Journal article
Natural biological variation of white matter microstructure is accentuated in Huntington's disease
Human brain mapping, Vol.39(9), pp.3516-3527
09/2018
DOI: 10.1002/hbm.24191
PMCID: PMC6099203
PMID: 29682858
Abstract
Huntington's disease (HD) is a monogenic neurodegenerative disorder caused by a CAG‐repeat expansion in the Huntingtin gene. Presence of this expansion signifies certainty of disease onset, but only partly explains age at which onset occurs. Genome‐wide association studies have shown that naturally occurring genetic variability influences HD pathogenesis and disease onset. Investigating the influence of biological traits in the normal population, such as variability in white matter properties, on HD pathogenesis could provide a complementary approach to understanding disease modification. We have previously shown that while white matter diffusivity patterns in the left sensorimotor network were similar in controls and HD gene‐carriers, they were more extreme in the HD group. We hypothesized that the influence of natural variation in diffusivity on effects of HD pathogenesis on white matter is not limited to the sensorimotor network but extends to cognitive, limbic, and visual networks. Using tractography, we investigated 32 bilateral pathways within HD‐related networks, including motor, cognitive, and limbic, and examined diffusivity metrics using principal components analysis. We identified three independent patterns of diffusivity common to controls and HD gene‐carriers that predicted HD status. The first pattern involved almost all tracts, the second was limited to sensorimotor tracts, and the third encompassed cognitive network tracts. Each diffusivity pattern was associated with network specific performance. The consistency in diffusivity patterns across both groups coupled with their association with disease status and task performance indicates that naturally‐occurring patterns of diffusivity can become accentuated in the presence of the HD gene mutation to influence clinical brain function.
Details
- Title: Subtitle
- Natural biological variation of white matter microstructure is accentuated in Huntington's disease
- Creators
- Sarah Gregory - Huntington's Disease Research Centre, UCL Institute of NeurologyHelen Crawford - Huntington's Disease Research Centre, UCL Institute of NeurologyKiran Seunarine - UCL Institute of Child HealthBlair Leavitt - University of British ColumbiaAlexandra Durr - Groupe Hospitalier Pitié‐Salpêtrière, and Institut du Cerveau et de la Moelle, INSERM U1127, CNRS UMR7225, Sorbonne Universités – UPMC Université Paris VI UMR_S1127Raymund A. C Roos - Leiden University Medical CentreRachael I Scahill - Huntington's Disease Research Centre, UCL Institute of NeurologySarah J Tabrizi - Huntington's Disease Research Centre, UCL Institute of NeurologyGeraint Rees - University College LondonDouglas Langbehn - University of IowaMichael Orth - Ulm University Hospital
- Resource Type
- Journal article
- Publication Details
- Human brain mapping, Vol.39(9), pp.3516-3527
- DOI
- 10.1002/hbm.24191
- PMID
- 29682858
- PMCID
- PMC6099203
- NLM abbreviation
- Hum Brain Mapp
- ISSN
- 1065-9471
- eISSN
- 1097-0193
- Number of pages
- 12
- Grant note
- Wellcome Trust UCLH/UCL Medical Research Council Department of Health's NIHR Biomedical Research Centre CHDI Foundation Wellcome Trust Collaborative Award (200181/Z/15/Z)
- Language
- English
- Date published
- 09/2018
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984003991002771
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