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The connectomics of Alzheimer’s risk: characterising brain temporal network dynamics in young adults at increased genetic risk for late-onset Alzheimer’s disease


Cardiff School of Psychology

Monday, November 23, 2020 Competition Funded PhD Project (European/UK Students Only)

About the Project

Using advanced imaging and novel mathematical approaches, we will identify spatio-temporal brain networks that show altered dynamics in young adults with genetic risk for Alzheimer’s disease. The PhD will provide grounding in network neuroscience — an evolving field using network theories to study the brain across multiple scales and modalities.

To reduce the burden of cognitive decline in neurodegeneration, a key challenge is to understand genetic influences on brain functions at the preclinical stage. This PhD focuses on the strongest genetic risk factor for Alzheimer’s disease: the ε4 allele of the APOE gene. We will establish, decades before the onset of clinical symptoms, whether young APOE-ε4 carriers show selective changes in brain network dynamics compared to non-carriers. Novel findings of network alternations in young APOE-ε4 carriers could help develop preventative interventions in early life. Our innovative data-driven approach combines:


[1. Unique resources from a longitudinal birth cohort]
This project links to a £1.8m MRC-funded multi-centre study, which will recruit >200 APOE-ε4 carriers and non-carriers (age 26~28) from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort for comprehensive brain-imaging and cognitive testing, with 204 participants completed to date. ALSPAC contains detailed demographical and neuropsychological data from >14,000 pregnancies since 1991.


[2. Cutting-edge brain-imaging]
We will integrate advanced multi-modal imaging to quantify brain networks: (1) high resolution (200 µm) 7T structural MRI for precise segmentation of brain regions; (2) high-gradient diffusion-weighted MRI for modelling structural connectivity; and (3) ultra-high field 7T functional MRI (fMRI) for measuring temporal networks during rest and movie viewing.


[3. Exciting opportunities for new mathematical approaches]
Starting with the static structural connectivity of each individual, we will use fMRI data during rest to quantify brain functional connectivity as time-varying networks. This allows measuring whole-brain functional connections as well as their dynamic changes over time. We will use the temporal-topological structure of these networks to identify network dynamics that show alternations in APOE-ε4 carriers. By relating the network measures to fMRI data acquired during free-viewing of movies, we will further identify the emergence of the atypical network dynamics essential to the known behavioural phenotype in APOE-ε4 carriers (i.e., impaired scene perception), thus contributing new knowledge on the systems level mechanisms by which genetic factors influence cognition.


Further added value includes (1) a GW4 supervisory team with interdisciplinary expertise in imaging (Cardiff) and network dynamics (Exeter, Bath), (2) three collaborators who are international experts in network sciences (Prof. Naoki Masuda, USA; Prof. Lorenzo Livi, Canada) and cognitive neuroscience (Prof. Kim Graham, Cardiff) and (3) the strong feasibility from being linked to a large MRC-funded study, including support from geneticists and fieldworkers at Bristol.


Beyond academic beneficiaries, outcomes will be disseminated to the public through regular engagement events, providing impact opportunities with clinicians, carers, and patients..

In addition to those with traditional biomedical or psychology backgrounds, the DTP welcomes students from non-medical backgrounds, especially in areas of computing, mathematics and the physical sciences. Further training can be provided to assist with discipline conversion for students from non-medical backgrounds.

International and EU students are eligible to apply for these studentships but should note that they may have to pay the difference between the home UKRI fee (https://www.ukri.org/skills/funding-for-research-training/) and the institutional International student fee (https://www.cardiff.ac.uk/study/postgraduate/tuition-fees). We will update applicants when further information becomes available

Funding Notes

A GW4 BioMed MRC DTP studentship includes full tuition fees at the UK/Home rate, a stipend at the minimum UKRI rate, a Research & Training Support Grant (RTSG) valued between £2-5k per year and £300 annual travel and conference grant based on a 3.5-year, full-time studentship.

These funding arrangements will be adjusted pro-rata for part-time studentships. Throughout the duration of the studentship, there will be opportunities to apply to the Flexible Funding Supplement for additional support to engage in high-cost training opportunities.

References

To begin a GW4 BioMed MRC DTP studentship, applicants must secure an offer of funding from the DTP by 5pm, Monday 23rd November - https://cardiff.onlinesurveys.ac.uk/gw4-biomed-mrc-doctoral-training-partnership-student-appl-2

and an offer of study from the home institution of the project for which the applicant was granted funding - https://www.cardiff.ac.uk/study/postgraduate/research/programmes/programme/psychology.

For queries about the GW4 BioMed MRC DTP or applying for an Offer of Funding, contact the DTP Team by emailing [email protected]

For queries about applying for an Offer to Study, contact Cardiff University: PGR Quality & Operations Team ([email protected])

Supervisors – Jiaxiang Zhang (Cardiff), Marc Goodfellow (Exeter), Andrew Lawrence (Cardiff) and Tim Rogers (Bath)

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