Cortical activations associated with spatial remapping of finger touch using EEG.

The spatial coding of tactile information is functionally essential for touch-based shape perception and motor control. However, the spatiotemporal dynamics of how tactile information is remapped from the somatotopic reference frame in the primary somatosensory cortex to the spatiotopic reference frame remains unclear. This study investigated how hand position in space or posture influences cortical somatosensory processing. Twenty-two healthy subjects received electrical stimulation to the right thumb (D1) or little finger (D5) in three position conditions: palm down on right side of the body (baseline), hand crossing the body midline (effect of position), and palm up (effect of posture). Somatosensory-evoked potentials (SEPs) were recorded using electroencephalography. One early-, two mid-, and two late-latency neurophysiological components were identified for both fingers: P50, P1, N125, P200, and N250. D1 and D5 showed different cortical activation patterns: compared with baseline, the crossing condition showed significant clustering at P1 for D1, and at P50 and N125 for D5; the change in posture showed a significant cluster at N125 for D5. Clusters predominated at centro-parietal electrodes. These results suggest that tactile remapping of fingers after electrical stimulation occurs around 100-125 ms in the parietal cortex.

Quantitative analysis of early-stage EEG reactivity predicts awakening and recovery of consciousness in patients with severe brain injury.

BACKGROUND: Decisions of withdrawal of life-sustaining therapy for patients with severe brain injury are often based on prognostic evaluations such as analysis of electroencephalography (EEG) reactivity (EEG-R). However, EEG-R usually relies on visual assessment, which requires neurophysiological expertise and is prone to inter-rater variability. We hypothesised that quantitative analysis of EEG-R obtained 3 days after patient admission can identify new markers of subsequent awakening and consciousness recovery. METHODS: In this prospective observational study of patients with severe brain injury requiring mechanical ventilation, quantitative EEG-R was assessed using standard 11-lead EEG with frequency-based (power spectral density) and functional connectivity-based (phase-lag index) analyses. Associations between awakening in the intensive care unit (ICU) and reactivity to auditory and nociceptive stimulations were assessed with logistic regression. Secondary outcomes included in-ICU mortality and 3-month Coma Recovery Scale-Revised (CRS-R) score. RESULTS: Of 116 patients, 86 (74%) awoke in the ICU. Among quantitative EEG-R markers, variation in phase-lag index connectivity in the delta frequency band after noise stimulation was associated with awakening (adjusted odds ratio=0.89, 95% confidence interval: 0.81-0.97, P=0.02 corrected for multiple tests), independently of age, baseline severity, and sedation. This new marker was independently associated with improved 3-month CRS-R (adjusted ß=-0.16, standard error 0.075, P=0.048), but not with mortality (adjusted odds ratio=1.08, 95% CI: 0.99-1.18, P=0.10). CONCLUSIONS: An early-stage quantitative EEG-R marker was independently associated with awakening and 3-month level of consciousness in patients with severe brain injury. This promising marker based on functional connectivity will need external validation before potential integration into a multimodal prognostic model.

Neurophysiological explorations across the spectrum of psychosis, autism, and depression, during wakefulness and sleep: protocol of a prospective case-control transdiagnostic multimodal study (DEMETER).

