Abstracts

Rationale: Quantitative neuroimaging studies suggest that Medial Temporal Lobe Epilepsy (MTLE) is associated with extra-hippocampal damage involving cortical and subcortical limbic structures. While these findings indicate that a system of brain structures is abnormal in MTLE, it is largely unknown whether the structural organization of connections within this system could lead to aberrant communication and excitation between epileptogenic structures. In this study, we aimed to investigate limbic networks in patients with MTLE using a combination of high resolution DTI and mathematical network analysis.Methods: We performed diffusion tensor magnetic resonance imaging scans on 12 consecutive patients with unilateral MTLE due to hippocampal sclerosis (6 left and 6 right MTLE) (Figure 1A) and 26 matched healthy subjects. We then applied whole brain probabilistic tractography to map the connectivity patterns of 10 bilateral anatomically defined limbic regions of interest (ROIs). The probabilistic fiber count between each ROI and all other ipsilateral and contralateral ROIs was computed (Figure 1B), resulting in a weighted 20x20 connectivity matrix (Figure 1C), which was then submitted to a threshold. The resulting binary matrices were then used to evaluate the following quantitative network properties: region degree, clustering coefficient, path length efficiency, density and centrality. The patient data was then parametrically compared to controls using a p-value set at p<0.005.Results: Compared with controls, in patients with MTLE the links between the ipsilateral hippocampus, thalamus, parahippocampal gyrus, fusiform area and inferior orbital region are significantly more influential to the global brain network as they have a higher fraction of participation in a large number of shortest paths. There was also an increased presence of certain connection motifs in the ispilateral thalamus, insula posterior cingulate and parahippocampal gyrus.Conclusions: These results indicate that MTLE is associated with an abnormal organization of limbic circuits. The local connectivity of hippocampal and perihippocampal structures in patients with MTLE is comprised of short-circuit motifs and participation in global network paths (Figure 1D). These findings are traditionally associated with network regions with significant influence over the global network, and they corroborate the hypothesis of a limbic system disease in MTLE.