Inter-individual body mass variations relate to fractionated functional brain hierarchies

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 associations between functional connectivity and inter-individual BMI variations. We utilized non-linear connectome manifold learning techniques to represent macroscale functional organization 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 a disrupted modular architecture and hierarchy of the brain. Transcriptomic decoding and gene enrichment analyses identified genes previously implicated in genome-wide associations to BMI and specific cortical, striatal, and cerebellar cell types. These findings illustrate functional connectome substrates of BMI variations in healthy young adults and point to potential molecular associations.