Dimensionality and Ramping: Signatures of Sentence Integration in the Dynamics of Brains and Deep Language Models.

A sentence is more than the sum of its words: its meaning depends on how they combine with one another. The brain mechanisms underlying such semantic composition remain poorly understood. To shed light on the neural vector code underlying semantic composition, we introduce two hypotheses: (1) the intrinsic dimensionality of the space of neural representations should increase as a sentence unfolds, paralleling the growing complexity of its semantic representation; and (2) this progressive integration should be reflected in ramping and sentence-final signals. To test these predictions, we designed a dataset of closely matched normal and jabberwocky sentences (composed of meaningless pseudo words) and displayed them to deep language models and to 11 human participants (5 men and 6 women) monitored with simultaneous MEG and intracranial EEG. In both deep language models and electrophysiological data, we found that representational dimensionality was higher for meaningful sentences than jabberwocky. Furthermore, multivariate decoding of normal versus jabberwocky confirmed three dynamic patterns: (1) a phasic pattern following each word, peaking in temporal and parietal areas; (2) a ramping pattern, characteristic of bilateral inferior and middle frontal gyri; and (3) a sentence-final pattern in left superior frontal gyrus and right orbitofrontal cortex. These results provide a first glimpse into the neural geometry of semantic integration and constrain the search for a neural code of linguistic composition.SIGNIFICANCE STATEMENT Starting from general linguistic concepts, we make two sets of predictions in neural signals evoked by reading multiword sentences. First, the intrinsic dimensionality of the representation should grow with additional meaningful words. Second, the neural dynamics should exhibit signatures of encoding, maintaining, and resolving semantic composition. We successfully validated these hypotheses in deep neural language models, artificial neural networks trained on text and performing very well on many natural language processing tasks. Then, using a unique combination of MEG and intracranial electrodes, we recorded high-resolution brain data from human participants while they read a controlled set of sentences. Time-resolved dimensionality analysis showed increasing dimensionality with meaning, and multivariate decoding allowed us to isolate the three dynamical patterns we had hypothesized.

GluK2 Is a Target for Gene Therapy in Drug-Resistant Temporal Lobe Epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) is characterized by recurrent seizures generated in the limbic system, particularly in the hippocampus. In TLE, recurrent mossy fiber sprouting from dentate gyrus granule cells (DGCs) crea an aberrant epileptogenic network between DGCs which operates via ectopically expressed GluK2/GluK5-containing kainate receptors (KARs). TLE patients are often resistant to anti-seizure medications and suffer significant comorbidities; hence, there is an urgent need for novel therapies. Previously, we have shown that GluK2 knockout mice are protected from seizures. This study aims at providing evidence that downregulating KARs in the hippocampus using gene therapy reduces chronic epileptic discharges in TLE. METHODS: We combined molecular biology and electrophysiology in rodent models of TLE and in hippocampal slices surgically resected from patients with drug-resistant TLE. RESULTS: Here, we confirmed the translational potential of KAR suppression using a non-selective KAR antagonist that markedly attenuated interictal-like epileptiform discharges (IEDs) in TLE patient-derived hippocampal slices. An adeno-associated virus (AAV) serotype-9 vector expressing anti-grik2 miRNA was engineered to specifically downregulate GluK2 expression. Direct delivery of AAV9-anti grik2 miRNA into the hippocampus of TLE mice led to a marked reduction in seizure activity. Transduction of TLE patient hippocampal slices reduced levels of GluK2 protein and, most importantly, significantly reduced IEDs. INTERPRETATION: Our gene silencing strategy to knock down aberrant GluK2 expression demonstrates inhibition of chronic seizure in a mouse TLE model and IEDs in cultured slices derived from TLE patients. These results provide proof-of-concept for a gene therapy approach targeting GluK2 KARs for drug-resistant TLE patients. ANN NEUROL 2023;94:745-761.

