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White matter connectivity reflects clinical and cognitive status in Huntington's disease
Poudel, Govinda R. Stout, Julie C. Domínguez, Juan F. Salmon, Louisa Churchyard, Andrew Chua, Phyllis Georgiou-Karistianis, Nellie Egan, Gary F.
Poudel, Govinda R.
Stout, Julie C.
Domínguez, Juan F.
Salmon, Louisa
Churchyard, Andrew
Chua, Phyllis
Georgiou-Karistianis, Nellie
Egan, Gary F.
Abstract
Objective: To investigate structural connectivity and the relationship between axonal microstructure and clinical, cognitive, and motor functions in premanifest (pre-HD) and symptomatic (symp-HD) Huntington's disease. Method: Diffusion tensor imaging (DTI) data were acquired from 35 pre-HD, 36 symp-HD, and 35 controls. Structural connectivity was mapped between 40 brain regions of interest using tractography. Between-group differences in structural connectivity were identified using network based statistics. Radial diffusivity (RD) and fractional anisotropy (FA) were compared in the white matter tracts from aberrant networks. RD values in aberrant tracts were correlated with clinical severity, and cognitive and motor performance. Results: A network connecting putamen with prefrontal and motor cortexdemonstrated significantly reduced tractography streamlines in pre-HD. Symp-HD individuals showed reduced streamlines in a network connecting prefrontal, motor, and parietal cortices with both caudate and putamen. The symp-HD group, compared to controls and pre-HD, showed both increased RD and decreased FA in the fronto-parietal and caudate-paracentral tracts and increased RD in the putamen-prefrontal and putamen-motor tracts. The pre-HDclose, compared to controls, showed increased RD in the putamen-prefrontal and fronto-parietal tracts. In the pre-HD group, significant negative correlations were observed between SDMT and Stroop performance and RD in the bilateral putamen-prefrontal tract. In the symp-HD group, RD in the fronto-parietal tract was significantly positively correlated with UHDRSmotor scores and significantly negatively correlated with performance on SDMT and Stroop tasks. Conclusions: We have provided evidence of aberrant connectivity and microstructural integrity in white matter networks in HD. Microstructural changes in the cortico-striatal fibers were associated with cognitive and motor performance in pre-HD, suggesting that changes in axonal integrity provide an early marker for clinically relevant impairment in HD.
Keywords
fMRI, Huntington's disease, connectivity, tractography, diffusion tensor imaging
Date
2014
Type
Journal article
Journal
Neurobiology of Disease
Book
Volume
65
Issue
Page Range
180-187
Article Number
ACU Department
Collections
Relation URI
Source URL
Event URL
Open Access Status
License
File Access
Controlled