A bstract Variations in body mass index (BMI) have been suggested to relate to atypical brain organization, yet connectome-level substrates of BMI and their neurobiological underpinnings remain unclear. Studying 325 healthy young adults, we examined association between functional connectome organization and BMI variations. We capitalized on connectome manifold learning techniques, which represent macroscale functional connectivity patterns along continuous hierarchical axes that dissociate low level and higher order brain systems. We observed an increased differentiation between unimodal and heteromodal association networks in individuals with higher BMI, indicative of an increasingly segregated modular architecture and a disruption in the hierarchical integration of different brain system. Transcriptomic decoding and subsequent gene enrichment analyses identified genes previously implicated in genome-wide associations to BMI and specific cortical, striatal, and cerebellar cell types. These findings provide novel insights for functional connectome substrates of BMI variations in healthy young adults and point to potential molecular associations.

Body mass variations relate to fractionated functional brain hierarchies