Authors
Jing Cong, Shaoling Zhao, Haoshu Xu, Xiaoyu Xu, Chao Li, Hongming Li, Ting Xu, Yang Li, Hang Yang, Zaixu Cui
Published in
Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 34. Pages e2604191123. Aug 25, 2026. Epub Aug 10, 2026.
Abstract
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.
PMID:
42574643
Bibliographic data and abstract were imported from PubMed on 11 Aug 2026.
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