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Introduction: Recent developments in neuroimaging techniques enable increasingly sensitive consideration of the cognitive impact of damage to white matter tract (WMT) microstructural organisation after mild traumatic brain injury (mTBI)., Objective: This study investigated the relationship between WMT microstructural properties and cognitive performance., Participants Setting and Design: Using an observational design, a group of 26 premorbidly healthy adults with mTBI and a group of 20 premorbidly healthy trauma control (TC) participants who were well-matched on age, sex, premorbid functioning and a range of physical, psychological and trauma-related variables, were recruited following hospital admission for traumatic injury., Main Measures: All participants underwent comprehensive unblinded neuropsychological examination and structural neuroimaging as outpatients 6-10 weeks after injury. Neuropsychological examination included measures of speed of processing, attention, memory, executive function, affective state, pain, fatigue and self-reported outcome. The WMT microstructural properties were estimated using both diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) modelling techniques. Tract properties were compared between the corpus callosum, inferior longitudinal fasciculus, uncinate fasciculus, anterior corona radiata and three segmented sections of the superior longitudinal fasciculus., Results: For the TC group, in all investigated tracts, with the exception of the uncinate fasciculus, two DTI metrics (fractional anisotropy and apparent diffusion coefficient) and one NODDI metric (intra-cellular volume fraction) revealed expected predictive linear relationships between extent of WMT microstructural organisation and processing speed, memory and executive function. The mTBI group showed a strikingly different pattern relative to the TC group, with no relationships evident between WMT microstructural organisation and cognition on most tracts., Conclusion: These findings indicate that the predictive relationship that normally exists in adults between WMT microstructural organisation and cognition, is significantly disrupted 6-10 weeks after mTBI and suggests that WMT microstructural organisation and cognitive function have disparate recovery trajectories., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Anderson, Oehr, Chen, Maller, Seal and Yang.)

Using diffusion-weighted imaging (DWI), research has demonstrated changes suggestive of damage to white matter tracts (WMT) following mild traumatic brain injury (mTBI). Yet due to the predominant use of the diffusion tensor imaging (DTI) model, which has numerous well-established limitations, it has not yet been possible to clearly examine the nature of changes to WMT microstructure following mTBI. This study used a second DWI-based technique, neurite orientation dispersion and density imaging (NODDI), in combination with DTI to measure microstructural changes within the corpus callosum, three long association and one projection WMTs at 6-12 weeks following mTBI, compared with matched trauma controls (TC). Between-groups differences were identified across all WMT for the DTI metric fractional anisotropy (FA), and the NODDI metrics orientation dispersion index (ODI) and isotropic volume fraction (ISO). No statistically significant between-groups differences were found for other DTI and NODDI metrics. Our study revealed that reduced FA was accompanied by increased ODI, suggesting that mTBI results in reduced coherence of axonal fiber bundles within the studied WMTs. These between-groups differences in WMT microstructure were found at 6-12 weeks post-injury, which suggests that structural recovery is not yet complete towards end of the typical 3-month recovery period.