Exposing asymmetric gray matter vulnerability in amyotrophic lateral sclerosis

Area of Science:

• Neuroscience
• Neurology
• Medical Imaging

Background:

• Amyotrophic lateral sclerosis (ALS) typically presents with asymmetric limb weakness.
• Limb dominance influences ALS onset and progression, but brain gray matter (GM) asymmetry in relation to dominance is understudied.

Purpose of the Study:

• To investigate gray matter (GM) asymmetry in the brains of individuals with ALS using voxel-based morphometry (VBM).
• To explore the relationship between limb dominance and patterns of GM atrophy in ALS.

Main Methods:

• Voxel-based morphometry (VBM) was employed on structural MRI data from 30 ALS patients and 17 healthy controls.
• Gray matter (GM) segmentations were generated, and patterns of atrophy were analyzed in ALS patients grouped by the side of initial limb weakness (right vs. left).
• A novel VBM protocol comparing native and mirror GM images was used to detect subtle hemispheric GM asymmetries.

Main Results:

• Individuals with ALS exhibited disproportionate atrophy in the dominant (left) motor cortex hand area, irrespective of the limb where weakness first appeared (p < 0.01).
• Asymmetric atrophy in the left somatosensory cortex and temporal gyri was observed exclusively in ALS patients who experienced initial weakness on the right side.
• The VBM protocol effectively detected asymmetric GM pathology in a small ALS cohort, surpassing standard methods.

Conclusions:

• The dominant upper limb representation shows particular vulnerability in ALS, corroborating prior clinical observations.
• These findings offer insights into cortical organization and selective vulnerability in the context of ALS.
• The advanced VBM method enhances the detection of subtle GM asymmetries in neurodegenerative diseases like ALS.