Epilepsy and Ecstatic Experiences: The Role of the Insula.

Ecstatic epilepsy is a rare form of focal epilepsy in which the aura (beginning of the seizures) consists of a blissful state of mental clarity/feeling of certainty. Such a state has also been described as a "religious" or mystical experience. While this form of epilepsy has long been recognized as a temporal lobe epilepsy, we have accumulated evidence converging toward the location of the symptomatogenic zone in the dorsal anterior insula during the 10 last years. The neurocognitive hypothesis for the genesis of a mental clarity is the suppression of the interoceptive prediction errors and of the unexpected surprise associated with any incoming internal or external signal, usually processed by the dorsal anterior insula. This mimics a perfect prediction of the world and induces a feeling of certainty. The ecstatic epilepsy is thus an amazing model for the role of anterior insula in uncertainty and surprise

Commentary: Integrating electrodermal biofeedback into pharmacologic treatment of grand mal seizures

Thirty percent of patients with epilepsy experience seizures despite optimal anticonvulsant drug treatment. Stress is frequently identified by patients with epilepsy as a precipitant of seizures (Spector et al., 2000; Ferlisi and Shorvon, 2014). Patients also often report using countermeasures to control the seizure onset. These are typically spontaneous and individualized such as increasing arousal by walking, breathing, standing, focusing attention, changing way of thinking, and more rarely inducing relaxation (Lee and No, 2005; Hether et al., 2013). In parallel, behavioral and psychological interventions, complementing conventional therapeutic methods for the management of epileptic seizures, have gained greater clinical attention over the past decade. Among these, Biofeedback (BFK) represents a noninvasive biobehavioral treatment that enables a patient to gain volitional control over a specific physiological process. BFK has already shown its value when applied to patients with epilepsy (Sterman and Friar, 1972; Rockstroh et al., 1993; Nagai et al., 2004a; Nagai, 2011; Micoulaud-Franchi et al., 2014a,b). Scrimali et al. (2015) have rightly pointed out the potential usefulness of electrodermal biofeedback in the management of refractory epilepsy. In a single case study, they report an effect of electrodermal activity (EDA) relaxation biofeedback in reducing seizures in a patient treated for 2 years. This case study supports the necessity to expand clinical armamentarium for treatment-resistant patients with few alternatives

Predicting the spatiotemporal diversity of seizure propagation and termination in human focal epilepsy

Recent studies have shown that seizures can spread and terminate across brain areas via a rich diversity of spatiotemporal patterns. In particular, while the location of the seizure onset area is usually in-variant across seizures in a same patient, the source of traveling (2-3 Hz) spike-and-wave discharges (SWDs) during seizures can either move with the slower propagating ictal wavefront or remain stationary at the seizure onset area. In addition, although most focal seizures terminate quasi-synchronously across brain areas, some evolve into distinct ictal clusters and terminate asynchronously. To provide a unifying perspective on the observed diversity of spatiotemporal dynamics for seizure spread and termination, we introduce here the Epileptor neural field model. Two mechanisms play an essential role. First, while the slow ictal wavefront propagates as a front in excitable neural media, the faster SWDs propagation results from coupled-oscillator dynamics. Second, multiple time scales interact during seizure spread, allowing for low-voltage fast-activity (>10 Hz) to hamper seizure spread and for SWD propagation to affect the way a seizure terminates. These dynamics, together with variations in short and long-range connectivity strength, play a central role on seizure spread, maintenance and termination. We demonstrate how Epileptor field models incorporating the above mechanisms predict the previously reported diversity in seizure spread patterns. Furthermore, we confirm the predictions for synchronous or asynchronous (clustered) seizure termination in human seizures recorded via stereotactic EEG. Our new insights into seizure spatiotemporal dynamics may also contribute to the development of new closed-loop neuromodulation therapies for focal epilepsy.Comment: 10 pages + 9 pages Supporting Information (SI), 7 figures, 1 SI table, 7 SI figure

Time-frequency strategies for increasing high frequency oscillation detectability in intracerebral EEG

