Search

Background and ObjectivesIt remains unknown to what extent ictal scalp EEG can accurately predict the localization of the intracerebral seizure onset in presurgical evaluation of drug-resistant epilepsies. In this study, we aimed to define homogeneous ictal scalp EEG profiles (based on their first ictal abnormality) and assess their localizing value using simultaneously recorded scalp EEG and stereo-EEG.MethodsWe retrospectively included consecutive patients with drug-resistant focal epilepsy who had simultaneous stereo-EEG and scalp EEG recordings of at least 1 seizure in the epileptology unit in Nancy, France. We analyzed 1 seizure per patient and used hierarchical cluster analysis to group similar seizure profiles on scalp EEG and then performed a descriptive analysis of their intracerebral correlates.ResultsWe enrolled 129 patients in this study. The hierarchical cluster analysis showed 6 profiles on scalp EEG first modification. None were specific to a single intracerebral localization. The “normal EEG” and “blurred EEG” clusters (early muscle artifacts) comprised only 5 patients each and corresponded to no preferential intracerebral localization. The “temporal discharge” cluster (n = 46) was characterized by theta or delta discharges on ipsilateral anterior temporal scalp electrodes and corresponded to a preferential mesial temporal intracerebral localization. The “posterior discharge” cluster (n = 42) was characterized by posterior ipsilateral or contralateral rhythmic alpha discharges or slow waves on scalp and corresponded to a preferential temporal localization. However, this profile was the statistically most frequent scalp EEG correlate of occipital and parietal seizures. The “diffuse suppression” cluster (n = 9) was characterized by a bilateral and diffuse background activity suppression on scalp and corresponded to mesial, and particularly insulo-opercular, localization. Finally, the “frontal discharge” cluster (n = 22) was characterized by bilateral frontal rhythmic fast activity or preictal spike on scalp and corresponded to preferential ventrodorsal frontal intracerebral localizations.DiscussionThe hierarchical cluster analysis identified 6 seizure profiles regarding the first abnormality on scalp EEG. None of them were specific of a single intracerebral localization. Nevertheless, the strong relationships between the “temporal,” “frontal,” “diffuse suppression,” and “posterior” profiles and intracerebral discharge localizations may contribute to hierarchize hypotheses derived from ictal scalp EEG analysis regarding intracerebral seizure onset.

International audience; Background: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is usually associated with a poor response to antiseizure medications. We focused on MTLE-HS patients who were seizure free on medication to: (1) determine the clinical factors associated with seizure freedom and (2) develop a machine-learning classifier to better earlier identify those patients.Methods: We performed a retrospective, multicentric study comparing 64 medically treated seizure-free MTLE-HS patients with 200 surgically treated drug-resistant MTLE-HS patients. First, we collected medical history and seizure semiology data. Then, we developed a machine-learning classifier based on clinical data.Results: Medically treated seizure-free MTLE-HS patients were seizure-free for at least 2 years, and for a median time of 7 years at last follow-up. Compared to drug-resistant MTLE-HS patients, they exhibited: an older age at epilepsy onset (22.5 vs 8.0 years, p < 0.001), a lesser rate of: febrile seizures (39.0% vs 57.5%, p = 0.035), focal aware seizures (previously referred to as aura)(56.7% vs 90.0%, p < 0.001), autonomic focal aware seizures in presence of focal aware seizure (17.6% vs 59.4%, p < 0.001), dystonic posturing of the limbs (9.8% vs 47.0%, p < 0.001), gestural (27.4% vs 94.0%, p < 0.001), oro-alimentary (32.3% vs 75.5%, p < 0.001) or verbal automatisms (12.9% vs 36.0%, p = 0.001). The classifier had a positive predictive value of 0.889, a sensitivity of 0.727, a specificity of 0.962, a negative predictive value of 0.893.Conclusions: Medically treated seizure-free MTLE-HS patients exhibit a distinct clinical profile. A classifier built with readily available clinical data can identify them accurately with excellent positive predictive value. This may help to individualize the management of MTLE-HS patients according to their expected pharmacosensitivity.

International audience; Background and purpose - A clinical risk score for sudden unexpected death in epilepsy (SUDEP) in patients with drug-resistant focal epilepsy could help improve prevention. Methods - A case-control study was conducted including (i) definite or probable SUDEP cases collected by the French National Sentinel Mortality Epilepsy Network and (ii) control patients from the French national research database of epilepsy monitoring units. Patients with drug-resistant focal epilepsy were eligible. Multiple logistic regressions were performed. After sensitivity analysis and internal validation, a simplified risk score was developed from the selected variables. Results - Sixty-two SUDEP cases and 620 controls were included. Of 21 potential predictors explored, seven were ultimately selected, including generalized seizure frequency (>1/month vs.

High-frequency cortical electrical stimulations (HF-CES) are the gold standard for presurgical functional mapping. In the dominant ventral temporal cortex (VTC) HF-CES can elicit transient naming impairment (eloquent sites), defining a basal temporal language area (BTLA).Whether naming impairments induced by HF-CES within the VTC are related to a specific pattern of connectivity of the BTLA within the temporal lobe remains unknown. We addressed this issue by comparing the connectivity of eloquent and non-eloquent sites from the VTC using cortico-cortical evoked potentials (CCEP).Low frequency cortical electrical stimulations (LF-CES) were used to evoke CCEP in nine individual brains explored with Stereo-Electroencephalography. We compared the connectivity of eloquent versus non eloquent sites within the VTC using Pearson's correlation matrix.Overall, within the VTC, eloquent sites were associated with increased functional connectivity compared to non-eloquent sites. Among the VTC structures, this pattern holds true for the inferior temporal gyrus and the parahippocampal gyrus while the fusiform gyrus specifically showed a high connectivity in both non eloquent and eloquent sites.Our findings suggest that the cognitive effects of focal HF-CES are related to the functional connectivity properties of the stimulated sites, and therefore to the disturbance of a wide cortical network. They further suggest that functional specialization of a cortical region emerges from its specific pattern of functional connectivity. Cortical electrical stimulation functional mapping protocols including LF coupled to HF-CES could provide valuable data characterizing both local and distant functional architecture.

