eprintid: 10048504
rev_number: 51
eprint_status: archive
userid: 608
dir: disk0/10/04/85/04
datestamp: 2018-05-17 10:07:16
lastmod: 2021-12-05 00:17:51
status_changed: 2019-02-20 17:35:46
type: article
metadata_visibility: show
creators_name: Gregory, S
creators_name: Crawford, H
creators_name: Seunarine, K
creators_name: Leavitt, B
creators_name: Durr, A
creators_name: Roos, RAC
creators_name: Scahill, RI
creators_name: Tabrizi, SJ
creators_name: Rees, G
creators_name: Langbehn, D
creators_name: Orth, M
title: Natural biological variation of white matter microstructure is accentuated in Huntington's disease
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F86
divisions: C08
divisions: D13
divisions: G26
keywords: Diffusion Tensor Imaging, Huntington's disease, natural variability
note: This work is licensed under a Creative Commons Attribution 4.0 International License. The images
or other third party material in this article are included in the article’s Creative Commons license,
unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material. To view a copy of this
license, visit http://creativecommons.org/licenses/by/4.0/
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.
date: 2018-09
date_type: published
official_url: https://doi.org/10.1002/hbm.24191
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: Journal Article
verified: verified_manual
elements_id: 1553099
doi: 10.1002/hbm.24191
lyricists_name: Gregory, Sarah
lyricists_name: Rees, Geraint
lyricists_name: Scahill, Rachael
lyricists_name: Seunarine, Kiran
lyricists_name: Tabrizi, Sarah
lyricists_id: SLGRE97
lyricists_id: GEREE91
lyricists_id: RSCAH26
lyricists_id: KKSEU35
lyricists_id: SJTAB21
actors_name: Stacey, Thomas
actors_id: TSSTA20
actors_role: owner
full_text_status: public
publication: Human Brain Mapping
volume: 39
number: 9
pagerange: 3516-3527
event_location: United States
issn: 1097-0193
citation:        Gregory, S;    Crawford, H;    Seunarine, K;    Leavitt, B;    Durr, A;    Roos, RAC;    Scahill, RI;                 ... Orth, M; + view all <#>        Gregory, S;  Crawford, H;  Seunarine, K;  Leavitt, B;  Durr, A;  Roos, RAC;  Scahill, RI;  Tabrizi, SJ;  Rees, G;  Langbehn, D;  Orth, M;   - view fewer <#>    (2018)    Natural biological variation of white matter microstructure is accentuated in Huntington's disease.                   Human Brain Mapping , 39  (9)   pp. 3516-3527.    10.1002/hbm.24191 <https://doi.org/10.1002/hbm.24191>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10048504/7/Gregory%20VoRGregory_et_al-2018-Human_Brain_Mapping.pdf