Abstracts

Rationale: The association between idiopathic generalized epilepsy (IGE) and generalized spike and wave discharges (GSWD) is well established, but the long-term effects of epileptogenic activity on the brain are not well understood. Simultaneous EEG/fMRI studies of IGE reveal deactivation in brain regions corresponding to the default mode network (DMN) during GSWD. Recent resting state EEG/fMRI studies of IGE have found that DMN functional connectivity is reduced even during periods of normal EEG commensurate with duration of disease. In this EEG/fMRI study we investigate the effect of uncontrolled seizures on DMN connectivity in IGE patients. Methods: 78 IGE patients and 38 healthy control subjects underwent 1-3 consecutive 20-minute EEG/fMRI scans at 4 Tesla with TR=3 seconds. 35 scans from 18 IGE patients out of 224 total scans were excluded because they contained GSWD. Group independent component analysis (ICA) was used to identify the DMN, and dual regression was used for group-level comparisons. Results: Duration was correlated with a significant reduction in DMN connectivity in the cohort of all IGE patients consistent with previous studies. However, when patients with controlled and uncontrolled seizures were considered separately, the effect of duration remained significant in uncontrolled seizures but not controlled seizures. When patients were compared to healthy controls, connectivity was found to be significantly reduced in uncontrolled but not controlled seizures. Patients with uncontrolled seizures had significantly lower connectivity than those with controlled seizures, even after accounting for the effect of duration. Conclusions: DMN functional connectivity is reduced in IGE patients even during periods of normal EEG and can distinguish between patients with controlled and uncontrolled seizures. Connectivity in patients with uncontrolled seizures declines with duration of disease. DMN abnormalities may present a new biomarker for poorly controlled IGE.