation of interictal spikes in the hippocampus during sleep and seizures specifically impair long-term memory consolidation. We hypothesize that hippocampal interictal spikes during sleep interrupt hippocampal-neocortical transfer of information. ANN NEUROL 2020;87:976-987.

Background An ecstatic phenomenon is an altered state of consciousness with a sense of “hyper-reality”, and a complete present-moment awareness with a feeling of union with the Universe. A better understanding of the network mechanisms underlying this fascinating subjective experience may help to unravel some mysteries of human consciousness. Insula has been recently proposed to be a key region to elicit these symptoms. Objective/Hypothesis We studied functional connectivity changes in several brain areas during the induction of ecstatic auras by direct electrical stimulation of the dorsal anterior insular cortex in patients with refractory focal epilepsy implanted with intracerebral electrodes (stereotactic-EEG, SEEG) in the context of their pre-surgical evaluation. Methods Three patients were selected on the basis of the occurrence of ecstatic symptoms triggered by direct intracerebral electrical stimulation (ES) of the antero-dorsal part of the insula. ES was performed (50 Hz, 1.5–2.1 mA, in a bipolar fashion to each contact in the gray matter during a 3 s period) to map functional cortices and trigger habitual seizures. One stimulation inducing ecstatic changes in each patient was analyzed. Functional connectivity analysis was performed by measuring interdependencies (nonlinear regression analysis based on the h2 coefficient) between SEEG signals before and after stimulations. Results In all patients, only the stimulation of dorsal anterior insula was able to reproduce an ecstatic aura. We observed a significant increase of functional connectivity values between several brain regions in the immediate period following stimulations. The most commonly implicated region was the dorsal anterior insula. Out-degrees (a measure intended to identify leading structures in a network) identified the dorsal anterior insula as the most common leading region in the induced networks. Conclusion(s) Our findings bring additional support in favor of a major role played by the dorsal anterior insula in ecstatic experiences.

Psychogenic nonepileptic seizures (PNES) are paroxysmal clinical events that are often misdiagnosed as epileptic seizures, but which are not associated with electrographic discharge. Brain connectivity changes occurring during PNES are not known. We studied functional connectivity (Fc) in two patients with drug-resistant epilepsy, explored by stereotactic electroencephalography (EEG), in whom we recorded both epileptic seizures (ES) and PNES. Functional connectivity using pair-wise nonlinear correlation was computed between signals from seven brain areas: amygdala, hippocampus, lateral temporal cortex, anterior insula, orbitofrontal cortex, prefrontal cortex, and lateral parietal cortex. We assessed changes in global Fc during PNES in comparison with a background period. During PNES, a global decrease of Fc occurred between the different brain regions studied, compared with the interictal period. In both patients, decreased Fc was prominent in connections involving the anterior insula and parietal cortex. In conclusion, some PNES are associated with ictal functional disconnection between brain areas, particularly involving the parietal cortices and the anterior insula.

The hippocampus and amygdala are key brain structures of the medial temporal lobe, involved in cognitive and emotional processes as well as pathological states such as epilepsy. Despite their importance, it is still unclear whether their neural activity can be recorded non-invasively. Here, using simultaneous intracerebral and magnetoencephalography (MEG) recordings in patients with focal drug-resistant epilepsy, we demonstrate a direct contribution of amygdala and hippocampal activity to surface MEG recordings. In particular, a method of blind source separation, independent component analysis, enabled activity arising from large neocortical networks to be disentangled from that of deeper structures, whose amplitude at the surface was small but significant. This finding is highly relevant for our understanding of hippocampal and amygdala brain activity as it implies that their activity could potentially be measured non-invasively.

