| Summary: | <p>Working memory (WM) — the means by which information is retained and manipulated over seconds — is a fundamental cognitive process that has been considered to have three phases: encoding, maintenance and retrieval. Although much research has focused on the first two of these, far less is understood about how information is retrieved from WM or how filtering of information in WM affects recall and forgetting, both in health and disease.</p>
<p>In the first part of the thesis, I gained mechanistic insight into the process of WM retrieval and the relationship between processing demands at different phases. Novel sensitive delayed-reproduction tests were developed, and mixture modelling of error applied to deconstruct the sources of error contributing to the pattern of recall performance. Additionally, to quantify the mechanisms of the decision process of recall, Hierarchical Bayesian Drift Diffusion modelling (HDDM) was implemented. In the second part, I investigated malfunctions of the underlying processes of WM in two different patient groups. First, I examined a rare group of people with medial temporal lobe (MTL) lesions following limbic encephalitis (LE). Second, as part of an experimental medicine study I assessed WM and the impact of emotional valence on WM in individuals with Parkinson’s disease (PD) both on and off citalopram, a selective serotonin reuptake inhibitor (SSRI).</p>
<p>Overall, the results demonstrated that the nature of retrieval cues can significantly affect memory reports, with more information at retrieval improving access to items in WM. Additionally, the quality of associative retrieval depends not only on the nature of the target, but also on features in a foil (distractor item) if this is also presented at probe, with the arrangement of non-spatial features modulating recall of relational information. Further studies provided data to suggest that filtering of information in WM is not a monolithic, single entity but rather underpinned by dissociable cognitive
processes that engage with the different phases of memory.</p>
<p>Finally, results from the second part of this thesis provided evidence for a role of the MTL and hippocampal regions in relational WM binding. While serotonergic modulation with citalopram revealed a possible role of serotonin in processing negative emotional information in PD, no effects on WM were found. Together, this work provides novel insights into the mechanisms underlying WM retrieval, filtering and examination of the effects of processing demands induced at different stages of WM in the healthy brain. It also contributes to the understanding of memory disturbances in patients with MTL damage and PD.</p>
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