Alterations of Neuronal Dynamics as a Mechanism for Cognitive Impairment in Epilepsy

Epilepsy is commonly associated with cognitive and behavioral deficits that dramatically affect the quality of life of patients. In order to identify novel therapeutic strategies aimed at reducing these deficits, it is critical first to understand the mechanisms leading to cognitive impairments in epilepsy. Traditionally, seizures and epileptiform activity in addition to neuronal injury have been considered to be the most significant contributors to cognitive dysfunction. In this review we however highlight the role of a new mechanism: alterations of neuronal dynamics, i.e. the timing at which neurons and networks receive and process neural information. These alterations, caused by the underlying etiologies of epilepsy syndromes, are observed in both animal models and patients in the form of abnormal oscillation patterns in unit firing, local field potentials, and electroencephalogram (EEG). Evidence suggests that such mechanisms significantly contribute to cognitive impairment in epilepsy, independently of seizures and interictal epileptiform activity. Therefore, therapeutic strategies directly targeting neuronal dynamics rather than seizure reduction may significantly benefit the quality of life of patients.