Spatial Heterogeneity and Subtypes of Functional Connectivity Development in Youth

The brain functional connectome development is fundamental to neurocognitive growth in youth. While brain age prediction has been widely used to assess connectome development at the individual level, traditional approaches providing a global index overlook the spatial variability and inter-individual heterogeneity of functional connectivity (FC) development across the cortex. In this study, we introduced a regional brain development index to assess spatially fine-grained FC development. We examined the spatial variability of FC development and stratified individuals into subtypes with distinct patterns of spatial heterogeneity in region-wise FC development across the cortex through clustering. An evaluation conducted on a sample of youths aged 8-23 years using fMRI data from the Philadelphia Neurodevelopmental Cohort (PNC) revealed three distinct FC development subtypes. Individuals with advanced FC development aligned with the hierarchical brain organization along the sensorimotor-association (S-A) axis demonstrated superior cognitive performance compared to those with other patterns. These patterns were replicated in the Human Connectome Project Development (HCP-D) cohort, confirming their robustness. Further analysis revealed associations between FC development and gene expression, with enriched genes linked to neural differentiation, synaptogenesis, and myelination. These findings suggest that spatial heterogeneity in FC development reflects underlying cortical microstructure and hierarchical cortical organization, underscoring its critical role in understanding neurocognitive maturation and individual variability during youth.