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Epileptic seizures and interictal epileptiform discharges (IEDs) are strongly influenced by sleep and circadian rhythms. However, human data on the effect of sleep on neuronal behavior during interictal activity have been lacking. We analyzed EEG data from epileptic patients implanted with macro and micro electrodes targeting mesial temporal structures. Sleep staging was performed on concomitantly recorded polysomnography and video-EEG. Automated IED detection identified thousands of IEDs per patient. Both the rate and amplitude of IEDs were increased with deeper stages of NREM sleep. Single unit activity (SUA) and multi-unit activity (MUA) increased their firing during the IED spike, and strongly decreased during the subsequent slow wave. These time-locked firing rate modulations were shown to increase during deeper stages of NREM sleep. Finally, during resting behaviour, neuronal firing rate, bursting rate and firing regularity were all shown to progressively decrease with deeper stages of NREM sleep.

Forecasting seizure risk aims to detect pro-ictal states in which seizures would be more likely to occur. Classical seizure prediction models are trained over long-term EEG recordings to detect specific preictal changes for each seizure, independently of those induced by shifts in states of vigilance. A daily single measure - during a vigilance-controlled period - to estimate the risk of upcoming seizure(s) would be more convenient. Here, we evaluated whether intracranial EEG connectivity (phase-locking value), estimated from daily vigilance-controlled resting-state recordings, could allow to distinguish interictal (no seizure) from preictal (seizure within the next 24hrs) states. We also assessed its relevance for daily forecasts of seizure risk using machine learning models. Connectivity in the theta band was found to provide best prediction performances (AUC≥0.7 in 80% of patients), with accurate daily and prospective probabilistic forecasts (mean Brier and skill Brier scores of 0.11 and 0.74, respectively). More efficient ambulatory clinical application could be considered using mobile EEG or chronic implanted devices.

Studies investigating the neural processing of musico-acoustic features have tended to do so using highly controlled musical stimuli. However, it is increasingly argued that failing to use naturalistic stimuli limits the extent to which findings from lab studies can be extrapolated to rich and varied real-world experiences. Here, we recorded electrical brain activity from 8 epileptic patients, implanted for pre-surgical evaluation with Stereo-encephalography (SEEG), while they listened to pieces from the western tonal music repertoire. We estimated the sound intensity and key and pulse clarity of the stimuli using a toolbox for automatic extraction of musico-acoustic features. We then used partial-correlation analyses to examine the patterns of neuro-oscillatory activity associated with the processing of these features. Our results showed clear tracking of sound intensity in high-gamma and alpha frequency bands in posterior superior temporal gyrus, reflecting neural firing and the transfer of auditory information from the thalamus to auditory cortices, respectively. Patterns of partial correlations, in line with our hypotheses, also suggested limbic and inferior frontal cortical tracking of tonal and rhythmic uncertainty, albeit without the robustness shown for sound intensity tracking in auditory areas. The study provides an important contribution to the existing literature in its adherence to the call for a greater use of ecologically valid stimuli in neuroscientific investigations of music listening. Our results, specifically, have implications for research on the neural processing of musical uncertainty and for future studies seeking to use intracranial EEG to examine naturalistic music processing.

Brain sensory processing is not passive, but is rather modulated by our internal state. Different research methods such as non-invasive imaging methods and intracranial recording of the local field potential (LFP) have been used to study to what extent sensory processing and the auditory cortex in particular are modulated by selective attention. However, at the level of the single- or multi-units the selective attention in humans has not been tested. In addition, most previous research on selective attention has explored externally-oriented attention, but attention can be also directed inward (i.e., internal attention), like spontaneous self-generated thoughts and mind-wandering. In the present study we had a rare opportunity to record multi-unit activity (MUA) in the auditory cortex of a patient. To complement, we also analyzed the LFP signal of the macro-contact in the auditory cortex. Our experiment consisted of two conditions with periodic beeping sounds. The participants were asked either to count the beeps (i.e., an "external attention" condition) or to recall the events of the previous day (i.e., an "internal attention" condition). We found that the four out of seven recorded units in the auditory cortex showed increased firing rates in "external attention" compared to "internal attention" condition. The beginning of this attentional modulation varied across multi-units between 30-50 msec and 130-150 msec from stimulus onset, a result that is compatible with an early selection view. The LFP evoked potential and induced high gamma activity both showed attentional modulation starting at about 70-80 msec. As the control, for the same experiment we recorded MUA activity in the amygdala and hippocampus of two additional patients. No major attentional modulation was found in the control regions. Overall, we believe that our results provide new empirical information and support for existing theoretical views on selective attention and spontaneous self-generated cognition.

Focal neuronal lipofuscinosis (FNL) is an uncommon epileptic disorder related to an excess of lipofuscin accumulation within dysmorphic-appearing neurons (DANs), whose epileptogenic mechanisms are still poorly understood. It shares some clinical and neuroimaging similarities with focal cortical dysplasia of type IIb (FCDIIb), but it represents a different pathological entity. Here, we identified two patients with FNL among a 10-year cohort of 323 patients who underwent neurosurgery for a focal pharmacoresistant epilepsy. We describe the electroclinical, metabolic and neuropathological features of both patients with FNL who benefited from a comprehensive presurgical investigation. While the previous reports showed frontal lobe localization of the lesion, FNL was identified in the temporal lobe, in one of our patients. EEG investigations in both patients showed striking focal and rich interictal activity resembling that described in FCDIIb. Besides focal intraneuronal lipofuscin accumulation, the neuropathological analysis demonstrated that somata of DANs were surrounded by a large amount of GABAergic presynaptic buttons, suggesting the involvement of interneurons in the epileptogenicity of FNL. To further explore the role of GABAergic transmission in the generation of epileptiform activity in FNL, we performed in vitro multi-electrode array recordings on the post-surgery tissue from one patient. Spontaneous interictal-like discharges (IILDs) were identified only in the restricted area displaying the highest density of lipofuscin-containing DANs, suggesting a close correlation between the density of lipofuscin-containing neurons and epileptogenicity. Moreover, IILDs were blocked by the GABAA receptor antagonist gabazine. All together, these findings showed how GABA signaling may contribute to the generation of interictal-like activity in FNL tissue.

