Abstract: Objective: Although altered large-scale brain network organization in patients withtemporal lobe epilepsy (TLE) has been shown using morphologic measurements suchas cortical thickness, these studies, have not included critical subcortical structures(such as hippocampus and amygdala) and have had relatively small sample sizes. Here,we investigated differences in topological organization of the brain volumetric net-works between patients with right TLE (RTLE) and left TLE (LTLE) with unilateral hip-pocampal atrophy. Methods: We performed a cross-sectional analysis of 86 LTLE patients, 70 RTLEpatients, and 116 controls. RTLE and LTLE groups were balanced for gender(p=0.64), seizure frequency (Mann-WhitneyUtest, p=0.94), age (p=0.39), age ofseizure onset (p=0.21), and duration of disease (p=0.69). Brain networks were con-structed by thresholding correlation matrices of volumes from 80 cortical/subcorticalregions (parcellated with Freesurfer v5.3 https://surfer.nmr.mgh.harvard.edu/) thatwere then analyzed using graph theoretical approaches. Results: We identified reduced cortical/subcortical connectivity including bilateral hip-pocampus in both TLE groups, with the most significant interregional correlationincreases occurring within the limbic system in LTLE and contralateral hemisphere inRTLE. Both TLE groups demonstrated less optimal topological organization, withdecreased global efficiency and increased local efficiency and clustering coefficient.LTLE also displayed a more pronounced network disruption. Contrary to controls,hub nodes in both TLE groups were not distributed across whole brain, but ratherfound primarily in the paralimbic/limbic and temporal association cortices. Regionswith increased centrality were concentrated in occipital lobes for LTLE and contralat-eral limbic/temporal areas for RTLE.Significance:These findings provide first evidence of altered topological organizationof the whole brain volumetric network in TLE, with disruption of the coordinated pat-terns of cortical/subcortical morphology Ver menos