BACKGROUND: Quantitative electroencephalography (EEG) analysis offers the opportunity to study high-level cognitive processes across psychiatric disorders. In particular, EEG microstates translate the temporal dynamics of neuronal networks throughout the brain. Their alteration may reflect transdiagnostic anomalies in neurophysiological functions that are impaired in mood, psychosis, and autism spectrum disorders, such as sensorimotor integration, speech, sleep, and sense of self. The main questions this study aims to answer are as follows: 1) Are EEG microstate anomalies associated with clinical and functional prognosis, both in resting conditions and during sleep, across psychiatric disorders? 2) Are EEG microstate anomalies associated with differences in sensorimotor integration, speech, sense of self, and sleep? 3) Can the dynamic of EEG microstates be modulated by a non-drug intervention such as light hypnosis? METHODS: This prospective cohort will include a population of adolescents and young adults, aged 15 to 30 years old, with ultra-high-risk of psychosis (UHR), first-episode psychosis (FEP), schizophrenia (SCZ), autism spectrum disorder (ASD), and major depressive disorder (MDD), as well as healthy controls (CTRL) (N = 21 × 6), who will be assessed at baseline and after one year of follow-up. Participants will undergo deep phenotyping based on psychopathology, neuropsychological assessments, 64-channel EEG recordings, and biological sampling at the two timepoints. At baseline, the EEG recording will also be coupled to a sensorimotor task and a recording of the characteristics of their speech (prosody and turn-taking), a one-night polysomnography, a self-reference effect task in virtual reality (only in UHR, FEP, and CTRL). An interventional ancillary study will involve only healthy controls, in order to assess whether light hypnosis can modify the EEG microstate architecture in a direction opposite to what is seen in disease. DISCUSSION: This transdiagnostic longitudinal case-control study will provide a multimodal neurophysiological assessment of clinical dimensions (sensorimotor integration, speech, sleep, and sense of self) that are disrupted across mood, psychosis, and autism spectrum disorders. It will further test the relevance of EEG microstates as dimensional functional biomarkers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT06045897.

Early Clinical and Electrophysiological Brain Dysfunction Is Associated With ICU Outcomes in COVID-19 Critically Ill Patients With Acute Respiratory Distress Syndrome: A Prospective Bicentric Observational Study.

OBJECTIVES: Describe the prevalence of acute cerebral dysfunction and assess the prognostic value of an early clinical and electroencephalography (EEG) assessment in ICU COVID-19 patients. DESIGN: Prospective observational study. SETTING: Two tertiary critical care units in Paris, France, between April and December 2020. PATIENTS: Adult critically ill patients with COVID-19 acute respiratory distress syndrome. INTERVENTIONS: Neurologic examination and EEG at two time points during the ICU stay, first under sedation and second 4-7 days after sedation discontinuation. MEASUREMENTS AND MAIN RESULTS: Association of EEG abnormalities (background reactivity, continuity, dominant frequency, and presence of paroxystic discharges) with day-28 mortality and neurologic outcomes (coma and delirium recovery). Fifty-two patients were included, mostly male (81%), median (interquartile range) age 68 years (56-74 yr). Delayed awakening was present in 68% of patients (median awakening time of 5 d [2-16 d]) and delirium in 74% of patients who awoke from coma (62% of mixed delirium, median duration of 5 d [3-8 d]). First, EEG background was slowed in the theta-delta range in 48 (93%) patients, discontinuous in 25 patients (48%), and nonreactive in 17 patients (33%). Bifrontal slow waves were observed in 17 patients (33%). Early nonreactive EEG was associated with lower day-28 ventilator-free days (0 vs 16; p = 0.025), coma-free days (6 vs 22; p = 0.006), delirium-free days (0 vs 17; p = 0.006), and higher mortality (41% vs 11%; p = 0.027), whereas discontinuous background was associated with lower ventilator-free days (0 vs 17; p = 0.010), coma-free days (1 vs 22; p < 0.001), delirium-free days (0 vs 17; p = 0.001), and higher mortality (40% vs 4%; p = 0.001), independently of sedation and analgesia. CONCLUSIONS: Clinical and neurophysiologic cerebral dysfunction is frequent in COVID-19 ARDS patients. Early severe EEG abnormalities with nonreactive and/or discontinuous background activity are associated with delayed awakening, delirium, and day-28 mortality.

Cathodal Transcranial Direct Current Stimulation in Acute Ischemic Stroke: Pilot Randomized Controlled Trial.

