Developmental changes of the white matter functional connectome

Emerging studies have consistently shown that blood-oxygenation-level-dependent signals within white matter (WM) appear to be related to neural activity. This recognition of WM functional signal has provided a great opportunity to investigate how the brain’s WM functionally evolves in youth as well as its relationship to developmental disorders. Using multimodal imaging data from 407 participants aged 8 to 22 years, we constructed the WM functional connectome (WMFC) as well as the WM structural connectome (WMSC). Our findings reveal a global three-stage reorganization process in WMFC characterized by a decreasing-increasing-decreasing pattern. Regional changes are marked by hierarchical development between primary networks and higher-order networks. In conjunction with the WMSC, we measured WM SC‒FC coupling, and found that coupling monotonically decreases with development. Treating these spatial patterns as phenotypes of WM function, we demonstrated significant regulation by neurotransmitter receptors and transcriptomic expression. Notably, WMFC significantly explained the heterogeneous regional vulnerability in neurodevelopmental disorders and outperformed the WMSC in predicting cognitive function. This study underscores the importance of investigating WM function in understanding the neural mechanisms of brain maturation and disorders.