Network perspectives on epilepsy using EEG/MEG source connectivity

The evolution of EEG/MEG source connectivity is both, a promising, and controversial advance in the characterization of epileptic brain activity. In this narrative review we elucidate the potential of this technology to provide an intuitive view of the epileptic network at its origin, the different brain regions involved in the epilepsy, without the limitation of electrodes at the scalp level. Several studies have confirmed the added value of using source connectivity to localize the seizure onset zone and irritative zone or to quantify the propagation of epileptic activity over time. It has been shown in pilot studies that source connectivity has the potential to obtain prognostic correlates, to assist in the diagnosis of the epilepsy type even in the absence of visually noticeable epileptic activity in the EEG/MEG, and to predict treatment outcome. Nevertheless, prospective validation studies in large and heterogeneous patient cohorts are still lacking and are needed to bring these techniques into clinical use. Moreover, the methodological approach is challenging, with several poorly examined parameters that most likely impact the resulting network patterns. These fundamental challenges affect all potential applications of EEG/MEG source connectivity analysis, be it in a resting, spiking, or ictal state, and also its application to cognitive activation of the eloquent area in presurgical evaluation. However, such method can allow unique insights into physiological and pathological brain functions and have great potential in (clinical) neuroscience

Seizure prediction : ready for a new era

Acknowledgements: The authors acknowledge colleagues in the international seizure prediction group for valuable discussions. L.K. acknowledges funding support from the National Health and Medical Research Council (APP1130468) and the James S. McDonnell Foundation (220020419) and acknowledges the contribution of Dean R. Freestone at the University of Melbourne, Australia, to the creation of Fig. 3.Peer reviewedPostprin

Epileptic Seizures and the EEG

A study of epilepsy from an engineering perspective, this volume begins by summarizing the physiology and the fundamental ideas behind the measurement, analysis and modeling of the epileptic brain. It introduces the EEG and provides an explanation of the type of brain activity likely to register in EEG measurements, offering an overview of how these EEG records are and have been analyzed in the past. The book focuses on the problem of seizure detection and surveys the physiologically based dynamic models of brain activity. Finally, it addresses the fundamental question: can seizures be predicted? Based on the authors' extensive research, the book concludes by exploring a range of future possibilities in seizure prediction

Development of Epilepsy-on-a-chip System for High-throughput Antiepileptogenic Drug Discovery

Epilepsy is one of the most common neurological disorders and affects millions of people in the United States. Currently available antiepileptic drugs require continuous administration for suppression of seizures and have not been shown to prevent the development of epilepsy (epileptogenesis). The discovery of antiepileptogenic drug is complicated by the long time course of epileptogenesis in animal models of epilepsy and the requirement of continuous monitoring of epileptiform activity in vivo for the assessment of drug efficacy. In recent years, organotypic hippocampal cultures have been increasingly used as an in vitro model of post-traumatic epilepsy in both basic and translational research. Epileptogenesis in this in vitro model has a compressed time scale and can be monitored by detection of electrographic and biochemical markers of seizure-like activity. However, the lack of a scalable chronic electrical recording platform is a significant bottleneck in high-throughput antiepileptogenic drug discovery using organotypic cultures.In an effort to circumvent the throughput limitations of in vitro antiepileptogenic drug discovery, a hybrid microfluidic-multiple electrode array (µflow-MEA) technology was developed for scalable chronic electrical assay of epileptogenesis in vitro. Specifically, the microfluidic perfusion technique was utilized to miniature the culture platform, which enabled the long-term maintenance of an organotypic culture array on a single device. The integration of the microfluidic perfusion system with a customized planar MEA allowed for parallel continuous recordings. As a proof-of-concept demonstration, a pilot screen of receptor tyrosine kinase (RTK) inhibitor library was performed on µflow-MEA based electrical assay platform. The screen results revealed significant antiepileptogenic effect of cFMS RTK inhibitor.This thesis also provides further validation of the organotypic hippocampal culture model of epilepsy by investigating the influence of culture medium composition on epileptogenesis. We found that epileptogenesis occurred in any culture medium that was capable of supporting neural survival, indicating that culture medium composition has limited influence on epileptogenesis in organotypic hippocampal cultures.It is hoped that the techniques presented in this thesis will accelerate the antiepileptogenic drug discovery and contribute to the development of new therapeutics to treat individuals at risk of epileptogenesis

