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

bioRxiv [Preprint]. 2026 Oct 26:2026.10.22.761188. doi: 10.64898/2026.10.22.761188.

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.

PMID:42990134 | PMC:PMC13733687 | DOI:10.64898/2026.10.22.761188