Epileptic spasms (ES) are common in tuberous sclerosis complex (TSC). However, the underlying network alterations and relationship with epileptogenic tubers are poorly understood. We examined interictal functional connectivity (FC) using stereo-electroencephalography (SEEG) in patients with TSC to investigate the relationship between tubers, epileptogenicity, and ES.We analyzed 18 patients with TSC who underwent SEEG (mean age = 11.5 years). The dominant tuber (DT) was defined as the most epileptogenic tuber using the epileptogenicity index. Epileptogenic zone (EZ) organization was quantitatively separated into focal (isolated DT) and complex (all other patterns). Using a 20-min interictal recording, FC was estimated with nonlinear regression, hSix patients had ES as a current seizure type at time of SEEG. ES patients had a greater number of tubers with a fluid-attenuated inversion recovery hypointense center (p .001), and none had TSC1 mutations. The presence of ES was independently associated with increased FC within both intrazone (p = .033) and interzone (p = .011) networks. Post hoc analyses identified that increased FC was associated with ES across tuber and nontuber networks. EZ organization and epileptogenicity biomarkers were not associated with FC.Increased cortical synchrony among both tuber and nontuber networks is characteristic of patients with ES and independent of both EZ organization and tuber epileptogenicity. This further supports the prospect of FC biomarkers aiding treatment paradigms in TSC.

The study included 107 right-handed patients that had undergone a presurgical interictalIncreased metabolic connectivity was observed in the IA compared to the IA group within the operated temporal lobe (respective clusters of 7.5 vs 3.3 cmMetabolic connectivity is associated with outcome in surgically treated TLE with a strengthened epileptogenic connectome in patients with non-free-seizure outcomes. The added value of seed correlation analysis in left TLE underlines the importance of evaluating metabolic connectivity in network related diseases.

Electrophysiological deficits in the visual cortical processing are reported in schizophrenia. Specifically, studies support the hypothesis of a magnocellular impairment in the psychiatric illness. However, recent findings reported electrophysiological anomalies as early as retina. Hence, question arises about the link between these retinal and cortical alterations, especially during magnocellular biased conditions among patients with schizophrenia. Their association with visual symptoms such as visual hallucinations was also investigated in this population. We recorded the P100 amplitude and latency in EEG during the projection of low or high spatial frequency gratings (LSF or HSF ; 0.5 or 15 cycles/degree) presented statically or dynamically (Temporal Frequency TF : 0Hz or 8Hz). We recruited 29 healthy controls (HC, n = 29) and 21 patients with schizophrenia (SZ, n = 21) divided in two subgroups according to the presence or absence of history of visual hallucinations : VH group (n = 9) and auditory hallucinations or no hallucinations group (AHNH group, n = 12). We compared P100 results to former results regarding retinal ganglion cells activity (N95) and visual cognition performances in participants 1. Data were compared between groups by repeated measures ANCOVA, linear regression analyses and mediation analyses. First, analysis showed a decreased P100 amplitude and an increased P100 latency in SZ compared to HC (p

International audience; Identifying factors whose fluctuations are associated with choice inconsistency is a major issue for rational decision theory. Here, we investigated the neuro-computational mechanisms through which mood fluctuations may bias human choice behavior. Intracerebral EEG data were collected in a large group of subjects (n=30) while they were performing interleaved quiz and choice tasks that were designed to examine how a series of unrelated feedbacks affect decisions between safe and risky options. Neural baseline activity preceding choice onset was confronted first to mood level, estimated by a computational model integrating the feedbacks received in the quiz task, and then to the weighting of option attributes, in a computational model predicting risk attitude in the choice task. Results showed that (1) elevated broadband gamma activity (BGA) in the ventromedial prefrontal cortex (vmPFC) and dorsal anterior insula (daIns) was respectively signaling periods of high and low mood, (2) increased vmPFC and daIns BGA respectively promoted and tempered risk taking by overweighting gain vs. loss prospects. Thus, incidental feedbacks induce brain states that correspond to different moods and bias the evaluation of risky options. More generally, these findings might explain why people experiencing positive (or negative) outcome in some part of their life tend to expect success (or failure) in any other.

International audience; In contrast to short-term cognitive outcomes, long-term cognitive outcomes (over 5 years) has been scarcely assessed so far. Yet, predicting long-term outcomes at any time point of the epilepsy, from initial diagnosis, to medically intractability is very important for therapeutic decision-making, patient information, and orientation. Assessing long-term cognitive outcomes in patients with epilepsy would ideally require longitudinal studies and a comparison with a healthy controls group. This issue has been addressed extensively, but with controversial results. However, there is a general consensus about the fact that cognitive outcome is not the same in all groups of patients with epilepsy. Possible prognostic factors include age at onset, duration of epilepsy, syndrome and etiology, seizure outcome and therapeutics. The multiplicity of factors makes it very difficult to assess their relative weight in individuals. Although long-term cognitive outcome studies are scarce, this issue has been specifically studied in newly diagnosed epilepsies and in focal drug-resistant epilepsies. In the first clinical setting, i.e. newly diagnosed epilepsy, it appears that cognitive deficits are already present at epilepsy onset in a significant proportion of patients but seem to remain stable over time. In focal drug-resistant epilepsies, cognitive deficits (mainly verbal memory) were generally shown to remain stable provided that seizures were controlled either by medication or by surgery. Beyond the possible correlation between seizure and cognitive outcome, no causal link however has been demonstrated between these two important outcomes.

