Govinda R Poudel1, Julie C Stout2, Juan F Domínguez D2, Louisa Salmon2, Andrew Churchyard3, Phyllis Chua2, Nellie Georgiou-Karistianis4, Gary F Egan5. 1. 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. 2. School of Psychological Sciences, Monash University, Clayton, Victoria, Australia. 3. Department of Neurology, Monash Medical Centre, Clayton, Victoria, Australia. 4. School of Psychological Sciences, Monash University, Clayton, Victoria, Australia. Electronic address: nellie.georgiou-karistianis@monash.edu. 5. 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.
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 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.
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 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.
Authors: Joseph J Shaffer; Ali Ghayoor; Jeffrey D Long; Regina Eun-Young Kim; Spencer Lourens; Lauren J O'Donnell; Carl-Fredrik Westin; Yogesh Rathi; Vincent Magnotta; Jane S Paulsen; Hans J Johnson Journal: Hum Brain Mapp Date: 2017-01-03 Impact factor: 5.038
Authors: Rodolfo G Gatto; Allen Q Ye; Luis Colon-Perez; Thomas H Mareci; Anna Lysakowski; Steven D Price; Scott T Brady; Muge Karaman; Gerardo Morfini; Richard L Magin Journal: MAGMA Date: 2019-02-15 Impact factor: 2.310
Authors: Rodolfo G Gatto; Yaping Chu; Allen Q Ye; Steven D Price; Ehsan Tavassoli; Andrea Buenaventura; Scott T Brady; Richard L Magin; Jeffrey H Kordower; Gerardo A Morfini Journal: Hum Mol Genet Date: 2015-06-29 Impact factor: 6.150
Authors: Costanza Ferrari Bardile; Marta Garcia-Miralles; Nicholas S Caron; Nirmala Arul Rayan; Sarah R Langley; Nathan Harmston; Ana Maria Rondelli; Roy Tang Yi Teo; Sabine Waltl; Lisa M Anderson; Han-Gyu Bae; Sangyong Jung; Anna Williams; Shyam Prabhakar; Enrico Petretto; Michael R Hayden; Mahmoud A Pouladi Journal: Proc Natl Acad Sci U S A Date: 2019-04-23 Impact factor: 11.205
Authors: Deborah L Harrington; Jeffrey D Long; Sally Durgerian; Lyla Mourany; Katherine Koenig; Aaron Bonner-Jackson; Jane S Paulsen; Stephen M Rao Journal: Mov Disord Date: 2016-09-13 Impact factor: 10.338
Authors: Hans-Peter Müller; Martin Gorges; Georg Grön; Jan Kassubek; G Bernhard Landwehrmeyer; Sigurd D Süßmuth; Robert Christian Wolf; Michael Orth Journal: J Neurol Date: 2016-01-13 Impact factor: 4.849