Spatial heterogeneity and subtypes of functional connectivity development in youth

Brain age prediction has been widely utilized to assess functional connectivity (FC) development, but conventional global brain age indices are limited in capturing spatial heterogeneity across the cortex. This study introduces a regional brain development index to characterize fine-grained FC maturation across cortical regions. We examined its spatial variability and stratified individuals into subtypes with distinct region-wise FC developmental patterns. Using data from the Philadelphia Neurodevelopmental Cohort (ages 8-23 years), we identified three distinct subtypes and found that individuals with advanced FC developmental pattern aligning with the sensorimotor-association axis exhibited superior cognitive performance. Robustness was confirmed through replication in the Human Connectome Project Development cohort. Further analyses revealed associations between FC development and gene expression linked to neural differentiation, synaptogenesis, and myelination. These findings suggest that spatial heterogeneity in FC development reflects cortical microstructure and hierarchical organization, underscoring its critical role in neurocognitive maturation during youth.