Brain Folding Trajectories in Amyotrophic Lateral Sclerosis

Area of Science:

• Neuroimaging
• Neurology
• Neurodegeneration

Background:

• Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative disease.
• Neuroimaging markers are crucial for understanding ALS variability.
• Cortical folding alterations in ALS are underexplored.

Purpose of the Study:

• To conduct the first whole-brain investigation of sulcal morphometry in ALS.
• To identify neuroimaging biomarkers for ALS detection and prognosis.
• To explore the relationship between sulcal changes and clinical progression.

Main Methods:

• Longitudinal study of 222 ALS patients and 194 healthy controls (HC).
• T1-weighted MRI processed using FreeSurfer and BrainVISA.
• Extraction of cortical thickness and four sulcal features (width, depth, surface area, length) across 123 sulci.

Main Results:

• Widespread sulcal alterations in ALS, with 19 sulci showing increased width/length and reduced depth/surface area, mainly in frontal and parietal regions.
• The central sulcus (CS) was most affected, with bilateral widening and reduced depth that tracked motor decline.
• Longitudinal analysis showed progressive CS changes mirroring disease progression and correlating with cortical thickness alterations.

Conclusions:

• Brain folding patterns, particularly in the CS, are altered in ALS.
• Sulcal morphometry changes correlate with clinical progression and motor symptoms.
• Sulcal metrics offer promising biomarkers for ALS early detection, prognosis, and patient stratification.