Semantic Cognition in Alzheimer's Disease: Neuroimaging Investigations of Representational Integrity and Controlled Retrieval

点击翻译按钮获取中文摘要

Whilst episodic memory decline is the hallmark symptom of Alzheimer's disease (AD), deficits in semantic knowledge are often evident early in the disease progression. The neural mechanisms behind these semantic deficits in AD remain poorly understood. Indeed, it is unknown whether semantic representations themselves are degraded in AD, or whether there is an impairment of access to otherwise intact representations. Recent advances in neuroimaging analysis techniques - namely representational similarity analysis (RSA; Kriegeskorte et al., 2008; Charest et al., 2014) and dynamic causal modelling (DCM; Friston et al., 2003) - have given us the tools to probe these mechanisms directly. RSA assesses the similarities of patterns of neural activation in order to reveal a brain region's representational geometry. If semantic representations are degraded in AD, then RSA should reveal systematic differences in representational geometry in cortical regions known to store semantic representations. DCM assesses the effective connectivity between brain regions in service of task performance, and importantly, how these connections are modulated by task demands. If semantic deficits in AD are caused by impaired access to semantic representations, then this should be apparent in the task-driven connections between regions associated with semantic control and those associated with representation. This project will investigate (i) how connectivity between brain regions supporting semantic control and representation is affected in AD; (ii) how semantic representational geometries (behavioural, neural) are affected in AD; (iii) the spatio-temporal dynamics of semantic representation and retrieval; and (iv) application of these measures to differentiate subtypes of AD (Stopford et al., 2008) or to identify those most at risk for AD. To achieve these aims, we will use multimodal neuroimaging (fMRI, EEG) and cognitive behavioural methods in older adults with and without AD. The student will have the opportunity to design the specific experiments (participant groups, stimuli, task, imaging modalities, analysis strategy) in service of the objectives presented above; however, it is expected that analyses will include RSA to assess representational integrity, DCM to assess effective connectivity between control and representation regions, and multimodal analyses of fMRI and EEG to assess spatio-temporal dynamics of semantic retrieval.