Functional connectome contractions in temporal lobe epilepsy

Abstract Objective Temporal lobe epilepsy (TLE) is classically associated with hippocampal pathology, and increasingly with structural changes beyond the mesiotemporal lobe. Functional anomalies, their link to cortical morphology and microstructure, and their utility in surgical prognosis, however, remain less well understood. Methods We studied 30 drug-resistant TLE patients and 57 healthy controls using multimodal 3T MRI. All patients had histologically-verified hippocampal sclerosis and underwent postoperative imaging to establish the extent of surgical resection. Our analysis leveraged a novel resting-state fMRI framework that parameterizes functional connectivity distance, consolidating functional and geometric properties of macroscale brain networks. Functional findings were integrated with morphological and microstructural metrics, and associations to post-surgical seizure outcome were examined using machine learning techniques. Results Compared to controls, TLE showed connectivity distance reductions in temporo-insular and dorsomedial prefrontal networks, with the former being more marked ipsilateral to the focus. Findings were driven by contractions in long-distance connections together with an excess in short-range connections, suggesting topological segregation of functional networks. Parallel structural profiling indicated that functional connectivity distance reductions in TLE were independent of atrophy but mediated by microstructural changes in the underlying white matter. Patients with persistent seizures showed anomalies a distinct network signature which predicted seizure outcome with 75±4% accuracy (using 5-fold cross-validation). Conclusions Our findings suggest connectivity distance contractions as a pathoconnectomic substrate of TLE. Functional topological isolation may represent a microstructurally mediated network mechanism that tilts the balance towards epileptogenesis in affected networks.