Abstracts

Rationale: In medial temporal lobe epilepsy (MTLE), structural MRI studies have detected neuronal loss in the epileptogenic hippocampus and the thalamus.(Barron et al., 2013) Diffusion MRI studies have detected Wallerian degeneration in thalamic connections with the medial temporal lobe (MTL).(Concha et al., 2010) Multiple thalamic nuclei have been implicated in MTLE seizure evolution, however, the location and functional significance of these thalamic projections remains to be determined. (Rosenberg et al., 2006; Bertram et al., 2008) Here we localize thalamic connectivity with distinct MTL sub-regions; evaluate thalamo-MTL Wallerian degeneration in these separate pathways; and relate connectivity changes to regional neuronal loss.Methods: Nineteen MTLE patients with unilateral HS (12R; 10 female) were compared to 19 age-matched controls. Five ROIs per hemisphere were created in native space using FreeSurfer: thalamus, amygdala, entorhinal cortex, hippocampus, and parahippocampus. Separate probabilistic tractography analyses were performed between the thalamus and each ipsilateral MTL sub-region (4 per hemisphere) using FMRIB s Diffusion Toolbox. Individual connectivity profiles and regional volumes were assessed in native space; group comparisons were performed in MNI305 space.Results: The medial pulvinar consistently showed the highest connection density with the hippocampus in healthy controls and in MTLE patients. Decreased thalamic connected volume was observed for thalamo-hippocampal pathways in MTLE patients. Regional hippocampal and thalamic atrophy was also observed, indicating gray and white matter loss in this pathway.Conclusions: We provide evidence that notwithstanding neuronal and axonal loss, thalamic connectivity with the hippocampus does not reorganize. To our knowledge, this is the first time MTLE Wallerian degeneration has been reported in terms of decreased connected volume and probable connectivity. We are currently testing the utility of connected volumes as biomarker of epileptogenesis in an expanded cohort. Funding: NINDS- F31 NS083160-01 (D.S.B.); NIHM RO1 MH074457 (P.T.F.) References: Barron, D. S., Fox, P. M., Laird, A. R., Robinson, J. L., and Fox, P. T. (2013). Thalamic medial dorsal nucleus atrophy in medial temporal lobe epilepsy: A VBM meta-analysis. NeuroImage: Clinical 2, 25 32. Bertram, E. H., Zhang, D., and Williamson, J. M. (2008). Multiple roles of midline dorsal thalamic nuclei in induction and spread of limbic seizures. Epilepsia 49, 256 268. Concha, L., Livy, D. J., Beaulieu, C., Wheatley, B. M., and Gross, D. W. (2010). In vivo diffusion tensor imaging and histopathology of the fimbria-fornix in temporal lobe epilepsy. Journal of Neuroscience 30, 996 1002. Rosenberg, D. S., Maugui re, F., Demarquay, G., Ryvlin, P., Isnard, J., Fischer, C., Gu not, M., and Magnin, M. (2006). Involvement of medial pulvinar thalamic nucleus in human temporal lobe seizures. Epilepsia 47, 98 107.