Motor cortex functional connectivity is associated with underlying neurochemistry in ALS

Area of Science:

• Neuroimaging
• Neuroscience
• Neurology

Background:

• Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons.
• Functional connectivity impairments in the primary motor cortex (PMC) are observed in ALS patients.
• Understanding the structural and neurochemical underpinnings of these impairments is crucial for developing biomarkers.

Purpose of the Study:

• To identify structural and neurochemical properties associated with primary motor cortex (PMC) functional connectivity deficits in amyotrophic lateral sclerosis (ALS).
• To investigate the relationship between these neuroimaging findings and clinical assessments of motor function.

Main Methods:

• Multimodal neuroimaging (resting-state fMRI, DTI, MRS) was performed on 52 ALS patients and 52 controls.
• Functional connectivity, diffusion metrics, and neurometabolite ratios (including N-acetyl aspartate - NAA) were analyzed.
• Clinical assessment of foot tapping frequency was used to evaluate upper motor neuron function.

Main Results:

• ALS patients exhibited reduced PMC functional connectivity with sensory, frontal, temporal, and putaminal regions compared to controls.
• Altered NAA levels and diffusion metrics (e.g., fractional anisotropy - FA) were found in the PMC of ALS patients.
• Foot tapping frequency correlated with NAA levels and white matter FA in the ALS cohort, and NAA levels were associated with altered motor cortex connectivity.

Conclusions:

• In vivo neurochemistry, specifically NAA levels, may serve as an effective imaging marker for impaired motor cortex functional connectivity in ALS.
• Structural changes, including white matter integrity, are linked to clinical motor deficits in ALS.
• Multimodal neuroimaging offers insights into the complex pathophysiology of ALS.