Transcriptional signatures of the cortical morphometric similarity network gradient in left temporal lobe epilepsy with different seizure symptoms

Background Temporal lobe epilepsy (TLE) manifests with diverse seizure symptoms, including focal to bilateral tonic—clonic seizures (FBTCS), linked to widespread brain network disruptions. The role of cortical morphometric similarity (MS) network gradients and their relationship with gene expression in TLE remains unclear. Methods We studied MS network gradient abnormalities through group comparisons among 87 left TLE patients (48 FBTCS−, 39 FBTCS+) and 63 healthy controls (HC). In addition, partial least squares (PLS) regression analysis was performed to investigate the association between gradient changes and whole-brain gene expression in left FBTCS+ TLE patients. Results FBTCS+ patients showed significant reductions in the principal MS network gradient within default mode network (DMN) regions compared to healthy controls, while FBTCS− patients exhibited no such abnormalities. Gradient alterations in FBTCS+ were linked to whole-brain expression of genes involved in neurobiological pathways, cell types, and cortical layers. Conclusion FBTCS+ TLE is associated with distinct MS network gradient alterations, which may reflect underlying molecular mechanisms contributing to structural changes linked to severe seizure symptoms.