Differences in paracingulate connectivity associated with epileptiform discharges and uncontrolled seizures in genetic generalized epilepsy.

Objective: Patients with genetic generalized epilepsy (GGE) frequently continue to have seizures despite appropriate clinical management. GGE is associated with changes in the resting-state networks modulated by clinical factors such as duration of disease and response to treatment. However, the effect of generalized spike and wave discharges (GSWDs) and/or seizures on resting-state functional connectivity (RSFC) is not well understood.

Methods: We investigated the effects of GSWD frequency (in GGE patients), GGE (patients vs. healthy controls), and seizures (uncontrolled vs. controlled) on RSFC using seed-based voxel correlation in simultaneous electroencephalography (EEG) and resting-state functional magnetic resonance imaging (fMRI) (EEG/fMRI) data from 72 GGE patients (23 with uncontrolled seizures) and 38 healthy controls. We used seeds in paracingulate cortex, thalamus, cerebellum, and posterior cingulate cortex to examine changes in cortical-subcortical resting-state networks and the default mode network (DMN). We excluded from analyses time points surrounding GSWDs to avoid possible contamination of the resting state.

Results: (1) Higher frequency of GSWDs was associated with an increase in seed-based voxel correlation with cortical and subcortical brain regions associated with executive function, attention, and the DMN; (2) RSFC in patients with GGE, when compared to healthy controls, was increased between paracingulate cortex and anterior, but not posterior, thalamus; and (3) GGE patients with uncontrolled seizures exhibited decreased cerebellar RSFC.

Significance: Our findings in this large sample of patients with GGE (1) demonstrate an effect of interictal GSWDs on resting-state networks, (2) provide evidence that different thalamic nuclei may be affected differently by GGE, and (3) suggest that cerebellum is a modulator of ictogenic circuits.