Abstract
OBJECTIVE: Genetic generalized epilepsies (GGEs) are characterized by generalized spike-wave discharges (GSWDs) in electroencephalography (EEG) recordings without underlying structural brain lesions. The origin of the epileptic activity remains unclear, although several studies have reported involvement of thalamus and default mode network (DMN). The aim of the current study was to investigate the networks involved in the generation and temporal evolution of GSWDs to elucidate the origin and propagation of the underlying generalized epileptic activity. METHODS: We examined 12 patients with GGE and GSWDs using EEG-functional magnetic resonance imaging (fMRI) and identified involved brain areas on the basis of a classical general linear model (GLM) analysis. The activation time courses of these areas were further investigated to reveal their temporal sequence of activations and deactivations. Dynamic causal modeling (DCM) was used to determine the generator of GSWDs in GGE. RESULTS: We observed activity changes in the thalamus, DMN, dorsal attention network (DAN), salience network (SN), basal ganglia, dorsolateral prefrontal cortex, and motor cortex with supplementary motor area, however, with a certain heterogeneity between patients. Investigation of the temporal sequence of activity changes showed deactivations in the DMN and DAN and activations in the SN and thalamus preceding the onset of GSWDs on EEG by several seconds. DCM analysis indicated that the DMN gates GSWDs in GGE. SIGNIFICANCE: The observed interplay between DMN, DAN, SN, and thalamus may indicate a downregulation of consciousness. The DMN seems to play a leading role as a driving force behind these changes. Overall, however, there were also clear differences in activation patterns between patients, reflecting a certain heterogeneity in this cohort of GGE patients.