The stimulus-evoked neural response is a widely explored phenomenon. Conscious awareness is associated in many cases with the corresponding selective stimulus-evoked response. For example, conscious awareness of a face stimulus is associated with or accompanied by stimulus-evoked activity in the fusiform face area (FFA). In addition to the stimulus-evoked response, spontaneous (i.e. task-unrelated) activity in the brain is also abundant. Notably, spontaneous activity is considered unconscious. For example, spontaneous activity in the FFA is not associated with conscious awareness of a face. The question is: what is the difference at the neural level between stimulus-evoked activity in a case that this activity is associated with conscious awareness of some content (e.g. activity in the FFA in response to fully visible face stimuli) and spontaneous activity in that same region of the brain? To answer this question, in the present study, we had a rare opportunity to record two face-selective multi-units in the vicinity of the FFA in a human patient. We compared multi-unit face-selective task-evoked activity with spontaneous prestimulus and a resting-state activity. We found that when activity was examined over relatively long temporal windows (e.g. 100–200 ms), face-selective stimulus-evoked firing in the recorded multi-units was much higher than the spontaneous activity. In contrast, when activity was examined over relatively short windows, we found many cases of high firing rates within the spontaneous activity that were comparable to stimulus-evoked activity. Our results thus indicate that the sustained activity is what might differentiate between stimulus-evoked activity that is associated with conscious awareness and spontaneous activity.

When we see someone's face, our brain usually effortlessly extracts a variety of information such as facial identity, expression, or gaze direction. While it is widely accepted that dedicated subsystems are responsible for different aspects of face processing, how these subsystems work together is not yet fully understood. To this extent, one of the most explored questions is whether and if so, to what extent facial expression processing interacts with other stages of facial processing. In the present study, we report a rare case of a patient for whom we were able to record multi-unit activity (MUA) in the proximity of the fusiform face area (FFA) while two out of four recorded multi-units were face-selective. In our experiment, the human subject was shown images of neutral and fearful faces as well as everyday objects and frightening images of natural disaster. We found that activity of both face-selective units was modulated by facial expression stimuli, starting at about 150 ms from stimulus onset. For both facial conditions we observed abrupt increase in firing rate with a simultaneous peak, suggesting that this activity and the modulation by facial expression stimuli likely reflected feed-forward processing. Interestingly, while in one multi-unit, the firing rate for fearful faces was higher than for neutral faces, in the other multi-units the polarity was reversed. Finally, modulation in the face-selective units was specific to emotional facial stimuli, but not to emotional stimuli in general. The present multi-unit results, albeit obtained only for several multi-units, nevertheless are potentially valuable for understanding mechanisms of facial processing in humans.

Occipito-temporal regions within the face network process perceptual and socio-emotional information, but the dynamics and interactions between different nodes within this network remain unknown. Here, we analyzed intracerebral EEG from 11 epileptic patients viewing a stimulus sequence beginning with a neutral face with direct gaze. The gaze could avert or remain direct, while the emotion changed to fearful or happy. N200 field potential peak latencies indicated that face processing begins in inferior occipital cortex and proceeds anteroventrally to fusiform and inferior temporal cortices, in parallel. The superior temporal sulcus responded preferentially to gaze changes with augmented field potential amplitudes for averted versus direct gaze, and large effect sizes relative to other regions of the network. An overlap analysis of posterior white matter tractography endpoints (from 1066 healthy brains) relative to active intracerebral electrodes from the 11 patients showed likely involvement of both dorsal and ventral posterior white matter pathways. The inferior occipital and temporal sulci likely broadcast their information - the former dorsally to intraparietal sulcus, and the latter between fusiform and superior temporal cortex. Overall, our data call for inclusion of inferior temporal cortex in face processing models, and anchor the superior temporal cortex in dynamic gaze processing.

SummaryExogenous attention, the process that makes external salient stimuli pop-out of a visual scene, is essential for survival. How attention-capturing events modulate processing dynamics in the human brain remains unclear. We obtained a comprehensive depiction of attentional cortical dynamics at high spatiotemporal resolution, by analyzing brain activity from 1,403 intracortical contacts implanted in 28 individuals, while they performed an exogenous attention task. The timing, location and task-relevance of attentional events defined a spatiotemporal gradient of three neural clusters, which mapped onto cortical core-periphery topography and presented a hierarchy of timescales, providing the scaffolding for attention temporal computations. Visual attributes modulated neural activity at one end of the gradient, while activity at the other end reflected the upcoming response timing, with attentional effects occurring at the intersection of visual and response signals. These findings reveal how the psychological construct of exogenous attention emerges over large-scale cortical gradients in the human brain.

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 (

Temporal pole epilepsy (TPE) is a poorly known and difficult to individualize subtype of temporal lobe epilepsy. Consequently, in drug-resistant TPE, there is still a debate on the need for a large surgical removal of the temporal pole and mesial temporal structures or a limited resection of the temporal pole. We reviewed all patients who underwent presurgical evaluation for drug-resistant epilepsy over a 17-year period, and report here 19 patients with proven drug-resistant temporal pole epilepsy who underwent a selective temporal pole resection with respect to mesial structures. Most (15) TPE patients exhibited seizures resembling mesiotemporal seizures, whereas the others exhibited nocturnal hyperkinetic seizures or an association of both seizure types. MRI revealed a temporal pole lesion in 58% of patients. Long-term postoperative outcome after a conservative surgery was excellent: 63% of patients were seizure-free (International League Against Epilepsy [ILAE] 1) at 1-year postsurgery and 78% at 5 years. These results show that TPE has no specific electroclinical features but is a distinct type of temporal lobe epilepsy allowing a conservative surgery. Respecting the mesiotemporal structures is a valid surgical approach for drug-resistant temporal pole epilepsy.

