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Natural variation in sensory-motor white matter organization influences manifestations of Huntington's disease

Orth, M; Gregory, S; Scahill, RI; Mayer, ISM; Minkova, L; Kloeppel, S; Seunarine, KK; ... Tabrizi, SJ; + view all (2016) Natural variation in sensory-motor white matter organization influences manifestations of Huntington's disease. Human Brain Mapping , 37 (12) pp. 4615-4628. 10.1002/hbm.23332. Green open access

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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.

Type: Article
Title: Natural variation in sensory-motor white matter organization influences manifestations of Huntington's disease
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/hbm.23332
Publisher version: http://dx.doi.org/10.1002/hbm.23332
Language: English
Additional information: Copyright © 2016 Wiley Periodicals, Inc. This is the peer reviewed version of the following article: [Orth, M. et al (2016), Natural variation in sensory-motor white matter organization influences manifestations of Huntington's disease. Hum. Brain Mapp., 37: 4615–4628. doi: 10.1002/hbm.23332], which has been published in final form at http://dx.doi.org/10.1002/hbm.23332. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Keywords: Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neuroimaging, Radiology, Nuclear Medicine & Medical Imaging, Neurosciences & Neurology, effective connectivity, cortical thickness, somatosensory evoked potentials, grip force, principal component analysis, biological variation, biological trait, Somatosensory Evoked-potentials, Clinical-trials, Cerebral-cortex, Diffusion, MRI, Abnormalities, Registration, Premanifest, Axonopathy, Expression
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1508109
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