Large scale functional and effective connectivity alterations cross the Huntington's disease integrated staging...

Area of Science:

• Neuroimaging
• Neurodegenerative Diseases

Background:

• Huntington's disease (HD) is a progressive neurodegenerative disorder with significant motor, cognitive, and behavioral impacts.
• Developing treatments to slow HD progression before symptom onset necessitates sensitive biomarkers for early disease stages.

Purpose of the Study:

• To evaluate functional and effective connectivity using fMRI as potential biomarkers for Huntington's disease progression.
• To assess alterations in brain connectivity across different stages of HD using the Huntington's Disease Integrated Staging System (HD-ISS).

Main Methods:

• Utilized advanced fMRI analysis on data from 231 participants (Track-On HD study) with up to three annual visits.
• Grouped participants into normative controls and four HD stages based on the HD-ISS.
• Applied model-free and model-based approaches to analyze functional and effective connectivity, considering in-scanner motion.

Main Results:

• Significant differences in functional and effective connectivity were observed between healthy controls and later HD-ISS stages.
• Attenuated connectivity in the caudate nucleus (HD-ISS-2) and extended corticostriatal connections (HD-ISS-3) were identified.
• Connectivity alterations were predominantly evident in advanced HD stages; widespread cortical changes or graph topography alterations were not observed.

Conclusions:

• fMRI-derived functional and effective connectivity measures can capture the attenuation of cortico-striatal pathways across Huntington's disease progression.
• These connectivity changes, particularly in earlier stages, may serve as valuable biomarkers for monitoring HD progression and evaluating early interventions.