Biophysically informed large-scale circuit modeling reveals regionspecific microscale dynamics in temporal lobe epilepsy

OBJECTIVE: Temporal lobe epilepsy (TLE) is frequently accompanied by hippocampal sclerosis (HS) and involves widespread alterations in brain structure and function. However, most neuroimaging studies rely on single-modality data and provide limited insight into the microscale neural mechanisms underlying these changes. The relationship between structural connectivity (SC) and functional connectivity (FC) also remains insufficiently understood. This study aims to integrate structural and functional data to investigate microscale neural dynamic alterations in TLE. Approach: A biophysically informed relaxed mean-field model (rMFM) was employed to estimate region-specific microscale parameters, including recurrent connection weight w and subcortical drive I, in healthy controls (HC) and left HS (LHS) or right HS (RHS) patients. Individual SC derived from diffusion MRI was used as anatomical constraints to simulate resting-state neural dynamics. Group differences in model-derived parameters were evaluated. In addition, graph-theoretical analyses were conducted to characterize alterations in structural and functional network topology and to examine associations between network metrics, microscale parameters, and clinical measures. Main results: Compared with the HC group, both LHS and RHS groups showed observable differences in recurrent connection weight w and subcortical drive I across multiple brain regions, including the superior parietal lobule, temporal pole, and insula cortex. These changes suggest disrupted local recurrent dynamics and altered subcortical modulation, potentially impairing large-scale network integration. Furthermore, microscale parameter alterations were significantly associated with changes in network topology, indicating that local circuit dysfunction can propagate to macroscopic network reorganization. Significance: This study provides mechanistic evidence for multiscale brain network remodeling in TLE and demonstrates the utility of biophysical modeling in linking structural architecture with functional dynamics, offering new insights into the pathophysiology of epilepsy.