International audience; General anesthesia (GA) is a reversible manipulation of consciousness whose mechanism is mysterious at the level of neural networks leaving space for several competing hypotheses. We recorded electrocorticography (ECoG) signals in patients who underwent intracranial monitoring during awake surgery for the treatment of cerebral tumors in functional areas of the brain. Therefore, we recorded the transition from unconsciousness to consciousness directly on the brain surface. Using frequency resolved interferometry; we studied the intermediate ECoG frequencies (4–40 Hz). In the theoretical study, we used a computational Jansen and Rit neuron model to simulate recovery of consciousness (ROC). During ROC, we found that f increased by a factor equal to 1.62 ± 0.09, and δf varied by the same factor (1.61 ± 0.09) suggesting the existence of a scaling factor. We accelerated the time course of an unconscious EEG trace by an approximate factor 1.6 and we showed that the resulting EEG trace match the conscious state. Using the theoretical model, we successfully reproduced this behavior. We show that the recovery of consciousness corresponds to a transition in the frequency (f, δf) space, which is exactly reproduced by a simple time rescaling. These findings may perhaps be applied to other altered consciousness states. General anesthesia (GA) is an example of a reversible manipulation of consciousness, which is performed every day in hospitals around the world. While the mechanisms that underlie the effects of anesthetics become clearer at the cellular level 1,2 , the effects of anesthetics on brain activity at the scale of functional neural networks are still debated, which leaves space for several competing hypotheses 3. GA shares many common pathways with sleep, specifically with respect to the loss and recovery of consciousness, but it also displays specific electrophysiological features that are related to drug effects. The changes in the EEG during sleep or anesthesia are empirically well described but their function and generation are still unknown 4. The loss of consciousness induced by the widely used anaesthetic propofol is associated with an increase of power in the low-frequencies of the EEG and the emergence of strong and highly structured rhythmic activities in the EEG 5–7 corresponding to frontal alpha oscillations (8 to 13 Hz) 5. Many anesthetics share the same effects 8. Moreover, for some authors, the characteristic changes in the EEG during GA are similar to those observed in the first stages of sleep 9,10. A consistent explanation for these findings is missing and the behavior is still debated, which has led to different models 3,11–14. In this article, we recorded Electrocorticography (ECOG) after stopping the infusion of anaesthetics for brain surgery requiring functional testing in awake patients. We investigated the reorganization of dynamics in local

Background In pharmacoresistant epilepsy, exploration with depth electrodes can be needed to precisely define the epileptogenic zone. Accurate location of these electrodes is thus essential for the interpretation of Stereotaxic EEG (SEEG) signals. As SEEG analysis increasingly relies on signal processing, it is crucial to make a link between these results and patient’s anatomy. Our aims were thus to develop a suite of software tools, called “EpiTools”, able to i) precisely and automatically localize the position of each SEEG contact and ii) display the results of signal analysis in each patient’s anatomy. New method The first tool, GARDEL (GUI for Automatic Registration and Depth Electrode Localization), is able to automatically localize SEEG contacts and to label each contact according to a pre-specified nomenclature (for instance that of FreeSurfer or MarsAtlas). The second tool, 3Dviewer, enables to visualize in the 3D anatomy of the patient the origin of signal processing results such as rate of biomarkers, connectivity graphs or Epileptogenicity Index. Results GARDEL was validated in 30 patients by clinicians and proved to be highly reliable to determine within the patient’s individual anatomy the actual location of contacts. Comparison with existing methods GARDEL is a fully automatic electrode localization tool needing limited user interaction (only for electrode naming or contact correction). The 3Dviewer is able to read signal processing results and to display them in link with patient’s anatomy. Conclusion EpiTools can help speeding up the interpretation of SEEG data and improving its precision.