Permutation entropy-derived parameters to estimate the epileptogenic zone network.

OBJECTIVE: Quantification of the epileptogenic zone network (EZN) most frequently implies analysis of seizure onset. However, important information can also be obtained from the postictal period, characterized by prominent changes in the EZN. We used permutation entropy (PE), a measure of signal complexity, to analyze the peri-ictal stereoelectroencephalography (SEEG) signal changes with emphasis on the postictal state. We sought to determine the best PE-derived parameter (PEDP) for identifying the EZN. METHODS: Several PEDPs were computed retrospectively on SEEG-recorded seizures of 86 patients operated on for drug-resistant epilepsy: mean baseline preictal entropy, minimum ictal entropy, maximum postictal entropy, the ratio between the maximum postictal and the minimum ictal entropy, and the ratio between the maximum postictal and the baseline preictal entropy. The performance of each biomarker was assessed by comparing the identified epileptogenic contacts or brain regions against the EZN defined by clinical analysis incorporating the Epileptogenicity Index and the connectivity epileptogenicity index methods (EZNc), using the receiver-operating characteristic and precision-recall. RESULTS: The ratio between the maximum postictal and the minimum ictal entropy (defined as the Permutation Entropy Index [PEI]) proved to be the best-performing PEDP to identify the EZNC . It demonstrated the highest area under the curve (AUC) and F1 score at the contact level (AUC 0.72; F1 0.39) and at the region level (AUC 0.78; F1 0.47). PEI values gradually decreased between the EZN, the propagation network, and the non-involved regions. PEI showed higher performance in patients with slow seizure-onset patterns than in those with fast seizure-onset patterns. The percentage of resected epileptogenic regions defined by PEI was significantly correlated with surgical outcome. SIGNIFICANCE: PEI is a promising tool to improve the delineation of the EZN. PEI combines ease and robustness in a routine clinical setting with high sensitivity for seizures without fast activity at seizure onset.

Psychiatric complications following SEEG-guided radiofrequency thermocoagulations in patients with drug-resistant epilepsy.

SEEG-guided radiofrequency thermocoagulation (RF-TC) in the epileptogenic regions is a therapeutic option for patients with drug-resistant focal epilepsy who may have or not indication for epilepsy surgery. The most common adverse events of RF-TC are seizures, headaches, somatic pain, and sensory-motor deficits. If RF-TC could lead to psychiatric complications is unknown. In the present study, seven out of 164 patients (4.2 %) experienced psychiatric decompensation with or without memory deterioration after RF-TC of bilateral or unilateral amygdala and hippocampus. The appearance of symptoms was either acute, subacute, or chronic and the symptoms were either transient or lasted for several months. Common features among these patients were female sex, mesial temporal epilepsy, and a pre-existing history of psychological distress and memory dysfunction. Our study highlights the possibility of neuropsychiatric deterioration in specific patients following SEEG-guided RF-TC, despite its rarity.

Asymmetric sampling in human auditory cortex reveals spectral processing hierarchy.

Speech perception is mediated by both left and right auditory cortices but with differential sensitivity to specific acoustic information contained in the speech signal. A detailed description of this functional asymmetry is missing, and the underlying models are widely debated. We analyzed cortical responses from 96 epilepsy patients with electrode implantation in left or right primary, secondary, and/or association auditory cortex (AAC). We presented short acoustic transients to noninvasively estimate the dynamical properties of multiple functional regions along the auditory cortical hierarchy. We show remarkably similar bimodal spectral response profiles in left and right primary and secondary regions, with evoked activity composed of dynamics in the theta (around 4-8 Hz) and beta-gamma (around 15-40 Hz) ranges. Beyond these first cortical levels of auditory processing, a hemispheric asymmetry emerged, with delta and beta band (3/15 Hz) responsivity prevailing in the right hemisphere and theta and gamma band (6/40 Hz) activity prevailing in the left. This asymmetry is also present during syllables presentation, but the evoked responses in AAC are more heterogeneous, with the co-occurrence of alpha (around 10 Hz) and gamma (>25 Hz) activity bilaterally. These intracranial data provide a more fine-grained and nuanced characterization of cortical auditory processing in the 2 hemispheres, shedding light on the neural dynamics that potentially shape auditory and speech processing at different levels of the cortical hierarchy.

