Abstracts Psychology

Neural circuitry of spatial orientation and episodic memory processing: investigation in neurodegenerative diseases

by Sicong Tu

Research into the neuroanatomical bases of memory has, for a long time, focused on medial temporal lobe brain structures, namely the hippocampus, which plays a key role in episodic memory (memory of specific events) and spatial memory processes. The work described in this thesis investigates the behavioural impact to episodic and spatial memory, resulting from neural changes beyond the hippocampus, in neurodegenerative conditions, such as Alzheimer’s disease (AD), frontotemporal dementia (FTD), and thalamic stroke. Novel cognitive tasks were employed in combination with advanced neuroimaging to examine dissociable episodic and spatial memory performance in these patient populations as a result of contrasting atrophy in a neuroanatomical circuit of memory, the circuit of Papez. Focus was placed on identifying specific memory functions associated with atrophy in the Papez memory circuit that could be targeted to improve differential clinical diagnosis of AD and FTD. Two clinically feasible behavioural tasks were developed to objectively assess spatial orientation and long-term contextual memory, respectively. Findings indicated spatial orientation is a key discriminating feature for AD and FTD patients, associated with integrity of the retrosplenial cortex, a region affected by early AD pathology, but not FTD. The long-term contextual memory task demonstrated focal damage to the thalamus, a region commonly affected in AD and FTD, can result in accelerated forgetting of newly learnt material over a 4-week period. Longitudinal neuroimaging identified divergent patterns of atrophy affecting brain structures in the Papez memory circuit in AD and FTD, specifically involving the posterior cingulate gyrus and anterior thalamus, consistent with observed pattern of behavioural performance on experimental tasks. Furthermore, additional longitudinal neuroimaging examining whole-brain white matter degeneration highlighted the potential application of diffusion weighted magnetic resonance imaging in detecting underlying disease pathology, in-vivo, in FTD. The findings from this thesis demonstrate unique changes are present in Papez memory structures beyond the hippocampus across dementia syndromes, which have a significant impact on episodic and spatial memory deficits, and can be used to develop sensitive clinical measures to improve differential diagnosis. Advisors/Committee Members: Hornberger, Michael, Norwich Medical School, University of East Anglia, United Kingdom, Piguet, Olivier, Faculty of Medicine, UNSW.