International audience; Interictal electrical source imaging (ESI) encompasses a risk of false localization due to complex relationships between irritative and epileptogenic networks. This study aimed to compare the localizing value of ESI derived from ictal and inter-ictal EEG discharges and to evaluate the localizing value of ESI according to three different subgroups: MRI lesion, presumed etiology and morphology of ictal EEG pattern. We prospectively analyzed 54 of 78 enrolled patients undergoing pre-surgical investigation for refractory epilepsy. Ictal and inter-ictal ESI results were interpreted blinded to- and subse-quently compared with stereoelectroencephalography as a reference method. Anatomical concordance was assessed at a sub-lobar level. Sensitivity and specificity of ictal, inter-ictal and ictal plus inter-ictal ESI were calculated and compared according to the different subgroups. Inter-ictal and ictal ESI sensitivity (84% and 75% respectively) and specificity (38% and 50% respectively) were not statistically different. Regarding the sensitivity, ictal ESI was never higher than inter-ictal ESI. Regarding the specificity, ictal ESI was higher than inter-ictal ESI in malformations of cortical development (MCD) (60% vs. 43%) and in MRI positive patients (49% vs. 30%). Within the ictal ESI analysis, we showed a higher specificity for ictal spikes (59%) and rhythmic discharges > 13 Hz (50%) than rhythmic discharges < 13 Hz (37%) and (ii) for MCD (60%) than in other etiologies (29%). This prospective study demonstrates the relevance of a combined interpretation of distinct inter-ictal and ictal analysis. Inter-ictal analysis gave the highest sensitivity. Ictal analysis gave the highest specificity especially in patients with MCD or a lesion on MRI.

International audience; Despite being of primary importance for fundamental research and clinical studies, the relationship between local neural population activity and scalp electroencephalography (EEG) in humans remains largely unknown. Here we report simultaneous scalp and intracerebral EEG responses to face stimuli in a unique epileptic patient implanted with 27 intracerebral recording contacts in the right occipitotemporal cortex. The patient was shown images of faces appearing at a frequency of 6 Hz, which elicits neural responses at this exact frequency. Response quantification at this frequency allowed to objectively relate the neural activity measured inside and outside the brain. The patient exhibited typical 6 Hz responses on the scalp at the right occipitotemporal sites. Moreover, there was a clear spatial correspondence between these scalp responses and intracerebral signals in the right lateral inferior occipital gyrus, both in amplitude and in phase. Nevertheless, the signal measured on the scalp and inside the brain at nearby locations showed a 10-fold difference in amplitude due to electrical insulation from the head. To further quantify the relationship between the scalp and intracerebral recordings, we used an approach correlating time-varying signals at the stimulation frequency across scalp and intracerebral channels. This analysis revealed a focused and right-lateralized correspondence between the scalp and intracerebral recordings that were specific to the face stimulation is more broadly distributed in various control situations. These results demonstrate the interest of a frequency tagging approach in characterizing the electrical propagation from brain sources to scalp EEG sensors and in identifying the cortical sources of brain functions from these recordings.

Objective\ud \ud Current concepts highlight the neurological and psychological heterogeneity of functional/dissociative seizures (FDS). However, it remains uncertain whether it is possible to distinguish between a limited number of subtypes of FDS disorders. We aimed to identify profiles of distinct FDS subtypes by cluster analysis of a multidimensional dataset without any a priori hypothesis.\ud \ud \ud \ud Methods\ud \ud We conducted an exploratory, prospective multicenter study of 169 patients with FDS. We collected biographical, trauma (childhood and adulthood traumatic experiences), semiological (seizure characteristics), and psychopathological data (psychiatric comorbidities, dissociation, and alexithymia) through psychiatric interviews and standardized scales. Clusters were identified by the Partitioning Around Medoids method. The similarity of patients was computed using Gower distance. The clusters were compared using analysis of variance, chi-squared, or Fisher exact tests.\ud \ud \ud \ud Results\ud \ud Three patient clusters were identified in this exploratory, hypothesis-generating study and named on the basis of their most prominent characteristics:\ud \ud 1. A “No/Single Trauma” group (31.4%), with more male patients, intellectual disabilities, and nonhyperkinetic seizures, and a low level of psychopathology;\ud \ud 2. A “Cumulative Lifetime Traumas” group (42.6%), with clear female predominance, hyperkinetic seizures, relatively common comorbid epilepsy, and a high level of psychopathology; and\ud \ud 3. A “Childhood Traumas” group (26%), commonly with comorbid epilepsy, history of childhood sexual abuse (75%), and posttraumatic stress disorder, but also with a high level of anxiety and dissociation.\ud \ud Significance\ud \ud Although our cluster analysis was undertaken without any a priori hypothesis, the nature of the trauma history emerged as the most important differentiator between three common FDS disorder subtypes. This subdifferentiation of FDS disorders may facilitate the development of more specific therapeutic programs for each patient profile.

International audience; The objective of this clinical practice guideline is to provide recommendations on the indications and minimum standards for inpatient long-term video-electroencephalographic monitoring (LTVEM). The Working Group of the International League Against Epilepsy and the International Federation of Clinical Neurophysiology develop guidelines aligned with the Epilepsy Guidelines Task Force. We reviewed published evidence using The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. We found limited high-level evidence aimed at specific aspects of diagnosis for LTVEM performed to evaluate patients with seizures and nonepileptic events (see Table S1). For classification of evidence, we used the Clinical Practice Guideline Process Manual of the American Academy of Neurology. We formulated recommendations for the indications, technical requirements, and essential practice elements of LTVEM to derive minimum standards used in the evaluation of patients with suspected epilepsy using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Further research is needed to obtain evidence about long-term outcome effects of LTVEM and establish its clinical utility.

