Gregory L. Holmes Seminars in Pediatric Neurology Volume 23, Issue 2, May 2016, Pages 120-126 Epilepsy is a complex disorder, which involves much more than seizures, encompassing a range of associated comorbid health conditions that can have significant health and quality-of-life implications. Of these comorbidities, cognitive impairment is one of the most common and distressing aspects of epilepsy. Clinical studies have demonstrated that refractory seizures, resistant to antiepileptic drugs, occurring early in life have significant adverse effects on cognitive function. Much of what has been learned about the neurobiological underpinnings of cognitive impairment following early-life seizures has come from animal models. While early-life seizures in rodents do not result in cell loss, seizures do result in changes in neurogenesis and synaptogenesis and alteration of excitatory/inhibitory balance, network connectivity and temporal coding. These morphological and physiological changes are accompanied by parallel impairment in cognitive skills. This increased understanding of the pathophysiological basis of seizure-induced cognitive deficits should allow investigators to develop novel targets for therapeutic interventions.Copyright © 2023 Elsevier Inc. All rights reserved.