Abstracts

Rationale: Temporal lobe epilepsy (TLE) is associated with both gray matter loss and cognitive dysfunction. The goal of this research is to examine the relationship between gray matter volume and resting state functional connectivity to the hippocampus in TLE patients on a voxel level. We hypothesize that decreases in gray matter volume (GMV) may be associated with changes in functional connectivity of the hippocampus to affected cortical regions in the epileptic network. Methods: We studied 15 patients with left TLE (LTLE) as demonstrated by presurgical evaluation, and 25 controls. MRI imaging was performed with a 3T MRI scanner (Philips Healthcare, Inc., Best, Netherlands). Imaging parameters: 1) 3D, T1-weighted high-resolution image series for gray matter analysis, 2) fMRI image series at rest with eyes closed 64x64, FOV = 240 mm, 30 axial slices, TE/TR = 35/2000 ms, 300 volumes (200 volumes for controls). Standard preprocessing and spatial normalization was performed. (1) Resting state functional connectivity analysis Functional connectivity measures the level of co-activation of fMRI time series between a seed region and other brain regions. Our seed region was the left hippocampus (LH), defined by WFUpickatlas (http://fmri.wfubmc.edu/software/PickAtlas). General linear model analysis was used to create functional connectivity maps to the LH. (2) Voxel-based morphometry (VBM) VBM analysis was performed using SPM2 and segmented gray matter images were created following the standard optimized VBM protocol. (3) Biological parametric mapping (BPM) - Multiple regression analysis was performed in BPM [1] and robust BPM [2] using segmented gray matter images as the dependent modality and resting state connectivity maps as the independent imaging covariate.Results: We found several regions that demonstrated a decrease in GMV with increased connectivity to the LH. We report the two most statistically significant regions (Fig. 1). A region in the right parahippocampal gyrus showed modest GMV decrease as functional connectivity to the LH increased, for both patients and controls (Fig. 2a). A region in the left midcingulate gyrus showed a decrease in GMV with an increase in negative functional connectivity to the LH (Fig. 2b). Negative functional connectivity represents the relationship between two regions temporally out of phase with each other. In these regions, there was no correlation between age of onset, duration of disease, or age with either connectivity to the LH or GMV.Conclusions: The decrease in GMV in the right parahippocampus and the left midcingulate with increased functional connectivity to the LH may reflect a nociferous influence of the epileptogenic LH on these structures. The increase in negative functional connectivity to the left hippocampus with decreasing GMV in the cingulate gyrus suggests an inhibitory influence, consistent with the network inhibition hypothesis [3]. [1] Casanova, R. et al. Neuroimage. 34. 137 (2007) [2] Yang, X. et al. Neuroimage. (2011) [3] Norden, A. and Blumenfeld H. Epilepsy and Behavior. 3. 219 (2002).