Abstracts

Rationale: Idiopathic generalized Epilepsy (IGE) is characterized by EEG recordings with generalized spike wave discharges (GSW) typically arising from normal background activity. While GSW are the result of highly synchronized activity in the thalamo-cortical network, EEG without GSW is believed to represent normal brain activity. The understanding of mechanisms that facilitate and cause GSW is still limited. The aim of this study was to investigate whether thalamocortical interactions are altered even during GSW-free EEG periods. Methods: EEG-fMRI resting state data sets (3T) from 21 IGE patients were selected according the following criteria: a) GSW free run, b) wakefulness c) motion during the investigation less than 1mm. EEG-fMRI resting state data of 19 age matched healthy subjects (inclusion criteria b and c) were selected for a control group. Functional data was corrected for motion, slice-timing, slow time drifts (freq < 0.01 Hz), structured physiological noise (Perlbarg et al. Magn Reson Imaging. 2007 25(1):35-46) and spatially smoothed (FWHM 6mm). BOLD signal changes were extracted from two seed regions (5mm radius spheres in right and left medial thalami). The averaged time course within each region was used as a regressor in a general linear model analysis, to detect brain regions with BOLD signal correlated with the signal of each seed. 1 to 4 runs were analyzed for each subject and results for all runs were combined using a fixed effects model. Results for each subject were then spatially normalized in the MNI stereotactic space. Inter-subject group analysis was performed using a mixed effects analysis (Worsley et al. Neuroimage 2002;15(1):1-15). Two t maps of group difference (patients - controls) were estimated and thresholded (corrected p<0.05 for spatial extent), showing respectively differences in functional connectivity with the right thalamus and with the left thalamus. Results: Group connectivity maps for IGE patients and controls were similar for the right and left thalamic seeds and showed connectivity between the ipsilateral and contralateral thalamus and widespread bilateral cortical areas with predominance of fronto-parietal and temporal areas. The difference between the two groups using either left or right thalamus seed revealed increased connectivity in bilateral frontal areas and in small occipital areas for IGE patients compared to controls. Less connectivity compared to controls was found in the thalami above the seed. Conclusions: IGE patients exhibit an increased connectivity between the thalamus and the frontal cortex and a decreased intra-thalamic connectivity, when connectivity is measured between GSW discharges and compared to that of control subjects. One may speculate that the combination of increased fronto-thalamic and decreased thalamic connectivity may facilitate the generation of GSW. The assumption that the brain activity in GSW-free periods is normal in IGE patients seems to be invalid: pathological interactions within the thalamo-cortical network seem to exist besides GSW. Supported by CIHR grant MOP-38079