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Summary   Objective  Genetic generalized epilepsies ( GGEs ) are characterized by generalized spike‐wave discharges ( GSWD s) 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  GSWD s to elucidate the origin and propagation of the underlying generalized epileptic activity.    Methods  We examined 12 patients with  GGE  and  GSWD s 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  GSWD s 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  GSWD s 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.

Unravelling the brain networks driving spike‐wave discharges in genetic generalized epilepsy—common patterns and individual differences