Cortical responses to looming sources are explained away by the auditory periphery.

A wealth of behavioral evidence indicate that sounds with increasing intensity (i.e. appear to be looming towards the listener) are processed with increased attentional and physiological resources compared to receding sounds. However, the neurophysiological mechanism responsible for such cognitive amplification remains elusive. Here, we show that the large differences seen between cortical responses to looming and receding sounds are in fact almost entirely explained away by nonlinear encoding at the level of the auditory periphery. We collected electroencephalography (EEG) data during an oddball paradigm to elicit mismatch negativity (MMN) and others Event Related Potentials (EPRs), in response to deviant stimuli with both dynamic (looming and receding) and constant level (flat) differences to the standard in the same participants. We then combined a computational model of the auditory periphery with generative EEG methods (temporal response functions, TRFs) to model the single-participant ERPs responses to flat deviants, and used them to predict the effect of the same mechanism on looming and receding stimuli. The flat model explained 45% variance of the looming response, and 33% of the receding response. This provide striking evidence that difference wave responses to looming and receding sounds result from the same cortical mechanism that generate responses to constant-level deviants: all such differences are the sole consequence of their particular physical morphology getting amplified and integrated by peripheral auditory mechanisms. Thus, not all effects seen cortically proceed from top-down modulations by high-level decision variables, but can rather be performed early and efficiently by feed-forward peripheral mechanisms that evolved precisely to sparing subsequent networks with the necessity to implement such mechanisms.

Prognostic value of early EEG abnormalities in severe stroke patients requiring mechanical ventilation: a pre-planned analysis of the SPICE prospective multicenter study.

INTRODUCTION: Prognostication of outcome in severe stroke patients necessitating invasive mechanical ventilation poses significant challenges. The objective of this study was to assess the prognostic significance and prevalence of early electroencephalogram (EEG) abnormalities in adult stroke patients receiving mechanical ventilation. METHODS: This study is a pre-planned ancillary investigation within the prospective multicenter SPICE cohort study (2017-2019), conducted in 33 intensive care units (ICUs) in the Paris area, France. We included adult stroke patients requiring invasive mechanical ventilation, who underwent at least one intermittent EEG examination during their ICU stay. The primary endpoint was the functional neurological outcome at one year, determined using the modified Rankin scale (mRS), and dichotomized as unfavorable (mRS 4-6, indicating severe disability or death) or favorable (mRS 0-3). Multivariable regression analyses were employed to identify EEG abnormalities associated with functional outcomes. RESULTS: Of the 364 patients enrolled in the SPICE study, 153 patients (49 ischemic strokes, 52 intracranial hemorrhages, and 52 subarachnoid hemorrhages) underwent at least one EEG at a median time of 4 (interquartile range 2-7) days post-stroke. Rates of diffuse slowing (70% vs. 63%, p = 0.37), focal slowing (38% vs. 32%, p = 0.15), periodic discharges (2.3% vs. 3.7%, p = 0.9), and electrographic seizures (4.5% vs. 3.7%, p = 0.4) were comparable between patients with unfavorable and favorable outcomes. Following adjustment for potential confounders, an unreactive EEG background to auditory and pain stimulations (OR 6.02, 95% CI 2.27-15.99) was independently associated with unfavorable outcomes. An unreactive EEG predicted unfavorable outcome with a specificity of 48% (95% CI 40-56), sensitivity of 79% (95% CI 72-85), and positive predictive value (PPV) of 74% (95% CI 67-81). Conversely, a benign EEG (defined as continuous and reactive background activity without seizure, periodic discharges, triphasic waves, or burst suppression) predicted favorable outcome with a specificity of 89% (95% CI 84-94), and a sensitivity of 37% (95% CI 30-45). CONCLUSION: The absence of EEG reactivity independently predicts unfavorable outcomes at one year in severe stroke patients requiring mechanical ventilation in the ICU, although its prognostic value remains limited. Conversely, a benign EEG pattern was associated with a favorable outcome.

Status epilepticus: what's new for the intensivist.