Frequency Selectivity of Persistent Cortical Oscillatory Responses to Auditory Rhythmic Stimulation.

Cortical oscillations have been proposed to play a functional role in speech and music perception, attentional selection, and working memory, via the mechanism of neural entrainment. One of the properties of neural entrainment that is often taken for granted is that its modulatory effect on ongoing oscillations outlasts rhythmic stimulation. We tested the existence of this phenomenon by studying cortical neural oscillations during and after presentation of melodic stimuli in a passive perception paradigm. Melodies were composed of ∼60 and ∼80 Hz tones embedded in a 2.5 Hz stream. Using intracranial and surface recordings in male and female humans, we reveal persistent oscillatory activity in the high-γ band in response to the tones throughout the cortex, well beyond auditory regions. By contrast, in response to the 2.5 Hz stream, no persistent activity in any frequency band was observed. We further show that our data are well captured by a model of damped harmonic oscillator and can be classified into three classes of neural dynamics, with distinct damping properties and eigenfrequencies. This model provides a mechanistic and quantitative explanation of the frequency selectivity of auditory neural entrainment in the human cortex.SIGNIFICANCE STATEMENT It has been proposed that the functional role of cortical oscillations is subtended by a mechanism of entrainment, the synchronization in phase or amplitude of neural oscillations to a periodic stimulation. One of the properties of neural entrainment that is often taken for granted is that its modulatory effect on ongoing oscillations outlasts rhythmic stimulation. Using intracranial and surface recordings of humans passively listening to rhythmic auditory stimuli, we reveal consistent oscillatory responses throughout the cortex, with persistent activity of high-γ oscillations. On the contrary, neural oscillations do not outlast low-frequency acoustic dynamics. We interpret our results as reflecting harmonic oscillator properties, a model ubiquitous in physics but rarely used in neuroscience.

An open-source toolbox for Multi-patient Intracranial EEG Analysis (MIA).

Intracranial EEG (iEEG) performed during the pre-surgical evaluation of refractory epilepsy provides a great opportunity to investigate the neurophysiology of human cognitive functions with exceptional spatial and temporal precisions. A difficulty of the iEEG approach for cognitive neuroscience, however, is the potential variability across patients in the anatomical location of implantations and in the functional responses therein recorded. In this context, we designed, implemented, and tested a user-friendly and efficient open-source toolbox for Multi-Patient Intracranial data Analysis (MIA), which can be used as standalone program or as a Brainstorm plugin. MIA helps analyzing event related iEEG signals while following good scientific practice recommendations, such as building reproducible analysis pipelines and applying robust statistics. The signals can be analyzed in the temporal and time-frequency domains, and the similarity of time courses across patients or contacts can be assessed within anatomical regions. MIA allows visualizing all these results in a variety of formats at every step of the analysis. Here, we present the toolbox architecture and illustrate the different steps and features of the analysis pipeline using a group dataset collected during a language task.

Magnetoencephalography can reveal deep brain network activities linked to memory processes.