Background Psychogenic non epileptic seizures (PNES) are a frequent, disabling and costly disorder for which there is no consensual caring. They are considered as a dissociative disorder and they share many common characteristics with post-traumatic stress disorder (PTSD). Nevertheless, their pathophysiology is still unclear. In this study, we plan to obtain new data comparing functional brain activity of participants suffering from PNES, from PTSD and healthy controls via functional brain MRI during resting state and under emotional visual stimulation. The protocol presented hereunder describes an observational study with no direct treatment implication. Nevertheless, it could lead to a better understanding of PNES and to identifying targets for specialised cares of post-traumatic or dissociative disorders, like repetitive transcranial magnetic stimulation. Methods & analysis This is a prospective, single-centre, interventional, non-randomized, open, controlled and exploratory clinical study. It will involve 75 adult French, right-handed women in 3 groups, either suffering from PNES or PTSD, or healthy controls. An informed consent will be signed by each participant. All of them will be given psychiatric tests to assess dissociation and alexithymia, psychopathological profile and history, and emotional recognition. Each participant will undergo a functional brain MRI. We will record anatomical images and five functional imaging sequences including emotional periodic oscillatory stimulation, standard emotional stimulation, Go / No Go task under emotional stimulation, and resting state. Analysis will include a descriptive analysis of all participants and the treatment for functional magnetic resonance imaging images of each sequence. Registration, ethics & dissemination This study was approved the regional Protection of Persons Committee under the reference 16.10.01 and by the French National Medical Security Agency under the reference 2016-A01295-46. The protocol and results will be published in peer-reviewed academic medical journals and disseminated to research teams, databases, specialised media and concerned patients’ organisations.

In vivo intracranial recordings of neural activity offer a unique opportunity to understand human brain function. Intracranial electrophysiological (iEEG) activity related to sensory, cognitive or motor events manifests mostly in two types of signals: event-related local field potentials in lower frequency bands (30 Hz, High frequency, HF). While most current studies rely exclusively on HF, thought to be more focal and closely related to spiking activity, the relationship between HF and LF signals is unclear, especially in human associative cortex. Here we provide a large-scale in-depth investigation of the spatial and functional relationship between these 2 signals based on intracranial recordings from 121 individual brains (8000 recording sites). We measure selective responses to complex ecologically salient visual stimuli – human faces - across a wide cortical territory in the ventral occipito-temporal cortex (VOTC), with a frequency-tagging method providing high signal-to-noise ratio (SNR) and the same objective quantification of signal and noise for the two frequency ranges. While LF face-selective activity has higher SNR across the VOTC, leading to a larger number of significant electrode contacts especially in the anterior temporal lobe, LF and HF display highly similar spatial, functional, and timing properties. Specifically, and contrary to a widespread assumption, our results point to nearly identical spatial distribution and local spatial extent of LF and HF activity at equal SNR. These observations go a long way towards clarifying the relationship between the two main iEEG signals and reestablish the informative value of LF iEEG to understand human brain function.

Purpose: Anxiety and depression are highly prevalent in patients with epilepsy (PWE), and these symptoms can even precede the onset of the pathology. We aimed to define the prevalence of anxiety and depressive symptoms at the time of the epilepsy diagnosis and the factors related to their presence in newly diagnosed adult patients.Methods: One hundred and twelve newly diagnosed patients were assessed, usually in the week after diagnosis. Patients were untreated at this time. We used the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E, cut-off ≥15) and the Generalized Anxiety Disorder 7-Item scale (GAD-7, cut-off >7). A semi-structured interview was conducted to collect sociodemographic and epilepsy data and patients' psychiatric history. We first compared patients with and without anxiety symptoms, then patients with and without depressive symptoms.Results: According to the GAD-7 scale, the prevalence of anxiety symptoms at the time of diagnosis was 35%. Patients with anxiety symptoms had significantly more psychiatric history (26%, p = 0.001) and more history of psychological trauma (51%, p = 0.003) than patients with no anxiety symptoms. According to the NDDI-E scores, the prevalence of depressive symptoms at the time of the diagnosis was 11%. Patients with depressive symptoms had significantly more psychiatric history (43%, p < 0.001) and more history of psychological trauma (65%, p = 0.007) than patients with no depressive symptoms. No difference between groups was found for other sociodemographic variables (age and gender), epilepsy characteristics (number of seizures prior to diagnosis, time from first seizure to diagnosis, type of epilepsy, and localization in focal epilepsy), or neurological comorbidities.Conclusions: Anxiety symptoms are common whereas depressive symptoms are less prevalent at the time of diagnosis. It appears essential to be aware of anxiety and depression in newly diagnosed epileptic patients. They should be screened and routinely monitored, especially those patients with a history of psychological trauma and/or psychiatric disorders. Longitudinal follow-up is required to identify whether these factors and anxiety and depression themselves have an impact on the future course of care.

