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White matter predicts functional connectivity in premanifest Huntington's disease
McColgan, Peter Gregory, Sarah Razi, Adeel Seunarine, Kiran K. Gargouri, Fatma Durr, Alexandra Roos, Raymund A. C. Leavitt, Blair R. Scahill, Rachael I. Clark, Chris A.
McColgan, Peter
Gregory, Sarah
Razi, Adeel
Seunarine, Kiran K.
Gargouri, Fatma
Durr, Alexandra
Roos, Raymund A. C.
Leavitt, Blair R.
Scahill, Rachael I.
Clark, Chris A.
Author
McColgan, Peter
Gregory, Sarah
Razi, Adeel
Seunarine, Kiran K.
Gargouri, Fatma
Durr, Alexandra
Roos, Raymund A. C.
Leavitt, Blair R.
Scahill, Rachael I.
Clark, Chris A.
Tabrizi, Sarah J.
Rees, Geraint
Coleman, Allison J.
Decolongon, J.
Fan, M.
Petkau, T.
Jauffret, Céline
Justo, Damian
Lehericy, S.
Nigaud, Kevin
Valabregue, R.
Schoonderbeek, A.
Hart, Ellen P.
Moss, D. J. Hensman
Crawford, H.
Johnson, Eileanoir
Papoutsi, Marina
Berna, C.
Reilmann, R.
Weber, N.
Stout, J.
Labuschagne, I.
Landwehrmeyer, B.
Orth, M.
Johnson, H.
Gregory, Sarah
Razi, Adeel
Seunarine, Kiran K.
Gargouri, Fatma
Durr, Alexandra
Roos, Raymund A. C.
Leavitt, Blair R.
Scahill, Rachael I.
Clark, Chris A.
Tabrizi, Sarah J.
Rees, Geraint
Coleman, Allison J.
Decolongon, J.
Fan, M.
Petkau, T.
Jauffret, Céline
Justo, Damian
Lehericy, S.
Nigaud, Kevin
Valabregue, R.
Schoonderbeek, A.
Hart, Ellen P.
Moss, D. J. Hensman
Crawford, H.
Johnson, Eileanoir
Papoutsi, Marina
Berna, C.
Reilmann, R.
Weber, N.
Stout, J.
Labuschagne, I.
Landwehrmeyer, B.
Orth, M.
Johnson, H.
Abstract
Objectives The distribution of pathology in neurodegenerative disease can be predicted by the organizational characteristics of white matter in healthy brains. However, we have very little evidence for the impact these pathological changes have on brain function. Understanding any such link between structure and function is critical for understanding how underlying brain pathology influences the progressive behavioral changes associated with neurodegeneration. Here, we demonstrate such a link between structure and function in individuals with premanifest Huntington's. Methods Using diffusion tractography and resting state functional magnetic resonance imaging to characterize white matter organization and functional connectivity, we investigate whether characteristic patterns of white matter organization in the healthy human brain shape the changes in functional coupling between brain regions in premanifest Huntington's disease. Results We find changes in functional connectivity in premanifest Huntington's disease that link directly to underlying patterns of white matter organization in healthy brains. Specifically, brain areas with strong structural connectivity show decreases in functional connectivity in premanifest Huntington's disease relative to controls, while regions with weak structural connectivity show increases in functional connectivity. Furthermore, we identify a pattern of dissociation in the strongest functional connections between anterior and posterior brain regions such that anterior functional connectivity increases in strength in premanifest Huntington's disease, while posterior functional connectivity decreases. Interpretation Our findings demonstrate that organizational principles of white matter underlie changes in functional connectivity in premanifest Huntington's disease. Furthermore, we demonstrate functional antero–posterior dissociation that is in keeping with the caudo–rostral gradient of striatal pathology in HD. The distribution of pathology in neurodegenerative disease can be predicted by the organizational characteristics of white matter in healthy brains. However, we have very little evidence for the impact these pathological changes have on brain function. Understanding any such link between structure and function is critical for understanding how underlying brain pathology influences the progressive behavioral changes associated with neurodegeneration. Here, we demonstrate such a link between structure and function in individuals with premanifest Huntington's. Methods Using diffusion tractography and resting state functional magnetic resonance imaging to characterize white matter organization and functional connectivity, we investigate whether characteristic patterns of white matter organization in the healthy human brain shape the changes in functional coupling between brain regions in premanifest Huntington's disease. Results We find changes in functional connectivity in premanifest Huntington's disease that link directly to underlying patterns of white matter organization in healthy brains. Specifically, brain areas with strong structural connectivity show decreases in functional connectivity in premanifest Huntington's disease relative to controls, while regions with weak structural connectivity show increases in functional connectivity. Furthermore, we identify a pattern of dissociation in the strongest functional connections between anterior and posterior brain regions such that anterior functional connectivity increases in strength in premanifest Huntington's disease, while posterior functional connectivity decreases. Interpretation Our findings demonstrate that organizational principles of white matter underlie changes in functional connectivity in premanifest Huntington's disease. Furthermore, we demonstrate functional antero–posterior dissociation that is in keeping with the caudo–rostral gradient of striatal pathology in HD.
Keywords
Date
2017
Type
Journal article
Journal
Annals of Clinical and Translational Neurology
Book
Volume
4
Issue
2
Page Range
106-118
Article Number
ACU Department
Institute for Religion and Critical Inquiry
Faculty of Theology and Philosophy
School of Behavioural and Health Sciences
Faculty of Health Sciences
School of Education
Faculty of Education and Arts
Faculty of Theology and Philosophy
School of Behavioural and Health Sciences
Faculty of Health Sciences
School of Education
Faculty of Education and Arts
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Relation URI
DOI
Source URL
Event URL
Open Access Status
Open access
License
CC BY 4.0
File Access
Open