Working memory binding: insights from neuroimaging, behavioural and clinical studies
Working memory binding (WMB) entails the integration of multiple sources of information to form and temporarily store coherent object representations (or conjunctions). To date, cognitive research on binding has mostly focused on visual WM and change detection paradigms (i.e., the WMB task), and documented that WMB is a function sensitive and specific to Alzheimer’s Disease (AD). Following a review of the most relevant studies on the topic in Chapter I, this PhD project aimed at addressing two main pending questions: 1) Whether deficits in WMB tasks reveal abnormalities in individuals at risk of developing dementia, such as those suffering from Mild Cognitive Impairment (MCI); 2) Whether visual WMB deficits observed in AD may generalise for material processed across different modalities (i.e., crossmodal WMB). The first aim was addressed in Chapters II and III. Chapter II reports on the results from an fMRI study showing that MCI patients’ conjunctive WMB abilities are impaired compared to healthy controls, and that such WMB deficits are coupled with lack of activation in key brain areas of the temporo-parietal-occipital network subtending WMB mechanisms for feature conjunctions. Results detailed in Chapter III reveal that MCI patients’ performance on the WMB task is associated with reduced connectivity of structural networks formed by white matter tracts across the whole brain. Importantly, this held true especially for those MCI patients with more severe WMB deficits. The second aim was addressed in Chapter IV, which reports on crossmodal WMB mechanisms found to be impaired in AD, but not in healthy ageing. This was true regardless of the modality though which features were integrated. Chapter V brings together the relevant findings from Chapter II through IV to review current understanding of WMB as a diagnostic tool for AD. Relevant contributions from the above-mentioned studies are discussed and further research questions generated in the light of current findings. This PhD thesis suggests that WMB functions are disrupted in the course of AD, thus, acknowledging that WMB deficits are a hallmark of the disease since the initial stages of its continuum. As such, WMB tasks are recommended as a valid neuropsychological tool to assess patients cross-sectionally or to screen for patients to be included in intervention trials aimed at investigating long-term effects on the disease progression.