White-matter functional connectivity uniquely predicts brain age, cognition, and psychopathology beyond gray-matter connectivity
2026-08-10
White-matter pathways form the structural backbone for communication across the human connectome, yet whether functional connectivity (FC) involving white matter carries information beyond gray-matter networks remains unclear. Here, we tested whether white-matter FC (W-M FC) uniquely predicted brain age, cognition, and psychopathology. Across four independent developmental cohorts spanning childhood to young adulthood (total n = 2,370), we showed that W-M FC, including both white–white and gray–white connectivity, robustly predicted individual differences in brain age. Critically, these predictions remained significant after controlling for gray-matter FC, demonstrating that W-M FC captures nonredundant functional information relevant to brain development. We further demonstrated that W-M FC similarly explained unique variance in cognitive performance ( n = 4,388) and ADHD symptoms ( n = 4,465). Feature-weight analyses revealed prominent contributions from commissural, projection, superficial, and association pathways, indicating a structured white-matter functional architecture that complements, rather than mirrors, gray-matter functional organization. Together, these findings establish W-M FC as a distinct and behaviorally meaningful component of the human connectome, extending models of human neurodevelopment beyond gray-matter FC alone.