期刊
NEUROBIOLOGY OF DISEASE
卷 95, 期 -, 页码 35-45出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2016.07.005
关键词
Diffusion MRI; DYT1 dystonia; Free-water; Functional connectivity; Functional MRI
资金
- Tyler's Hope for a Dystonia Cure, Inc.
- National Institutes of Health [R01 NS075012, R01 NS058487, R01 NS082244, T32 NS082168]
- University of Florida McKnight Brain Institute pilot imaging grant
- National Science Foundation [DMR-1157490]
- State of Florida
- National Institutes of Health award [S10RR025671]
Developing in vivo functional and structural neuroimaging assays in Dyti Delta GAG heterozygous knock-in (Dyt1 KI) mice provide insight into the pathophysiology underlying DYT1 dystonia. In the current study, we examined in vivo functional connectivity of large-scale cortical and subcortical networks in Dyt1 KI mice and wild-type (WT) controls using resting-state functional magnetic resonance imaging (MRI) and an independent component analysis. In addition, using diffusion MRI we examined how structural integrity across the basal ganglia and cerebellum directly relates to impairments in functional connectivity. Compared to WT mice, Dyt1 KI mice revealed increased functional connectivity across the striatum, thalamus, and somatosensory cortex; and reduced functional connectivity in the motor and cerebellar cortices. Further, Dyt1 KI mice demonstrated elevated free water (FW) in the striatum and cerebellum compared to WT mice, and increased FW was correlated with impairments in functional connectivity across basal ganglia, cerebellum, and sensorimotor cortex. The current study provides the first in vivo MRI-based evidence in support of the hypothesis that the deletion of a 3-base pair (Delta GAG) sequence in the Dyt1 gene encoding torsinA has network level effects on in vivo functional connectivity and microstructural integrity across the sensorimotor cortex, basal ganglia, and cerebellum. (C) 2016 Elsevier Inc. All rights reserved.
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