Exposing asymmetric gray matter vulnerability in amyotrophic lateral sclerosis

Limb weakness in amyotrophic lateral sclerosis (ALS) is typically asymmetric. Previous studies have identified an effect of limb dominance on onset and spread of weakness, however relative atrophy of dominant and non-dominant brain regions has not been investigated. Our objective was to use voxel-based morphometry (VBM) to explore gray matter (GM) asymmetry in ALS, in the context of limb dominance. 30 ALS subjects were matched with 17 healthy controls. All subjects were right-handed. Each underwent a structural MRI sequence, from which GM segmentations were generated. Patterns of GM atrophy were assessed in ALS subjects with first weakness in a right-sided limb (n = 15) or left-sided limb (n = 15). Within each group, a voxelwise comparison was also performed between native and mirror GM images, to identify regions of hemispheric GM asymmetry. Subjects with ALS showed disproportionate atrophy of the dominant (left) motor cortex hand area, irrespective of the side of first limb weakness (p

Highlights • GM asymmetry was assessed, using VBM, in right-handed ALS and control subjects. • The dominant motor hand area underwent disproportionate atrophy in ALS (p ≤ 0.01). • In subjects with dominant limb onset, there was greater atrophy of language areas. • A VBM asymmetry protocol is more sensitive than standard group comparisons. • Asymmetric vulnerability of cortical GM supports a role for brain development in the pathogenesis of ALS.