Functional and connectivity changes during working memory in Huntington's disease: 18 month longitudinal data from...

Area of Science:

• Neuroimaging
• Cognitive Neuroscience
• Neurodegenerative Diseases

Background:

• Huntington's disease (HD) is a neurodegenerative disorder.
• Pre-HD individuals show subtle cognitive changes before symptom onset.
• Longitudinal changes in brain function during working memory are not well understood in pre-HD.

Purpose of the Study:

• To characterize 18-month longitudinal changes in functional activation and connectivity during working memory in premanifest Huntington's disease (pre-HD) and symptomatic HD (symp-HD).
• To compare these changes with healthy controls.

Main Methods:

• Functional magnetic resonance imaging (fMRI) was used.
• Participants performed an N-BACK task (0-BACK and 1-BACK).
• Longitudinal fMRI data were collected at baseline and 18-month follow-up for whole-brain activation and region-of-interest functional connectivity analyses.

Main Results:

• Pre-HD showed increased longitudinal activation in cortical and subcortical areas during a working memory task compared to controls.
• Increased activation in pre-HD correlated with disease burden and response time.
• Functional connectivity between the right dorsolateral prefrontal cortex (DLPFC) and other brain regions decreased over 18 months in pre-HD.

Conclusions:

• Reduced functional connectivity in pre-HD may indicate early cortico-striatal disconnectivity.
• Increased brain activation in pre-HD might be a compensatory mechanism.
• Functional imaging can detect early brain changes and assess treatment responses in HD.