Recording from deep neural structures such as hippocampus noninvasively and yet with high temporal resolution remains a major challenge for human neuroscience. Although it has been proposed that deep neuronal activity might be recordable during cognitive tasks using magnetoencephalography (MEG), this remains to be demonstrated as the contribution of deep structures to MEG recordings may be too small to be detected or might be eclipsed by the activity of large-scale neocortical networks. In the present study, we disentangled mesial activity and large-scale networks from the MEG signals thanks to blind source separation (BSS). We then validated the MEG BSS components using intracerebral EEG signals recorded simultaneously in patients during their presurgical evaluation of epilepsy. In the MEG signals obtained during a memory task involving the recognition of old and new images, we identified with BSS a putative mesial component, which was present in all patients and all control subjects. The time course of the component selectively correlated with stereo-electroencephalography signals recorded from hippocampus and rhinal cortex, thus confirming its mesial origin. This finding complements previous studies with epileptic activity and opens new possibilities for using MEG to study deep brain structures in cognition and in brain disorders.

Long-term cognitive outcome after radiosurgery in epileptic hypothalamic hamartomas and review of the literature.

OBJECTIVE: Epileptic patients with hypothalamic hamartoma (HH) frequently present cognitive impairments. Surgical techniques aiming at HH can be very efficient for epilepsy relief and cognitive improvement but are also demonstrated to carry a significant risk of additional reduction in memory function in these already disabled patients. Gamma knife radiosurgery (GKS) offers an efficient minimally invasive procedure. We evaluated the effect of stereotactic radiosurgery on cognitive outcome. METHODS: We designed a prospective single-center case series study. Thirty-nine epileptic patients (median age = 17 years, range = 4-50) with HH underwent preoperative and postoperative testing of intelligence quotient (IQ; all patients), including a working memory component, and other memory function testing (for patients ≥16 years old). All patients were prospectively evaluated and underwent complete presurgical and postsurgical clinical, electrophysiological, endocrinal, and visual assessments. In all patients, the postoperative assessment was performed at least 3 years after radiosurgery. We explored what variables correlate with cognitive outcome. Literature review was done for other surgical techniques and their risks for cognitive complications after surgery. RESULTS: No decline was observed in intellectual ability (including working memory) after GKS, and no memory decline was seen in adults. We observed significant improvement (>1 SD in z-score) in working memory index (46%) and processing speed index (35%), as well as improvement in full-scale IQ (24%), verbal comprehension index (11%), perceptual organization index (21%), verbal learning (20%), and visual learning (33%). Before GKS, the probability of seizure cessation was higher in patients with higher cognitive performance. After GKS, the cognitive improvement was significantly higher in the seizure-free patients compared to the non-seizure-free patients. SIGNIFICANCE: We found clear cognitive improvement in a high percentage of patients but importantly no significant decline in intellectual ability (including working memory) and no decline in memory in adult patients 3 years after GKS. GKS compares favorably to the other surgical techniques in terms of cognitive outcome, with similar seizure freedom.

Changes in epileptogenicity biomarkers after stereotactic thermocoagulation.

OBJECTIVE: Stereo-electroencephalography (SEEG)-guided radiofrequency thermocoagulation (RF-TC) aims at modifying epileptogenic networks to reduce seizure frequency. High-frequency oscillations (HFOs), spikes, and cross-rate are quantifiable epileptogenic biomarkers. In this study, we sought to evaluate, using SEEG signals recorded before and after thermocoagulation, whether a variation in these markers is related to the therapeutic effect of this procedure and to the outcome of surgery. METHODS: Interictal segments of SEEG signals were analyzed in 38 patients during presurgical evaluation. We used an automatized method to quantify the rate of spikes, rate of HFOs, and cross-rate (a measure combining spikes and HFOs) before and after thermocoagulation. We analyzed the differences both at an individual level with a surrogate approach and at a group level with analysis of variance. We then evaluated the correlation between these variations and the clinical response to RF-TC and to subsequent resective surgery. RESULTS: After thermocoagulation, 19 patients showed a clinical improvement. At the individual level, clinically improved patients more frequently had a reduction in spikes and cross-rate in the epileptogenic zone than patients without clinical improvement (p = .002, p = .02). At a group level, there was a greater decrease of HFOs in epileptogenic and thermocoagulated zones in patients with clinical improvement (p < .05) compared to those with no clinical benefit. Eventually, a significant decrease of all the markers after RF-TC was found in patients with a favorable outcome of resective surgery (spikes, p = .026; HFOs, p = .03; cross-rate, p = .03). SIGNIFICANCE: Quantified changes in the rate of spikes, rate of HFOs, and cross-rate can be observed after thermocoagulation, and the reduction of these markers correlates with a favorable clinical outcome after RF-TC and with successful resective surgery. This may suggest that interictal biomarker modifications after RF-TC can be clinically used to predict the effectiveness of the thermocoagulation procedure and the outcome of resective surgery.