International audienceBackground: High Frequency Oscillations (HFOs) are considered to be highly representative of brain tissues capable of producing epileptic seizures. The visual review of HFOs on intracerebral electroencephalography is time-consuming and tedious, and it can be improved by time-frequency (TF) analysis. The main issue is that the signal is dominated by lower frequencies that mask the HFOs. Our aim was to flatten (i.e. whiten) the frequency spectrum to enhance the fast oscillations while preserving an optimal Signal to Noise Ratio (SNR). Method: We investigated 8 methods of data whitening based on either prewhitening or TF normalization in order to improve the detectability of HFOs. We detected all local maxima of the TF image above a range of thresholds in the HFO band. Results: We obtained the Precision and Recall curves at different SNR and for different HFO types and illustrate the added value of whitening both in the time-frequency plane and in time domain. Conclusion: The normalization strategies based on a baseline and on our proposed method (the " H0 z-score ") are more precise than the others. Significance: The H0 z-score provides an optimal framework for representing and detecting HFOs, independent of a baseline and a priori frequency bands

GABAergic inhibition shapes interictal dynamics in awake epileptic mice

International audienceEpilepsy is characterized by recurrent seizures and brief, synchronous bursts called interictal spikes that are present in-between seizures and observed as transient events in EEG signals. While GABAergic transmission is known to play an important role in shaping healthy brain activity, the role of inhibition in these pathological epileptic dynamics remains unclear. Examining the microcircuits that participate in interictal spikes is thus an important first step towards addressing this issue, as the function of these transient synchronizations in either promoting or prohibiting seizures is currently under debate. To identify the microcircuits recruited in spontaneous interictal spikes in the absence of any proconvulsive drug or anaesthetic agent, we combine a chronic model of epilepsy with in vivo two-photon calcium imaging and multiunit extracellular recordings to map cellular recruitment within large populations of CA1 neurons in mice free to run on a self-paced treadmill. We show that GABAergic neurons, as opposed to their glutamatergic counterparts, are preferentially recruited during spontaneous interictal activity in the CA1 region of the epileptic mouse hippocampus. Although the specific cellular dynamics of interictal spikes are found to be highly variable, they are consistently associated with the activation of GABAergic neurons, resulting in a perisomatic inhibitory restraint that reduces neuronal spiking in the principal cell layer. Given the role of GABAergic neurons in shaping brain activity during normal cognitive function, their aberrant unbalanced recruitment during these transient events could have important downstream effects with clinical implications

European Expert Opinion on ANT-DBS therapy for patients with drug-resistant epilepsy (a Delphi consensus)

Introduction: Although deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) represents an established third-line therapy for patients with drug-resistant focal epilepsy, guiding reports on practical treatment principles remain scarce. Methods: An Expert Panel (EP) of 10 European neurologists and 4 neurosurgeons was assembled to share their experience with ANT-DBS therapy. The process included a review of the current literature, which served as a basis for an online survey completed by the EP prior to and following a face-to-face meeting (Delphi method). An agreement level of >= 71 % was considered as consensus. Results: Out of 86 reviewed studies, 46 (53 %) were selected to extract information on the most reported criteria for patient selection, management, and outcome. The Delphi process yielded EP consensus on 4 parameters for selection of good candidates and patient management as well as 7 reasons of concern for this therapy. Since it was not possible to give strict device programming advice due to low levels of evidence, the experts shared their clinical practice: all of them start with monopolar stimulation, 79 % using the cycling mode. Most (93 %) EP members set the initial stimulation frequency and pulse width according to the SANTE parameters, while there is more variability in the amplitudes used. Further agreement was achieved on a list of 7 patient outcome parameters to be monitored during the follow-up. Conclusions: Although current evidence is too low for definite practical guidelines, this EP report could support the selection and management of patients with ANT-DBS

Interictal Functional Connectivity of Human Epileptic Networks Assessed by Intracerebral EEG and BOLD Signal Fluctuations

