SEIZURES | A New Look into Epilepsy as a Dynamical Disorder : Seizure Prediction, Resetting and Control

Abstract

Epilepsy is characterized by intermittent (aperiodical, sporadic), paroxysmal (abrupt onset and offset), hypersynchronous (simultaneous activation of a considerable neural mass) electrical activity, which may remain localized or spread and severely disrupt the brain's normal operation. Epileptic seizures and interictal spikes are typical manifestations of such activity, and are reminiscent of crises in nonlinear systems. It is only recently that prediction and control of epileptic seizures have been the subject of intensive interdisciplinary research. Within this context, we investigate epilepsy from the point of view of pathology of the dynamics of the electrical activity of the brain. Three critical aspects of the dynamics of epileptic seizures are discussed in this article: a) seizures are preceded by a long-term (on the order of minutes to hours) entrainment (synchronization of dynamics) of brain sites by the epileptogenic focus/zone; b) seizures typically reset the aforementioned dynamical entrainment and lead to the disentrainment (desynchronization of dynamics) of the focus from the rest of the brain; c) seizures may occur due to a failure of global or local internal feedback loops in the brain, normally responsible for keeping the spatial correlations/interactions within strict limits (time-wise and space-wise), and thus being able to support the brain's fast multi-processing and multi-task function. These aspects, taken together, constitute the basis for a dynamical interpretation of ictogenesis that may lead to the detection of seizure susceptibility periods, long-term prediction of seizures, epileptogenic focus localization, and potentially to the development of innovative treatments for epilepsy through timely interventions (e.g., electrical stimulation and/or in situ drug delivery) to control (ideally suppress) seizure occurrence. Preliminary evidence from dynamical analysis of EEG from patients with focal epilepsy and patients in status epilepticus, as well as from rodent and simulation models of epilepsy, supports the feasibility of these goals.