Novak, Marianne Jacqueline Una;
(2019)
Characterisation of early structural and functional brain changes in Huntington's disease.
Doctoral thesis (Ph.D), UCL (University College London).
Abstract
Huntington’s disease (HD) is an inherited neurodegenerative disease which causes relentlessly progressive motor, cognitive and behavioural symptoms. The disease currently has no cure. In the work described in this thesis I have used magnetic resonance imaging (MRI) and clinical assessments to characterise aspects of altered brain structure and function in premanifest and early manifest HD gene carriers. I will present a series of studies in which different aspects of early HD brain changes have been assessed. I have analysed MRI data in all the studies but have used different analysis methods to address my hypotheses in each one. The studies I will describe in this thesis comprise analyses of the following: grey matter structure; neural activity during emotion processing; white matter diffusion properties; and basal ganglia-cortical structural connectivity. In all studies, HD data have been compared with control data. The MRI data have been analysed alongside clinical and genetic data and I have examined the associations between these datasets wherever possible. These studies are presented in four experimental chapters. In chapter 3, grey matter volume and clinical signs are assessed in premanifest HD gene carriers; impaired motor and cognitive function and reduced grey matter volume are shown. In chapter 4, functional imaging is used as a marker of brain activity in premanifest subjects as they view pictures of facial expressions; extensive altered brain activity, associated with HD genetic load, is demonstrated. In chapter 5, the relationship between caudate and white matter volumes and white matter diffusion properties is assessed in premanifest and early manifest subjects, and caudate volume and white matter diffusion metrics are shown to be predictive of disease progression. In chapter 6, basal ganglia-cortical structural connectivity is characterised in premanifest and early manifest subjects, and the association between this and clinical phenotype and HD genetic load is explored.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Characterisation of early structural and functional brain changes in Huntington's disease |
| Event: | UCL (University College London) |
| Language: | English |
| UCL classification: | UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10052539 |
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