Microstructure and gene expression influence gyrification in amyotrophic lateral sclerosis

Area of Science:

• Neuroscience
• Neurodegenerative Diseases
• Medical Imaging

Background:

• Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease.
• Cortical gyrification changes are a recent observation in ALS.
• The clinical relevance and molecular basis of these changes are unclear.

Purpose of the Study:

• Investigate the microstructural and transcriptional basis of cortical gyrification alterations in ALS.
• Examine the relationship between gyrification, white matter integrity, and clinical outcomes in ALS.
• Explore the molecular underpinnings of these neuroimaging findings.

Main Methods:

• Structural and diffusion MRI in 60 ALS patients and 60 controls.
• Analysis of local gyrification index (LGI) and fractional anisotropy (FA).
• Integration of neuroimaging data with transcriptomic data from the Allen Human Brain Atlas.

Main Results:

• ALS patients showed reduced LGI in specific cortical regions and reduced FA in white matter tracts (corticospinal tract, corpus callosum).
• Higher LGI and FA correlated with better motor function (ALSFRS-R) and cognitive status.
• FA partially mediated the relationship between LGI and functional disability.

Conclusions:

• Cortical gyrification abnormalities in ALS are linked to white matter degeneration.
• These changes contribute to functional impairment and cognitive status.
• Findings suggest a multiscale pathology involving genetic vulnerability and disrupted neural pathways in ALS.