Background and Purpose: In acute stroke, preventing infarct growth until complete recanalization occurs is a promising approach as an adjunct to reperfusion therapies to reduce infarct size and improve outcome. In rodent models, cathodal transcranial direct current stimulation (C-tDCS) decreases peri-infarct depolarizations and reduces infarct volume. We hypothesized that C-tDCS would nonpharmacologically reduce infarct growth in hyperacute middle cerebral artery territory stroke patients receiving reperfusion therapy. Methods: STICA (Cathodal Transcranial Direct Stimulation in Acute Middle Cerebral Artery Stroke) was a pilot single-center, double-blind, 2-arms 1:1 randomized trial evaluating the safety, feasibility, and efficacy of C-tDCS versus sham stimulation in patients eligible for recanalization therapies. Magnetic resonance imaging was obtained both on admission and 24 hours later. The primary end point was 24-hour infarct growth. Secondary outcomes were (1) National Institutes of Health Stroke Scale score difference between day 7 and admission and (2) 3-month modified Rankin Scale score. Results: Forty-five patients were randomized. Median magnetic resonance imaging-to-C-tDCS start time was 45 minutes; C-tDCS was started before completion of recanalization procedure in all patients. The intervention proved feasible in all patients. No major adverse effects occurred in either group. There was no significant difference between active and sham groups for any end point. However, an apparent trend towards smaller infarct growth in the C-tDCS arm was observed in the whole group (unadjusted median difference [IC95%]: −2.2 mL [−12.2 to 1.5]) and in the prespecified subsamples with moderate-to-severe stroke and large vessel occlusion (−5.7 mL [−21.6 to 2.6] and −7.7 mL [−24.2 to 2.6], respectively). Conclusions: C-tDCS was feasible and well tolerated. No significant difference was found between the active and sham groups. However, the data suggest potential benefits of C-tDCS in patients with National Institutes of Health Stroke Scale score of >10 or large vessel occlusion. Using the observed effect size and standard α=5% and ß=20%, samples of 102 and 86, respectively, can be estimated for future trials in patients with these characteristics. Randomized trials particularly targeting these populations may be warranted.

Respective Contribution of Ictal and Inter-ictal Electrical Source Imaging to Epileptogenic Zone Localization.

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

Value and mechanisms of EEG reactivity in the prognosis of patients with impaired consciousness: a systematic review.

BACKGROUND: Electroencephalography (EEG) is a well-established tool for assessing brain function that is available at the bedside in the intensive care unit (ICU). This review aims to discuss the relevance of electroencephalographic reactivity (EEG-R) in patients with impaired consciousness and to describe the neurophysiological mechanisms involved. METHODS: We conducted a systematic search of the term "EEG reactivity and coma" using the PubMed database. The search encompassed articles published from inception to March 2018 and produced 202 articles, of which 42 were deemed relevant, assessing the importance of EEG-R in relationship to outcomes in patients with impaired consciousness, and were therefore included in this review. RESULTS: Although definitions, characteristics and methods used to assess EEG-R are heterogeneous, several studies underline that a lack of EEG-R is associated with mortality and unfavorable outcome in patients with impaired consciousness. However, preserved EEG-R is linked to better odds of survival. Exploring EEG-R to nociceptive, auditory, and visual stimuli enables a noninvasive trimodal functional assessment of peripheral and central sensory ascending pathways that project to the brainstem, the thalamus and the cerebral cortex. A lack of EEG-R in patients with impaired consciousness may result from altered modulation of thalamocortical loop activity by afferent sensory input due to neural impairment. Assessing EEG-R is a valuable tool for the diagnosis and outcome prediction of severe brain dysfunction in critically ill patients. CONCLUSIONS: This review emphasizes that whatever the etiology, patients with impaired consciousness featuring a reactive electroencephalogram are more likely to have a favorable outcome, whereas those with a nonreactive electroencephalogram are prone to having an unfavorable outcome. EEG-R is therefore a valuable prognostic parameter and warrants a rigorous assessment. However, current assessment methods are heterogeneous, and no consensus exists. Standardization of stimulation and interpretation methods is needed.

Seizure-onset patterns in focal cortical dysplasia and neurodevelopmental tumors: Relationship with surgical prognosis and neuropathologic subtypes.

