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Exposing asymmetric gray matter vulnerability in amyotrophic lateral sclerosis.

Devine MS, Pannek K, Coulthard A, McCombe PA, Rose SE, Henderson RD - Neuroimage Clin (2015)

Bottom Line: Within each group, a voxelwise comparison was also performed between native and mirror GM images, to identify regions of hemispheric GM asymmetry.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.

View Article: PubMed Central - PubMed

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.

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.

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Patterns of gray matter asymmetry in ALS and control subjects. Selected axial plane reconstructions from 17 right-handed controls (Row A), 15 ALS subjects with a right-sided index limb (Row B), and 15 ALS subjects with a left-sided index limb (Row C). Significant regions of GM asymmetry (p ≤ 0.01, TFCE-corrected) are shown. Regions coloured in orange-yellow represent leftward asymmetry (i.e. higher GM density in the left hemisphere), whereas blue clusters signify rightward asymmetry. In control subjects, there is a cluster of leftward GM asymmetry which incorporates the centre-of-gravity of the dominant thenar representation area (shown by the intersection of the two red lines). PreCG = precentral gyrus; PostCG = postcentral gyrus; PCG = posterior cingulate gyrus; STG = superior temporal gyrus; TTG = transverse temporal gyrus; IFG = inferior frontal gyrus; OG = orbital gyrus; RG = rectal gyrus; Thal = thalamus.
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f0010: Patterns of gray matter asymmetry in ALS and control subjects. Selected axial plane reconstructions from 17 right-handed controls (Row A), 15 ALS subjects with a right-sided index limb (Row B), and 15 ALS subjects with a left-sided index limb (Row C). Significant regions of GM asymmetry (p ≤ 0.01, TFCE-corrected) are shown. Regions coloured in orange-yellow represent leftward asymmetry (i.e. higher GM density in the left hemisphere), whereas blue clusters signify rightward asymmetry. In control subjects, there is a cluster of leftward GM asymmetry which incorporates the centre-of-gravity of the dominant thenar representation area (shown by the intersection of the two red lines). PreCG = precentral gyrus; PostCG = postcentral gyrus; PCG = posterior cingulate gyrus; STG = superior temporal gyrus; TTG = transverse temporal gyrus; IFG = inferior frontal gyrus; OG = orbital gyrus; RG = rectal gyrus; Thal = thalamus.

Mentions: In the 17 right-handed control subjects, multiple statistical clusters of both rightward and leftward asymmetries were identified (Table 2, Fig. 2A). Of particular note was an area of leftward asymmetry (p ≤ 0.01) encompassing a dorsolateral region of the precentral and postcentral gyri. This area corresponded closely with the centre-of-gravity of the dominant thenar representation area, previously defined using transcranial magnetic stimulation (TMS) (Niskanen et al., 2010). Control subjects also demonstrated significant leftward asymmetry of a region of the superior and transverse temporal gyri, adjacent to the Sylvian fissure. There were no significant asymmetries of lower limb or bulbar representation areas, indicating that these regions were of a similar density in the right and left hemispheres.


Exposing asymmetric gray matter vulnerability in amyotrophic lateral sclerosis.

Devine MS, Pannek K, Coulthard A, McCombe PA, Rose SE, Henderson RD - Neuroimage Clin (2015)

Patterns of gray matter asymmetry in ALS and control subjects. Selected axial plane reconstructions from 17 right-handed controls (Row A), 15 ALS subjects with a right-sided index limb (Row B), and 15 ALS subjects with a left-sided index limb (Row C). Significant regions of GM asymmetry (p ≤ 0.01, TFCE-corrected) are shown. Regions coloured in orange-yellow represent leftward asymmetry (i.e. higher GM density in the left hemisphere), whereas blue clusters signify rightward asymmetry. In control subjects, there is a cluster of leftward GM asymmetry which incorporates the centre-of-gravity of the dominant thenar representation area (shown by the intersection of the two red lines). PreCG = precentral gyrus; PostCG = postcentral gyrus; PCG = posterior cingulate gyrus; STG = superior temporal gyrus; TTG = transverse temporal gyrus; IFG = inferior frontal gyrus; OG = orbital gyrus; RG = rectal gyrus; Thal = thalamus.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4375643&req=5

f0010: Patterns of gray matter asymmetry in ALS and control subjects. Selected axial plane reconstructions from 17 right-handed controls (Row A), 15 ALS subjects with a right-sided index limb (Row B), and 15 ALS subjects with a left-sided index limb (Row C). Significant regions of GM asymmetry (p ≤ 0.01, TFCE-corrected) are shown. Regions coloured in orange-yellow represent leftward asymmetry (i.e. higher GM density in the left hemisphere), whereas blue clusters signify rightward asymmetry. In control subjects, there is a cluster of leftward GM asymmetry which incorporates the centre-of-gravity of the dominant thenar representation area (shown by the intersection of the two red lines). PreCG = precentral gyrus; PostCG = postcentral gyrus; PCG = posterior cingulate gyrus; STG = superior temporal gyrus; TTG = transverse temporal gyrus; IFG = inferior frontal gyrus; OG = orbital gyrus; RG = rectal gyrus; Thal = thalamus.
Mentions: In the 17 right-handed control subjects, multiple statistical clusters of both rightward and leftward asymmetries were identified (Table 2, Fig. 2A). Of particular note was an area of leftward asymmetry (p ≤ 0.01) encompassing a dorsolateral region of the precentral and postcentral gyri. This area corresponded closely with the centre-of-gravity of the dominant thenar representation area, previously defined using transcranial magnetic stimulation (TMS) (Niskanen et al., 2010). Control subjects also demonstrated significant leftward asymmetry of a region of the superior and transverse temporal gyri, adjacent to the Sylvian fissure. There were no significant asymmetries of lower limb or bulbar representation areas, indicating that these regions were of a similar density in the right and left hemispheres.

Bottom Line: Within each group, a voxelwise comparison was also performed between native and mirror GM images, to identify regions of hemispheric GM asymmetry.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.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus