title: Exposing asymmetric gray matter vulnerability in amyotrophic lateral sclerosis.
abstract: 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 < 0.01). Asymmetric atrophy of the left somatosensory cortex and temporal gyri was only observed in ALS subjects with right-sided onset of limb weakness. Our VBM protocol, contrasting native and mirror images, was able to more sensitively detect asymmetric GM pathology in a small cohort, compared with standard methods. These findings indicate particular vulnerability of dominant upper limb representation in ALS, supporting previous clinical studies, and with implications for cortical organisation and selective vulnerability.
authors.affiliation: Department of Neurology, Royal Brisbane and Women's Hospital, Herston, QLD 4006, Australia ; School of Medicine, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Devine
authors.affiliation: School of Medicine, The University of Queensland, St. Lucia, QLD 4072, Australia ; Australian e-Health Research Centre, CSIRO, Digital Productivity & Services Flagship, Royal Brisbane and Women's Hospital, Herston, QLD 4006, Australia.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Pannek
authors.affiliation: School of Medicine, The University of Queensland, St. Lucia, QLD 4072, Australia ; Department of Medical Imaging, Royal Brisbane and Women's Hospital, Herston, QLD 4006, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Coulthard
authors.affiliation: Department of Neurology, Royal Brisbane and Women's Hospital, Herston, QLD 4006, Australia ; School of Medicine, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: McCombe
authors.affiliation: Australian e-Health Research Centre, CSIRO, Digital Productivity & Services Flagship, Royal Brisbane and Women's Hospital, Herston, QLD 4006, Australia.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Rose
authors.affiliation: Department of Neurology, Royal Brisbane and Women's Hospital, Herston, QLD 4006, Australia.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Henderson
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000473:pathology*; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged
keywords: ALS, amyotrophic lateral sclerosis; Amyotrophic lateral sclerosis; Asymmetry; GM, gray matter; LMN, lower motor neuron; Limb dominance; Motor neuron disease; UMN, upper motor neuron; VBM, voxel-based morphometry; Voxel-based morphometry
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