Objective: The present study aimed to evaluate the prevalence of traumatic experienced seizures (TES) and of postepileptic seizure PTSD (PS-PTSD) in patients with pharmacoresistant focal epilepsy and to explore the determining factors of TES.Methods: We conducted an observational study enrolling 107 adult refractory epilepsy patients. We used the DSM-5 criteria of traumatic events and PTSD to define TES and PS-PTSD. We assessed all traumatic life events unrelated to epilepsy, general and specific psychiatric comorbidities, and quality of life.Results: Nearly half (n = 48) of the 107 participants reported at least one TES (44.85%). Among these, one-third (n = 16) developed PS-PTSD. The TES group was more likely to experience traumatic events unrelated to epilepsy (p < 0.001), to have generalized anxiety disorder (p = 0.019), and to have specific psychiatric comorbidities [e.g., interictal dysphoric disorder (p = 0.024) or anticipatory anxiety of seizures (p = 0.005)]. They reported a severe impact of epilepsy on their life (p = 0.01). The determining factors of TES according to the multifactorial model were the experience of trauma (p = 0.008), a history of at least one psychiatric disorder (p = 0.03), and a strong tendency toward dissociation (p = 0.03).Significance: Epileptic seizures may be a traumatic experience in some patients who suffer from pharmacoresistant epilepsy and may be the source of the development of PS-PTSD. Previous trauma unrelated to epilepsy and psychiatric history are determining factors of TES. These clinical entities should be explored systematically.

International audience; Objective: The stereo electroencephalogram (SEEG) recordings are the sate of the art tool used in pre-surgical evaluation of drug-unresponsive epileptic patients. Coupled with SEEG, electrical cortical stimulation (CS) offer a complementary tool to investigate the lesioned/healthy brain regions and to identify the epileptic zones with precision. However, the propagation of this stimulation inside the brain masks the cerebral activity recorded by nearby multi-contact SEEG electrodes. The objective of this paper is to propose a novel filtering approach for suppressing the CS artifact in SEEG signals using time, frequency as well as spatial information.Methods: The method combines spatial filtering with tunable-Q wavelet transform (TQWT). SEEG signals are spatially filtered to isolate the CS artifacts within a few number of sources/components. The artifacted components are then decomposed into oscillatory background and sharp varying transient signals using tunable-Q wavelet transform (TQWT). The CS artifact is assumed to lie in the transient part of the signal. Using prior known time-frequency information of the CS artifacts, we selectively mask the wavelet coefficients of the transient signal and extract out any remaining significant electro-physiological activity.Results: We have applied our proposed method of CS artifact suppression on simulated and real SEEG signals with convincing performance. The experimental A. Bhattacharyya 2 results indicate the effectiveness of the proposed approach.Conclusion: The proposed method suppresses CS artifacts without affecting the background SEEG signal. Significance: The proposed method can be applied for suppressing both low and high frequency CS artifacts and outperforms current methods from the literature. Index Terms cortical stimulation, SEEG, tunable-Q wavelet transform, subspace correlation approach, blind source separation.

International audience; The supplementary motor area (SMA) has been shown to be involved in interval timing but its precise role remains a matter of debate. The present study was aimed at examining, by means of intracerebral EEG recordings, the time course of the activity in this structure, as well as in other functionally connected cortical (frontal, cingulate, insular and temporal) areas, during a visual time reproduction task. Four patients undergoing stereo-electroencephalography (SEEG) for presurgical investigation of refractory focal epilepsy were enrolled. They were selected on the presence of depth electrodes implanted within the SMA. They were instructed to encode, keep in memory and then reproduce the duration (3, 5 and 7 s) of emotionally-neutral or negative pictures. Emotional stimuli were used with the aim of examining neural correlates of temporal distortions induced by emotion. Event-related potentials (ERPs) were analyzed during three periods: During and at the extinction of the target interval (TI) and at the beginning of the reproduction interval (RI). Electrophysiological data revealed an ERP time-locked to TI-offset whose amplitude varied monotonically with TI-duration. This effect was observed in three out of the four patients, especially within the SMA and the insula. It also involved the middle and anterior cingulate cortex, the superior, middle and inferior frontal gyri and the paracentral lobule. These effects were modulated by the prior TI-duration and predicted variations in temporal reproduction accuracy. In contrast, modulations of ERPs with TI-duration, emotion or temporal performance during the target or the reproduction interval were modest and less consistent across patients. These results demonstrate that, during reproduction of supra-second time intervals, the SMA, in concert with a fronto-insular network, is involved at the end of the target interval, and suggest a role in the duration categorization and decision making operations or alternatively in the preparedness of the timing of the future movement that will be executed during the reproduction phase.

Previous researches have shown that the inferior frontal gyrus (IFG) is involved in time and numerosity processing. This study aimed at examining (i) interval timing and (ii) interaction between duration and numerosity processing in four drug-resistant epileptic patients with postoperative lesions in the IFG in comparison with thirteen healthy controls. The duration reproduction and discrimination tasks performed in the sub- and supra-second ranges did not reveal any significant differences between patients and controls. The duration discrimination task of stimuli varying in numerosity (DurN) and the numerosity discrimination task of stimuli varying in duration (NumD) revealed that only numerosity judgment was altered in IFG patients. A time-order effect was notably observed in the NumD task but in opposite directions for the two groups: The second patch was perceived as more numerous than the first patch in controls and conversely as less numerous in patients. Finally in the DurN task, we observed a congruency effect which was dependent on numerical distance in patients but not in controls. These converging results suggest that the IFG would be more specifically involved in numerosity than in duration processing, possibly playing a role in numerical decision.

International audience; The objective of this clinical practice guideline is to provide recommendations on the indications and minimum standards for inpatient long-term video-electroencephalographic monitoring (LTVEM). The Working Group of the International League Against Epilepsy and the International Federation of Clinical Neurophysiology develop guidelines aligned with the Epilepsy Guidelines Task Force. We reviewed published evidence using the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) statement. We found limited high-level evidence aimed at specific aspects of diagnosis for LTVEM performed to evaluate patients with seizures and nonepileptic events. For classification of evidence, we used the Clinical Practice Guideline Process Manual of the American Academy of Neurology. We formulated recommendations for the indications, technical requirements, and essential practice elements of LTVEM to derive minimum standards used in the evaluation of patients with suspected epilepsy using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Further research is needed to obtain evidence about long-term outcome effects of LTVEM and to establish its clinical utility.