OBJECTIVES: The study of intracerebral electroencephalography (EEG) seizure-onset patterns is crucial to accurately define the epileptogenic zone and guide successful surgical resection. It also raises important pathophysiologic issues concerning mechanisms of seizure generation. Until now, several seizure-onset patterns have been described using distinct recording methods (subdural, depth electrode), mostly in temporal lobe epilepsies or with heterogeneous neocortical lesions. METHODS: We analyzed data from a cohort of 53 consecutive patients explored by stereoelectroencephalography (SEEG) and with pathologically confirmed malformation of cortical development (MCD; including focal cortical dysplasia [FCD] and neurodevelopmental tumors [NDTs]). RESULTS: We identified six seizure-onset patterns using visual and time-frequency analysis: low-voltage fast activity (LVFA); preictal spiking followed by LVFA; burst of polyspikes followed by LVFA; slow wave/DC shift followed by LVFA; theta/alpha sharp waves; and rhythmic spikes/spike-waves. We found a high prevalence of patterns that included LVFA (83%), indicating nevertheless that LVFA is not a constant characteristic of seizure onset. An association between seizure-onset patterns and histologic types was found (p = 001). The more prevalent patterns were as follows: (1) in FCD type I LVFA (23.1%) and slow wave/baseline shift followed by LVFA (15.4%); (2) in FCD type II burst of polyspikes followed by LVFA (31%), LVFA (27.6%), and preictal spiking followed by LVFA (27.6%); (3) in NDT, LVFA (54.5%). We found that a seizure-onset pattern that included LVFA was associated with favorable postsurgical outcome, but the completeness of the EZ resection was the sole independent predictive variable. SIGNIFICANCE: Six different seizure-onset patterns can be described in FCD and NDT. Better postsurgical outcome is associated with patterns that incorporate LVFA.

Ictal Magnetic Source Imaging in Presurgical Assessment.

Ictal MEG recordings constitute rare data. The objective of this study was to evaluate ictal magnetic source localization (MSI), using two algorithms: linearly constrained minimum variance (LCMV), a beamforming technique and equivalent current dipole (ECD). Ictal MSI was studied in six patients. Three of them were undergoing post-operative re-evaluation. For all patients, results were validated by the stereoelectroencephalographic (SEEG) definition of the epileptogenic zone (EZ). EZ was quantified using the epileptogenicity index (EI) method, which accounts for both the propensity of a brain area to generate rapid discharges and the time for this area to become involved in the seizure. EI values range from 0 (no epileptogenicity) to 1 (maximal epileptogenicity). Levels of concordance between ictal MSI and EZ were determined as follows: A: ictal MSI localized the site whose value EI = 1, B: MSI localized a part of the EZ (not corresponding to the maximal value of EI = 1), C: a region could be identified on ictal MSI but not on SEEG, D: a region could be identified on SEEG but not on MSI, E: different regions were localized on MSI and SEEG. Ictal MEG pattern consisted of rhythmic activities between 10 and 20 Hz for all patients. For LCMV (first maxima), levels of concordance were A (two cases), B (two cases) and E (two cases). For ECD fitted on each time point separately (location characterized by the best goodness-of-fit value), levels of concordance were A (one case), B (one case), D (three cases) and E (one case). For ECD calculated for the whole time window, levels of concordance were A (two cases) and D (four cases). Source localization methods performed on rhythmic patterns can localize the EZ as validated by SEEG. In terms of concordance, LCMV was superior to ECD. In some cases, LCMV allows extraction of several maxima that could reflect ictal dynamics. In a medial temporal lobe epilepsy case, ictal MSI indicated an area of delayed propagation and was non-contributory to the presurgical assessment.

Comparison of Brain Networks During Interictal Oscillations and Spikes on Magnetoencephalography and Intracerebral EEG.

Electromagnetic source localization in electroencephalography (EEG) and magnetoencephalography (MEG) allows finding the generators of transient interictal epileptiform discharges ('interictal spikes'). In intracerebral EEG (iEEG), oscillatory activity (above 30 Hz) has also been shown to be a marker of neuronal dysfunction. Still, the difference between networks involved in transient and oscillatory activities remains largely unknown. Our goal was thus to extract and compare the networks involved in interictal oscillations and spikes, and to compare the non-invasive results to those obtained directly within the brain. In five patients with both MEG and iEEG recordings, we computed correlation graphs across regions, for (1) interictal spikes and (2) epileptic oscillations around 30 Hz. We show that the corresponding networks can involve a widespread set of regions (average of 10 per patient), with only partial overlap (38 % of the total number of regions in MEG, 50 % in iEEG). The non-invasive results were concordant with intracerebral recordings (79 % for the spikes and 50 % for the oscillations). We compared our interictal results to iEEG ictal data. The regions labeled as seizure onset zone (SOZ) belonged to interictal networks in a large proportion of cases: 75 % (resp. 58 %) for spikes and 58 % (resp. 33 %) for oscillations in iEEG (resp. MEG). A subset of SOZ regions were detected by one type of discharges but not the other (25 % for spikes and 8 % for oscillations). Our study suggests that spike and oscillatory activities involve overlapping but distinct networks, and are complementary for presurgical mapping.