Converging intracortical signatures of two separated processing timescales in human early auditory cortex.

Neural oscillations in auditory cortex are argued to support parsing and representing speech constituents at their corresponding temporal scales. Yet, how incoming sensory information interacts with ongoing spontaneous brain activity, what features of the neuronal microcircuitry underlie spontaneous and stimulus-evoked spectral fingerprints, and what these fingerprints entail for stimulus encoding, remain largely open questions. We used a combination of human invasive electrophysiology, computational modeling and decoding techniques to assess the information encoding properties of brain activity and to relate them to a plausible underlying neuronal microarchitecture. We analyzed intracortical auditory EEG activity from 10 patients while they were listening to short sentences. Pre-stimulus neural activity in early auditory cortical regions often exhibited power spectra with a shoulder in the delta range and a small bump in the beta range. Speech decreased power in the beta range, and increased power in the delta-theta and gamma ranges. Using multivariate machine learning techniques, we assessed the spectral profile of information content for two aspects of speech processing: detection and discrimination. We obtained better phase than power information decoding, and a bimodal spectral profile of information content with better decoding at low (delta-theta) and high (gamma) frequencies than at intermediate (beta) frequencies. These experimental data were reproduced by a simple rate model made of two subnetworks with different timescales, each composed of coupled excitatory and inhibitory units, and connected via a negative feedback loop. Modeling and experimental results were similar in terms of pre-stimulus spectral profile (except for the iEEG beta bump), spectral modulations with speech, and spectral profile of information content. Altogether, we provide converging evidence from both univariate spectral analysis and decoding approaches for a dual timescale processing infrastructure in human auditory cortex, and show that it is consistent with the dynamics of a simple rate model.

Electrical stimulation for seizure induction during SEEG exploration: a useful predictor of postoperative seizure recurrence?

OBJECTIVE: Direct electrical stimulations of cerebral cortex are a traditional part of stereoelectroencephalography (SEEG) practice, but their value as a predictive factor for seizure outcome has never been carefully investigated. PATIENTS AND METHOD: We retrospectively analysed a cohort of 346 patients operated on for drug-resistant focal epilepsy after SEEG exploration. As potential predictors we included: aetiology, MRI data, age of onset, duration of epilepsy, age at surgery, topography of surgery and whether a seizure was induced by either low frequency electrical stimulation (LFS) or high frequency electrical stimulation. RESULTS: Of 346 patients, 63.6% had good outcome (no seizure recurrence, Engel I). Univariate analysis demonstrated significant correlation with favourable outcome (Engel I) for: aetiology, positive MRI and seizure induced by stimulation. At multivariate analysis, informative MRI, type II focal cortical dysplasia and tumour reduced the risk of seizure recurrence (SR) by 47%, 58% and 81%, respectively. Compared with the absence of induced seizures, the occurrence of ictal events after LFS significantly predicts a favourable outcome on seizures, with only 44% chance of disabling SR at last follow-up. CONCLUSION: Among the already known predictors outcome, seizure induction by LFS therefore represents a positive predictive factor for seizure outcome after surgery.

Relationship between PET metabolism and SEEG epileptogenicity in focal lesional epilepsy.

