Structural and functional changes linked to cognitive impairment in Idiopathic Generalized Epilepsy

Background and PurposeWhile the idiopathic generalized epilepsy (IGE) comprise around one fifth of all epilepsy, the pathogenesis of it is largely unknown. Previous studies identified cognitive deficits in IGE patients, nevertheless, whether (and how) the brain structure and functional connectivity (FC) reflect these deficits remains underexplored. Here, we aim to find structural and FC differences in cognitively impaired IGE patients. Materials and MethodsWe recruited 36 IGE patients and 49 matched healthy controls (HC) in this cross-sectional study. All participants underwent structural and resting-state fMRI (rs-fMRI) scanning with a 3 Tesla MRI. Voxel-based morphometric analysis (VBM) was used to assessed structure differences, and seed-based analysis of rs-fMRI was used to examine FC. We examined the cognitive performance of patient with MoCA (Montreal Cognitive Assessment), grouped them into high (HMoCA, >25) and low (LMoCA, [&le;]25) group, and further examined the brain structural changes functional changes in each group. ResultsIGE patients showed right significant decrease in cerebellar gray matter volume (GMV), negatively correlating with the disease duration (r=-0.542, p=0.001), and increase in the left dorsolateral superior frontal gyrus GMV. Right cerebellum showed increased connectivity to the precuneus and angular gyrus, decreased connectivity to the postcentral gyrus and Rolandic operculum. Surprisingly, we found that LMoCA IGE patients (with more cognitive deficits) had increased right nucleus accumbens (NAc) GMV (t = -4.413, p < 0.001) and FC and a stronger NAc - prefrontal cortex FC (t = -2.683, p = 0.013), in comparison with the patients with high MoCA. ConclusionsCognitive impairment in IGE patients is linked to the NAc structural changes and NAc-prefrontal circuit alterations. These results provide novel circuit-level insights into understanding the cognitive impairment in IGE patients, contributing to revealing the pathophysiological mechanisms of IGE.