Objective The scope of unconscious cognition stretched its limits dramatically during the last 40 years, yet most unconscious processes and representations that have been described so far are fleeting and very short-lived, whereas conscious representations can be actively maintained in working memory for a virtually unlimited period. In the present work we aimed at exploring conscious and unconscious lasting (>1 second) expectancy effects. Methods In a series of four experiments we engaged participants in the foreperiod paradigm while using both unmasked and masked cues that were informative about the presence/absence of an upcoming target. We recorded behavioral responses, high-density scalp EEG (Exp. 2a), and intra-cranial EEG (Exp. 2b). Results While conscious expectancy was associated with a large behavioral effect (~150 ms), unconscious expectancy effect was significant but much smaller (4 ms). Both conscious and unconscious expectancy Contingent Negative Variations (CNVs) originated from temporal cortices, but only the late component of conscious CNV originated from an additional source located in the vicinity of mesio-frontal areas and supplementary motor areas. Finally, only conscious expectancy was accessible to introspection. Conclusions Both unmasked and masked cues had an impact on response times and on brain activity. Significance These results support a two-stage model of the underlying mechanisms of expectancy.

5,10-Methylene-tetrahydrofolate reductase (MTHFR) deficiency is a genetic disorder that can occur at any age and can be easily detected by increased homocysteinemia. In adolescence/adult onset forms, the clinical picture is often complex with association of various neurological features and thrombosis. Here we report the cases of two adult siblings who experienced focal epilepsy at 18 years old as a first disease manifestation, without other symptom during several years. Upon diagnosis, both patients received metabolic treatment comprising B9, B12 and betaine which has stopped the occurrence of seizures, allowing discontinuation of anti-epileptic drugs. Among 24 reviewed adolescent/adult onset patients with MTHFR deficiency in the literature, clinical manifestations included gait disorder (96%, from motor central or peripheral origin), cognitive decline (74%), epileptic syndromes (50%), encephalopathy (30%), psychotic symptoms (17%), and thrombotic events (21%). A total of 41% presented a single neurological manifestation that could stay isolated during at least 3 years, delaying achievement of the diagnosis. Brain MRI showed a mostly periventricular white matter changes in 71% of cases. All patients stabilized or improved following metabolic treatment. Despite being rare, adolescence/adult onset MTHFR deficiency can nevertheless be successfully treated. Therefore, homocysteinemia should be tested in various unexplained neuro-psychiatric syndromes like epilepsy or spastic paraparesis, even if isolated, since waiting for completion of the clinical picture is likely to increase the risk of irreversible neurological damage. Electronic supplementary material The online version of this article (10.1186/s13023-018-0767-9) contains supplementary material, which is available to authorized users.

International audience; Epileptic syndromes are distinctive disorders with specific features, which when taken together, permit a specific diagnosis. There is actually a debate on that medial temporal lobe epilepsy with hippocampal sclerosis is an epileptic syndrome. To address this issue, we searched for discriminative semiological features between temporal lobe epilepsy patients with hippocampal sclerosis (TLE-HS patients or group 1), TLE patients with medial structural lesion other than hippocampal sclerosis or in MRI-negative cases with medial onset on further investigations (group 2) and lateral TLE patients (LTLE or group 3). We retrospectively collected data from medical and EEG-video records of 523 TLE patients, referred for surgery to the Pitié-Salpêtrière Epileptology Unit between 1991 and 2014. We identified 389 patients belonging to group 1, 61 patients belonging to group 2, and 73 patients belonging to group 3 and performed a comparative analysis of their clinical data and surgical outcomes. TLE-HS patients (group 1): (1) began epilepsy earlier (11 ± 9 vs. 20 ± 10 vs. 15 ± 9 years); (2) exhibited more frequently early febrile convulsions (FC) (59 vs 7 vs 5%); (3) presented more: ictal gestural automatisms (90 vs 54 vs 67%), dystonic posturing (47 vs 20 vs 23%), and secondary generalized tonic–clonic seizures (GTCS) (70 vs 44% vs 48%) as compared to both groups 2 and 3 patients (all p < 0.001). With respect to auras, abdominal visceral auras were more reported by TLE-HS than by LTLE patients (49 vs 16%). Three cardinal criteria correctly classified 94% of patients into TLE-HS group: history of FC, dystonic posturing, and secondary GTCS. Postoperative outcome was significantly better in TLE-HS group than in the two other groups (p = 0.03 and 0.003). Our study demonstrates that cardinal criteria are reliably helpful to distinguish patients with TLE-HS from those with other TLE and may allow considering TLE-HS as a distinctive syndrome.

Periventricular nodular heterotopia (PNH) is a malformation of cortical development that frequently causes drug-resistant epilepsy. The epileptogenicity of ectopic neurons in PNH as well as their role in generating interictal and ictal activity is still a matter of debate. We report the first in vivo microelectrode recording of heterotopic neurons in humans. Highly consistent interictal patterns (IPs) were identified within the nodules: 1) Periodic Discharges PLUS Fast activity (PD+F), Sporadic discharges PLUS Fast activity (SD+F), and 3) epileptic spikes (ES). Neuronal firing rates were significantly modulated during all IPs, suggesting that multiple IPs were generated by the same local neuronal populations. Furthermore, firing rates closely followed IP morphologies. Among the different IPs, SD+FA pattern was found only in the three nodules that were actively involved in seizure generation, but was never observed in the nodule that did not take part in ictal discharges. On the contrary, PD+F and ES were identified in all nodules. Units that were modulated during the IPs were also found to participate in seizures, increasing their firing rate at seizure onset and maintaining an elevated rate during the seizures. Together, nodules in PNH are highly epileptogenic, and show several IPs that provide promising pathognomonic signatures of PNH. Furthermore, our results show that PNH nodules may well initiate seizures.HighlightsFirst in vivo microelectrode description of local epileptic activities in human PNHRecordings revealed multiple microscopic epileptic interictal patternsFiring rates of all detected units were significantly modulated during all interictal patternsSeizures recruited the same units that are involved in interictal activity

