Computational models of epileptic activity: a bridge between observation and pathophysiological interpretation

Epilepsy is a neurological disorder characterized by the recurrence of seizures. It affects 50 million people worldwide. Although a considerable number of new antiepileptic drugs with reduced side effects and toxicity have been introduced since the 1950s, 30% of patients remain pharmacoresistant. Although epilepsy research is making progress, advances in understanding drug resistance have been hampered by the complexity of the underlying neuronal systems responsible for epileptic activity. In such systems where short- or long-term plasticity plays a role, pathophysiological alterations may take place at subcellular (i.e., membrane ion channels and neurotransmitter receptors), cellular (neurons), tissular (networks of neurons) and regional (networks of networks of neurons) scales. In such a context, the demand for integrative approaches is high and neurocomputational models become recognized tools for tackling the complexity of epileptic phenomena. The purpose of this report is to provide an overview on computational modeling as a way of structuring and interpreting multimodal data recorded from the epileptic brain. Some examples are briefly described, which illustrate how computational models closely related with either experimental or clinical data can markedly advance our understanding of essential issues in epilepsy such as the transition from background to seizure activity. A commentary is also made on the potential use of such models in the study of therapeutic strategies such as rational drug design or electrical stimulations.