PURPOSE OF REVIEW: Status epilepticus (SE) is a common neurologic emergency affecting about 36.1/100 000 person-years that frequently requires intensive care unit (ICU) admission. There have been advances in our understanding of epidemiology, pathophysiology, and EEG monitoring of SE, and there have been large-scale treatment trials, discussed in this review. RECENT FINDINGS: Recent changes in the definitions of SE have helped guide management protocols and we have much better predictors of outcome. Observational studies have confirmed the efficacy of benzodiazepines and large treatment trials indicate that all routinely used second line treatments (i.e., levetiracetam, valproate and fosphenytoin) are equally effective. Better understanding of the pathophysiology has indicated that nonanti-seizure medications aimed at underlying pathological processes should perhaps be considered in the treatment of SE; already immunosuppressant treatments are being more widely used in particular for new onset refractory status epilepticus (NORSE) and Febrile infection-related epilepsy syndrome (FIRES) that sometimes revealed autoimmune or paraneoplastic encephalitis. Growing evidence for ICU EEG monitoring and major advances in automated analysis of the EEG could help intensivist to assess the control of electrographic seizures. SUMMARY: Research into the morbi-mortality of SE has highlighted the potential devastating effects of this condition, emphasizing the need for rapid and aggressive treatment, with particular attention to cardiorespiratory and neurological complications. Although we now have a good evidence-base for the initial status epilepticus management, the best treatments for the later stages are still unclear and clinical trials of potentially disease-modifying therapies are long overdue.

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.

Electroencephalography microstates imbalance across the spectrum of early psychosis, autism, and mood disorders.

BACKGROUND: Electroencephalography (EEG) microstates translate resting-state temporal dynamics of neuronal networks throughout the brain and could constitute possible markers of psychiatric disorders. We tested the hypothesis of an increased imbalance between a predominant self-referential mode (microstate C) and a decreased attentional mode (microstate D) in psychosis, mood, and autism spectrum disorders. METHODS: We retrospectively included 135 subjects from an early psychosis outpatient unit, with available eyes-closed resting-state 19 electrodes EEG. Individual-level then group-level modified K-means clustering in controls provided four microstate maps that were then backfitted to all groups. Differences between microstate parameters (occurrence, coverage, and mean duration) were computed between controls and each group, and between disease groups. RESULTS: Microstate class D parameters were systematically decreased in disease groups compared with controls, with an effect size increasing along the psychosis spectrum, but also in autism. There was no difference in class C. C/D ratios of mean duration were increased only in SCZ compared with controls. CONCLUSIONS: The decrease in microstate class D may be a marker of stage of psychosis, but it is not specific to it and may rather reflect a shared dimension along the schizophrenia-autism spectrum. C/D microstate imbalance may be more specific to schizophrenia.

Discrepancies in the late auditory potentials of post-anoxic patients: Watch out for focal brain lesions, a pilot retrospective study.

AIMS: Late auditory evoked potentials, and notably mismatch negativity (MMN) and P3 responses, can be used as part of the multimodal prognostic evaluation in post-anoxic disorders of consciousness (DOC). MMN response preferentially stems from the temporal cortex and the arcuate fasciculus. Situations with discrepant evaluations, for example MMN absent but P3 present, are frequent and difficult to interpret. We hypothesize that discrepant MMN-/P3+ results could reflect a higher prevalence of lesions in MMN generating regions. This study presents correlations between neurophysiological and neuroradiological results. METHODS: This retrospective study was conducted on 38 post-anoxic DOC patients. Brain lesions were analyzed on 3T MRI both anatomically and through computation of the local arcuate fasciculus fractional anisotropy values on Diffusion Tensor Imaging sequences. Neurophysiological data and outcome were also analyzed. RESULTS: Our cohort included 8 MMN-/P3+, 7 MMN+/P3+, 21 MMN-/P3- and 2 MMN-/P3+ patients, assessed at a median delay of 20.5 days since cardiac arrest. Our results show that MMN-/P3+ patients tended to have fewer temporal and basal ganglia lesions than MMN-/P3- patients, and more than MMN+/P3+ patients (p-values for trend: p = 0.02 for temporal and p = 0.02 for basal ganglia lesions). There was a statistical difference across groups for mean fractional anisotropy values in the arcuate fasciculus (p = 0.008). The percentage of patients regaining consciousness at three months in MMN-/P3+ patients was higher than in MMN-/P3- patients and lower than in MMN+/P3+ patients. CONCLUSION: This study suggests that discrepancies in late auditory evoked potentials may be linked to focal post-anoxic brain lesions, visible on brain MRI.

