Scaffolding of brain operations: the role of beta oscillations in forming flexible neural ensembles

大脑运作的脚手架：β振荡在形成灵活的神经系统中的作用

• 批准号: 10248491
• 负责人: Saskia Haegens
• 金额: $ 45.81万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10248491
• 关键词: Address; Animals; Apical; Architecture; Area; Auditory; Behavior; Behavioral; Beta Rhythm; Biological Markers; Brain; Cells; Cognition; Cognitive deficits; Communication; Decision Making; Dendrites; Destinations; Distal; Electroencephalography; Electrophysiology (science); Environment; Event; Feedback; Frequencies; Future; Generations; Goals; Impaired cognition; Impairment; Investigation; Link; Location; Maintenance; Mediating; Methods; Microscopic; Modality; Modeling; Mus; Opsin; Outcome; Paper; Parietal; Parkinson Disease; Patients; Pattern; Perception; Performance; Physiology; Play; Population; Prefrontal Cortex; Process; Pyramidal Cells; Research; Research Project Grants; Rodent; Role; Route; Sampling; Schizophrenia; Sensory; Short-Term Memory; Signal Transduction; Site; Stimulus; Tactile; Task Performances; Techniques; Testing; Thalamic structure; Visual; Work; awake; base; biomarker identification; cell assembly; design; flexibility; human subject; information processing; insight; neuronal circuitry; neuroregulation; novel; operation; optogenetics; programs; relating to nervous system; scaffold; source localization

PROJECT SUMMARY The brain constantly makes decisions based on perceptual input as well as internal signals, quickly weighing and processing information, leading to goal-directed behavior. One key aspect crucial to all these processes is communication: the transfer of information from one brain network to the next. However, we are only beginning to understand how the brain accomplishes this. Here we propose to study exactly this question. The overarching goal of this project is to elucidate how the brain sets up the functional neural architecture involved in working memory and decision- making. We argue that brain oscillations in the beta frequency band (15–30 Hz) play a critical role in forming flexible neural ensembles. We propose a novel theoretical framework, delineating how the beta rhythm flexibly sets up transient networks, linking neuronal circuits that are relevant to current task demands, especially in terms of endogenous information processing (e.g., working memory, decision-making). In this view, beta provides the scaffolding for information transfer, routing information through the brain by temporarily connecting relevant nodes such that exchange of information can take place. We propose that the beta rhythm briefly activates a neural ensemble, allowing it to broadcast its message—encoded in (population) spike activity—such that it can be efficiently and effectively received. To test this framework, we here aim to: 1) examine the role of beta oscillations in dynamic neural ensemble formation and its relation to behavioral performance, 2) identify the underlying circuit-level physiology of beta-mediated ensemble formation, and 3) establish the generality of beta-mediated ensemble formation and identify non- invasive biomarkers. We will use a combination of EEG recordings in healthy human subjects, and intracranial electrophysiology and optogenetic neuromodulation in awake-behaving rodents. Both human subjects and animals will perform a spatial working-memory paradigm, critically allowing vertical integration across recording levels. Human subjects will additionally perform working-memory tasks in different sensory modalities and at higher levels of abstraction to guarantee generalizability of results, and to allow for identification of biomarkers to be used in future patient studies. This approach is designed to answer core mechanistic questions: how are local ensembles formed and how are these modulated? Critically, we will determine the effect of these mechanisms on behavior. The project will provide fundamental insights that will set the stage for further detailed investigations in healthy human subjects and patients with impaired beta functioning and cognitive impairment, such as in Parkinson’s disease and schizophrenia.

项目摘要 大脑不断地根据感知输入和内部信号做出决定， 快速权衡和处理信息，导致目标导向的行为。一个关键方面 对所有这些过程至关重要的是沟通：从一个大脑网络传递信息 到下一个。然而，我们才刚刚开始了解大脑是如何做到这一点的。这里 我们建议研究的正是这个问题。这个项目的首要目标是阐明如何 大脑建立起与工作记忆和决策有关的功能性神经结构， 制作。我们认为，在β频段（15-30赫兹）的脑振荡发挥了关键作用 形成灵活的神经系统。我们提出了一个新的理论框架，描绘如何 β节律灵活地建立了瞬时网络，将与以下相关的神经元回路连接起来： 当前任务需求，特别是在内源性信息处理方面（例如，工作 记忆，决策）。从这个角度来看，beta为信息传递提供了框架， 通过临时连接相关节点，在大脑中传递信息， 可以进行信息交换。我们认为β节律短暂地激活了一个神经元 集合，允许它广播它的消息-编码在（人口）尖峰活动-这样， 它可以被高效地和有效地接收。为了测试这个框架，我们的目标是：1）检查 β振荡在动态神经系综形成中作用及其与行为学的关系 性能，2）识别β介导的整体的潜在回路水平生理学 形成，和3）建立β-介导的整体形成的一般性，并确定非 侵入性生物标志物。我们将使用健康人类受试者的脑电图记录， 以及清醒行为啮齿动物的颅内电生理学和光遗传神经调节。 人类和动物都将严格执行空间工作记忆范式， 允许在记录级别上的垂直集成。人类受试者将额外执行 工作记忆任务在不同的感官形式和更高层次的抽象， 保证结果的普遍性，并允许鉴定用于 未来的患者研究这种方法旨在回答核心的机械问题： 当地的合奏形成，这些是如何调制？关键是，我们将确定 这些行为机制。该项目将提供基本的见解， 在健康人类受试者和β受体受损患者中进行进一步详细研究的阶段 功能和认知障碍，如帕金森病和精神分裂症。