Abstracts

Rationale: Previous diffusion tensor imaging (DTI) studies have demonstrated white matter (WM) abnormalities in subjects with temporal lobe epilepsy (TLE). Here we further examine this using tract-based spatial statistics (TBSS), which examines whole-brain WM integrity among groups, and is less vulnerable to concerns raised with other approaches, such as nonuniform ROI placement/size, and spatial misalignment. TBSS computes voxelwise statistics of fractional anisotropy (FA), a measure of WM integrity that reflects myelination, axon density, and intravoxel coherence of fiber orientation. The current hypothesis is that subjects with TLE have regional changes in temporal lobe WM integrity, expressed as FA, when compared to age-matched healthy controls. We further examined the relationship between WM integrity and age of seizure onset as well as epilepsy duration.Methods: DTI data were acquired on 12 subjects with unilateral TLE (10 left/2 right; mean ± SD age at exam, 37.9 ± 10.7 yrs; age of seizure onset, 14.3 ± 12.4 yrs; duration of epilepsy, 23.6 ± 12.9 yrs) and 10 healthy controls (age 42.1 ± 10.1). Scanning used a 3-Tesla MR scanner with gradients applied in 12 non-collinear directions with b value=1000 s/mm2. In order to maintain consistent side of seizure onset, data for the two right TLE subjects were transformed across the midline. Voxelwise statistical analysis of the fractional anisotropy (FA) data was carried out using TBSS [Smith et al., NeuroImage, 2006, 31:19]. TBSS projects all subjects' FA data onto a mean FA tract skeleton, before applying voxelwise cross-subject statistics. Individual FA data were then projected onto the skeleton, and then correction for multiple comparisons was performed using permutation-based inference with a cluster-forming threshold of t=2 and a corrected cluster size significance level of p<0.05.Results: The TLE group, as compared to healthy controls, showed a cluster of significantly decreased FA in the anterior temporal lobe on the side of seizure onset. Also, earlier age of seizure onset was linearly related to lower FA in the posterior corpus callosum. No significant correlation was found between FA and duration of epilepsy.Conclusions: TLE is associated with reduced WM integrity in the anterior temporal lobe of the affected side, suggesting WM derangement in the region of the epileptogenic zone. In addition, earlier onset of epilepsy is associated with increased altered integrity of posterior corpus callosum, a region that in part connects the two temporal lobes, indicating adverse neurodevelopmental impact of TLE on interhemispheric connectivity. Funding supported by: NIH T32 NS45540, PI: Baram, T. Z. and GCRC at UC Irvine.