Effect of Seizures on the Developing Brain and Cognition

Abstract

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, and 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. Although early-life seizures in rodents do not result in cell loss, seizures cause in changes in neurogenesis and synaptogenesis and alteration of excitatory or 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.

Fig. 1

There are many factors that determine cognitive outcome with early-life seizures. Etiology is the primary determinant of cognitive outcome. For example, channelopathies, such as occur in Dravet syndrome, may have major effects on cognition. Likewise, seizures, antiepileptic drugs and interictal spikes contribute to cognitive impairment.

Fig. 2

Place cell recordings. The recording cylinder with cue card is shown in A. Examples of place cells (B,D) and an interneuron (C) are shown. The place cell in B is at approximately 5 o’clock while the place cell in D is at approximately 7 o’clock but is closer to the center of the cylinder than the cell depicted in B. Firing frequency is color coded. Yellow shows areas of the cylinder in which the cell did not fire while the green, blue and purple colors show high firing rates in the place firing field. Wavefroms from the tetrodes are shown next to the color coded firing rates. The neuron recorded in C is an interneuron which shows a higher firing rate but no clear place preference.