Regular cannabis using causes vision impairment by affecting human retinal neurotransmission. However, studies less considered its impact on the subsequent visual cortical processing, key feature for the integration of the visual signal in brain. We aimed at investigating this purpose in regular cannabis users using spatial frequencies and temporal frequencies filtered visual stimuli. We recruited 45 regular cannabis users and 25 age-matched controls. We recorded visual evoked potentials during the projection of low spatial frequency (0.5 cycles/degree) or high spatial frequency gratings (15 cycles/degree), which were presented statically (0 Hz) or dynamically (8 Hz). We analyzed the amplitude, latency, and area under the curve of both P100 and N170, best EEG markers for early visual processing. Data were compared between groups by repeated measures ANCOVA. Results showed a significant decrease in P100 amplitude among regular cannabis users in low spatial frequency (F(1,67) = 4.43; p = 0.04) and in dynamic condition (F(1,67) = 4.35; p = 0.04). Analysis also reported a decrease in P100 area under the curve in regular cannabis users to low spatial frequency (F(1,67) = 4.31; p = 0.04) and in dynamic condition (F(1,67) = 7.65; p 0.01). No effect was found on P100 latency, N170 amplitude, latency, or area under the curve. We found alteration of P100 responses to low spatial frequency and dynamic stimuli in regular cannabis users. This result could be interpreted as a preferential magnocellular impairment where such deficit could be linked to glutamatergic dysfunction. As mentioned in the literature, visual and electrophysiological anomalies in schizophrenia are related to a magnocellular dysfunction. Further studies are needed to clarify electrophysiological deficits in both populations. CLINICAL TRIALS REGISTRATION: Electrophysiological Study of the Functioning of Magnocellular Visual Pathway in Regular Cannabis Users (CAUSA MAP). [NCT02864680; ID 2013-A00097-38]. https://clinicaltrials.gov/ct2/show/NCT02864680?cond=Cannabiscntry=FRdraw=2rank=1.

Functional seizures (FS) known also as psychogenic non-epileptic seizures or dissociative seizures, present with ictal semiological manifestations, along with various comorbid neurological and psychological disorders. Terminology inconsistencies and discrepancies in nomenclatures of FS may reflect limitations in understanding the neuropsychiatric intricacies of this disorder. Psychological and neurobiological processes of FS are incompletely understood. Nevertheless, important advances have been made on underlying neuropsychopathophysiological mechanisms of FS. These advances provide valuable information about the underlying mechanisms of mind–body interactions. From this perspective, this narrative review summarises recent studies about aetiopathogenesis of FS at two levels: possible risk factors (why) and different aetiopathogenic models of FS (how). We divided possible risk factors for FS into three categories, namely neurobiological, psychological and cognitive risk factors. We also presented different models of FS based on psychological and neuroanatomical understanding, multilevel models and integrative understanding of FS. This work should help professionals to better understand current views on the multifactorial mechanisms involved in the development of FS. Shedding light on the different FS profiles in terms of aetiopathogenesis will help guide how best to direct therapy, based on these different underlying mechanisms.

Stereo-electroencephalography (sEEG) is a method that uses stereotactically implanted depth electrodes for extra-operative mapping of epileptogenic and functional networks. sEEG derived functional mapping is achieved using electrical cortical stimulations (ECS) that are currently the gold standard for delineating eloquent cortex. As this stands true especially for primary cortices (e.g., visual, sensitive, motor, etc.), ECS applied to higher order brain areas determine more subtle behavioral responses. While anterior and posterior language areas in the dorsal language stream seem to share characteristics with primary cortices, basal temporal language area (BTLA) in the ventral temporal cortex (VTC) behaves as a highly associative cortex. After a short introduction and considerations about methodological aspects of ECS using sEEG, we review the sEEG language mapping literature in this perspective. We first establish the validity of this technique to map indispensable language cortices in the dorsal language stream. Second, we highlight the contrast between the growing empirical ECS experience and the lack of understanding regarding the fundamental mechanisms underlying ECS behavioral effects, especially concerning the dispensable language cortex in the VTC. Evidences for considering network architecture as determinant for ECS behavioral response complexities are discussed. Further, we address the importance of designing new research in network organization of language as this could enhance ECS ability to map interindividual variability, pathology driven reorganization, and ultimately identify network resilience markers in order to better predict post-operative language deficit. Finally, based on a whole body of available studies, we believe there is strong evidence to consider sEEG as a valid, safe and reliable method for defining eloquent language cortices although there have been no proper comparisons between surgical resections with or without extra-operative or intra-operative language mapping.

Emotional expressions are quickly and automatically read from human faces under natural viewing conditions. Yet, categorization of facial expressions is typically measured in experimental contexts with homogenous sets of face stimuli. Here we evaluated how the 6 basic facial emotions (Fear, Disgust, Happiness, Anger, Surprise or Sadness) can be rapidly and automatically categorized with faces varying in head orientation, lighting condition, identity, gender, age, ethnic origin and background context. High-density electroencephalography was recorded in 17 participants viewing 50 s sequences with natural variable images of neutral-expression faces alternating at a 6 Hz rate. Every five stimuli (1.2 Hz), variable natural images of one of the six basic expressions were presented. Despite the wide physical variability across images, a significant F/5 = 1.2 Hz response and its harmonics (e.g., 2F/5 = 2.4 Hz, etc.) was observed for all expression changes at the group-level and in every individual participant. Facial categorization responses were found mainly over occipito-temporal sites, with distinct hemispheric lateralization and cortical topographies according to the different expressions. Specifically, a stronger response was found to Sadness categorization, especially over the left hemisphere, as compared to Fear and Happiness, together with a right hemispheric dominance for categorization of Fearful faces. Importantly, these differences were specific to upright faces, ruling out the contribution of low-level visual cues. Overall, these observations point to robust rapid and automatic facial expression categorization processes in the human brain.

