White matter connectivity reflects clinical and cognitive status in Huntington's disease.
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.


METHODS
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 cortex demonstrated 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 UHDRS motor 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.
School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Monash Biomedical Imaging (MBI), Monash University, Melbourne, VIC, Australia; VLSCI Life Sciences Computation Centre, Melbourne, Victoria, Australia.
Govinda R
GR
Poudel
School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
Julie C
JC
Stout
School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
Juan F
JF
Domínguez D
School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
Louisa
L
Salmon
Department of Neurology, Monash Medical Centre, Clayton, Victoria, Australia.
Andrew
A
Churchyard
School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
Phyllis
P
Chua
School of Psychological Sciences, Monash University, Clayton, Victoria, Australia. Electronic address: nellie.georgiou-karistianis@monash.edu.
Nellie
N
Georgiou-Karistianis
School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Monash Biomedical Imaging (MBI), Monash University, Melbourne, VIC, Australia; Centre for Neuroscience, University of Melbourne, Parkville, Victoria, Australia; VLSCI Life Sciences Computation Centre, Melbourne, Victoria, Australia.
Gary F
GF
Egan
D000328:Adult; D000368:Aged; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D003072:Cognition Disorders / Q000209:etiology*; D003342:Corpus Striatum / Q000473:pathology; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000150:complications* / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009483:Neuropsychological Tests; D012720:Severity of Illness Index; D055815:Young Adult
Connectivity; Diffusion tensor imaging; Huntington's disease; Tractography; fMRI