In this study, we aimed to demonstrate whether spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal derived from resting state functional magnetic resonance imaging (fMRI) reflect spontaneous neuronal activity in pathological brain regions as well as in regions spared by epileptiform discharges. This is a crucial issue as coherent fluctuations of fMRI signals between remote brain areas are now widely used to define functional connectivity in physiology and in pathophysiology. We quantified functional connectivity using non-linear measures of cross-correlation between signals obtained from intracerebral EEG (iEEG) and resting-state functional MRI (fMRI) in 5 patients suffering from intractable temporal lobe epilepsy (TLE). Functional connectivity was quantified with both modalities in areas exhibiting different electrophysiological states (epileptic and non affected regions) during the interictal period. Functional connectivity as measured from the iEEG signal was higher in regions affected by electrical epileptiform abnormalities relative to non-affected areas, whereas an opposite pattern was found for functional connectivity measured from the BOLD signal. Significant negative correlations were found between the functional connectivities of iEEG and BOLD signal when considering all pairs of signals (theta, alpha, beta and broadband) and when considering pairs of signals in regions spared by epileptiform discharges (in broadband signal). This suggests differential effects of epileptic phenomena on electrophysiological and hemodynamic signals and/or an alteration of the neurovascular coupling secondary to pathological plasticity in TLE even in regions spared by epileptiform discharges. In addition, indices of directionality calculated from both modalities were consistent showing that the epileptogenic regions exert a significant influence onto the non epileptic areas during the interictal period. This study shows that functional connectivity measured by iEEG and BOLD signals give complementary but sometimes inconsistent information in TLE

Self-control of epileptic seizures by nonpharmacological strategies

Despite the unpredictability of epileptic seizures, many patients report that they can anticipate seizure occurrence. Using certain alert symptoms (i.e., auras, prodromes, precipitant factors), patients can adopt behaviors to avoid injury during and after the seizure or may implement spontaneous cognitive and emotional strategies to try to control the seizure itself. From the patient's view point, potential means of enhancing seizure prediction and developing seizure control supports are seen as very important issues, especially when the epilepsy is drug-resistant. In this review, we first describe how some patients anticipate their seizures and whether this is effective in terms of seizure prediction. Secondly, we examine how these anticipatory elements might help patients to prevent or control their seizures and how the patient's neuropsychological profile, specifically parameters of perceived self-control (PSC) and locus of control (LOC), might impact these strategies and quality of life (QOL). Thirdly, we review the external supports that can help patients to better predict seizures. Finally, we look at nonpharmacological means of increasing perceived self-control and achieving potential reduction of seizure frequency (i.e., stress-based and arousal-based strategies). In the past few years, various approaches for detection and control of seizures have gained greater interest, but more research is needed to confirm a positive effect on seizure frequency as well as on QOL

Highlights From the Annual Meeting of the American Epilepsy Society 2022

With more than 6000 attendees between in-person and virtual offerings, the American Epilepsy Society Meeting 2022 in Nashville, felt as busy as in prepandemic times. An ever-growing number of physicians, scientists, and allied health professionals gathered to learn a variety of topics about epilepsy. The program was carefully tailored to meet the needs of professionals with different interests and career stages. This article summarizes the different symposia presented at the meeting. Basic science lectures addressed the primary elements of seizure generation and pathophysiology of epilepsy in different disease states. Scientists congregated to learn about anti-seizure medications, mechanisms of action, and new tools to treat epilepsy including surgery and neurostimulation. Some symposia were also dedicated to discuss epilepsy comorbidities and practical issues regarding epilepsy care. An increasing number of patient advocates discussing their stories were intertwined within scientific activities. Many smaller group sessions targeted more specific topics to encourage member participation, including Special Interest Groups, Investigator, and Skills Workshops. Special lectures included the renown Hoyer and Lombroso, an ILAE/IBE joint session, a spotlight on the impact of Dobbs v. Jackson on reproductive health in epilepsy, and a joint session with the NAEC on coding and reimbursement policies. The hot topics symposium was focused on traumatic brain injury and post-traumatic epilepsy. A balanced collaboration with the industry allowed presentations of the latest pharmaceutical and engineering advances in satellite symposia