PURPOSE: This study aims to evaluate the performance of 18F-FDG PET for distinguishing the epileptogenic zone (EZ) from propagation and non-involved zones at brain area level, as defined using stereo-EEG (SEEG), in patients with pharmacoresistant epilepsy due to malformations of cortical development (MCD). Additionally, we seek to determine the relationship between 18F-FDG-PET data and post-surgical seizure outcome. METHODS: Thirty-eight patients with MCD were explored with 18F-FDG PET and SEEG. We compared PET metabolism of each patient to a control population of healthy subjects. Based on MRI and SEEG, we separated 4 distinct zones at individual level: lesional, epileptogenic non-lesional, propagation, and non-involved. Then, we analysed (1) difference of PET metabolism within these four distinct zones; (2) performance of PET in defining the EZ within the SEEG-sampled areas; and (3) relation between extension of PET hypometabolism and post-surgical seizure outcome. RESULTS: We found (1) a gradient of PET hypometabolism from non-involved to propagation, then to epileptogenic and lesional zones (p < 0.001); (2) good performance of PET in defining the EZ (AUC of ROC curve = 0.82); (3) poorer post-surgical prognosis associated with PET hypometabolism extension beyond SEEG sampling (p = 0.024). CONCLUSION: 18F-FDG-PET has good accuracy in determining EZ in patients with MCD even if the hypometabolism is not limited to the EZ. Furthermore, hypometabolic extension is unfavourably associated with post-surgical prognosis.

Quantitative analysis of hyperkinetic seizures and correlation with seizure onset zone.

OBJECTIVE: Hyperkinetic epileptic seizures (HKS) are difficult to characterize and localize according to semiologic features. We propose a multicriteria scale to help visual analysis and report results of cerebral localization. METHODS: We assessed seizures from 37 patients with HKS, explored with stereoelectroencephalography during presurgical evaluation. We used a multicriteria scale (hyperkinetic seizure scale [HSS]) with 10 semiologic features, scored independently by two neurologists. The item scores were used to group seizures using the k-means method. Semiologic features were correlated with the seizure onset zone (SOZ) localization (temporal, prefrontal dorsolateral, prefrontal ventromesial, parietal, insular). RESULTS: Fifty-five seizures were analyzed, and each item of the HSS was compared between the two examiners with good interrater agreement (85.3%). Dystonia, integrated behavior, and bilateral or unilateral hyperkinetic movements were statistically significant according to localization. Three clusters were identified according to the HSS and correlated with different patterns of anatomic localization of SOZ. Cluster 1 was characterized clinically by asymmetric hyperkinetic movements associated with marked dystonia and vocalization. It mainly included parietal seizures. Cluster 2 was characterized by bilateral and symmetrical stereotyped hyperkinetic movements without dystonia. It represented half of temporal seizures and one-third of prefrontal seizures (dorsolateral). Cluster 3 was characterized by seizures with strong emotionality and vocalization with bilateral and symmetrical hyperkinetic movements and integrated behavior. It involved half of temporal seizures and a majority of prefrontal (ventromesial) seizures. SIGNIFICANCE: We propose a first attempt to quantify clinical patterns of HKS. The HSS may help to predict SOZ localization according to three main groups of hyperkinetic seizures.

Contributions of electrophysiology for identifying cortical language systems in patients with epilepsy.

A crucial element of the surgical treatment of medically refractory epilepsy is to delineate cortical areas that must be spared in order to avoid clinically relevant neurological and neuropsychological deficits postoperatively. For each patient, this typically necessitates determining the language lateralization between hemispheres and language localization within hemisphere. Understanding cortical language systems is complicated by two primary challenges: the extent of the neural tissue involved and the substantial variability across individuals, especially in pathological populations. We review the contributions made through the study of electrophysiological activity to address these challenges. These contributions are based on the techniques of magnetoencephalography (MEG), intracerebral recordings, electrical-cortical stimulation (ECS), and the electrovideo analyses of seizures and their semiology. We highlight why no single modality alone is adequate to identify cortical language systems and suggest avenues for improving current practice.

