Some patients after mild traumatic brain injury (mTBI) experience microstructural damages in the long-distance white matter (WM) connections, which disrupts the functional connectome of large-scale brain networks that support cognitive function. Patterns of WM structural damage following mTBI were well documented using diffusion tensor imaging (DTI). However, the functional organization of WM and its association with gray matter functional networks (GM-FNs) and its DTI metrics remain unknown. The present study adopted resting-state functional magnetic resonance imaging to explore WM functional properties in mTBI patients (108 acute patients, 48 chronic patients, 46 healthy controls [HCs]). Eleven large-scale WM functional networks (WM-FNs) were constructed by the k-means clustering algorithm of voxel-wise WM functional connectivity (FC). Compared with HCs, acute mTBI patients observed enhanced FC between inferior fronto-occipital fasciculus (IFOF) WM-FN and primary sensorimotor WM-FNs, and cortical primary sensorimotor GM-FNs. Further, acute mTBI patients showed increased DTI metrics (mean diffusivity, axial diffusivity, and radial diffusivity) in deep WM-FNs and higher-order cognitive WM-FNs. Moreover, mTBI patients demonstrated full recovery of FC and partial recovery of DTI metrics in the chronic stage. Additionally, enhanced FC between IFOF WM-FN and anterior cerebellar GM-FN was correlated with impaired information processing speed. Our findings provide novel evidence for functional and structural alteration of WM-FNs in mTBI patients. Importantly, the convergent damage of the IFOF network might imply its crucial role in our understanding of the pathophysiology mechanism of mTBI patients.
Keywords: compensatory mechanism; fMRI; mild traumatic brain injury; resting-state functional connectivity; white matter functional networks.