White matter variability, cognition, and disorders: a systematic review

Inter-individual differences can inform treatment procedures and - if accounted for - can significantly improve patient outcomes. However, when studying brain anatomy, these inter-individual variations are largely unaccounted for, despite reports of differences in gross anatomical features, cross-sectional and connectional anatomy. Brain connections are essential to mediate brain functional organisation and, when severed, cause functional impairments or complete loss of function. Hence the study of cerebral white matter may be an ideal compromise to capture inter-individual variability in structure and function. Here we reviewed the wealth of studies that associate functions and clinical symptoms with individual tracts using diffusion tractography. Our systematic review indicates that tractography has proven to be a sensitive method in neurology, psychiatry and healthy populations to identify variability and its functional correlates. However, the literature may be biased, as we identified that the most commonly reported tracts are not necessarily those with the highest sensitivity to cognitive functions and pathologies. Finally, we demonstrate that tracts, as we define them, are not usually correlated with only one, but rather multiple cognitive domains or pathologies. While our systematic review identified some methodological caveats, it also suggests that tract-function correlations might be a promising biomarker for precision medicine as it characterises variations in brain anatomy, differences in functional organisation and predict resilience or recovery in patients.