A description of verbal and gestural communication during postictal aphasia.

Patients suffering from drug-resistant temporal lobe epilepsy show substantial language deficits (i.e., anomia) during their seizures and in the postictal period (postictal aphasia). Verbal impairments observed during the postictal period may be studied to help localizing the epileptogenic zone. These explorations have been essentially based on simple tasks focused on speech, thus disregarding the multimodal nature of verbal communication, particularly the fact that, when speakers want to communicate, they often produce gestures of various kinds. Here, we propose an innovative procedure for testing postictal language and communication abilities, including the assessment of co-speech gestures. We provide a preliminary description of the changes induced on communication during postictal aphasia. We studied 21 seizures that induced postictal aphasia from 12 patients with drug-refractory epilepsy, including left temporal and left frontal seizures. The experimental task required patients to memorize a highly detailed picture and, briefly after, to describe what they had seen, thus eliciting a communicative meaningful monologue. This allowed comparing verbal communication in postictal and interictal conditions within the same individuals. Co-speech gestures were coded according to two categories: "Rhythmic" gestures, thought to be produced in support of speech building, and "illustrative" gestures, thought to be produced to complement the speech content. When postictal and interictal conditions were compared, there was decreased speech flow along with an increase of rhythmic gesture production at the expense of illustrative gesture production. The communication patterns did not differ significantly after temporal and frontal seizures, yet they were illustrated separately, owing to the clinical importance of the distinction, along with considerations of interindividual variability. A contrast between rhythmic and illustrative gestures production is congruent with previous literature in which rhythmic gestures have been linked to lexical retrieval processes. If confirmed in further studies, such evidence for a facilitative role of co-speech gestures in language difficulties could be put to use in the context of multimodal language therapies.

Prefrontal seizure classification based on stereo-EEG quantification and automatic clustering.

PURPOSE: Frontal seizures are organized according to anatomo-functional subdivisions of the frontal lobe. Prefrontal seizures have been the subject of few detailed studies to date. The objective of this study was to identify subcategories of prefrontal seizures based on seizure onset quantification and to look for semiological differences. METHODS: Consecutive patients who underwent stereoelectroencephalography (SEEG) for drug-resistant prefrontal epilepsy between 2000 and 2018 were included. The different prefrontal regions investigated in our patients were dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), dorsomedial prefrontal cortex (DMPFC), ventromedial prefrontal cortex (VMPFC), and orbitofrontal cortex (OFC). The seizure onset zone (SOZ) was determined from one or two seizures in each patient, using the epileptogenicity index (EI) method. The presence or absence of 16 clinical ictal manifestations was analyzed. Classification of prefrontal networks was performed using the k-means automatic classification method. RESULTS: A total of 51 seizures from 31 patients were analyzed. The optimal clustering was 4 subgroups of prefrontal seizures: a "pure DLPF" group, a "pure VMPF" group, a "pure OFC" group, and a "global prefrontal" group. The first 3 groups showed a mean EI considered epileptogenic (>0.4) only in one predominant structure, while the fourth group showed a high mean EI in almost all prefrontal structures. The median number of epileptogenic structures per seizure (prefrontal or extrafrontal) was 5 for the "global prefrontal" group and 2 for the other groups. We found that the most common signs were altered consciousness, automatisms/stereotypies, integrated gestural motor behavior, and hyperkinetic motor behavior. We found no significant difference in the distribution of ictal signs between the different groups. CONCLUSION: Our study showed that although most prefrontal seizures manifest as a network of several anatomically distinct structures, we were able to determine a sublobar organization of prefrontal seizure onset with four groups.

Anatomoelectroclinical features of SEEG-confirmed pure insular-onset epilepsy.

