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Characterising the structural brain changes in Huntington’s disease using translational neuroimaging

Steventon, Jessica 2014. Characterising the structural brain changes in Huntington’s disease using translational neuroimaging. PhD Thesis, Cardiff University.
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Abstract

This thesis examined the macro-structural and micro-structural changes in Huntington’s disease (HD) in order to improve understanding of the temporal and spatial patterns of neurodegeneration, and the functional relevance of these changes. Translational techniques were employed using genetic mouse models of HD in combination with a patient cohort to examine grey and white matter changes with a particular focus on white matter microstructure. In the patient cohort, the cognitive profile was examined using a cognitive battery not before applied in HD. Specific deficits were found in set-shifting and flexibility, verbal reasoning, working memory and paired associate learning, along with subtle differences in response inhibition that were sensitive to disease burden. A composite cognitive score was produced to examine the relationship between cognitive function and brain structure. A multi-modal examination of white matter tract-specific microstructural measurements revealed abnormalities in the corpus callosum and cingulum bundle that were sensitive to disease burden (chapter 4). In chapter 5, multiple analysis techniques converged to reveal tissue macrostructure abnormalities that were also sensitive to disease burden in HD. Cortical changes were less consistent, and unlike the microstructure findings, white matter macrostructural abnormalities were not related to disease burden. In chapters 6 and 7, genetic mouse models of HD were used to examine changes across the disease course, and to pilot an interventional design. In vivo diffusion MRI and T2-weighted MRI sequences were acquired at 2 different time points in the HdhQ150 knock-in model of HD and imaging data is presented alongside behavioural results and immunohistochemistry. In chapter 7, an environmental modification regime was tested in the YAC128 mouse model using in vivo MRI. Environmental intervention reduced the degree of disease-related atrophy, altered tissue microstructure and improve motor but not cognitive performance in YAC128 mice.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Psychology
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Funders: Wellcome Trust
Date of First Compliant Deposit: 30 March 2016
Last Modified: 05 Jun 2017 04:52
URI: http://orca.cf.ac.uk/id/eprint/71204

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