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Auditory probes of neural dysfunction in prodromal Alzheimer’s disease


Project Description

Applications are invited from graduates with a BSc (First or Upper Second) or MSc (Distinction), or equivalent, to work within the Wolfson Institute of Preventive Medicine. This 3 year studentship will commence in Spring 2020 and will be based at the Charterhouse Square Campus. This is an exciting opportunity for a graduate from disciplines related to epidemiology, statistics, and behavioural sciences.

Project description

In the healthy brain, a network of regions including superior temporal auditory cortex and hippocampus rapidly detects and tracks the statistical properties of sound sequences1. Violations in the statistical structure of such sequences cause pupil dilatation mediated by norepinephrine and the locus coeruleus2.

Alzheimer’s disease (AD) causes early central auditory dysfunction3, including attenuation of auditory evoked potentials in presymptomatic disease4. Moreover, the earliest anatomical regions to be affected by AD pathology include locus coeruleus and hippocampus5. It is likely, therefore, that responses to acoustic sequence structure become abnormal early in the course of the disease.

This project aims to determine whether behavioural, pupillary and brain responses to sound sequences that reflect the function of auditory cortex, hippocampus and locus coeruleus might serve as early markers of prodromal AD. If so, they would have great potential to detect early disease non-invasively, supporting the identification of those most likely to benefit from preventive interventions, and identifying those with mild cognitive impairment (MCI) at greatest risk of progression to AD.

This project capitalises on a new collaboration between the Preventive Neurology Unit at QMUL and the UCL Ear Institute, benefitting from the clinical expertise and patient cohorts at the PNU and the auditory neuroscience expertise of the Ear Institute. There will be opportunities for the student to develop skills including; design and conduct of clinical research, psychophysics, pupillometry and neurophysiology (EEG or MEG). The plan for the project will be as follows:

• Literature review on auditory function and pattern analysis in health and disease, design and refinement of experiments (months 0-6)
• Experiment 1: Psychophysical and pupillary responses to acoustic sequence structure in patients with early AD and healthy age-matched controls (data collection months 6-12, analysis and writeup months 12-15)
• Experiment 2: Psychophysical and pupillary responses to acoustic sequence structure in a stratified MCI group (data collection months 12-18, analysis and writeup months 18-21)
• Experiment 3: Neurophysiological signatures (EEG or MEG) of acoustic sequence structure in early AD, MCI and healthy age-matched controls (data collection months 18-27, analysis and writeup months 27-30)
• PhD writeup (months 30-36)

Informal enquiries can be made to via email: Charles Marshall –

How to apply
Your application should consist of a CV and contact details of two academic referees. You must also include a personal statement (1,000 words maximum) describing your suitability for the selected project including how your research experience and interests relate to the project.

Please submit your application to: Patrick Mullan ().


Funding Notes

This 3 year PhD studentship is funded by the Wolfson Institute of Preventive Medicine and comes with a tax-free stipend of £21,000. It is open to UK Nationals, EEA/Swiss migrant workers and non-UK nationals with indefinite leave to remain in the UK who will have three years ordinary residence in the EU prior to the start of the studentship. University tuition fees (at UK/EU levels) will be met by the Institute.

References

1. Barascud N, Pearce MT, Griffiths TD, Friston KJ, Chait M. Brain responses in humans reveal ideal observer-like sensitivity to complex acoustic patterns. Proceedings of the National Academy of Sciences 2016; 113(5): E616-E25.
2. Zhao S, Chait M, Dick F, Dayan P, Furukawa S, Liao H-I. Pupil-linked phasic arousal evoked by violation but not emergence of regularity within rapid sound sequences. Nature communications 2019; 10.
3. Hardy CJD, Marshall CR, Golden HL, Clark CN, Mummery CJ, Griffiths TD, et al. Hearing and dementia. Journal of neurology 2016: 1-16.
4. Golob EJ, Ringman JM, Irimajiri R, Bright S, Schaffer B, Medina LD, et al. Cortical event-related potentials in preclinical familial Alzheimer disease. Neurology 2009; 73(20): 1649-55.
5. Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. Journal of Neuropathology & Experimental Neurology 2011; 70(11): 960-9.

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