Temporal lobe epilepsy (TLE) is increasingly reconceptualised as a network disorder, with a growing literature suggesting concurrent structural and functional changes in large-scale network organization. In the current work, we developed a novel framework consolidating topological and spatial properties of brain networks and applied it to unveil shifts in the connectional distance distribution in TLE. Patients showed marked connectivity reductions in ipsilateral temporal, insular, and dorsomedial prefrontal networks—regions which coincide with high-degree, transmodal systems. Importantly, distance reductions occurred independently of cortical atrophy but were mediated by microstructural damage, thus emphasizing the clinical importance of physically-grounded measures of functional connectivity.
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