Etiology-specific trajectories of longitudinal functional connectivity and network topology in posttraumatic and mesial temporal lobe epileptogenesis.

The latent period of epileptogenesis represents a critical window for early diagnosis and preventive intervention before the disease progresses. Among epilepsy subtypes, posttraumatic epilepsy (PTE) and mesial temporal lobe epilepsy (mTLE) account for a significant proportion of cases. However, it remains unclear whether these two subtypes share common longitudinal network biomarkers during the latent phase. To address this question, we performed longitudinal functional and structural MRI in rat models of PTE induced by lateral fluid percussion injury (LFPI) and mTLE induced by intrahippocampal kainic acid (KA). The final dataset included 31 rats, comprising 18 KA/mTLE rats and 13 LFPI/PTE rats, with available MRI scans at pre-induction baseline, 1 week, and/or 8 weeks post-induction. We quantified lesion volume (LV), resting-state functional connectivity (rsFC), network topology, longitudinal changes, and rsFC-LV associations. In mTLE model, hippocampal rsFC increased at 1 week relative to baseline (p = 0.024) and declined globally at 8 weeks. Hippocampal rsFC was negatively associated with LV in the left hippocampus (week 1, p = 0.036), right hippocampus (week 8, p = 0.02), and sensorimotor cortex (week 8, p = 0.041). Network topology showed an early reduction followed by a later increase in clustering coefficient. In contrast, the PTE model displayed progressive rsFC reductions from baseline at both post-induction time points and higher clustering coefficient than mTLE. Despite overall rsFC declines in both models, mTLE retained greater prefrontal rsFC but lower hippocampal rsFC than PTE at 8 weeks. Etiology-specific LV differences were observed in hippocampus and sensorimotor cortex at week 8 (mTLE < PTE, p < 0.037). These findings demonstrate distinct, etiology-specific trajectories of rsFC, topology, and structure-function coupling in established rodent models of epileptogenesis.