Objectif L’objectif de ce travail est d’etudier l’impact des pointes epileptiques hippocampiques grâce a des enregistrements intracrâniens (stereoencephalographie, SEEG) sur les capacites de consolidation mnesique a long terme (plusieurs jours), en etudiant egalement l’effet sur les fuseaux du sommeil hippocampiques. Methodes Un total de 20 patients explores en SEEG dans le cadre du bilan prechirurgical d’une epilepsie focale pharmaco-resistante, avec une implantation hippocampique uni ou bilaterale, ont ete inclus. Ils ont passe des tests de memoire 48 h apres l’implantation des electrodes puis un rappel une semaine plus tard. Les analyses ont ete effectuees sur la nuit suivant la premiere session de tests mnesiques : detection des pointes epileptiques hippocampiques et detection des fuseaux de sommeil hippocampiques. Resultats On retrouve une correlation negative entre la frequence des pointes au cours du sommeil lent et les performances mnesiques a une semaine. Il existe une correlation negative entre la frequence des pointes epileptiques au cours du sommeil lent et la frequence des fuseaux hippocampiques. Neanmoins, aucune correlation n’est retrouvee entre la frequence des fuseaux de sommeil hippocampiques et les performances mnesiques a une semaine. Conclusion Ces resultats suggerent que les pointes epileptiques hippocampiques survenant au cours du sommeil lent interferent avec les processus responsables de la consolidation de la memoire a long terme. Les fuseaux hippocampiques ne semblent pas directement associes aux processus de consolidation mnesique a long terme.

Objective The simultaneous recording of intracerebral EEG (stereotaxic EEG, SEEG) and magnetoencephalography (MEG) is a promising strategy that provides both local and global views on brain pathological activity. Yet, acquiring simultaneous signals poses difficult technical issues that hamper their use in clinical routine. Our objective was thus to develop a set of solutions for recording a high number of SEEG channels while preserving signal quality. Approach We recorded data in a patient with drug resistant epilepsy during presurgical evaluation. We used dedicated insertion screws and optically insulated amplifiers. We recorded 137 SEEG contacts on 10 depth electrodes (5-15 contacts each) and 248 MEG channels (magnetometers). Signal quality was assessed by comparing the distribution of RMS values in different frequency bands to a reference set of MEG acquisitions. Main results The quality of signals was excellent for both MEG and SEEG; for MEG, it was comparable to that of MEG signals without concurrent SEEG. Discharges involving several structures on SEEG were visible on MEG, whereas discharges limited in space were not seen at the surface. Significance SEEG can now be recorded simultaneously with whole-head MEG in routine. This opens new avenues, both methodologically for understanding signals and improving signal processing methods, and clinically for future combined analyses.

International audience; Interictal or ictal events in partial epilepsies may project on scalp EEG contralaterally to the side of the epileptogenic lesion. Such paradoxical lateralization can be observed in case of para-sagittal generators, and is likely due to the spatial orientation of the generator, presenting an oblique projection towards the midline. We present here a case of medial occipital epilepsy investigated using EEG, MEG and stereoelectroencephalography (SEEG). MRI displayed a focal cortical dysplasia in the superior margin of the right calcarine fissure. SEEG demonstrated bilateral medial occipital interictal spikes, with an inversion of polarity at the level of the lesion and a contralateral propagation occurring in 10 ms. Interictal iterative EEG cartographies showed a large posterior field, with a maximum contralateral to the initial generator (EEG paradoxical lateralization). With the same number of channels, interictal iterative MEG cartographies were more precise and more complex than EEG ones, indicating an onset accurately lateralized. A few milliseconds later, MEG cartographies were quadripolar, thus indicating two homotopic active generators. These MEG and EEG cartographies have been reproduced using BESA dipole simulator. Relative merits of MEG and EEG are still debated. With 151 channels, MEG source localizations indicated the right medial occipital area, as demonstrated by SEEG. An investigation with a corresponding number of EEG channels was not performed. After a down sampling to 64 sensors, this precision was lost. MEG and EEG source localization results, both with 64 channels, were quite comparable, indicating both medial occipital areas. However, a careful analysis of MEG/EEG iterative cartographies, performed with the same number of channels in both modalities, demonstrated that, in this configuration, MEG sensitivity was superior to the EEG one, allowing separating two medial occipital sources, characterized in SEEG by a time delay of 10 ms.

International audience; 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.