Understanding the Network Mechanisms that Control Working Memory

项目摘要/摘要 工作记忆是一种“记住”事物的能力。它是认知的核心，为 复杂的行为。然而，尽管它具有批判性，但工作记忆却出人意料地有限，只有3-4个 一次一个项目。为了弥补这种有限的容量，工作内存是动态控制的：访问 工作记忆受到严格的控制，工作记忆中的表征被有选择地操纵。 扰乱一个人控制工作记忆的能力可能是病态的。这种干扰被认为是一种 精神分裂症的核心认知缺陷1，并可能是焦虑和抑郁的侵入性思维的基础。至 开发新的、机械信息的、针对这些疾病的治疗方法，我们必须首先开发一种详细的 了解控制工作记忆的神经机制。我们建议通过三种方式进行调查 其中工作记忆是受控制的： 首先，一个人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到记忆中，而被忽略的刺激则不是。我们的首要目标是 区分关于该选通信号来源的假设。我们将利用我们的新型多电极 非人灵长类动物的记录技术，以测试前额叶皮质和基底皮质之间的相互作用 将神经节门表示输入到内存中。此外，我们还将测试选通会改变 感觉表征的时间动力学，以使它们保持在记忆中。 其次，一旦一组项目进入工作记忆，人们就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)测试将这些机制与控制注意力的机制联系起来的假设。 第三，当记忆多个刺激时，必须明智地分配有限的工作资源 其中包括记忆：行为相关性更强的刺激应该被更准确地记住。我们的 第三个目标将确定前额叶和顶叶皮质神经元如何控制项目的优先顺序 以及这种优先顺序如何影响整个前额叶的工作记忆表征， 顶叶皮质和感觉皮质。 虽然我们提出的研究在本质上是基础的，但我们相信这是机械论的重要的第一步。 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方法来改善精神健康 认知障碍。特别是，我们希望利用我们的结果来开发将改进的生理标记 检测，允许早期干预，并指导有针对性的治疗。

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.