Changes in activity of striato-thalamo-cortical network precede generalized spike wave discharges

The pathophysiology of generalized spike wave discharges (GSW) is not completely understood. Thalamus, basal ganglia and neocortex have been implicated in the generation of GSW, yet the specific role of each structure remains to be clarified. In six children with idiopathic generalized epilepsy (IGE), we performed combined EEG-fMRI to identify GSW-related changes in blood oxygen level-dependent (BOLD) signal in the striato-thalamo-cortical network. In all patients, within-subject analysis demonstrated BOLD signal changes that preceded the GSW. An increase in BOLD signal in the medial thalamus started 6 s before the onset of the GSW. Decreases in cortical BOLD signal were mainly found in frontoparietal areas and precuneus starting 6 to 3 s before the GSW. All patients showed a decrease in BOLD signal in the head of the caudate nucleus with a variable onset. The temporospatial pattern of BOLD signal changes suggests that GSW on the cortical surface is preceded by a sequence of neuronal events in the thalamo-cortical-striatal network. Approximately 6 s before the GSW, the thalamus shows an increase in neuronal activity along with regional decreases in cortical activity. These changes in thalamo-cortical activity are followed by a deactivation of the caudate nucleus. These early changes in BOLD signal may reflect changes in neuronal activity that contribute to the generation of GSW and may contribute to the transition from a normal to a generalized hypersynchronous pattern of neuronal activity. Our preliminary findings warrant further studies on a larger number of patients to explore the influence of age, medication and type of epileptic syndrome.