Controversies on the network theory of epilepsy : Debates held during the ICTALS 2019 conference

Acknowledgements We would like to acknowledge the contributions of the discussants to the exposition and discussion of the six debate topics. The discussants for debates 1-6 were Fabrice Wendling, Mark Cook, Mark Richardson, Thorsten Rings, Klaus Lehnertz and Piotr Suffczynski, respectively. Funding for ICTALS 2019 was received from the following foundations and industry partners: UCB S.A. (Belgium), American Epilepsy Society (AES), Epilepsy Innovation Institute (Ei2) and Epilepsy Foundation of America (EFA), NeuraLynx (Bozeman, MT, USA) and LivaNova (London, UK). The contribution of HZ was supported by award R01NS109062 from the National Institutes of Health, MG by the EPSRC via grants EP/P021417/1 and EP/N014391/1 and a Wellcome Trust Institutional Strategic Support Award (WT105618MA), and PJ by awards from the Ministry of Health of the Czech Republic AZV 17-28427A and the Czech Science Foundation 20-25298S. The opinions expressed in this article do not necessarily reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government.Peer reviewedPostprin

EXPERIMENTAL-COMPUTATIONAL ANALYSIS OF VIGILANCE DYNAMICS FOR APPLICATIONS IN SLEEP AND EPILEPSY

Epilepsy is a neurological disorder characterized by recurrent seizures. Sleep problems can cooccur with epilepsy, and adversely affect seizure diagnosis and treatment. In fact, the relationship between sleep and seizures in individuals with epilepsy is a complex one. Seizures disturb sleep and sleep deprivation aggravates seizures. Antiepileptic drugs may also impair sleep quality at the cost of controlling seizures. In general, particular vigilance states may inhibit or facilitate seizure generation, and changes in vigilance state can affect the predictability of seizures. A clear understanding of sleep-seizure interactions will therefore benefit epilepsy care providers and improve quality of life in patients. Notable progress in neuroscience research—and particularly sleep and epilepsy—has been achieved through experimentation on animals. Experimental models of epilepsy provide us with the opportunity to explore or even manipulate the sleep-seizure relationship in order to decipher different aspects of their interactions. Important in this process is the development of techniques for modeling and tracking sleep dynamics using electrophysiological measurements. In this dissertation experimental and computational approaches are proposed for modeling vigilance dynamics and their utility demonstrated in nonepileptic control mice. The general framework of hidden Markov models is used to automatically model and track sleep state and dynamics from electrophysiological as well as novel motion measurements. In addition, a closed-loop sensory stimulation technique is proposed that, in conjunction with this model, provides the means to concurrently track and modulate 3 vigilance dynamics in animals. The feasibility of the proposed techniques for modeling and altering sleep are demonstrated for experimental applications related to epilepsy. Finally, preliminary data from a mouse model of temporal lobe epilepsy are employed to suggest applications of these techniques and directions for future research. The methodologies developed here have clear implications the design of intelligent neuromodulation strategies for clinical epilepsy therapy

Modeling of age-dependent epileptogenesis by differential homeostatic synaptic scaling

Homeostatic synaptic plasticity (HSP) has been implicated in the development of hyperexcitability and epileptic seizures following traumatic brain injury (TBI). Our in vivo experimental studies in cats revealed that the severity of TBI-mediated epileptogenesis depends on the age of the animal. To characterize mechanisms of these differences, we studied the properties of the TBI-induced epileptogenesis in a biophysically realistic cortical network model with dynamic ion concentrations. After deafferentation, which was induced by dissection of the afferent inputs, there was a reduction of the network activity and upregulation of excitatory connections leading to spontaneous spike-and-wave type seizures. When axonal sprouting was implemented, the seizure threshold increased in the model of young but not the older animals, which had slower or unidirectional homeostatic processes. Our study suggests that age-related changes in the HSP mechanisms are sufficient to explain the difference in the likelihood of seizure onset in young versus older animals