The development of cortical functional hierarchy is associated with the molecular organization of prenatal/postnatal periods.

The human cerebral cortex conforms to specific functional hierarchies facilitating information processing and higher-order cognition. Prior studies in adults have unveiled a dominant functional hierarchy spanning from sensorimotor regions to transmodal regions, which is also present in younger cohorts. However, how the functional hierarchy develops and the underlying molecular mechanisms remain to be investigated. Here, we set out to investigate the developmental patterns of the functional hierarchy for preschool children (#scans = 141, age = 2.41-6.90 years) using a parsimonious general linear model and the underlying biological mechanisms by combining the neuroimaging developmental pattern with two separate transcriptomic datasets (i.e. Allen Human Brain Atlas and BrainSpan Atlas). Our results indicated that transmodal regions were further segregated from sensorimotor regions and that such changes were potentially driven by two gene clusters with distinct enrichment profiles, namely prenatal gene cluster and postnatal gene cluster. Additionally, we found similar developmental profiles manifested in subsequent developmental periods by conducting identical analyses on the Human Connectome Projects in Development (#scans = 638, age = 5.58-21.92 years) and Philadelphia Neurodevelopment Cohort datasets (#scans = 795, age = 8-21 years), driven by concordant two gene clusters. Together, these findings illuminate a comprehensive developmental principle of the functional hierarchy and the underpinning molecular factors, and thus may shed light on the potential pathobiology of neurodevelopmental disorders.