Face perception is thought to be mediated by neural activity in the occipital and posterior temporal cortex.1,2 However, the face-selective neurons at the cellular level in these areas in humans have never been demonstrated. We had a rare opportunity to record intracranial multi-unit activity in an epilepsy patient near the fusiform face area2 (figure 1A). We identified 2 units with highly face-selective response to static images of familiar (famous) and unfamiliar faces (figure 1B and video 1; figure e-1a, doi.org/10.5061/dryad.81t0fq1) as well as to human and animal faces that appeared in a movie (figure 1C, video 1, figure e-1b).

International audience; Estimating the value of alternative options is a key process in decision-making. Human functional magnetic resonance imaging and monkey electrophysiology studies have identified brain regions, such as the ventromedial prefrontal cortex (vmPFC) and lateral orbitofrontal cortex (lOFC), composing a value system. In the present study, in an effort to bridge across species and techniques, we investigated the neural representation of value ratings in 36 people with epilepsy, using intracranial electroencephalography. We found that subjective value was positively reflected in both vmPFC and lOFC high-frequency activity, plus several other brain regions, including the hippocampus. We then demonstrated that subjective value could be decoded (1) in pre-stimulus activity, (2) for various categories of items, (3) even during a distractive task and (4) as both linear and quadratic signals (encoding both value and confidence). Thus, our findings specify key functional properties of neural value signals (anticipation, generality, automaticity, quadraticity), which might provide insights into human irrational choice behaviors.

The first researches on nuclear fusion for energy applications marked the entrance of hot plasmas into the laboratory. It became necessary to understand the behavior of such plasmas and to learn how to manipulate them. Theoreticians and experimentalists, building on the foundations of empirical laws, had to construct this new plasma physics from first principles and to explain the results of more and more complicated experiments. Along this line, two important topics emerged: wave-particle and wave-wave interactions. Here, their history is recalled as it has been lived by a French team from the end of the sixties to the beginning of the twenty-first century.

Transthyretin familial amyloid polyneuropathy (FAP) is a rare disease with autosomal transmission due to point mutation of the transthyretin (TTR) gene. It is the most disabling hereditary neuropathy affecting sensory, motor and autonomic nerves, and is irreversible and fatal within 7 to 12 years of onset in the absence of therapy. Diagnosis is usually delayed for 1-5 years because the onset is usually insidious, and a positive family history is lacking in 50% of late-onset cases. Penetrance is variable, and depends of the age of the carrier and age of onset in family members. Two treatments are available: liver transplantation, to suppress the main source of systemic production of mutant TTR; and TTR tetramer stabilizer drugs, to avoid the release of highly amyloidogenic monomers and oligomers. These therapies are able to stop or slow the progression of the disease in its early stages. Genetic counseling is crucial to detect carriers at risk of developing the disease. The European network for TTR-FAP recommends careful baseline assessment by questionnaire, clinical examination and neurophysiological tests, and periodic consultations to detect the onset of disease in time to start anti-amyloid therapy after biopsy findings of amyloid deposition. A therapeutic educational program is important for improving patients' awareness. Patients are considered symptomatic and ill when they themselves perceive symptoms or changes, including changes from baseline measurements on neurophysiological tests, followed by findings of amyloid deposition on biopsy. The most sensitive biopsies are from the labial salivary gland and skin.

In patients with pharmaco-resistant focal epilepsies investigated with intracranial electroencephalography (iEEG), direct electrical stimulations of a cortical region induce cortico-cortical evoked potentials (CCEP) in distant cerebral cortex, which properties can be used to infer large scale brain connectivity. In 2013, we proposed a new probabilistic functional tractography methodology to study human brain connectivity. We have now been revisiting this method in the F-TRACT project (f-tract.eu) by developing a large multicenter CCEP database of several thousand stimulation runs performed in several hundred patients, and associated processing tools to create a probabilistic atlas of human cortico-cortical connections. Here, we wish to present a snapshot of the methods and data of F-TRACT using a pool of 213 epilepsy patients, all studied by stereo-encephalography with intracerebral depth electrodes. The CCEPs were processed using an automated pipeline with the following consecutive steps: detection of each stimulation run from stimulation artifacts in raw intracranial EEG (iEEG) files, bad channels detection with a machine learning approach, model-based stimulation artifact correction, robust averaging over stimulation pulses. Effective connectivity between the stimulated and recording areas is then inferred from the properties of the first CCEP component, i.e. onset and peak latency, amplitude, duration and integral of the significant part. Finally, group statistics of CCEP features are implemented for each brain parcel explored by iEEG electrodes. The localization (coordinates, white/gray matter relative positioning) of electrode contacts were obtained from imaging data (anatomical MRI or CT scans before and after electrodes implantation). The iEEG contacts were repositioned in different brain parcellations from the segmentation of patients' anatomical MRI or from templates in the MNI coordinate system. The F-TRACT database using the first pool of 213 patients provided connectivity probability values for 95% of possible intrahemispheric and 56% of interhemispheric connections and CCEP features for 78% of intrahemisheric and 14% of interhemispheric connections. In this report, we show some examples of anatomo-functional connectivity matrices, and associated directional maps. We also indicate how CCEP features, especially latencies, are related to spatial distances, and allow estimating the velocity distribution of neuronal signals at a large scale. Finally, we describe the impact on the estimated connectivity of the stimulation charge and of the contact localization according to the white or gray matter. The most relevant maps for the scientific community are available for download on f-tract. eu (David et al., 2017) and will be regularly updated during the following months with the addition of more data in the F-TRACT database. This will provide an unprecedented knowledge on the dynamical properties of large fiber tracts in human. he research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement n. 616268 “F-TRACT”. All the computations presented in this paper were performed using the CIMENT infrastructure (https://ciment.ujf-grenoble.fr), which is supported by the Rhône-Alpes region (GRANT CPER07_13 CIRA: http://www.ci-ra.org). We thank Bruno Bzenik and Romain Cavagna for their help on the CIMENT facility, and Jean-François Mangin and Cyril Poupon from Neurospin, CEA Saclay, for providing us with the ARCHI DTI database.

