Essential Cortical Mechanisms for Working Memory

尽管如此，许多高级认知的失败是由于支持工作记忆的资源有限 (WM)，我们对这些WM限制的神经机制几乎一无所知， 减轻我们记忆力局限的策略。我们知识上的这一差距至关重要，因为 的神经精神障碍患者患有WM功能障碍。我们的长期目标是了解 WM表示受到哪些限制以及如何减轻这些限制。我们的总体假设是 双重的1)大脑皮层区域的网络支持WM，其中不同节点内的种群动态 编码和维持刺激特征和记忆策略。2)可用WM资源的数量为 与节点群体的某些属性成比例（例如，这些动态所处的位置。的 该项目的中心目标是解剖支持工作记忆的皮层网络，将典型的工作记忆因果地联系起来 额叶、顶叶和枕叶皮层的视野映射机制，并确定潜在的 限制WM的机制。这项研究的基本原理是，随着我们更好地了解神经系统， 工作记忆的机制，一个强大的理论框架将出现，其中的理解策略 个体差异和认知功能障碍的治疗将会出现。利用脑功能成像， 经颅磁刺激（TMS）和计算建模，我们测试我们的中心假设， 追求三个具体目标。1)编码WM表征的神经群体的结构 限制了WM的精确性，容量和弹性; 2）前额叶和顶叶皮层使关键，但 3）早期视皮层对视觉工作记忆的维持是必要的。强 初步数据表明了拟议工作的可行性以及对假设的初步支持。 在目标1下，视网膜定位定义的额叶和顶叶视野图的大小预测了个体 WM的精度和TMS影响WM的程度的差异。在目标2下，TMS至顶骨 额叶皮层的扰动影响记忆精度，而额叶皮层的扰动影响WM的策略分配 资源在目标3下，对初级视觉皮层的TMS导致记忆项目的精确度损失 编码在视野的扰动部分，支持视觉皮层作为一个模型， WM期间自上而下反馈信号的工作空间。总的来说，拟议的工作将产生所需的数据， 解剖支持WM的皮层网络，将典型WM机制与视野图因果联系起来 在额叶，顶叶和枕叶皮层，并确定潜在的机制，限制WM。的方法 是创新的，因为它结合了计算神经成像，建模和因果关系技术，直接 在一个定义明确的地形组织人群的试验床上测试WM理论。拟议 这项研究意义重大，因为它有望为人类WM限制的原因提供关键见解， 此外，还为精神病、神经病和老年人群的认知补救提供了新的靶点。

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.