Investigating Atypical Neural Dynamics and Gene Expression in Temporal Lobe Epilepsy: Insights From Co-Activation Patterns

Abstract

Temporal lobe epilepsy (TLE) is a focal epilepsy extensively examined through advanced neuroimaging techniques to elucidate its pathophysiological mechanisms. This study investigates the differences in dynamic brain activity and gene expression in TLE patients. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 60 TLE patients and 30 healthy controls (HC). Dynamic amplitude of low-frequency fluctuations (dALFF) was employed to identify regions with dALFF variance differences, which were then designated as regions of interest (ROIs). Co-activation patterns (CAP) was constructed to compare brain dynamic changes. Pearson's correlation analysis and pathway enrichment analysis were used to explore the potential molecular mechanisms associated with atypical neural dynamics in TLE. Five CAP states were identified from the rs-fMRI data. Compared to HC, TLE with cognitive normal (TLE-CN) and TLE with cognitive impairment (TLE-CI) patients exhibited atypical state-specific temporal characteristics, including number of states (counts), fraction of time, persistence, resilience, and transition probability (TP) between states. Importantly, dynamic indicators of CAP states were significantly correlated with cognitive performance. Furthermore, 2752 genes were significantly associated with atypical dynamic brain states in TLE, with these genes primarily enriched in synapse-related pathways. This study offers novel insights into atypical neural dynamics from a temporal perspective. The brain network dynamics defined by CAP analysis deepen our understanding of the neurobiological underpinnings of TLE and TLE-CI, revealing a link between atypical neural architecture and gene expression in TLE.