About the Project
Background:
Stressful experiences are considered the main risk factor for most non-communicable diseases and are suspected to accelerate ageing. However, how different affective experiences affect the brain, how these effects accumulate over lifetime and how they interact with ageing processes is largely unknown. The goal of this PhD studentship is to answer these questions. Human studies are limited by self-report, retrospective assessment of past experiences, and the difficulty of running randomised longitudinal studies determining whether brain characteristics identified are the cause or the consequence of the exposure to stress. The similarity of non-human primates to humans in terms of brain connectivity, social behaviour, and hypothalamic-pituitary-adrenal (HPA) axis development make them the model of choice to overcome the limitations of human studies, and answer the fundamental questions about stressful experiences.
Objectives and Experimental Approach:
This studentship will take advantage of our on-going longitudinal database unique in the world that combines biannual structural (T1, T2 and DTI) and functional (resting-state) MRI scans of healthy macaque brains, video recordings of home-cage behaviour, blood and hair samples and detailed records of health and exposures to scientific and husbandry procedures. The student will first characterise along two orthogonal dimensions, arousal and valence (positive versus negative), the affective experiences of macaques induced by procedures randomly assigned to animals, using complementary approaches based on blood and MRI biomarkers, behaviour, and cortisol levels. The PhD student will then assess how both ageing and different affective experiences modify structural and functional brain networks over time, and whether affective experiences accelerate or decelerate ageing effects. This will be done using a within-subject longitudinal approach, by applying cutting-edge statistical and computational methods to our MRI datasets, combining approached from fractal geometry, topology, graph theory, and predictive modelling. Finally, these results will also be compared to brain networks of human patients suffering from affective disorders, identified from large publicly available databases.
Impact:
This project will identify brain networks modified by affective experiences and will test the hypothesis that experiences can accelerate or decelerate brain ageing. This knowledge can then be used to assess the efficiency of new interventions at normalizing these networks in affective disorders where these networks are abnormal.
Training:
This project will allow the PhD student to develop interdisciplinary skills combining whole organism in-vivo physiology and behaviour with quantitative skills, matching the three main training skills identified by the MRC as unmet employers’ needs. More specifically, the PhD student will be trained in primate behaviour and physiology, neuroimaging and brain network analyses. In terms of quantitative skills, the student will be exposed to cutting-edge machine learning and computational methods. The fourth supervisor will bring a clinician perspective, allowing the student to develop skills at the interface of biology and medicine.
Supervision team:
Dr Colline Poirier (https://www.ncl.ac.uk/ion/staff/profile/collinepoirier.html#background);
Dr Yujiang Wang (https://www.ncl.ac.uk/ageing/staff/profile/yujiangwangnewcastleacuk.html#background)
Prof Chris Petkov (https://www.ncl.ac.uk/ion/staff/profile/chrispetkov.html#background)
Dr John-Paul Taylor (https://www.ncl.ac.uk/ion/staff/profile/john-paultaylor.html#background)
Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards
Further information on the programme can be found on our website:
http://www.dimen.org.uk/
References
Milham MP, Ai L; Koo B, Xu T, Amiez C, Balezeau F, Baxter MG, Blezer ELA, Brochier T, Chen, A, Croxson PL, Damatac CG, Dehaene S, Everling S, Fair DA, Fleysher L, Freiwald W, Froudist-Walsh S, Griffiths TD, Guedj C, Hadj-Bouziane F, Ben Hamed S, Harel N, Hiba B, Jarraya B, Jung B, Kastner S, Klink PC, Kwok, SC, Laland KN, Leopold DA, Lindenfors P, Mars RB, Menon RS, Messinger A, Meunier M, Mok K, Morrison JH, Nacef J, Nagy J, Ortiz-Rios M, Petkov CI, Pinsk M, Poirier C, Procyk E, Rajimehr R, Reader S, Roelfsema P, Rudko DA, Rushworth MFS, Russ BE, Sallet J, Schmid MC, Schwiedrzik CM, Seidlitz J, Sein J, Shmuel A, Sullivan EL, Ungerleider L, Thiele A, Todorov OS, Tsao D, Wang Z, Wilson CRE, Yacoub E, Ye FQ, Zarco W, Zhou Y, Margulies DS, Schroeder CES. An Open Resource for Non-human Primate Imaging. Neuron, 2018, 100: 61-74.
Wang Y, Necus J, Kaiser M, Mota B. Universality in human cortical folding in health and disease. Proceedings of the National Academy of Sciences of the USA 2016, 113(45), 12820-12825.
Robinson L, Tang E, Taylor JP. Dementia: timely diagnosis and early intervention. British Medical Journal 2015, 350, h3029.