Longitudinal alterations of cortical structural‐functional coupling in temporal lobe epilepsy

Abstract Background and Purpose To investigate the longitudinal alterations of cortical structural‐functional coupling (SF coupling) in patients with temporal lobe epilepsy (TLE) over a 2‐year follow‐up, thereby exploring the neuropathophysiological mechanisms of TLE. Methods Twenty‐eight TLE patients and 42 age‐ and gender‐matched healthy controls (HCs) were recruited. We used resting‐state functional MRI and diffusion‐weighted imaging to estimate and compare SF coupling at the multiscale network level (whole‐brain, modular, and regional levels). Then, we analyzed the relationships between the spatial patterns of SF coupling, the principal functional connectivity (FC) gradient, and the functional participation coefficient (PC). Finally, we related regional SF coupling changes between baseline and follow‐up to the expression of regional TLE‐specific genes. Results Compared with HCs, TLE patients showed higher baseline SF couplings within the whole‐brain, limbic, and default‐mode modules. SF couplings within visual and dorsal attention modules were increased at follow‐up compared to baseline. In all three groups, the spatial patterns of SF coupling aligned with the principal FC gradient and the functional PC. The longitudinal change in regional SF coupling in TLE patients was significantly positively correlated with the expression of the CUX2 gene. Conclusions Aberrant SF coupling was revealed in TLE and related to macroscale cortical hierarchies, functional segregation, and TLE‐specific gene expression; these data help increase our understanding of the neuropathophysiological mechanisms underlying TLE.