Objective Fear of having a seizure called anticipatory anxiety of epileptic seizure (AAS), constitutes a daily life burden but has been rarely studied. Our aim was to assess the prevalence and the determining factors of AAS in patients with drug-resistant focal epilepsy, a dimension that has not been thoroughly investigated before. Methods We conducted an observational, prospective study enrolling patients with drug-resistant focal epilepsy. The psychiatric assessment aimed to evaluate psychiatric comorbidities, trauma history, and quality of life using hetero-evaluation and self-assessment tools. Dimensions of anxiety specifically related to epilepsy (peri-and-inter-ictal) were explored as exhaustively as possible. Results AAS was found in 53 % of the 87 patients. We compared the two groups of patients: with or without AAS. Patients with AAS had a significantly shorter duration of epilepsy (p = 0.04). There was no difference between groups with respect to psychiatric disorders, except for cannabis dependence, more frequent in patients with AAS (p = 0.02). Compared to patients without AAS, those with AAS presented more subjective ictal anxiety (p = 0.0003) and postictal anxiety (p = 0.02), were more likely to avoid outdoor social situations due to seizure fear (p = 0.001), and had a poorer quality of life (QOLIE emotional well-being; p = 0.03). Additionally, they had experienced more traumatic events in their lifetime (p = 0.005) and reported more frequently a feeling of being unsafe during their seizures (p = 0.00002). Significance AAS is a specific dimension of anxiety, possibly linked to trauma history. AAS is strongly linked to subjective ictal anxiety but not to the objective severity of seizures or frequency.

Epilepsy presurgical investigation may include focal intracortical single-pulse electrical stimulations with depth electrodes, which induce cortico-cortical evoked potentials at distant sites because of white matter connectivity. Cortico-cortical evoked potentials provide a unique window on functional brain networks because they contain sufficient information to infer dynamical properties of large-scale brain connectivity, such as preferred directionality and propagation latencies. Here, we developed a biologically informed modelling approach to estimate the neural physiological parameters of brain functional networks from the cortico-cortical evoked potentials recorded in a large multicentric database. Specifically, we considered each cortico-cortical evoked potential as the output of a transient stimulus entering the stimulated region, which directly propagated to the recording region. Both regions were modelled as coupled neural mass models, the parameters of which were estimated from the first cortico-cortical evoked potential component, occurring before 80 ms, using dynamic causal modelling and Bayesian model inversion. This methodology was applied to the data of 780 patients with epilepsy from the F-TRACT database, providing a total of 34 354 bipolar stimulations and 774 445 cortico-cortical evoked potentials. The cortical mapping of the local excitatory and inhibitory synaptic time constants and of the axonal conduction delays between cortical regions was obtained at the population level using anatomy-based averaging procedures, based on the Lausanne2008 and the HCP-MMP1 parcellation schemes, containing 130 and 360 parcels, respectively. To rule out brain maturation effects, a separate analysis was performed for older (>15 years) and younger patients (

International audience; Background: Epilepsy seems to be an important comorbidity in patients with early onset Alzheimer’s disease (EOAD). Currently, seizures are still underestimated in this population. However, seizures may interact with AD evolution with possible acceleration of cognitive decline. Objective: To better define the epileptic disorders observed in patients with EOAD. Methods: All patients diagnosed as EOAD in our hospital between 2013 and 2019 with positive CSF biomarkers for AD were selected. The usual follow-up was extended with a 3-h EEG and a consultation with an epilepsy expert. Information on epilepsy and AD were collected and analyzed. Results: Among the 25 included patients, 10 (40%) were classified as epileptic. Seizure types were tonic-clonic (25%), typical temporal seizures (25%), myoclonus (25%), focal extra-temporal seizures (8%), and other seizure types (17%). AD-E patients had a significant lower MMSE (15.3±8.4 AD-E versus 22.1±5.1 AD-NE, p = 0.036) and a lower autonomy (IADL 4.1±2.7 AD-E versus 6.4±1.9 AD-NE, p = 0.046) at AD diagnosis with comparable ages between AD-E and AD-NE. Epileptic patients seemed to present a faster cognitive decline ([ΔMMSE per year 1.7±1.3 AD-E versus 0.9±1.4 AD-NE; p = 0.09). All patients with severe cognitive impairment (MMSE ≤ 10) had an epileptic comorbidity. Conclusion: Epilepsy is a frequent comorbidity in EOAD patients, with a percentage of 40%in our study. This comorbidity may be associated with a severe form of EOAD. The role of epilepsy in the acceleration of cognitive decline and the positive impact of antiepileptic drugs on cognition need further research.

