Spatiotemporal dynamics of seizure networks: Progressive posterior hippocampal recruitment in mesial temporal lobe epilepsy

OBJECTIVE: This study aims to characterize the spatiotemporal dynamics of hippocampal atrophy and epileptogenicity in mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS), and to investigate their relationship with disease duration. METHODS: We conducted a cross-sectional study integrating structural magnetic resonance imagingandstereoelectroencephalographic (SEEG) data from 156 mTLE-HS patients. Hippocampal subfield volumetry was performed. In patients with SEEG (n = 67), interictal periodic and aperiodic components were quantified using the FOOOF ("fitting oscillations and one over f") algorithm, and ictal epileptogenicity index (EI) was calculated. Correlation analysis, along with linear statistical model and restricted cubic splines (RCS), were employed to examine the relationships between disease duration, hippocampal volumetry, and electrophysiological metrics, focusing on anterior versus posterior hippocampus. RESULTS: Hippocampal volume showed a negative correlation with disease duration in all subfields (head: r = -.185, p = .021; body: r = -.237, p = .003; tail: r = -.253, p = .001). RCS analysis indicated a nonlinear association, where the slope linking disease duration to volume loss appeared steeper (suggestive of accelerated atrophy) beyond approximately 15 years (p < .001). Electrophysiologically, the aperiodic exponent decreased significantly in both anterior (r = -.271, p = .012) and posterior hippocampus (r = -.323, p = .009). A significant positive correlation was found between disease duration and the EI specifically in the posterior hippocampus (r = .550, p < .001), and the group with high EI (≥.3) had a significantly longer disease duration compared to the low EI group (16.0 ± 8.0 vs. 11.3 ± 7.5 years, p = .015). SIGNIFICANCE: mTLE-HS is characterized by a dual pattern of association with disease duration: a nonlinear (potentially accelerating) association with structural atrophy beyond ~15 years and an association between longer duration and higher epileptogenicity in posterior hippocampal regions. This spatiotemporal pattern provides a mechanistic basis for considering individualized extension of surgical resection in chronic cases, a strategy requiring prospective evaluation.