Assessing the Functional-Structural Reorganization of Connector Hubs in Temporal Lobe Epilepsy

Abstract Temporal lobe epilepsy (TLE) is associated with altered functional connectivity, yet its effects on connector hubs, regions supporting long-range and inter-network communication, remain poorly understood. We used SParsity-based Analysis of Reliable k- hubness to characterize connector hub reorganization in unilateral TLE compared with healthy controls. Patients exhibited significant widespread reductions in k- hubness involving the occipital, cingulate, and precuneus regions, ipsilateral hippocampus, and the bilateral pallidum. Compared to the distribution of k- hubness in healthy controls, the hub disruption index revealed rapid loss of k- hubness alongside emergence of new hubs in contralateral homologous regions. To investigate microstructural substrates of these functional changes, apparent diffusion coefficient and fractional anisotropy from diffusion magnetic resonance imaging were examined. The strongest associations with k- hubness were observed in subcortical structures and the hippocampus. These findings demonstrate that TLE is characterized by widespread, asymmetric connector hub reorganization extending beyond the epileptogenic temporal lobe, revealing distinct patterns of network disruption and reorganization across the brain.