Computational models of epilepsy

Purpose: Approximately 30% of epilepsy patients suffer from medically refractory epilepsy, in which seizures can not controlled by the use of anti-epileptic drugs (AEDs). Understanding the mechanisms underlying these forms of drug-resistant epileptic seizures and the development of alternative effective treatment strategies are fundamental challenges for modern epilepsy research. In this context, computational modeling has gained prominence as an important tool for tackling the complexity of the epileptic phenomenon. In this review article, we present a survey of computational models of epilepsy from the point of view that epilepsy is a dynamical brain disease that is primarily characterized by unprovoked spontaneous epileptic seizures. Method: We introduce key concepts from the mathematical theory of dynamical systems, such as multi-stability and bifurcations, and explain how these concepts aid in our understanding of the brain mechanisms involved in the emergence of epileptic seizures. Results: We present a literature survey of the different computational modeling approaches that are used in the study of epilepsy. Special emphasis is placed on highlighting the fine balance between the degree of model simplification and the extent of biological realism that modelers seek in order to address relevant questions. In this context, we discuss three specific examples from published literature, which exemplify different approaches used for developing computational models of epilepsy. We further explore the potential of recently developed optogenetics tools to provide novel avenue for seizure control. Conclusion: We conclude with a discussion on the utility of computational models for the development of new epilepsy treatment protocols. (C) 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.