Occipital and occipital "plus" epilepsies: A study of involved epileptogenic networks through SEEG quantification.

Compared with temporal or frontal lobe epilepsies, the occipital lobe epilepsies (OLE) remain poorly characterized. In this study, we aimed at classifying the ictal networks involving OLE and investigated clinical features of the OLE network subtypes. We studied 194 seizures from 29 consecutive patients presenting with OLE and investigated by stereoelectroencephalography (SEEG). Epileptogenicity of occipital and extraoccipital regions was quantified according to the 'epileptogenicity index' (EI) method. We found that 79% of patients showed widespread epileptogenic zone organization, involving parietal or temporal regions in addition to the occipital lobe. Two main groups of epileptogenic zone organization within occipital lobe seizures were identified: a pure occipital group and an occipital "plus" group, the latter including two further subgroups, occipitotemporal and occipitoparietal. In 29% of patients, the epileptogenic zone was found to have a bilateral organization. The most epileptogenic structure was the fusiform gyrus (mean EI: 0.53). Surgery was proposed in 18/29 patients, leading to seizure freedom in 55% (Engel Class I). Results suggest that, in patient candidates for surgery, the majority of cases are characterized by complex organization of the EZ, corresponding to the occipital plus group.

Rapid detection of generalized anxiety disorder and major depression in epilepsy: Validation of the GAD-7 as a complementary tool to the NDDI-E in a French sample.

OBJECTIVE: Generalized anxiety disorder (GAD) in people with epilepsy (PWE) is underdiagnosed and undertreated. The GAD-7 is a screening questionnaire to detect GAD. However, the usefulness of the GAD-7 as a screening tool in PWE remains to be validated. Thus, we aimed to: (1) validate the GAD-7 in French PWE and (2) assess its complementarity with regard to the previously validated screening tool for depression, the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E). METHODS: This study was performed under the auspices of the ILAE Commission on Neuropsychiatry. People with epilepsy >18 years of age were recruited from the specialist epilepsy unit in Marseille, France. The Mini-International Neuropsychiatric Interview (MINI) was performed as gold standard, and the Penn State Worry Questionnaire (PSWQ) and the NDDI-E were performed for external validity. Data were compared between PWE with/without GAD using Chi(2) test and Student's t-test. Internal structural validity, external validity, and receiver operator characteristics were analyzed. A principal component factor analysis with Varimax rotation was performed on the 13 items of the GAD-7 (7 items) plus the NDDI-E (6 items). RESULTS: Testing was performed on 145 PWE: mean age = 39.38 years old (SD=14.01, range: 18-75); 63.4% (92) women; 75.9% with focal epilepsy. Using the MINI, 49 (33.8%) patients had current GAD. Cronbach's alpha coefficient was 0.898, indicating satisfactory internal consistency. Correlation between GAD-7 and the PSQW scores was high (r (145)=.549, P<.0001), indicating good external validity. Factor analysis shows that the anxiety investigated with the GAD-7 and depression investigated with the NDDI-E reflect distinct factors. Receiver operator characteristic analysis showed area under the curve of 0.899 (95% CI 0.838-0.943, P < 0.0001) indicating good capacity of the GAD-7 to detect GAD (defined by MINI). Cutoff for maximal sensitivity and specificity was 7. Mean GAD-7 score in PWE with GAD was 13.22 (SD = 3.99), and that without GAD was 5.17 (SD = 4.66). SIGNIFICANCE: This study validates the French language version of the GAD-7 screening tool for generalized anxiety in PWE, with a cutoff score of 7/21 for GAD, and also confirms that the GAD-7 is a short and easily administered test. Factor analysis shows that the GAD-7 (screening for generalized anxiety disorder) and the NDDI-E (screening for major depression) provide complementary information. The routine use of both GAD-7 and NDDI-E should be considered in clinical evaluation of patients with epilepsy.

Intraoperative spinal cord monitoring in children under 4 years old.

