Understanding the Network Mechanisms that Control Working Memory

了解控制工作记忆的网络机制

• 批准号: 10005468
• 负责人: Timothy J. Buschman
• 金额: $ 50.56万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10005468
• 关键词: Address; Anxiety; Area; Attention; Basal Ganglia; Behavior; Behavioral; Brain; Brain region; Cognition; Cognition Disorders; Cognitive; Cognitive deficits; Complex; Corpus striatum structure; Custom; Detection; Development; Disease; Disease Marker; Early Intervention; Electrodes; Electrophysiology (science); Evolution; Frequencies; Intervention; Knowledge; Memory; Mental Depression; Mental Health; Mental disorders; Mind; Modeling; Monkeys; Nature; Neurons; Parietal; Parietal Lobe; Pathologic; Physiological; Population; Positioning Attribute; Prefrontal Cortex; Process; Research; Resources; Role; Schizophrenia; Sensory; Short-Term Memory; Signal Transduction; Source; Stimulus; Techniques; Testing; Theoretical model; Thinking; Time; Training; Visual; Visual Cortex; Work; attentional control; awake; human imaging; imaging study; improved; insight; mind control; neuromechanism; nonhuman primate; novel; novel diagnostics; predictive modeling; relating to nervous system; sensory cortex; theories

PROJECT SUMMARY/ABSTRACT Working memory is the ability to hold items ‘in mind’. It is at the core of cognition, providing the workspace for complex behaviors. However, despite its critical nature, working memory is surprisingly limited, holding 3-4 items at a time. To compensate for this limited capacity, working memory is dynamically controlled: access to working memory is tightly regulated and representations in working memory are selectively manipulated. Disrupting one’s ability to control working memory can be pathological. Such disruptions are believed to be a core cognitive deficit in schizophrenia1 and may underlie intrusive thoughts in anxiety2 and depression3. To develop novel, mechanistically-informed, treatments for these diseases, we must first develop a detailed understanding of the neural mechanisms that control working memory. We propose to investigate three ways in which working memory is controlled: First, one must be able to control access to working memory. A ‘gating’ signal is thought to provide this control: to-be-remembered stimuli are gated into memory; to-be-ignored stimuli are not. Our first aim will distinguish hypotheses on the source of this gating signal. We will leverage our novel many-electrode recording techniques in non-human primates to test how interactions between prefrontal cortex and basal ganglia gate representations into memory. In addition, we will test the prediction that gating changes the temporal dynamics of sensory representations to maintain them in memory. Second, once a set of items are in working memory, one must be able to select a specific item to use it to guide behavior. This process is akin to attention, which selects specific external stimuli. Our second aim will use our many-electrode recording techniques to a) discover the neural mechanisms that control selection from working memory and b) test hypotheses that relate these mechanisms to those that control attention. Third, when remembering multiple stimuli, one must judiciously allocate the limited resource of working memory amongst them: stimuli with greater behavioral relevance should be more accurately remembered. Our third aim will determine how neurons in prefrontal and parietal cortex control the prioritization of items in working memory and how this prioritization impacts working memory representations throughout prefrontal, parietal, and sensory cortices. While our proposed research is basic in nature, we believe it is an important first step in a mechanistic understanding of the core cognitive deficits of several mental illnesses, including schizophrenia and anxiety. Our hope is that this understanding will improve mental health by leading to new diagnostics and treatments for cognitive disorders. In particular, we hope to use our results to develop physiological markers that will improve detection, allow for earlier intervention, and guide targeted treatments.

项目总结/摘要 工作记忆是一种将事物“记住”的能力。它是认知的核心，为 复杂的行为然而，尽管它的关键性质，工作记忆是惊人的有限，持有3-4 物品一次。为了弥补这种有限的容量，工作记忆是动态控制的： 工作记忆受到严格的调节，并且工作记忆中的表征被选择性地操纵。 扰乱一个人控制工作记忆的能力可能是病态的。这种破坏被认为是一种 精神分裂症的核心认知缺陷1，可能是焦虑2和抑郁3的侵入性想法的基础。到 开发新的，机械信息，治疗这些疾病，我们必须首先制定一个详细的 了解控制工作记忆的神经机制。我们建议研究三种方法 工作记忆是受控制的 首先，必须能够控制对工作记忆的访问。一个“门控”信号被认为提供了这一点 控制：要记住的刺激被门控进入记忆;要忽略的刺激则不是。我们的首要目标是 区分关于该选通信号的源的假设。我们将利用我们新颖的多电极 记录技术在非人类灵长类动物，以测试如何之间的相互作用前额皮质和基底 神经节将表征输入记忆。此外，我们将测试门控改变 感觉表征的时间动态来维持它们在记忆中。 第二，一旦一组项目进入工作记忆，人们必须能够选择一个特定的项目来使用它。 引导行为。这个过程类似于注意力，它选择特定的外部刺激。我们的第二个目标是 使用我们的多电极记录技术，a）发现控制选择的神经机制， 工作记忆和B）测试假设，这些机制与那些控制注意力。 第三，当记忆多种刺激时，必须明智地分配有限的工作资源 其中记忆：与行为相关性更大的刺激应该更准确地记住。我们 第三个目标将确定前额叶和顶叶皮层的神经元如何控制项目的优先级， 工作记忆以及这种优先顺序如何影响整个前额叶的工作记忆表征， 顶叶和感觉皮层 虽然我们提出的研究本质上是基础性的，但我们相信这是机械的重要的第一步。 了解几种精神疾病的核心认知缺陷，包括精神分裂症和焦虑症。 我们希望这种理解将通过导致新的诊断和治疗来改善心理健康。 认知障碍特别是，我们希望利用我们的研究结果来开发生理标记， 检测，允许早期干预，并指导针对性治疗。