Summary Both mild and severe epilepsies are influenced by variants in the same genes, yet an explanation for the resulting phenotypic variation is unknown. As part of the ongoing Epi25 Collaboration, we performed a whole-exome sequencing analysis of 13,487 epilepsy-affected individuals and 15,678 control individuals. While prior Epi25 studies focused on gene-based collapsing analyses, we asked how the pattern of variation within genes differs by epilepsy type. Specifically, we compared the genetic architectures of severe developmental and epileptic encephalopathies (DEEs) and two generally less severe epilepsies, genetic generalized epilepsy and non-acquired focal epilepsy (NAFE). Our gene-based rare variant collapsing analysis used geographic ancestry-based clustering that included broader ancestries than previously possible and revealed novel associations. Using the missense intolerance ratio (MTR), we found that variants in DEE-affected individuals are in significantly more intolerant genic sub-regions than those in NAFE-affected individuals. Only previously reported pathogenic variants absent in available genomic datasets showed a significant burden in epilepsy-affected individuals compared with control individuals, and the ultra-rare pathogenic variants associated with DEE were located in more intolerant genic sub-regions than variants associated with non-DEE epilepsies. MTR filtering improved the yield of ultra-rare pathogenic variants in affected individuals compared with control individuals. Finally, analysis of variants in genes without a disease association revealed a significant burden of loss-of-function variants in the genes most intolerant to such variation, indicating additional epilepsy-risk genes yet to be discovered. Taken together, our study suggests that genic and sub-genic intolerance are critical characteristics for interpreting the effects of variation in genes that influence epilepsy.

International audience; Patients with chronic mesial temporal lobe epilepsy have difficulties at identifying familiar faces as well as at explicit old/new face recognition tasks. However, the extent to which these difficulties can be attributed to visual individuation of faces, independently of general explicit learning and semantic memory processes, is unknown. We tested 42 mesial temporal lobe epilepsy patients divided into two groups according to the side of epilepsy (left and right) and 42 matched controls on an extensive series of individuation tasks of unfamiliar faces and control visual stimuli, as well as on face detection, famous face recognition and naming, and face and non-face learning. Overall, both patient groups had difficulties at identifying and naming famous faces, and at explicitly learning face and non-face images. However, there was no group difference in accuracy between patients and controls at the two most widely used neuropsychological tests assessing visual individuation of unfamiliar faces (Benton Facial Recognition Test and Cambridge Face Memory Test). While patients with right mesial temporal lobe epilepsy were slowed down at all tasks, this effect was not specific to faces or even high-level stimuli. Importantly, both groups showed the same profile of response as typical participants across various stimulus manipulations, showing no evidence of qualitative processing impairments. Overall, these results point to largely preserved visual face individuation processes in patients with mesial temporal lobe epilepsy, with semantic and episodic memory difficulties being consistent with the localization of the neural structures involved in their epilepsy (anterior temporal cortex and hippocampus). These observations have implications for the prediction of neuropsychological outcomes in the case of surgery and support the validity of intracranial electroencephalographic recordings performed in this population to understand neural mechanisms of human face individuation, notably through intracranial electrophysiological recordings and stimulations.

International audience; Purpose: Recent etiopathogenic models place emotional dysregulation at the core of psychogenic nonepileptic seizure (PNES). Our purpose was to assess physiological, cognitive, and behavioral emotional responses of PNES patients.Methods: This study compared three types of emotional responses to visual emotional stimuli between 34 female PNES group and 34 matched healthy controls: physiological response measured by skin conductance response (SCR) (rate, amplitude and latency) and heart rate deceleration; cognitive response measured by valence and arousal elicited by the images; and behavioural response measured by latency of ratings. The groups were characterized on psychiatric comorbidities, traumatic history, alexithymia, and dissociation.Results: Compared to controls, PNES group displayed lower SCR for all images (p = 0.038), shorter amplitude of heart rate deceleration (p = 0.024) and faster arousal rating for all images (p = 0.019), but no difference on cognitive rating of images. Within-groups analyses showed only in PNES subjects increased rate (+19.35%, p = 0.046) SCR for negative stimuli with strong arousal compared to negative with low arousal. PNES physiological response (SCR and heart rate deceleration) was negatively correlated to dissociation tendency (r=-0.48, p = 0.0083) and alexithymia (r=-0.44, p = 0.012)). For cognitive response, no correlation was found.Conclusion: These results are in favour of a lower physiological emotional response but with an over-reactivity at behavioral level contrasting with similar cognitive assessment. For strong aversive stimuli, PNES might present a trend to overreact at physiological and behavioural levels. Our results suggest that dissociation and difficulty in describing feelings are associated with an altered physiological response in PNES women only.

International audience; In March 2020, we treated a cohort of 26 critically ill hospitalized SARS-CoV-2-infected patients who underwent electroencephalography to assess unexplained altered mental status, loss of consciousness, or poor arousal and responsiveness. Of the 26 patients studied, 5 patients had electroencephalograms that showed periodic discharges consisting of high-amplitude frontal monomorphic delta waves with absence of epileptic activity. These findings may suggest central nervous system injury potentially related to COVID-19 in these patients. ANN NEUROL 2020.

International audience; Objective: The purpose of this prospective study was to identify predictive factors of the evolution of the number of seizures.Methods: We included 85 individuals with a diagnosis of Psychogenic Nonepileptic Seizure (PNES) who completed at least two clinical interviews spaced by 6 months during a 24-month follow-up. Participants underwent a structured interview with an experimented clinician in PNES to complete standardized evaluation and validated scales. We collected sociodemographic and clinical data on PNES (number of seizures, duration of the disease), anxiety, depression, history of traumas, alexithymia, dissociation, and post-traumatic stress disorder (PTSD). We used a multivariate linear regression analysis to predict the characteristics independently associated with the evolution of the number of seizures in percentage.Results: Dissociation score was significantly associated with a negative evolution of the number of seizures (p < 0.002). Conversely, the diagnosis of PTSD at inclusion was correlated to a positive evolution of the number of seizures (p < 0.029).Conclusion: Dissociation was related to a more pejorative evolution of the number of seizures while PTSD diagnosis was associated with a decreased number of seizures. It is therefore essential to improve detection and treatment of post-traumatic dissociation. Further studies are required to understand the impact of PTSD on the evolution of the number of seizures.