International audience; Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a heterogeneous syndrome. Surgery results in seizure freedom for most pharmacoresistant patients, but the epileptic and cognitive prognosis remains variable. The 2013 International League Against Epilepsy (ILAE) histopathological classification of hippocampal sclerosis (HS) has fostered research to understand MTLE-HS heterogeneity. We investigated the associations between histopathological features (ILAE types, hypertrophic CA4 neurons, granule cell layer alterations, CD34 immunopositive cells) and clinical features (presurgical history, postsurgical outcome) in a monocentric series of 247 MTLE-HS patients treated by surgery. NeuN, GFAP and CD34 immunostainings and a double independent pathological examination were performed. 186 samples were type 1, 47 type 2, 7 type 3 and 7 samples were gliosis only but no neuronal loss (noHS). In the type 1, hypertrophic CA4 neurons were associated with a worse postsurgical outcome and granule cell layer duplication was associated with generalized seizures and episodes of status epilepticus. In the type 2, granule cell layer duplication was associated with generalized seizures. CD34+ stellate cells were more frequent in the type 2, type 3 and in noHS. These cells had a Nestin and SOX2 positive, immature neural immunophenotype. Patients with nodules of CD34+ cells had more frequent dysmnesic auras. CD34+ stellate cells in scarce pattern were associated with higher ratio of normal MRI and of stereo-electroencephalographic studies. CD34+ cells were associated with a trend for a better postsurgical outcome. Among CD34+ cases, we proposed a new entity of BRAF V600E positive HS and we described three hippocampal multinodular and vacuolating neuronal tumours. To conclude, our data identified new clinicopathological associations with ILAE types. They showed the prognostic value of CA4 hypertrophic neurons. They highlighted CD34+ stellate cells and BRAF V600E as biomarkers to further decipher MTLE-HS heterogeneity. This article is protected by copyright. All rights reserved.

Focal seizures are assumed to arise from a hypersynchronous activity affecting a circumscribed brain region. Using microelectrodes in seizure-generating deep mesial regions of 9 patients, we investigated the firing of hundreds of single neurons before, during, and after ictal electroencephalogram (EEG) discharges. Neuronal spiking activity at seizure initiation was highly heterogeneous and not hypersynchronous. Furthermore, groups of neurons showed significant changes in activity minutes before the seizure with no concomitant changes in the corresponding macroscopic EEG recordings. Altogether, our findings suggest that only limited subsets of neurons in epileptic depth regions initiate the seizure-onset and that ictogenic mechanisms operate in submillimeter-scale microdomains. Ann Neurol 2017 Ann Neurol 2017;82:1022-1028.

Epilepsy contributes little to road traffic accidents (0.25% of accidents) compared, for instance, to alcohol abuse (at least 30 times higher). Current factors, such as age and sex, or other chronic medical conditions also increase the risk of road traffic accidents but do not carry driving restrictions. So, the European Commission fairly established rules permitting individuals having experienced one or more epileptic seizures to drive if their road accident risk is low. Road accident risk related to epileptic seizures in various clinical situations is evaluated by the driving license commission, mainly with the aid of criteria based on seizure-free periods. A person who has had an epileptic seizure should notify the authorities. He should be advised by treating physician not to drive before. In case of an authorisation, any new relevant event should be notified to the authorities in the course of legal follow-up. Improvements of the current regulations by European data registries are under way.

International audience

To delineate the clinical and EEG features of adults with focal epilepsy associated with a generalized paroxysmal fast activity (GPFA) pattern on EEG who developed refractory seizures, notably drop attacks, but do not fulfill the classical triad for the diagnosis of Lennox–Gastaut syndrome (LGS) and provide further insight into LGS mechanisms. Among 957 patients admitted to video-EEG monitoring between 2002 and 2015, we retrospectively research adult patients with refractory focal epilepsy, drop attacks and GPFA on EEG. We collected demographic, anamnestic, and clinical data from medical records. We reviewed for all patients the interictal and ictal video-EEG recordings. We identified ten patients with focal epilepsy and electro-clinical features of LGS. As compared to classical LGS patients, our patients: (1) began epilepsy later (15.4 ± 8 years); (2) exhibited exclusively focal onset seizures, including drop attacks seizures linked to focal asymmetrical tonic posturing seizures; (3) had a stable cognition over time and (4) evolved favourably with a good secondary response to treatments in 80% of cases. Interestingly, all patients exhibited apparent diffuse interictal and ictal EEG abnormalities but a detailed analysis revealed that 50% had asymmetrical GPFA and 70% secondary bilateral synchrony processes. We may hypothesize here that a process of “secondary LGS” occurred which produced a worsening of seizures with the apparition of drop attacks and GPFA on EEG. This study brings arguments to consider that some cases of LGS could be linked to the development of a “secondary epileptic network” driven by a primary focal epileptic zone.

