Physiological imaging and improved task design for the assessment of episodic memory using blood oxygenation level-dependent functional magnetic resonance imaging

Abstract

Understanding the impact of ageing and Alzheimer’s disease (AD) on episodic memory is essential to enable targeted therapy and risk prediction. By using functional magnetic resonance imaging (fMRI), it is possible to measure hippocampal function in the prodromal stage of AD. Such studies should use optimal stimuli and tasks and control for the physiological changes that accompany the progression from healthy ageing to mild cognitive impairment (MCI). This thesis developed such a task, validating it in a large cohort, and applied physiological MRI techniques to allow better interpretation of task-based changes in blood-oxygen-level-dependent (BOLD) fMRI. Four projects were conducted. For two of these, functional and physiological MRI data were collected and enabled the integration of baseline vascular physiology to BOLD signal estimation. They revealed the benefits of including cerebral blood flow and venous oxygenation estimates in general linear models for fMRI data in cognitively healthy adults and MCI patients. Furthermore, the advantages of non-parametric permutation testing and physiological noise modelling were explored. The third project examined brain perfusion measurements in AD patients to help determine the core requirements for robust scanning protocols for studying large numbers of subjects across multiple sites. Considering data analysis, this highlighted the importance of choosing an appropriate post labelling delay value with an outlook for the most problematic cases. Due to episodic memory failure being a hallmark of AD progression, the final project investigated a visuospatial paired-associate learning task adapted for fMRI. This large-scale online behavioural study explored the impact of individual lifestyle differences, age and education on episodic memory performance in (self-reported) cognitively healthy adults. Collectively, these projects provide a set of practical insights and recommendations that lay the methodological foundation for future studies regarding the functional consequences of healthy ageing and neurodegeneration with a specific focus on episodic memory.

Date of Award	3 Oct 2023
Original language	English
Awarding Institution	University of Bristol
Sponsors	BRACE
Supervisor	Jonathan Brooks (Supervisor), E J Coulthard (Supervisor) & Markus F Damian (Supervisor)