Work

Shared segregation failure and targeted limbic decoupling in temporal lobe epilepsy with and without FBTCS

Year: 2026

Type: article

Abstract: Background Focal impaired awareness seizures (FIAS) and focal-to-bilateral tonic-clonic seizures (FBTCS) represent two different seizure types of temporal lobe epilepsy (TLE). However, the interictal connectomic architecture associated with seizure containment versus whole-brain generalization remains incompletely understood. This cross-sectional, observational study aims to delineate the macroscopic topological associations that differentiate the focal-only seizure type from the FBTCS-prone seizure type. Methods We modeled functional brain networks as complex networks in 38 patients with unilateral TLE. The patients were categorized into a focal-only group (n=19) and an FBTCS group (n=19)—alongside 19 age-matched healthy controls (HCs). We applied resting-state fMRI and graph-theoretical analyses to evaluate network parameters quantifying global integration, functional segregation, and nodal centrality. We further performed exploratory subgroup analyses for right-sided TLE. Results Both the focal-only and FBTCS groups exhibited disrupted local functional segregation (reduced normalized clustering and local efficiency) compared to healthy controls, suggesting a shared baseline network vulnerability. Additionally, the FBTCS group showed increased nodal efficiency in the left middle occipital gyrus. Conversely, exploratory analyses of right-sided TLE subgroups revealed that the right focal-only seizure type followed a distinct pattern characterized by significantly reduced nodal efficiency in right mesial temporal regions (the right hippocampus, parahippocampus, and amygdala) and an associated increased nodal clustering coefficient in the right middle frontal gyrus. Additionally, no statistically significant differences in global integration were detected in the right-sided TLE subgroups. Conclusion TLE seizure types exhibit divergent patterns of interictal network reorganization. The shared decrease in local segregation may conceptually reflect a weakened "modular firewall". Rather than adopting a massive global disconnection, right focal-only TLE is uniquely associated with a localized "targeted limbic decoupling." We hypothesize that this conceptually isolates the core epileptogenic generators, though cross-sectional static data limit definitive causal inferences.

Source: BMC Neurology

DOI: 10.1186/s12883-026-05523-y

Authors: Jinping Liu, Qiaoqiao Liao, Xia Zhou, Zhao Zhang, Jinou Zheng