PURPOSE: In this study, we aimed to improve our knowledge of insular epilepsy by studying anatomoelectroclinical correlations in pure insular-onset epilepsy and characterizing differences between anterior and posterior insular-onset seizures. METHODS: Patients in whom seizure-onset zone was confined to the insula and peri-insular sulcus were selected from 301 consecutive presurgical stereo-electroencephalography (EEG) recordings performed between years 2010 and 2017 in two epilepsy centers. Ictal-onset zone in stereo-EEG was delineated visually and quantitatively using epileptogenic index method. Seizure characteristics were reanalyzed, and anatomoelectroclinical correlations were assessed. Characteristics of posterior and anterior insular-onset seizures were compared. RESULTS: Eleven insular cases were identified, five of them with an anterior insular seizure onset and six with a posterior one. Nonpainful somatosensory symptoms and autonomic symptoms were the most common symptoms (73% of patients) followed by speech-related symptoms (55%) and ipsilateral eye blinking (45%). Six patients had seizures restricted to somatosensory or viscerosensory symptoms. In all patients, seizures progressed to motor symptoms. Somatosensory symptoms did not differentiate anterior from posterior insular seizures. However, hyperkinetic signs, speech modifications, and viscerosensory symptoms were related to an anterior insular seizure-onset zone. Pain, asymmetric tonic, focal clonic, and tonic symptoms were more frequent in patients with a posterior insular seizure onset. CONCLUSIONS: Seizure semiology is heterogeneous in pure insular-onset epilepsy. Differences between the anterior and posterior insular seizures reflect the functional organization of the insula. Particularly, the different types of motor symptoms may help to distinguish anterior from posterior insular seizure onset.

Stereoelectroencephalography (SEEG) and epilepsy surgery in posttraumatic epilepsy: A multicenter retrospective study.

PURPOSE: Posttraumatic epilepsy (PTE) is a common cause of drug-resistant epilepsy, especially in young adults. Nevertheless, such patients are not common candidates for intracranial presurgical evaluation. We investigated the role of stereoelectroencephalography (SEEG) in defining epileptogenicity and surgical strategy in patients with PTE. METHODS: We analyzed ictal SEEG recordings from 18 patients. We determined the seizure onset zone (SOZ) by quantifying the epileptogenicity of the sampled structures, using the "epileptogenicity index" (EI). We also identified seizure onset patterns (SOPs) through visual and frequency analysis. Postsurgical outcome was assessed by Engel's classification. RESULTS: The SOZ in PTE was most often located in temporal lobes, followed by frontal lobes. The SOZ was network-organized in the majority of the cases. Half of the SOP did not contain fast discharges. Half of the recordings showed SOZ that were less extensive than the posttraumatic lesions seen on brain magnetic resonance imaging (MRI). All but one operated patient benefited from tailored cortectomy. Only 3 patients were contraindicated for surgical resection due to bilateral epileptogenicity. The overall surgical outcome was good in majority of patients (67% Engel I). CONCLUSION: Despite the potential risk of bilateral or multifocal epilepsy, patients with PTE may benefit from presurgical assessment in well-selected cases. In this context, SEEG allows guidance of tailored resections adapted to the SOZ.

VNS implantation in a NF1 patient: massive nerve hypertrophy discovered intra-operatively preventing successful electrode placement. Case report.

For the vast majority of surgeons, no specific investigation is necessary before vagal nerve stimulation (VNS) implantation. We report our intraoperative unexpected finding of a massively enlarged vagus nerve in a patient with neurofibromatosis type 1 (NF1). The nerve hypertrophy prevented wrapping the coils of the helical electrode. The patient had no signs of vagus nerve dysfunction preoperatively (no hoarseness or dysphonia). This exceptional mishap is undoubtedly related to NF1-associated peripheral nerve sheath tumors. Even though it is not advisable to routinely perform any imaging prior to VNS, in such specific context, preoperative imaging work-up, especially cervical ultrasound, might be judicious to rule out any asymptomatic enlarged left vagus nerve.