PURPOSE: The purpose was to study intraoperative spinal cord monitoring (IOM) particularities and performances in children under 4 years old with congenital spinal deformities. IOM is characterized by specific difficulties due to the immaturity of sensory-motor pathways in such young patients. To the best of our knowledge, this study is the largest dedicated to IOM in this challenging population. METHODS: This study was retrospective and monocentric. 78 IOM in children under 4 years old were analyzed. Somatosensory evoked potentials (SSEP), neurogenic mixed evoked potentials (NMEP) and D waves were performed. Patients were classified into one of four categories with respect to IOM data and clinical outcome: true positive, false positive, true negative and false negative. Sensitivity and specificity were then calculated accordingly. RESULTS: There were 6 true positive, 3 false positive, 67 true negative and 1 false negative outcomes. One patient was characterized by unreliable baseline IOM data. IOM sensitivity was 86 %. IOM specificity was 96 %. The false negative case was monitored using SSEP alone. IOM was difficult in 10/77 cases, being unilateral because of a planned fibular graft harvest. NMEP were characterized by higher signal-to-noise ratio than SSEP. CONCLUSIONS: Immaturity of sensory-motor pathways predominates in the central rather than the peripheral nervous system in young children. MEP and D waves could thus be difficult to obtain. Although non-specific to motor pathways, it could be useful to "by-pass" the brain, using NMEP. In regard to maturational particularities, IOM in children under 4 years old should be performed by experienced neurophysiologists, avoiding in these cases surgeon-guided devices.

18FDG-PET in different subtypes of temporal lobe epilepsy: SEEG validation and predictive value.

OBJECTIVE: The objective of the study was to characterize interictal 18-fluorodeoxyglucose-positron emission tomography ((18) FDG-PET) whole-brain voxel-based metabolic patterns among distinct subtypes of temporal lobe epilepsy (TLE), as defined by stereo-electroencephalography (SEEG) and to determine predictive value of PET result on postoperative outcome. METHODS: Fifty-four consecutive patients with pharmacoresistant TLE were enrolled retrospectively after a comprehensive presurgical evaluation. This evaluation defined: 7 lateral TLE, 17 mesial TLE, 14 "plus" TLE, and 16 bilateral TLE. Whole-brain voxel-based brain metabolism was studied in each group of patients, in comparison to 23 healthy subjects, and individual classification was evaluated by cross-validation using the found clusters. An (18) FDG-PET index was moreover calculated for each patient, based on the individual Z-score of the most significant cluster extracted on the comparison between patients' subgroup and healthy subjects. Logistic regression analysis was used to estimate factors associated with postoperative outcome (Engel's classes III-IV vs. I-II), including age, gender, disease duration, seizure frequency, as well as magnetic resonance imaging (MRI) and PET findings. RESULTS: Different patterns of hypometabolism were found inside and outside the epileptogenic zone, among patients with distinct subgroups of TLE, in comparison to healthy subjects (p < 0.001, corrected for the cluster). At individual level, cross-validation showed satisfactory discrimination between the four groups with 71.4-88.2% overall accuracy. Multivariate analysis shows that (18) FDG-PET index was the only significant predictor of postoperative outcome to distinguish between Engel's classes I-II and III-IV (p = 0.037). SIGNIFICANCE: Overall, this whole-brain voxel-based analysis validates specific patterns of hypometabolism, inside and outside the EZ, in distinct subgroups of patients with TLE, as defined by SEEG gold standard, and in relation with postoperative outcome.

Magnetic source imaging in posterior cortex epilepsies.

