Keywords: Neurodegeneration, fMRI (resting state), Huntington disease, striatum, data-driven multi-voxel pattern analysisHuntington disease (HD) is a progressive, autosomal dominant disease caused by a pathological expansion of CAG repeats in the HTT gene1,2. A clinical diagnosis of HD is made at the appearance of unequivocal motor signs. However, in the “premanifest” stage, due to slowly progressive neurodegenerative changes1,2, subtle motor, psychiatric and cognitive decline occurs many years prior to diagnosis3. The sequelae of neural circuit dysfunction remains unclear. Improving our mechanistic understanding of functional brain connectivity alterations prior to disease manifestation will help identify sensitive biomarkers of disease progression1,4–6. Data-driven analysis of high-quality functional magnetic resonance imaging data will guide such efforts.
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