International audience; OBJECTIVE:The reasons for failure of surgical treatment for mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) remain unclear. This retrospective study analyzed seizure, cognitive, and psychiatric outcomes, searching for factors associated with seizure relapse or cognitive and psychiatric deterioration after MTLE-HS surgery.METHODS:Seizure, cognitive, and psychiatric outcomes were reviewed after 389 surgeries performed between 1990 and 2015 on patients aged 15-67 years at a tertiary center. Three surgical approaches were used: anterior temporal lobectomy (ATL; n = 209), transcortical selective amygdalohippocampectomy (SAH; n = 144), and transsylvian SAH (n = 36).RESULTS:With an average follow-up of 8.7 years (range = 1.0-25.2), seizure outcome was classified as Engel I in 83.7% and Engel Ia in 57.1% of patients. The histological classification of HS was type 1 for 75.3% of patients, type 2 for 18.7%, and type 3 for 1.2%. Two factors were significantly associated with seizure recurrence: past history of status epilepticus and preoperative intracranial electroencephalographic recording. In contrast, neither HS type, the presence of a dual pathology, nor surgical approach was associated with seizure outcome. Risk of cognitive impairment was 3.12 (95% confidence interval = 1.27-7.70), greater in patients after ATL than in patients after transcortical SAH. A presurgical psychiatric history and postoperative cognitive impairment were associated with poor psychiatric outcome.SIGNIFICANCE:The SAH and ATL approaches have similar beneficial effects on seizure control, whereas transcortical SAH tends to minimize cognitive deterioration after surgery. Variation in postsurgical outcome with the class of HS should be investigated further.

In a quest for direct evidence of oscillation entrainment, we analyzed intracerebral electroencephalographic recordings obtained during intracranial electrical stimulation in a cohort of three medication-resistant epilepsy patients tested pre-surgically. Spectral analyses of non-epileptogenic cerebral sites stimulated directly with high frequency electrical bursts yielded episodic local enhancements of frequency-specific rhythmic activity, phase-locked to each individual pulse. These outcomes reveal an entrainment of physiological oscillatory activity within a frequency band dictated by the rhythm of the stimulation source. Our results support future uses of rhythmic stimulation to elucidate the causal contributions of synchrony to specific aspects of human cognition and to further develop the therapeutic manipulation of dysfunctional rhythmic activity subtending the symptoms of some neuropsychiatric conditions. En una búsqueda de evidencia directa de arrastre de oscilación, se analizaron los registros electroencefalográficos intracerebrales obtenidos durante la estimulación eléctrica intracraneal en una cohorte de tres pacientes epilépticos resistentes a la medicación probados prequirúrgicamente. Los análisis espectrales de puntos cerebrales no epileptógenos estimulados directamente con ráfagas eléctricas de alta frecuencia produjeron mejoras episódicas locales de la actividad rítmica específica de frecuencia, bloqueada de fase a cada impulso individual. Estos resultados revelan un arrastre de la actividad oscilatoria fisiológica dentro de una banda de frecuencia dictada por el ritmo de la fuente de estimulación. Nuestros resultados apoyan los usos futuros de la estimulación rítmica para dilucidar las contribuciones causales de la sincronía a aspectos específicos de la cognición humana y para desarrollar aún más la manipulación terapéutica de la actividad rítmica disfuncional que subtiende los síntomas de algunas afecciones neuropsiquiátricas. En una recerca d'evidència directa d'arrossegament d'oscil·lació, es van analitzar els registres electroencefalogràfics intracerebrals obtinguts durant l'estimulació elèctrica intracranial en una cohort de tres pacients epilèptics resistents a la medicació provats prequirúrgicament. Les anàlisis espectrals de punts cerebrals no epileptògens estimulats directament amb ràfegues elèctriques d'alta freqüència van produir millores episòdiques locals de l'activitat rítmica específica de freqüència, bloquejada de fase a cada impuls individual. Aquests resultats revelen un arrossegament de l'activitat oscil·latòria fisiològica dins d'una banda de freqüència dictada pel ritme de la font d'estimulació. Els nostres resultats recolzen els usos futurs de l'estimulació rítmica per dilucidar les contribucions causals de la sincronia a aspectes específics de la cognició humana i per desenvolupar encara més la manipulació terapèutica de l'activitat rítmica disfuncional que subtendeix els símptomes d'algunes afeccions neuropsiquiàtriques.

International audience; BackgroundHippocampal sclerosis is the most common cause of drug-resistant epilepsy amenable for surgical treatment and seizure control. This study aimed to analyze morbidities related to surgery of mesial temporal lobe epilepsy associated with hippocampal sclerosis and to identify possible risk factors for complications.MethodsA retrospective analysis of postoperative complications was made for 389 operations performed between 1990 and 2015 on patients aged 15 to 67 years (mean 36.8). Three surgical approaches were used: anterior temporal lobectomy (ATL) (n=209), transcortical selective amygdalohippocampectomy (SAH) (n=144) and transylvian SAH (n=36). Complications were classified as minor, or major if there was a neurological impairment or if further surgical or medical treatment was needed.ResultsComplications followed 15.4% of operations. They were classed as major for 4.1% of patients, but there were no mortalities. Persistent neurological deficits occurred in 0.5% of patients. In 3 cases (0.8%) additional surgery was needed to treat an intracranial hematoma, a delayed hydrocephalus and a subdural empyema. Symptomatic visual field defects (VFDs) were frequent and included contralateral superior quadrantanopia (8.2%) or hemianopia (1.3%). Overall complications (P=0.04) and symptomatic VFDs (P=0.04) were most frequent in operations on men. Major complications occurred most often with the ATL surgical approach than with transcortical SAH (P=0.03).ConclusionsMajor complications occur rarely after mesial temporal surgery on epileptic patients. They occur more often following ATL than transcortical SAH approach. Complications tend to be temporary with symptoms of limited duration for surgery performed by experienced teams on carefully selected and evaluated patients.Key Words