Posterior cortex epilepsies (PCE) are characterized by less satisfying postoperative results than temporal lobe epilepsies and are thus challenging for non-invasive presurgical investigations. The objective of this study was to evaluate the performance of magnetic source imaging (MSI) in PCE, validating the results by the SEEG (stereoelectroencephalography) definition of irritative and epileptogenic zones (IZ and EZ). Fourteen PCE surgery candidates were investigated using MSI and SEEG. LCMV (Linearly Constrained Minimum Variance) and MUSIC algorithms were used. IZ was quantified using a semi-automatic detection of interictal spikes. EZ was quantified using the epileptogenicity index (EI) method that accounts for both the propensity of a brain area to generate rapid discharges and the time for this area to get involved in the seizure. EI values range from 0 (no epileptogenicity) to 1 (maximal epileptogenicity). Levels of concordance between MSI and IZ, MSI and EZ were determined as follows: A = localized on MSI and SEEG for the site of value 1 (IZ and EZ quantification), B = localized on MSI and SEEG for a part of the IZ or a structure involved in the EZ (without the maximal value 1), C = localized on MSI and not SEEG, D = localized on SEEG and not MSI, E = localized on MSI and SEEG, discordant for site. Five PCE cases were characterized by focal IZ, nine by distributed IZ between several distant brain areas. MSI allowed to determinate IZ in 4/5 focal IZ cases. In case of distributed IZ, levels of concordance were A (2 cases), B (4 cases) and D (3 cases). In most distributed cases, MSI allowed to localize only a part of the IZ. Medial temporal involvement in the IZ was frequent (9/12 cases) and not evidenced by MSI. The brain area that demonstrated the maximal value of EI was shown by MSI in four out of five (80 %) focal IZ cases, in two out of nine (22 %) distributed cases. MSI results depend on IZ characteristics. A distributed IZ organization presents difficulties for MSI and highlights the need for further methodological approaches.

One step closer to a global tool for rapid screening of major depression in epilepsy: validation of the French NDDI-E.

OBJECTIVE: Depression in people with epilepsy (PWE) is underdiagnosed and undertreated. The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) is a screening questionnaire used for detecting major depressive episode (MDE) in PWE, and is already validated in 10 languages. However a version in French, one of the world's widely spoken languages, was, until now, lacking. We aimed to translate and validate the French NDDI-E. METHODS: This study was performed under the auspices of the ILAE. People with epilepsy >18years of age were recruited from 2 specialist epilepsy units in Marseille, France. Two native French speakers and 2 native English speakers performed a forward-backward translation. The Mini International Neuropsychiatric Interview (MINI) was performed as the gold standard, and the Center for Epidemiological Studies Depression symptoms index (CES-D) was performed for external validity. Data were compared between PWE with MDE and PWE without MDE using the chi-square test and Student's t-test. Internal structural validity, external validity, and receiver operator characteristics were analyzed. RESULTS: Testing was performed on 116 PWE: mean age=40.39years (SD=13.83, range: [18-81]years old); 58.6% (68) were women; 87.1% had focal epilepsy. Using the MINI, we found that 33 (28.4%) patients had current MDE and that 15 (12.9%) patients had dysthymia; also, we found that 37 (31.9%) patients presented suicidal ideation and/or behavior. Cronbach's alpha coefficient was 0.838, indicating satisfactory internal consistency. Correlation between the NDDI-E and the CES-D scores was high (r(116)=0.817, p<0.0001), indicating good external validity. Receiver operator characteristic analysis showed an area under the curve of 0.958 (95% CI=0.904-0.986), (p<0.0001), indicating good capacity of the NDDI-E to detect MDE (defined by MINI). The cutoff for maximal sensitivity and specificity was 15. The mean NDDI-E score in PWE with MDE was 18.27 (SD=2.28), and the mean NDDI-E score in PWE without MDE was 10.61 (SD=3.63). SIGNIFICANCE: This study validated the French NDDI-E, with a cutoff score of 15/24 for MDE, similar to previous studies, and reinforces the NDDI-E as a global tool for detection of MDE.

Simultaneous recording of MEG, EEG and intracerebral EEG during visual stimulation: from feasibility to single-trial analysis.

