TY - JOUR
T1 - In vivo imaging reveals impaired connectivity across cortical and subcortical networks in a mouse model of DYT1 dystonia
AU - DeSimone, Jesse C.
AU - Febo, Marcelo
AU - Shukla, Priyank
AU - Ofori, Edward
AU - Colon-Perez, Luis M.
AU - Li, Yuqing
AU - Vaillancourt, David E.
N1 - Funding Information:
Mouse template atlas provided by Ekam Solutions, LLC (Craig F. Ferris and Praveen Kulkarni). Funding: This research was supported by grants from Tyler's Hope for a Dystonia Cure, Inc. , the National Institutes of Health (grant numbers R01 NS075012 , R01 NS058487 , R01 NS082244 , T32 NS082168 ), and a University of Florida McKnight Brain Institute pilot imaging grant. Data collection was performed in the McKnight Brain Institute at the National High Magnetic Field Laboratory's AMRIS Facility, which is supported by National Science Foundation Cooperative Agreement No. DMR-1157490 and the State of Florida. This work was supported in part by a National Institutes of Health award ( S10RR025671 ) for MRI/S instrumentation.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Developing in vivo functional and structural neuroimaging assays in Dyt1 ΔGAG 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 (ΔGAG) 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.
AB - Developing in vivo functional and structural neuroimaging assays in Dyt1 ΔGAG 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 (ΔGAG) 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.
KW - Diffusion MRI
KW - DYT1 dystonia
KW - Free-water
KW - Functional connectivity
KW - Functional MRI
UR - http://www.scopus.com/inward/record.url?scp=84978761815&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2016.07.005
DO - 10.1016/j.nbd.2016.07.005
M3 - Article
C2 - 27404940
AN - SCOPUS:84978761815
SN - 0969-9961
VL - 95
SP - 35
EP - 45
JO - Neurobiology of Disease
JF - Neurobiology of Disease
ER -