International audience; Auditory novelty detection has been associated with different cognitive processes. Bekinschtein et al. (2009) developed an experimental paradigm to dissociate these processes, using local and global novelty, which were associated, respectively, with automatic versus strategic perceptual processing. They have mostly been studied using event-related potentials (ERPs), but local spiking activity as indexed by gamma (60-120 Hz) power and interactions between brain regions as indexed by modulations in beta-band (13-25 Hz) power and functional connectivity have not been explored. We thus recorded 9 epileptic patients with intracranial electrodes to compare the precise dynamics of the responses to local and global novelty. Local novelty triggered an early response observed as an intracranial mismatch negativity (MMN) contemporary with a strong power increase in the gamma band and an increase in connectivity in the beta band. Importantly, all these responses were strictly confined to the temporal auditory cortex. In contrast, global novelty gave rise to a late ERP response distributed across brain areas, contemporary with a sustained power decrease in the beta band (13-25 Hz) and an increase in connectivity in the alpha band (8-13 Hz) within the frontal lobe. We discuss these multi-facet signatures in terms of conscious access to perceptual information.

Objectif Le delai diagnostique de la narcolepsie de type 1 (NT1) reste de nos jours considerable. L’epilepsie constitue un diagnostic differentiel parfois delicat. Nous rapportons ici le cas d’un patient souffrant de « secousses du membre superieur », resistant a deux ans de traitement antiepileptique, dont l’analyse du monitorage video-electroencephalographique (EEG) a permis de porter un diagnostic de cataplexie partielle. Methodes Analyse video-EEG et electromyogramme (EMG) et recapitulatif des caracteristiques electrocliniques pouvant orienter entre les diagnostics d’epilepsie et de NT1. Resultats Le patient de 26 ans developpait des malaises brefs et stereotypes (secousses du membre superieur droit, trouble du langage, rares chutes). L’analyse de la video et de l’EMG permettait d’affirmer la presence d’une atonie partielle intermittente, notamment faciale, a l’origine d’un emoussement du langage, et de secousses des membres superieures, voisines de myoclonies negatives. Le diagnostic de NT1 etait confirme par l’etude du sommeil. Nous resumons les caracteristiques d’atonie liee a la NT1 et aux syndromes epileptiques bien definis (syndrome de Doose et de Lennox Gastaut, souvent associes a un retard mental), et ceux d’autres mecanismes de chute (myoclonies positives, asystolie ictale). Conclusion La NT1 continue de poser de difficultes diagnostiques, notamment dans un contexte de cataplexie partielle pretant a confusion avec l’epilepsie focale.

Voluntary control of oscillatory activity represents a key target in the self-regulation of brain function. Using a real-time closed-loop paradigm and simultaneous macro- and micro-electrode recordings, we studied the effects of self-induced intracortical oscillatory activity (4–8 Hz) in seven neurosurgical patients. Subjects learned to robustly and specifically induce oscillations in the target frequency, confirmed by increased oscillatory event density. We have found that the session-to-session variability in performance was explained by the functional long-range decoupling of the target area suggesting a training-induced network reorganization. Downstream effects on more local activities included progressive cross-frequency-coupling with gamma oscillations (30–120 Hz), and the dynamic modulation of neuronal firing rates and spike timing, indicating an improved temporal coordination of local circuits. These findings suggest that effects of voluntary control of intracortical oscillations can be exploited to specifically target plasticity processes to reconfigure network activity, with a particular relevance for memory function or skill acquisition.

Objective To compare the performance of 4h-video EEG monitoring (VEEG) and 1h-nap-VEEG in an Epileptology Unit. Methods We examined short-term VEEG data from 196 patients admitted to characterize their: (i) clinical events; (ii) epileptic syndromes or (iii) state after status epilepticus or surgery. We compared the 4h-VEEG and 1h-nap-VEEG performances using three measures: (i) the capability to detect epileptic seizures (ES), psychogenic non-epileptic seizures (PNES), interictal epileptiform abnormalities (IEA) and sleep-related IEA; (ii) the usefulness to answer questions on referral; (iii) the sensitivity for the final diagnosis. Results The 4h-VEEG test recorded clinical events in 53.6% of 196 patients, IEA in 41.3%, sleep-related IEA in 34.7%, and was judged as useful in 66.8%. The 4h-VEEG was compared to the 1h-nap-VEEG in 129 patients. 4h-VEEG had a better capability to record clinical events (50.3% vs. 6.2%, p usefulness (63.5% vs . 37.2%, p sensitivity for both ES (69.3% vs. 49.3%, p =0.0035) and PNES (61.3% vs. 15.4%, p =0.0014) than nap-EEG. Conclusions This work found 4h-VEEG records were superior to the 1h-nap-VEEG test on the basis of three complementary measures, capability, usefulness and sensitivity. Significance 4h-VEEG is a useful alternative investigation tool in an Epileptology Unit.

From the very beginning the seizure prediction community faced problems concerning evaluation, standardization, and reproducibility of its studies. One of the main reasons for these shortcomings was the lack of access to high-quality long-term electroencephalography (EEG) data. In this article we present the EPILEPSIAE database, which was made publicly available in 2012. We illustrate its content and scope. The EPILEPSIAE database provides long-term EEG recordings of 275 patients as well as extensive metadata and standardized annotation of the data sets. It will adhere to the current standards in the field of prediction and facilitate reproducibility and comparison of those studies. Beyond seizure prediction, it may also be of considerable benefit for studies focusing on seizure detection, basic neurophysiology, and other fields.

