From micro-architecture to networks: canonical neurobiological architecture of functional brain organization across the lifespan and in psychopathology

Abstract

Understanding how macroscale functional network connectivity (FNC) across the lifespan and in psychopathology is spatially organized with respect to microscale neurobiological architecture remains a challenge. Here, we constructed a cross-omics mapping framework by linking resting-state fMRI data (5,349 individuals, 6-80 years) with 49 neurobiological markers (24 cell types, 19 neurotransmitters, 6 mitochondria). We show that FNC development and aging unfold along cellular and molecular gradients. Specifically, spatial correspondence between age-related FNC changes and neurobiological microprofile networks varied by life stage, peaking for cell types in adolescence, neurotransmitter systems in mid-young adulthood and mitochondrial phenotypes in early adulthood. Applying normative modeling to 5 psychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder, autism, and attention-deficit/hyperactivity disorder), we identified disorder-specific and cross-disorder FNC phenotypes spatially associated with neurobiological architecture. Together, these findings provide a hypothesis-generating framework linking functional brain organization and dysfunction to canonical neurobiological architecture across the lifespan and psychiatric disorders.