Resting State Functional Connectivity Demonstrates Increased Segregation in Bilateral Temporal Lobe Epilepsy

Abstract Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy. An increasingly identified subset of patients with TLE consists of those who show bilaterally independent temporal lobe involvement during seizures. Bilateral TLE (BiTLE) remains understudied, likely due to its complex underlying pathophysiology and heterogeneous clinical presentation. In this study, using a multicenter resting state functional MRI (rs-fMRI) dataset, we constructed whole brain functional networks of 19 patients with BiTLE, and compared them to those of 75 patients with unilateral TLE (UTLE). We quantified resting-state, whole-brain topological properties using metrics derived from network theory, including clustering coefficient, global efficiency, participation coefficient, and modularity. For each metric, we computed an average across all brain regions, and iterated this process across network densities ranging from 0.10-0.50. Curves of network density versus each network metric were compared between groups. Finally, we derived a combined metric, which we term the “integration-segregation axis”, by combining whole brain average clustering coefficient and global efficiency curves and applying principal component analysis (PCA)-based dimensionality reduction. Compared to UTLE, BiTLE had decreased global efficiency (p=0.026), increased whole brain average clustering coefficient (p=0.035), and decreased whole brain average participation coefficient across a range of network densities (p=0.001). Modularity maximization yielded a larger number of smaller communities in BiTLE than in UTLE (p=0.016). Differences in network properties separate BiTLE and UTLE along the integration-segregation axis: 68% of patients with BiTLE were identified within the high segregation region, while only 41% of the UTLE patients were identified in the same region (p=0.042). Along the integration-segregation axis, UTLE patients with poor surgical outcomes were more similar to BiTLE than those with good surgical outcomes (p=0.72). Increased interictal whole brain network segregation, as measured by rs-fMRI, is specific to BiTLE, and may assist in non-invasively identifying this patient population prior to intracranial EEG or device implantation.