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.

Prognostication after cardiac arrest: how EEG and evoked potentials may improve the challenge.

About 80% of patients resuscitated from CA are comatose at ICU admission and nearly 50% of survivors are still unawake at 72 h. Predicting neurological outcome of these patients is important to provide correct information to patient's relatives, avoid disproportionate care in patients with irreversible hypoxic-ischemic brain injury (HIBI) and inappropriate withdrawal of care in patients with a possible favorable neurological recovery. ERC/ESICM 2021 algorithm allows a classification as "poor outcome likely" in 32%, the outcome remaining "indeterminate" in 68%. The crucial question is to know how we could improve the assessment of both unfavorable but also favorable outcome prediction. Neurophysiological tests, i.e., electroencephalography (EEG) and evoked-potentials (EPs) are a non-invasive bedside investigations. The EEG is the record of brain electrical fields, characterized by a high temporal resolution but a low spatial resolution. EEG is largely available, and represented the most widely tool use in recent survey examining current neuro-prognostication practices. The severity of HIBI is correlated with the predominant frequency and background continuity of EEG leading to "highly malignant" patterns as suppression or burst suppression in the most severe HIBI. EPs differ from EEG signals as they are stimulus induced and represent the summated activities of large populations of neurons firing in synchrony, requiring the average of numerous stimulations. Different EPs (i.e., somato sensory EPs (SSEPs), brainstem auditory EPs (BAEPs), middle latency auditory EPs (MLAEPs) and long latency event-related potentials (ERPs) with mismatch negativity (MMN) and P300 responses) can be assessed in ICU, with different brain generators and prognostic values. In the present review, we summarize EEG and EPs signal generators, recording modalities, interpretation and prognostic values of these different neurophysiological tools. Finally, we assess the perspective for futures neurophysiological investigations, aiming to reduce prognostic uncertainty in comatose and disorders of consciousness (DoC) patients after CA.

It's not what you say, it's how you say it: A retrospective study of the impact of prosody on own-name P300 in comatose patients.

OBJECTIVE: The acoustic characteristics of stimuli influence the characteristics of the corresponding evoked potentials in healthy subjects. Own-name stimuli are used in clinical practice to assess the level of consciousness in intensive care units. The influence of the acoustic variability of these stimuli has never been evaluated. Here, we explored the influence of this variability on the characteristics of the subject's own name (SON) P300. METHODS: We retrospectively analyzed 251 disorders of consciousness patients from Lyon and Paris Hospitals who underwent an "own-name protocol". A reverse correlation analysis was performed to test for an association between acoustic properties of own-names stimuli used and the characteristics of the P300 wave observed. RESULTS: Own-names pronounced with increasing pitch prosody showed P300 responses 66 ms earlier than own-names that had a decreasing prosody [IC95% = 6.36; 125.9 ms]. CONCLUSIONS: Speech prosody of the stimuli in the "own name protocol" is associated with latencies differences of the P300 response among patients for whom these responses were observed. Further investigations are needed to confirm these results. SIGNIFICANCE: Speech prosody of the stimuli in the "own name protocol" is a non-negligible parameter, associated with P300 latency differences. Speech prosody should be standardized in SON P300 studies.

Evoked and Event-Related Potentials as Biomarkers of Consciousness State and Recovery.

SUMMARY: The definition of consciousness has been the subject of great interest for many scientists and philosophers. To better understand how evoked potentials may be identified as biomarkers of consciousness and recovery, the different theoretical models sustaining neural correlates of consciousness are reviewed. A multimodal approach can help to better predict clinical outcome in patients presenting with disorders of consciousness. Evoked potentials are inexpensive and easy-to-implement bedside examination techniques. Evoked potentials are an integral part of prognostic evaluation, particularly in cases of cognitive motor dissociation. Prognostic criteria are well established in postanoxic disorders of consciousness, especially postcardiac arrest but are less well determined in other etiologies. In the early examination, bilateral absence of N20 in disorder of consciousness patients is strongly associated with unfavorable outcome (i.e., death or unresponsive wakefulness syndrome) especially in postanoxic etiologies. This predictive value is lower in other etiologies and probably also in children. Both N20 and mismatch negativity are proven outcome predictors for acute coma. Many studies have shown that mismatch negativity and P3a are characterized by a high prognostic value for awakening, but some patients presenting unresponsive wakefulness syndrome also process a P3a. The presence of long-latency event-related potential components in response to stimuli is indicative of a better recovery. All neurophysiological data must be integrated within a multimodal approach combining repeated clinical evaluation, neuroimaging, functional imaging, biology, and neurophysiology combining passive and active paradigms.

