Abstracts

Rationale: Childhood absence seizures consist of brief 5-10 second episodes of unresponsiveness associated with 3Hz “spike-wave” discharges (SWD) on EEG. However, recent studies suggested that more subtle EEG and behavioral abnormalities may occur during the interictal period of these brief episodes. Resting functional connectivity is an effective, non-invasive method which allows the investigation of the intra- and inter-hemispheric connectivity in defined regions by analyzing the spontaneous fluctuations of fMRI signals in the resting state. Methods: Simultaneous EEG and fMRI measurement were conducted in 7 pediatric patients with childhood absence epilepsy, and 7 age-matched normal controls. Analysis of 38 seizure episodes was performed using SPM2, but the onset of the hemodynamic response function (HRF) was systematically shifted from -20s to +20s relative to seizure onset. 13 regions of interest (ROI) were defined by overlapping the fMRI changes with absence seizures shown in t-maps over time and 13 anatomic regions segmented from SPM MRI template. For fMRI data used in correlational analyses, both a high-pass filter (0.01Hz) and a low-pass filter (0.08Hz) were applied. Reference time courses for a single subject were then computed, by averaging the time courses across all voxels in the left and right area of each ROI separately. Then, these reference time courses were correlated with the time course of every other voxel in the brain. Group statistics comparing patients and normal subjects were evaluated by an ANOVA method, performed on mean correlation values for 13 defined ROIs. For this analysis, we used the mean correlation of all voxels between the right and left areas for each region. Results: In both patients and controls, we found that correlations between brain areas were significantly increased as the distance between those brain areas decreased. Comparing group analysis of 13 ROIs in patients with healthy subjects, our results showed significantly increased interhemispheric correlation specifically in the orbitofrontal cortex of patients (F= 5.51, P = 0.0408, ANOVA, n= 6 patients, 6 healthy subjects). Conclusions: These results demonstrate that the orbital frontal cortex shows increased resting functional connectivity in patients with childhood absence epilepsy, even when seizures are not occurring. It suggests that resting brain functional connectivity analysis may provide a promising biomarker of disease severity, and may also increase our understanding of fundamental network dysfunction in this form of epilepsy.