Changes in Cerebellar Functional Gradients and Molecular Genetic Mechanisms in Patients with Temporal Lobe Epilepsy:...

To investigate the characteristics of cross-sectional and longitudinal changes in cerebellar functional gradients in patients with temporal lobe epilepsy (TLE) and to explore the underlying molecular genetic mechanisms.This study included both cross-sectional and longitudinal phases. The cross-sectional study included 115 TLE patients and 75 healthy controls (HCs) and analyzed the cerebellar functional connectivity gradient using resting-state functional magnetic resonance imaging (rs-fMRI); the longitudinal study followed 29 TLE patients and 29 HCs and assessed the changes in the cerebellar functional connectivity gradient over a four-year period (44.24 ± 16.64 months). Gene expression data from the Allen Human Brain Atlas were used to analyze the association of differences in gradient changes with gene expression. (1) Both TLE patients and HCs showed typical functional cerebellar gradient patterns. (2) Cross-sectional analyses revealed that TLE patients had a contracted range of main cerebellar gradients and significantly higher gradient values in the default mode network (DMN). (3) Longitudinal analyses showed that cerebellar DMN gradients were initially abnormal in TLE patients at baseline（BL）; with disease progression, the DMN stabilized. (4) 151 genes associated with gradient differences were identified, and GO enrichment analysis mainly involved endocytosis, synaptic structure, metabolism, and ion channels. Protein interaction network analysis identified WASF1, RAC1 and MTG1 as key hub genes. This study provides initial evidence of dynamic changes in cerebellar functional gradients and their potential molecular correlates in TLE patients for the first time by functional magnetic resonance imaging gradient analysis, providing a new perspective for understanding the neuroplasticity of TLE.