Tract-Specific White Matter Hyperintensities Disrupt Brain Networks and Associated With Cognitive Impairment in Mild...

Traumatic brain injury (TBI) is considered to initiate cerebrovascular pathology, involving in the development of multiple forms of neurodegeneration. However, it is unknown the relationships between imaging marker of cerebrovascular injury (white matter hyperintensity, WMH), its load on white matter tract and disrupted brain dynamics with cognitive function in mild TBI (mTBI). MRI data and neuropsychological assessments were collected from 85 mTBI patients and 52 healthy controls. Between-group difference was conducted for the tract-specific WMH volumes, white matter integrity, and dynamic brain connectivity (i.e., fractional occupancies [%], dwell times [seconds], and state transitions). Regression analysis was used to examine associations between white matter damage, brain dynamics, and cognitive function. Increased WMH volumes induced by mTBI within the thalamic radiation and corpus callosum were highest among all tract fibers, and related with altered fractional anisotropy (FA) within the same tracts. Clustering identified two brain states, segregated state characterized by the sparse inter-independent component connections, and default mode network (DMN)-centered integrated state with strongly internetwork connections between DMN and other networks. In mTBI, higher WMH loads contributed to the longer dwell time and larger fractional occupancies in DMN-centered integrated state. Every 1 mL increase in WMH volume within the left thalamic radiation was associated with a 47% increase fractional occupancies, and contributed to 65.6 s delay in completion of cognitive processing speed test. Our study provided the first evidence for the structural determinants (i.e., small vessel lesions) that mediate the spatiotemporal brain dynamics to cognitive impairments in mTBI.