Impact of skull-to-brain conductivity ratio for high resolution EEG source localization.

Objective. To measure the impact of skull-to-brain conductivity ratios on interictal spikes source localizations, using high resolution EEG (HR EEG). In previous studies, two ratios were mainly employed: 1/80 and 1/40. Consequences of the employed ratios on source localization results are poorly studied.Methods. Twenty patients with drug-resistant epilepsy were studied using HR EEG (sixty-four scalp electrodes). For each patient, three-layers realistic head models based on individual MRI were elaborated using boundary element model. For each interictal spike, source localization was performed six times, using six skull-to-brain conductivity ratios (1/80, 1/50, 1/40, 1/30, 1/20 and 1/10), exploring all the spectrum of values reported in the literature. We then measured distances between the different sources obtained and between the sources and the anterior commissure (in order to estimate sources depth).Results. We measured a mean distance of 5.3 mm (sd: 3 mm) between the sources obtained with 1/40 versus 1/80 ratio. This distance increased when the discrepancy between the two evaluated ratios increased. We measured a mean distance of 14.2 mm (sd: 4.9 mm) between sources obtained with 1/10 ratio versus 1/80 ratio. Sources localized using 1/40 ratio were 4.3 mm closer to the anterior commissure than sources localized using 1/80 ratio.Significance. Skull-to-brain conductivity ratio is an often-neglected parameter in source localization studies. The different ratios mainly used in the litterature (1/80 and 1/40) lead to significant differences in source localizations. These variations mainly occur in source depth. A more accurate estimation of skull-to-brain conductivity is needed to increase source localization accuracy.Abbreviations. ECD: equivalent current dipole; EIT: electric impedance tomography, HR EEG: High resolution Electroencephalography, IIS: Inter ictal spikes, MEG: Magnetoencephalography, MRI: Magnetic resonance imaging, mS/m: milli-Siemens/m, S/m: Siemens/m, SD: Standard deviation.

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.

The Effectiveness of Vagus Nerve Stimulation in Drug-Resistant Epilepsy Correlates with Vagus Nerve Stimulation-Induced Electroencephalography Desynchronization.

Introduction: VNS is an adjunctive neuromodulation therapy for patients with drug-refractory epilepsy. The antiseizure effect of VNS is thought to be related to a diffuse modulation of functional connectivity but remains to be confirmed. Aim: To investigate electroencephalographic (EEG) metrics of functional connectivity in patients with drug-refractory epilepsy treated by vagus nerve stimulation (VNS), between VNS-stimulated "ON" and nonstimulated "OFF" periods and between responder (R) and nonresponder (NR) patients. Methods: Scalp-EEG was performed for 35 patients treated by VNS, using 21 channels and 2 additional electrodes on the neck to detect the VNS stimulation. Patients were defined as VNS responders if a reduction of seizure frequency of ∼50% was documented. We analyzed the synchronization in EEG time series during "ON" and "OFF" periods of stimulation, using average phase lag index (PLI) in signal space and phase-locking value (PLV) between 10 sources. Based on graph theory, we computed brain network models and analyzed minimum spanning tree (MST) for responder and nonresponder patients. Results: Among 35 patients treated by VNS for a median time of 7 years (range 4 months to 22 years), 20 were R and 15 were NR. For responder patients, PLI during ON periods was significantly lower than that during OFF periods in delta (p = 0.009), theta (p = 0.02), and beta (p = 0.04) frequency bands. For nonresponder patients, there were no significant differences between ON and OFF periods. Moreover, variations of seizure frequency with VNS correlated with the PLI OFF/ON ratio in delta (p = 0.02), theta (p = 0.04), and beta (p = 0.03) frequency bands. Our results were confirmed using PLV in theta band (p < 0.05). No significant differences in MST were observed between R and NR patients. Conclusion: The correlation between VNS-induced interictal EEG time-series desynchronization and decrease in seizure frequency suggested that VNS therapeutic impact might be related to changes in interictal functional connectivity. Impact statement Electroencephalography (EEG) desynchronization has been proposed to be a mechanism for antiepileptic effect of vagus nerve stimulation (VNS). We measured interictal EEG time-series synchronization during stimulated (ON) and nonstimulated (OFF) periods in epileptic patients treated by VNS. Phase lag index differences between ON and OFF periods were measured in delta, theta, and beta bands only in responder patients. To our knowledge, our study is the first to statistically correlate interictal cortical desynchronization during ON periods with reduction in seizure frequency. Our result supports the hypothesis that the antiseizure effect of VNS is mediated by cortical desynchronization.

