Potential molecular mechanisms explaining progressive alterations of the structural network in temporal lobe epilepsy

The effect of recurrent seizures on the gradual deterioration of the white matter structural network and the potential molecular mechanisms that underlie the baseline and longitudinal changes in network topology in temporal lobe epilepsy (TLE) remain unclear. Therefore, we used diffusion tensor imaging (DTI) scans and neuropsychiatric assessments for 28 patients with unilateral TLE at baseline and follow-up, and for 28 healthy controls (HC). The topological properties of the structural network were calculated using graph theoretical analyses. Transcription-neuroimaging association analyses were used to explore the spatial associations between gene expression data from the Allen Human Brain Atlas and baseline and longitudinal topological alterations of the structural network. Subsequently, enrichment analyses were performed on associated genes. Extensive topological changes and aberrant neuropsychiatric assessments were observed in patients with TLE at baseline compared to those in HC. Additionally, decreased nodal efficiency (NE) in the right cuneus was positively correlated with cognitive impairment in TLE at baseline. Decreased NE in the right amygdala was identified in TLE at follow-up, with a duration of 30.5 ± 13.4 months (mean ± SD). Moreover, topological changes in the structural network in TLE at baseline were associated with gene expression related to cell metabolism, RNA splicing, and mRNA processing. The dynamic evolution of the network topology in TLE at follow-up was related to gene expression associated with catabolic processes, immune processes, and inflammatory mediators. To the best of our knowledge, this is one of the first studies to combine longitudinal structural network analysis using DTI with spatial transcriptomic data in TLE. Our results provide new perspectives on the potential molecular mechanisms underlying the evolution of the structural network in TLE, which may facilitate the development of precision therapeutic strategies.