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Updated: Aug 11, 2026
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Whole-brain Segmentation and Change-point Analysis of Anatomical Brain MRI—Application in Premanifest Huntington's Disease
Published on: June 9, 2018
Early Longitudinal Brain Network Changes in Huntington's Disease Before Clinical Motor Onset
Michela Leocadi1, Nicola Z Hobbs1, Mena Farag1
1Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Summary
Longitudinal study reveals early functional connectivity changes in the brain for individuals with the Huntington
Area of Science:
- Neuroscience
- Functional Neuroimaging
- Neurodegenerative Diseases
Background:
- Longitudinal studies on seed-based functional connectivity (SBFC) in young adult Huntington's disease gene-expanded (HDGE) individuals are scarce.
- Previous research has not examined adult HDGE cohorts decades before predicted clinical motor diagnosis.
- Understanding early brain changes in HDGE is crucial for timely intervention.
Purpose of the Study:
- To investigate longitudinal changes in functional connectivity (FC) over approximately 4.8 years in adult HDGE individuals.
- To compare FC changes in HDGE individuals with matched controls from the HD Young Adult Study (HD-YAS) cohort.
- To focus on bilateral caudate and putamen as seed regions for FC analysis.
Main Methods:
- Resting-state functional magnetic resonance imaging (fMRI) was conducted on 71 participants (43 HDGEs, 28 controls) from the HD-YAS cohort at two time points, ~4.8 years apart.
- Seed-based functional connectivity (SBFC) analyses utilized bilateral caudate and putamen as seeds.
- Mixed-effects analysis of variance (ANOVA) with false discovery rate (FDR) correction was employed to analyze group, time, and group × time interaction effects.
Main Results:
- HDGE individuals exhibited reduced FC between the putamen and cerebellar vermis/lobules and brainstem, and increased connectivity with the precuneus, supramarginal, and angular gyri.
- Over ~4.8 years, HDGEs showed distinct FC trajectories compared to controls, with reductions in FC between the right caudate and paracingulate, frontal, occipital, and striatal regions.
- Significant findings were corrected for multiple comparisons using FDR.
Conclusions:
- This study presents the first longitudinal evidence of early cortico-striatal and cerebellar functional network alterations in adult HDGE individuals, occurring decades before motor diagnosis.
- Potential compensatory mechanisms within default mode network hubs were observed in HDGE individuals.
- These early FC changes suggest a dynamic interplay between neurodegeneration and adaptive brain reorganization.
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