Thalamocortical white matter microstructure and cognition following mild traumatic brain injury: A fixel-based...

The thalamus, an essential hub for cognitive integration across distributed brain networks, has emerged as a key structure implicated in mild traumatic brain injury (mTBI). However, while white matter microstructural injury is considered a core pathophysiological substrate of mTBI, few studies have examined thalamocortical microstructure following injury. The present study applied an advanced diffusion MRI-based white matter microstructural model, fixel-based analysis (FBA), to examine thalamocortical white matter microstructure and its associations with cognitive performance at approximately two-months following mTBI. The final analysed dataset included 39 mTBI patients and 28 trauma control (TC) patients aged 18-60 years, who were recruited following hospital admission for physical injury. Participants completed a range of cognitive tests and an MRI protocol including diffusion weighted sequences at 6-12 weeks following injury. Thalamocortical tracts were delineated bilaterally using the TractSeg algorithm, an automated white matter bundle segmentation tool. While whole-brain FBA showed no statistically significant differences in fixel metrics between groups, tract-based analyses showed that mTBI was associated with reduced fibre density (FD) of the right thalamo-precentral (BF₁₀ = 6.849), right thalamo-parietal (BF₁₀ = 3.708) and left thalamo-precentral (BF₁₀ = 1.276) tracts. Despite these structural differences, the groups were comparable with respect to performance on cognitive tests. However, models with interaction effects indicated that associations between thalamocortical FD and cognitive performance differed between groups, most frequently on measures of processing speed and attention. Together, these findings indicate at this stage of recovery, changes in white matter microstructure are detectable in thalamocortical tracts, and that structure-cognition relationships may differ between mTBI and TC groups even in the absence of objective cognitive impairment.