Electroencephalography (EEG), magnetoencephalography (MEG), and intracerebral stereotaxic EEG (SEEG) are the three neurophysiological recording techniques, which are thought to capture the same type of brain activity. Still, the relationships between non-invasive (EEG, MEG) and invasive (SEEG) signals remain to be further investigated. In early attempts at comparing SEEG with either EEG or MEG, the recordings were performed separately for each modality. However such an approach presents substantial limitations in terms of signal analysis. The goal of this technical note is to investigate the feasibility of simultaneously recording these three signal modalities (EEG, MEG and SEEG), and to provide strategies for analyzing this new kind of data. Intracerebral electrodes were implanted in a patient with intractable epilepsy for presurgical evaluation purposes. This patient was presented with a visual stimulation paradigm while the three types of signals were simultaneously recorded. The analysis started with a characterization of the MEG artifact caused by the SEEG equipment. Next, the average evoked activities were computed at the sensor level, and cortical source activations were estimated for both the EEG and MEG recordings; these were shown to be compatible with the spatiotemporal dynamics of the SEEG signals. In the average time-frequency domain, concordant patterns between the MEG/EEG and SEEG recordings were found below the 40 Hz level. Finally, a fine-grained coupling between the amplitudes of the three recording modalities was detected in the time domain, at the level of single evoked responses. Importantly, these correlations have shown a high level of spatial and temporal specificity. These findings provide a case for the ability of trimodal recordings (EEG, MEG, and SEEG) to reach a greater level of specificity in the investigation of brain signals and functions.

Interictal networks in magnetoencephalography.

Epileptic networks involve complex relationships across several brain areas. Such networks have been shown on intracerebral EEG (stereotaxic EEG, SEEG), an invasive technique. Magnetoencephalography (MEG) is a noninvasive tool, which was recently proven to be efficient for localizing the generators of epileptiform discharges. However, despite the importance of characterizing non-invasively network aspects in partial epilepsies, only few studies have attempted to retrieve fine spatiotemporal dynamics of interictal discharges with MEG. Our goal was to assess the relevance of magnetoencephalography for detecting and characterizing the brain networks involved in interictal epileptic discharges. We propose here a semi-automatic method based on independent component analysis (ICA) and on co-occurrence of events across components. The method was evaluated in a series of seven patients by comparing its results with networks identified in SEEG. On both MEG and SEEG, we found that interictal discharges can involve remote regions which are acting in synchrony. More regions were identified in SEEG (38 in total) than in MEG (20). All MEG regions were confirmed by SEEG when an electrode was present in the vicinity. In all patients, at least one region could be identified as leading according to our criteria. A majority (71%) of MEG leaders were confirmed by SEEG. We have therefore shown that MEG measurements can extract a significant proportion of the networks visible in SEEG. This suggests that MEG can be a useful tool for defining noninvasively interictal epileptic networks, in terms of regions and patterns of connectivity, in search for a "primary irritative zone".

Frontal lobe seizures: from clinical semiology to localization.

OBJECTIVE: Frontal lobe seizures are difficult to characterize according to semiologic and electrical features. We wished to establish whether different semiologic subgroups can be identified and whether these relate to anatomic organization. METHODS: We assessed all seizures from 54 patients with frontal lobe epilepsy that were explored with stereoelectroencephalography (SEEG) during presurgical evaluation. Semiologic features and concomitant intracerebral EEG changes were documented and quantified. These variables were examined using Principal Component Analysis and Cluster Analysis, and semiologic features correlated with anatomic localization. RESULTS: Four main groups of patients were identified according to semiologic features, and correlated with specific patterns of anatomic seizure localization. Group 1 was characterized clinically by elementary motor signs and involved precentral and premotor regions. Group 2 was characterized by a combination of elementary motor signs and nonintegrated gestural motor behavior, and involved both premotor and prefrontal regions. Group 3 was characterized by integrated gestural motor behavior with distal stereotypies and involved anterior lateral and medial prefrontal regions. Group 4 was characterized by seizures with fearful behavior and involved the paralimbic system (ventromedial prefrontal cortex ± anterior temporal structures). The groups were organized along a rostrocaudal axis, representing bands within a spectrum rather than rigid categories. The more anterior the seizure organization, the more likely was the occurrence of integrated behavior during seizures. Distal stereotypies were associated with the most anterior prefrontal localizations, whereas proximal stereotypies occurred in more posterior prefrontal regions. SIGNIFICANCE: Meaningful categorization of frontal seizures in terms of semiology is possible and correlates with anatomic organization along a rostrocaudal axis, in keeping with current hypotheses of frontal lobe hierarchical organization. The proposed electroclinical categorization offers pointers as to the likely zone of organization of networks underlying semiologic production, thus aiding presurgical localization. Furthermore, analysis of ictal motor behavior in prefrontal seizures, including stereotypies, leads to deciphering the cortico-subcortical networks that produce such behaviors.