Design and Methodology of a Pilot Randomized Controlled Trial of Transcranial Direct Current Stimulation in Acute Middle Cerebral Artery Stroke (STICA).

Background: Stroke is a major cause of death and disability worldwide. The related burden is expected to further increase due to aging populations, calling for more efficient treatment. Ischemic stroke results from a focal reduction in cerebral blood flow due to the sudden occlusion of a brain artery. Ischemic brain injury results from a sequence of pathophysiological events that evolve over time and space. This cascade includes excitotoxicity and peri-infarct depolarizations (PIDs). Focal impairment of cerebral blood flow restricts the delivery of energetics substrates and impairs ionic gradients. Membrane potential is eventually lost, and neurons depolarize. Although recanalization therapies target the ischemic penumbra, they can only rescue the penumbra still present at the time of reperfusion. A promising novel approach is to "freeze" the penumbra until reperfusion occurs. Transcranial direct current stimulation (tDCS) is a non-invasive method of neuromodulation. Based on preclinical evidence, we propose to test the penumbra freezing concept in a clinical phase IIa trial assessing whether cathodal tDCS-shown in rodents to reduce infarction volume-prevents early infarct growth in human acute Middle Cerebral Artery (MCA) stroke, in adjunction to conventional revascularization methods. Methods: This is a monocentric randomized, double-blind, and placebo-controlled trial performed in patients with acute MCA stroke eligible to revascularization procedures. Primary outcome is infarct volume growth on diffusion weighted imaging (DWI) at day 1 relative to baseline. Secondary outcomes include safety and clinical efficacy. Significance: Results from this clinical trial are expected to provide rationale for a phase III study. Clinical trial registration-EUDRACT: 2016-A00160-51.

Prevalence of benign epileptiform variants during initial EEG examination in French military aircrew.

INTRODUCTION: In France, a systematic EEG is performed during initial examination in military aircrew applicants, which may provide an estimation of the prevalence of benign epileptiform variants in healthy adults. METHODS: We analyzed standard EEG (21 scalp electrodes, 20minutes, 400Hz sampling rate) of military aircrew applicants examined in the French Main Aeromedical Center in 2016. EEGs were analyzed using both bipolar and referential montages. The collected data were EEG abnormalities and benign epileptiform variants. The kappa inter-observer index for the detection of benign epileptiform variants was calculated. RESULTS: Our population was composed of 495 subjects (86.7% males, mean age 22.5±4.8 years), wishing to become a pilot in 69.7% of cases. None of the applicants reported any neurological disease and none was taking regular medication. EEG was considered as normal for 96.4% of them. Encountered EEG abnormalities were mainly asymmetric and sharp slow wave bursts. Drowsiness was recorded during 13.9% of these EEG. Benign epileptiform variants were present in 7.7% of our population: anterior theta activities (4%), posterior slow waves (2.8%), alpha variants (0.6%) and wicket spikes (0.2%). Hyperventilation induced EEG slowing in 14.1% of cases. During intermittent photic stimulation, physiological photic driving was observed in 15.2% of subjects. DISCUSSION: Many previous studies have been dedicated to the prevalence of benign epileptiform variants but results are often heterogeneous and based on patients in whom there was an indication for EEG. Our results thus bring data on benign epileptiform variants prevalence in a young adult population characterized by the absence of neurologic disorders. Our study demonstrates that anterior theta activities, posterior slow waves, alpha variants and wicket spikes are the most frequent benign EEG variants in such a young adult population.