Project ID BE-MI2024_24


Co Supervisor 1A Institute of Psychiatry, Psychology & Neuroscience,School of Neuroscience, Department of NeuroimagingWebsite

Co Supervisor 1B Institute of Psychiatry, Psychology & Neuroscience, School of Neuroscience, Department of NeuroimagingWebsite

Multimodal neuroimaging biomarkers for Huntington’s disease.

Huntington’s Disease (HD) is an inherited neurodegenerative disorder caused by a CAG (codon that codes for amino acid glutamine) repeat expansion in the huntingtin gene (HTT). The prevalence of HD varies by ethnic origin and occurs mainly in Caucasian populations. Clinically HD is characterised by progressive motor dysfunction, cognitive decline, and psychiatric disturbances and the onset of symptoms is inversely associated with the size of the CAG repeat expansion. Nonetheless, subclinical changes and pathological processes are thought to precede the initiation of clinical symptoms by several years and not all variation in symptom and disease onset is explained by CAG repeat length, in particular not non-motor symptoms, including apathy, depression, and cognitive decline. Therefore, identification of easily obtainable, reliable, and robust biomarkers of HD progression, moving away from the strong focus on HTT CAG repeat length alone, is crucial for the development and evaluation of disease- modifying treatments. The latter is the aim of the ambitious iMarkHD study in the form of neuroimaging (PET and MRI) changes and their link to extensive clinical phenotyping.

The aim of this project is to characterise a time path across different stages of HD for temporal changes in cognitive and neuropsychiatric symptoms in people with HD using dynamic connectivity MRI analysis. In addition, the student can champion specific elements of PET and MRI imaging and their association with clinical measures that are being collected as part of the iMarkHD study. During the project the PhD student will develop skills and knowledge related to analyses of MRI and PET data as well as statistical analyses related to clinical data and their association with neuroimaging outcomes. The students will develop knowledge for understanding research and interpreting data in applied settings, conduct methodologically sound research, and will disseminate research in public forums and through peer-reviewed publications.

Representative Publications

1. ‘Duff E, Zelaya F, Almagro FA, Miller KL, Martin N, Nichols TE, Taschler B, Griffanti L, Arthofer C, Douaud G, Wang C. Reliability of multi-site UK Biobank MRI brain phenotypes for the assessment of neuropsychiatric complications of SARS-CoV-2 infection: The COVID-CNS travelling heads study. Plos one. 2022;17(9):e0273704.;

2. Wood TC, Cash D, MacNicol E et al. Non-Invasive measurement of the cerebral metabolic rate of oxygen using MRI in rodents. Wellcome Open Res 2022, 6:109. (

3. Damestani NL, O’Daly O, Solana AB, Wiesinger F, Lythgoe DJ, Hill S, de Lara Rubio A, Makovac E, Williams SC, Zelaya F. Revealing the mechanisms behind novel auditory stimuli discrimination: An evaluation of silent functional MRI using looping star. Human Brain Mapping. 2021;42(9):2833-50.

1. van Wamelen DJ, Shan L, Aziz NA, Anink JJ, Bao AM, Roos RA, Swaab DF. Functional increase of brain histaminergic signaling in Huntington’s disease. Brain Pathol. 2011;21(4):419-27. doi: 10.1111/j.1750-3639.2010.00465.x;

2. van Wamelen DJ, Aziz NA, Anink JJ, van Steenhoven R, Angeloni D, Fraschini F, Jockers R, Roos RA, Swaab DF. Suprachiasmatic nucleus neuropeptide expression in patients with Huntington’s Disease. Sleep. 2013;36(1):117-25. doi: 10.5665/sleep.2314;

3. ten Harmsen BL, van Rumund A, Aerts MB, Bergkamp MI, Esselink RAJ, Richard E, Meijer FJA, Bloem BR, van Wamelen DJ. Clinical correlates of cerebral white matter abnormalities in patients with Parkinson’s disease. Parkinsonism Relat Disord. 2018;49:28-33. doi: 10.1016/j.parkreldis.2017.12.029.