The large-scale structure of myelinated, long-range axonal projections has recently emerged as imaging biomarker of disease progression in Amyotrophic Lateral Sclerosis (ALS): DTI investigation of the integrity of cortico-efferent axonal tracts has revealed the progressive involvement of cortico-spinal, cortico-rubral and cortico-striatal subpopulations of projection neurons in human patients [17], in agreement with the pattern of ALS-related pathobiochemistry (i.e., tar DNA binding protein 43 (TDP-43) inclusions) detected in neuropathological studies [4]. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.