White matter predicts functional connectivity in premanifest Huntington's disease.
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.



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.



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.



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.
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
Peter
P
McColgan
Wellcome Trust Centre for Neuroimaging UCL Institute of Neurology London WC1N 3BG United Kingdom.
Sarah
S
Gregory
Wellcome Trust Centre for Neuroimaging UCL Institute of Neurology London WC1N 3BG United Kingdom; Department of Electronic Engineering NED University of Engineering and Technology Karachi Pakistan.
Adeel
A
Razi
Developmental Imaging and Biophysics Section UCL Institute of Child Health London WC1N 1EH United Kingdom.
Kiran K
KK
Seunarine
APHP Department of Genetics Groupe Hospitalier Pitié-Salpêtrière and ICM (Brain and Spine Institute) INSERM U1127 CNRS UMR 7225 Sorbonne Universités - UPMC Université Paris VI UMR_S 1127 Paris France.
Fatma
F
Gargouri
APHP Department of Genetics Groupe Hospitalier Pitié-Salpêtrière and ICM (Brain and Spine Institute) INSERM U1127 CNRS UMR 7225 Sorbonne Universités - UPMC Université Paris VI UMR_S 1127 Paris France.
Alexandra
A
Durr
Department of Neurology Leiden University Medical Centre Leiden 2300RC The Netherlands.
Raymund A C
RA
Roos
Department of Medical Genetics Centre for Molecular Medicine and Therapeutics University of British Columbia 950 West 28th Avenue Vancouver BC V5Z 4H4 Canada.
Blair R
BR
Leavitt
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
Rachael I
RI
Scahill
Developmental Imaging and Biophysics Section UCL Institute of Child Health London WC1N 1EH United Kingdom.
Chris A
CA
Clark
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom; National Hospital for Neurology and Neurosurgery Queen Square London WC1N 3BG United Kingdom.
Sarah J
SJ
Tabrizi
Wellcome Trust Centre for Neuroimaging UCL Institute of Neurology London WC1N 3BG United Kingdom.
Geraint
G
Rees
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
A
A
Coleman
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
J
J
Decolongon
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
M
M
Fan
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
T
T
Petkau
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
C
C
Jauffret
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
D
D
Justo
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
S
S
Lehericy
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
K
K
Nigaud
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
R
R
Valabrègue
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
A
A
Choonderbeek
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
E P T
EP
Hart
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
D J
DJ
Hensman Moss
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
H
H
Crawford
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
E
E
Johnson
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
M
M
Papoutsi
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
C
C
Berna
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
R
R
Reilmann
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
N
N
Weber
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
J
J
Stout
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
I
I
Labuschagne
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
B
B
Landwehrmeyer
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
M
M
Orth
Department of Neurodegenerative Disease UCL Institute of Neurology London WC1N 3BG United Kingdom.
H
H
Johnson