Epilepsy, a neurological disorder in which patients suffer from recurring seizures, affects approximately 1% of the world population. In spite of available drug and surgical treatment options, more than 25% of individuals with epilepsy have seizures that are uncontrollable. For these patients with intractable epilepsy, the unpredictability of seizure occurrence underlies an enhanced risk of sudden unexpected death or morbidity. A system that could warn the patient of the impending event or trigger an antiepileptic device would dramatically increase the quality of life for those patients. Here, we proposed a patient-specific algorithm for possible seizure warning using machine learning classification of 34 algorithmic features derived from EEG–ECG recordings. We evaluated our algorithm on unselected and continuous recordings of 12 patients (total of 108 seizures and 3178-h). Good out-of-sample performances were observed around 25% of the patients with an average preictal period around 30 min and independently of the EEG type (scalp or intracranial). Inspection of the most discriminative EEG–ECG features revealed that good classification rates reflected specific physiological precursors, particularly related to certain stages of sleep. From these observations, we conclude that our algorithmic strategy enables a quantitative way to identify “pro-ictal” states with a high risk of seizure generation.

A 69-year-old woman had insomnia, restless legs syndrome, and violent movements during sleep; she had had a generalized seizure several years previously. She underwent 4 days of video-EEG investigation for these movements (table, and figure e-1 on the Neurology ® Web site at [Neurology.org][1]). There was no epileptic activity, but repetitive, stereotyped movements (88 movements/hour; movement duration: 2.5 seconds) occurred only during sleep, which were typical of periodic leg movements but associated with atypical, polyphasic hand cycling/rubbing movements (see video). This complex motor pattern might be confused with a focal epileptic seizure. [1]: http://neurology.org/lookup/doi/10.1212/WNL.0000000000002224

International audience; PURPOSE: Idiopathic generalized epilepsies (IGE) are age-related epileptic syndromes mainly described in children and adolescence. Our aim is to describe their electroclinical features in the elderly. METHODS: Patients aged 70 years or more were prospectively selected in a geriatric EEG laboratory on the basis of rhythmic generalized spikes and waves discharges. Their clinical data were then examined to ascertain the syndromic diagnosis. RESULTS: Among 1181 geriatric patients referred for EEG over a 30-month period, IGE were identified in 10 cases. Eight patients began seizures in childhood or adulthood (3 childhood absence epilepsies, 2 juvenile/adult myoclonic epilepsies and 3 epilepsies with-generalized-tonic-clonic-seizures alone (EGTCS)) and 2 very late in life with EGTCS. The early-onset IGE cases had usually experienced a quiescent long period in adulthood before relapsing late in life. This relapse, mostly severe, consisted of absence status, myoclonic status or repeated generalized tonic clonic seizures and was often not-situation related. Absence status and myoclonic status were stopped by Clonazepam. The two late-onset IGE cases had familial history of epilepsy. Inappropriate antiepileptic drugs (AED) previously given in four patients with two worsenings were corrected. CONCLUSIONS: In this study, the non-negligible number of elderly cases observed over a short period of time suggests that IGE are frequent in the elderly but underestimated until recently. IGE may be lifelong with late severe exacerbations. A few very late-onset IGE cases exist. EEG remains useful in contributing to diagnose IGE and AED adjustment continues to be beneficial at extreme age.

Resume Introduction De nombreux arguments cliniques, metaboliques et electrophysiologiques suggerent l’existence d’un etat precritique, transition entre l’etat intercritique et la crise. Etat des connaissances L’analyse de l’EEG intracrânien par des methodes mathematiques a montre l’existence de changements de la dynamique cerebrale plusieurs minutes avant la survenue de crises partielles. Ces modifications dynamiques precritiques ne semblent pas limitees au foyer epileptogene, ce qui explique qu’elles puissent aussi etre apprehendees par l’EEG de scalp et dans des epilepsies partielles qu’un foyer epileptogene soit ou non identifie. Plusieurs scenarios peuvent rendre compte de la periode precritique : recrutement progressif des neurones, comme le suggerent des analyses a un niveau cellulaire, ou etat facilitateur, a haute probabilite de survenue de crises, comme le suggerent des analyses a l’echelle de reseaux neuronaux. Aucune methode de prediction des crises ne peut aujourd’hui etre proposee aux patients, car le taux de faux-positifs reste trop important. Perspectives Une etude multicentrique europeenne ( Evolving platform for improving living expectation of patients suffering from IctAl events [EPILEPSIAE]) evalue actuellement une combinaison de plus de 44 methodes d’analyse des signaux EEG et ECG, sur des enregistrements issus d’une vaste base de donnees. Conclusion D’importants efforts doivent etre poursuivis en combinant les analyses de signaux a de multiples niveaux : EEG intracrânien, microelectrodes intracerebrales, EEG de scalp, analyse in vitro de tissus post-operatoires.

Points essentiels La chirurgie de l’epilepsie s’adresse a tout patient ayant une epilepsie partielle pharmacoresitante, des lors qu’elle est invalidante. Les candidats peuvent etre aussi bien des adultes que des enfants. Un bilan prechirurgical, adapte a chaque patient, doit d’une part identifier le plus precisement possible la region corticale, d’ou partent les crises, en s’aidant de faisceaux d’arguments : semiologie clinique et electroencephalographique des crises, imagerie cerebrale structurelle et parfois fonctionnelle ; d’autre part, s’assurer que la resection du foyer epileptogene ne va pas entrainer de troubles neurologiques ou cognitifs, en s’aidant d’une evaluation neuropsychologique et parfois d’imageries cerebrales fonctionnelles. Il est important d’evoquer rapidement cette strategie therapeutique chez des patients dont l’epilepsie s’avere pharmacoresistante, et de les adresser dans des centres specialises. Les resultats de la chirurgie different selon l’origine lobaire du foyer epileptique et selon l’existence d’une lesion visible sur l’IRM cerebrale. Une evaluation multidisciplinaire du rapport entre les benefices et les risques doit etre presentee au patient. Le plus souvent, quand un foyer a pu etre identifie et que les tests neuropsychologiques ne predisent pas de deficit, les resultats de la chirurgie de l’epilepsie sont excellents.