Journal article
Natural variation in sensory-motor white matter organization influences manifestations of Huntington's disease
Human brain mapping, Vol.37(12), pp.4615-4628
12/2016
DOI: 10.1002/hbm.23332
PMCID: PMC6867476
PMID: 27477323
Abstract
While the HTT CAG-repeat expansion mutation causing Huntington's disease (HD) is highly correlated with the rate of pathogenesis leading to disease onset, considerable variance in age-at-onset remains unexplained. Therefore, other factors must influence the pathogenic process. We asked whether these factors were related to natural biological variation in the sensory-motor system. In 243 participants (96 premanifest and 35 manifest HD; 112 controls), sensory-motor structural MRI, tractography, resting-state fMRI, electrophysiology (including SEP amplitudes), motor score ratings, and grip force as sensory-motor performance were measured. Following individual modality analyses, we used principal component analysis (PCA) to identify patterns associated with sensory-motor performance, and manifest versus premanifest HD discrimination. We did not detect longitudinal differences over 12 months. PCA showed a pattern of loss of caudate, grey and white matter volume, cortical thickness in premotor and sensory cortex, and disturbed diffusivity in sensory-motor white matter tracts that was connected to CAG repeat length. Two further major principal components appeared in controls and HD individuals indicating that they represent natural biological variation unconnected to the HD mutation. One of these components did not influence HD while the other non-CAG-driven component of axial versus radial diffusivity contrast in white matter tracts were associated with sensory-motor performance and manifest HD. The first component reflects the expected CAG expansion effects on HD pathogenesis. One non-CAG-driven component reveals an independent influence on pathogenesis of biological variation in white matter tracts and merits further investigation to delineate the underlying mechanism and the potential it offers for disease modification. Hum Brain Mapp 37:4615-4628, 2016. © 2016 Wiley Periodicals, Inc.
Details
- Title: Subtitle
- Natural variation in sensory-motor white matter organization influences manifestations of Huntington's disease
- Creators
- Douglas Langbehn - University of Iowa, PsychiatryMichael Orth - Department of Neurology, Ulm University Hospital, Ulm, GermanySarah Gregory - Wellcome Trust Centre for Neuroimaging, University College London, London, United KingdomRachael I Scahill - HD Research Group, UCL Institute of Neurology, Queen Square, London, United KingdomIsabella Sm Mayer - Sobell Department of Motor Neuroscience and Movement Disorders, University College London Institute of Neurology, Queen Square, London, United KingdomLora Minkova - Department of Psychiatry and Psychotherapy, Freiburg Brain Imaging, University Medical Center, Albert-Ludwigs-University Freiburg, Freiburg, GermanyStefan Klöppel - Department of Neurology, Freiburg Brain Imaging, University Medical Center, Albert-Ludwigs-University Freiburg, Freiburg, GermanyKiran K Seunarine - Developmental Imaging and Biophysics Section, UCL Institute of Child Health, London, United KingdomLara Boyd - University of British ColumbiaBeth Borowsky - CHDI Foundation Inc, Princeton, New JerseyRalf Reilmann - George-Huntington-Institute, Technology-Park Muenster, Muenster, GermanyG Bernhard Landwehrmeyer - Department of Neurology, Ulm University Hospital, Ulm, GermanyBlair R Leavitt - Center for Molecular Medicine and Therapeutics and Department of Medical Genetics, Child and Family Research Institute, University of British Columbia, Vancouver, CanadaRaymund Ac Roos - Department of Neurology, Leiden University Medical Centre, Leiden, NetherlandsAlexandra Durr - APHP Department of Genetics, Groupe Hospitalier Pitié-Salpêtrière, and Institut Du Cerveau Et De La Moelle, INSERM U1127, CNRS UMR7225, UPMC Université Paris VI UMR_S1127, Paris, FranceGeraint Rees - Wellcome Trust Centre for Neuroimaging, University College London, London, United KingdomJohn C Rothwell - Sobell Department of Motor Neuroscience and Movement Disorders, University College London Institute of Neurology, Queen Square, London, United KingdomSarah J Tabrizi - Department of Neurodegenerative Disease, University College London, Institute of Neurology, Queen Square, London, United Kingdom
- Resource Type
- Journal article
- Publication Details
- Human brain mapping, Vol.37(12), pp.4615-4628
- Publisher
- United States
- DOI
- 10.1002/hbm.23332
- PMID
- 27477323
- PMCID
- PMC6867476
- ISSN
- 1065-9471
- eISSN
- 1097-0193
- Grant note
- 200181/Z/15/Z / Wellcome Trust\r\nMR/L012936/1 / Medical Research Council\r\n091593 / Wellcome Trust
- Language
- English
- Date published
- 12/2016
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984066142002771
Metrics
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