Brain volumetric signatures of neighborhood disadvantage in focal epilepsy

Abstract Objective Social disadvantage is an important determinant of health in focal epilepsy, but its neurobiological basis remains unclear. We examined whether brain morphometric alterations represent a structural signature of deprivation. Methods We performed a retrospective cohort study of 340 adults with pharmacoresistant focal epilepsy evaluated at the Cleveland Clinic (2010–2022). Age‐ and sex‐adjusted volumetric percentiles were derived from 3‐T brain magnetic resonance imaging. To account for hemispheric network differences, analyses were stratified by epilepsy laterality (right vs. left), adjusting for seizure localization, seizure burden, and lesional status. Neighborhood disadvantage was quantified using the Area Deprivation Index (ADI) and categorized into low, moderate, and high deprivation using the R sociome package. To identify coordinated structural patterns, least absolute shrinkage and selection operator regression with 10‐fold cross‐validation was applied to high‐dimensional volumetric data, followed by latent Dirichlet allocation (LDA) to derive latent volumetric networks. Associations between network expression and ADI were assessed using Spearman correlation and Kruskal–Wallis with false discovery rate (FDR) correction. Regional patterns were visualized using ggseg. Results In right‐sided epilepsy, LDA‐derived networks were significantly associated with ADI (FDR p = .01). Occipitoparietal and frontal opercular networks showed declining membership with increasing deprivation ( ρ = −.23, FDR p = .01). All top‐loading regions demonstrated negative volume–ADI correlations, with pericalcarine cortex and cuneus volumes decreasing by 27.1 and 24.4 percentile points, respectively, from lowest to highest deprivation. Associations were weaker but directionally consistent in left‐sided epilepsy (FDR p = .053). The visual and ventral attention networks emerged as most heavily ADI‐sensitive. No individual regional volumes showed significant associations with ADI. Significance Neighborhood disadvantage was linked to network‐level, but not focal, brain alterations in adults with focal epilepsy, with laterality‐specific vulnerability patterns supporting incorporation of neighborhood metrics into epilepsy research and care.