Essential Cortical Mechanisms for Working Memory

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Despite that many failures of high-level cognition are due to the limited resources that support working memory (WM), we know almost nothing about the neural mechanisms underlying these WM limitations, nor the strategies employed to mitigate the limits of our memory. This gap in our knowledge is critical because a host of neuropsychiatric disorders suffer from WM dysfunction. Our long-term goal is to understand the mechanisms by which WM representations are limited and how these limitations can be mitigated. Our overall hypothesis is two-fold. 1) A network of cortical areas support WM, where the population dynamics within distinct nodes encode and maintain stimulus features and mnemonic strategies. 2) The amount of available WM resources is proportional to some properties of the node’s population (e.g., size) within which these dynamics reside. The central aim of the project is to dissect the cortical network that supports WM, causally linking canonical WM mechanisms to visual field maps in frontal, parietal, and occipital cortex, and identifying the underlying mechanisms that limit WM. The rationale for the proposed research is that, as we better understand the neural mechanisms of WM, a strong theoretical framework will emerge within which strategies for understanding individual differences and treating cognitive dysfunction will emerge. Using functional brain imaging, transcranial magnetic stimulation (TMS), and computational modeling, we test our central hypothesis by pursuing three specific aims. 1) The structure of the neural populations that encode WM representations constrain the precision, capacity, and resilience of WM; 2) Prefrontal and parietal cortex make critical but distinct contributions to WM; and 3) Early visual cortex is necessary for the maintenance of visual WM. Strong preliminary data demonstrate the feasibility of proposed work as well as initial support for the hypotheses. Under Aim 1, the size of retinotopically-defined frontal and parietal visual field maps predicts both individual differences in the precision of WM and the degree to which TMS affects WM. Under Aim 2, TMS to parietal cortex impacts memory precision, while perturbation of frontal cortex affected the strategic allocation of WM resources. Under Aim 3, TMS to primary visual cortex causes a loss of precision for remembered items encoded in the perturbed portion of the visual field, supporting a model by which visual cortex acts as a workspace for top-down feedback signals during WM. Overall, the proposed work will generate data needed to dissect the cortical network that supports WM, causally linking canonical WM mechanisms to visual field maps in frontal, parietal, and occipital cortex, and identifying the underlying mechanisms that limit WM. The approach is innovative because it combines computational neuroimaging, modeling, and causal techniques to directly test WM theories within a test bed of well-defined topographically organized populations. The proposed research is significant because it is expected to provide key insights into the causes of WM limits in humans, in addition to providing new targets for cognitive remediation in psychiatric, neurologic, and geriatric populations.