Essential Cortical Mechanisms for Working Memory

尽管许多高级认知的失败都是由于支持工作记忆的有限资源造成的 (WM)，我们对这些WM限制背后的神经机制几乎一无所知，也不知道 用来缓解我们记忆限制的策略。我们知识中的这一差距是至关重要的，因为一个宿主 大多数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这些机制 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 两倍。1)大脑皮层区域网络支持WM，其中不同节点内的种群动态 编码和维护刺激特征和助记策略。2)可用的WM资源量为 与这些动态所在的节点种群的某些属性(例如，大小)成比例。这个 该项目的中心目标是解剖支持WM的大脑皮层网络，将规范的WM因果联系起来 额叶、顶叶和枕叶皮质视野图的机制，并识别潜在的 限制WM的机制。这项拟议研究的基本原理是，随着我们更好地了解神经 WM的机制，将出现一个强大的理论框架，在其中策略的理解 个体差异和认知功能障碍的治疗将会出现。利用脑功能成像技术， 经颅磁刺激(TMS)和计算建模，我们通过以下方式验证我们的中心假设 追求三个具体目标。1)编码WM表示的神经种群的结构 限制WM的精确度、容量和弹性；2)前额叶和顶叶皮质使关键但 3)早期的视皮层是维持视觉WM所必需的。强壮 初步数据证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，视网膜定位的额叶和顶叶视野图的大小可以预测个体 WM的精确度和TMS对WM的影响程度的差异。在目标2下，TMS至顶叶 大脑皮质影响记忆的精确度，而额叶皮质的扰动影响工作记忆的策略分配 资源。在目标3下，对初级视皮层的TMS会导致记忆项目的精确度下降 编码在视野的扰动部分中，支持视觉皮质作为 WM期间用于自上而下反馈信号的工作空间。总体而言，拟议的工作将产生必要的数据 剖析支持WM的大脑皮层网络，将规范的WM机制与视野图进行因果链接 额叶、顶叶和枕叶皮质，并确定限制WM的潜在机制。该方法 是创新的，因为它结合了计算神经成像、建模和因果技术，直接 在定义良好、按地形组织的人口试验台上测试WM理论。建议数 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的见解， 除了为精神科、神经科和老年人群的认知治疗提供新的目标之外。

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.