SCIeNTIfIC RepoRtS | 7: 16742 | DOI:10.1038/s41598-017-17026-5
Resting-state functional MRI
reveals altered brain connectivity
and its correlation with motor
dysfunction in a mouse model of
, Gang Li
, Dan Wu
, Hanbing Lu
, Zhipeng Hou
, Christopher A. Ross
, Jiangyang Zhang
& Wenzhen Duan
Huntington’s disease (HD) is an autosomal dominant inherited neurodegenerative disorder, and no
cure is available currently. Treatment of HD is likely to be most benecial in the early, possibly pre-
manifestation stage. The challenge is to determine the best time for intervention and evaluate putative
ecacy in the absence of clinical symptoms. Resting-state functional MRI may represent a promising
tool to develop biomarker reecting early neuronal dysfunction in HD brain, because it can examine
multiple brain networks without confounding eects of cognitive ability, which makes the resting-
state fMRI promising as a translational bridge between preclinical study in animal models and clinical
ndings in HD patients. In this study, we examined brain regional connectivity and its correlation to
brain atrophy, as well as motor function in the 18-week-old N171-82Q HD mice. HD mice exhibited
signicantly altered functional connectivity in multiple networks. Particularly, the weaker intra-
striatum connectivity was positively correlated with striatal atrophy, while striatum-retrosplenial
cortex connectivity is negatively correlated with striatal atrophy. The resting-state brain regional
connectivity had no signicant correlation with motor decits in HD mice. Our results suggest that
altered brain connectivity detected by resting-state fMRI might serve as an early disease biomarker in
Huntington disease (HD) is a neurodegenerative disorder resulting from a trinucleotide repeat expansion in the
huntingtin gene. To date, proven neuroprotective strategies remain elusive. Part of the problem has been that
most of the trials have attempted intervening at a time when the degenerative process is already far advanced
and hence when it would be dicult even for the most eective therapy to demonstrate any benet. Treatment
of HD is likely to be most benecial in the early, possibly pre-manifestation stage. e challenge is to determine
the best time for intervention and how to evaluate putative neuroprotection in the absence of clinical symptoms.
erefore noninvasive and objective early biomarkers which are sensitive to changes in neuronal dysfunction
during the presymptomatic phase are strongly needed.
Multiple neuroimaging modalities have been explored in this regard. Among the biomarkers, the striatal vol-
ume is a notably robust marker in HD patients reported by many studies
as well as in HD mouse models in
Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
of Radiology, Tangdu Hospital, Xi’an, Shaanxi, China.
Division of Neurobiology, Department of Psychiatry and
Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD, 21287,
Department of Pharmacology, Inner Mongolian Medical University School of Pharmacy, Inner Mongolian,
Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Pharmacology and
Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Radiology,
New York University School of Medicine, New York, NY, USA.
Program in Cellular and Molecular Medicine, Johns
Hopkins University School of Medicine, Baltimore, MD, USA. Correspondence and requests for materials should be
addressed to J.Z. (email: Jiangyang.Zhang@nyumc.org) or W.D. (email: firstname.lastname@example.org)
Received: 20 July 2017
Accepted: 21 November 2017
Published: xx xx xxxx