The proposed research focuses on the neural substrates of human working memory (WM) i.e. the processes enabling the brief retention and manipulation of information when it is no longer present in the environment towards attaining behavioural goals. There is evidence that the prefrontal cortex (PFC) may be involved in controlling what is to be retained in WM, and that storage occurs in connected but distant brain regions i.e. in posterior cortex. Thus, the PFC may be the source of “top down” influences in WM. Furthermore, differences across individuals in the amount of information they can store (i.e. memory capacity) may depend, in part, on what is being stored, rather than the amount. Such individual capacity differences are reflected by differences in neural activity in storage-related brain regions. The proposed series of experiments aims to exploit these capacity-related differences in neural activity in order to provide causal evidence that (1) the retention of object-based information occurs in posterior cortex; (2) the PFC is functionally connected to these posterior storage regions and is the source of encoding signals directing what is to be stored; (3) differences in memory capacity across individuals is due, at least in part, to whether not relevant or irrelevant information is stored; (4) modulation of prefrontal encoding signals will result in changes in the both capacity-related neural activity in posterior storage regions, and in the psychological measures of individuals’ memory capacity. These aims will be explored using the cutting-edge combinations of both functional magnetic resonance (fMRI)-guided transcranial magnetic stimulation (TMS) and concurrent TMS-fMRI. The ability of fMRI to visual whole-brain activity during a task in combination with the causal information provided by TMS will allow for the first direct evidence in human WM of both the existence of and the nature of effective connections between distant regions.
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