White matter predicts functional connectivity in premanifest Huntington's disease

Area of Science:

• Neuroscience
• Neuroimaging
• Neurology

Background:

• White matter organization influences neurodegenerative disease pathology distribution.
• The impact of pathological changes on brain function remains poorly understood.
• Linking brain structure and function is crucial for understanding neurodegeneration-related behavioral changes.

Purpose of the Study:

• To investigate the link between white matter organization and functional connectivity changes in premanifest Huntington's disease.
• To determine if healthy brain white matter patterns predict functional coupling alterations in early Huntington's disease.

Main Methods:

• Diffusion tractography to characterize white matter organization.
• Resting-state functional magnetic resonance imaging (fMRI) to assess functional connectivity.
• Comparison of functional coupling patterns between individuals with premanifest Huntington's disease and healthy controls.

Main Results:

• Individuals with premanifest Huntington's disease exhibit altered functional connectivity directly related to white matter organization patterns observed in healthy brains.
• Brain regions with strong structural connectivity show reduced functional connectivity, while those with weak structural connectivity show increased functional connectivity.
• A dissociation in functional connectivity was observed: anterior connections strengthened, while posterior connections weakened, consistent with the known pathology gradient in Huntington's disease.

Conclusions:

• White matter organizational principles underpin functional connectivity changes in premanifest Huntington's disease.
• The observed antero-posterior functional dissociation aligns with the caudo-rostral gradient of striatal pathology in Huntington's disease.