BACKGROUND: Diffusion MRI is sensitive to white matter changes in amyotrophic lateral sclerosis (ALS). The current study aimed to establish disease profiles across core motor pathways, and their relevance to clinical progression in ALS. METHODS: Sixty-five participants (ALS = 47
Control = 18) were recruited for the study. White matter integrity of motor, somatosensory, and premotor subdivisions within the corticospinal tract and corpus callosum were quantified by fibre density, fibre-bundle cross-section, structural connectivity, and fractional anisotropy. Analyses focused on identifying diffusion metrics and tract profiles sensitive to ALS pathology, and their association with clinical progression. RESULTS: Reduced fibre density of the motor subdivision of the corpus callosum (CC) and corticospinal tract (CST) demonstrated best performance in classifying ALS from controls (area-under-curve: CC CONCLUSION: Current findings suggest that ALS does not uniformly impact the corticospinal tract and corpus callosum. There is a preferential disease profile of neurodegeneration mainly impacting primary motor fibres. Microstructural white matter abnormality indicated presence of ALS pathology while macrostructural white matter abnormality was associated with severity of functional impairment. Quantification of white matter abnormality in corticospinal tract and callosal subdivisions holds translational potential as an imaging biomarker for neurodegeneration in ALS.