Causal investigation of the functional interactions of theta and alpha neural oscillations in output-gating

输出门控中 theta 和 alpha 神经振荡功能相互作用的因果研究

• 批准号: 10397141
• 负责人: Flavio Frohlich
• 金额: $ 68.9万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-23 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10397141
• 关键词: Address; Agreement; Attention; Behavior; Behavioral; Brain; Clinical; Cognition; Cognitive deficits; Cues; Data; Development; Electroencephalography; Electrophysiology (science); Epilepsy; Ferrets; Fostering; Foundations; Frequencies; Future; Health; Human; Impaired cognition; Implanted Electrodes; Individual; Intervention; Investigation; Location; Maps; Mediating; Memory; Mental disorders; Mission; Neurons; North Carolina; Outcome; Output; Parietal; Parietal Lobe; Participant; Patients; Pattern; Periodicity; Play; Prefrontal Cortex; Process; Proxy; Public Health; Research; Resolution; Resources; Role; Short-Term Memory; Signal Transduction; Site; Source; Task Performances; Testing; Transcranial magnetic stimulation; Translating; United States National Institutes of Health; Universities; Visual attention; Work; brain dysfunction; cognitive control; cognitive function; cognitive process; density; improved; information processing; innovation; neurotransmission; noninvasive brain stimulation; novel therapeutic intervention; optogenetics; recruit; relating to nervous system; restoration; treatment strategy

PROJECT SUMMARY – UNIVERSITY OF NORTH CAROLINA-CHAPEL HILL, FROHLICH Cognitive control requires the brain to dynamically allocate limited resources to manipulate internal representations as a function of behavioral demands, a process referred to as output-gating. Output-gating comprises two intertwined cognitive processes: the selection of relevant information and the suppression of irrelevant information. These two cognitive processes have been correlated with oscillatory neuronal network activity in two distinct frequency bands and network locations: theta oscillations (4-7 Hz) in prefrontal cortex (PFC) for selection and alpha oscillations (8-12 Hz) in posterior parietal cortex for suppression. However, the causal role of these oscillations and their interactions in output-gating has yet to be established. To address this gap, this proposal examines the causal role of theta and alpha oscillations in output-gating across multiple scales with individualized brain stimulation paradigms to provide a mechanistic delineation of how these oscillations support behavior, coordinate network activity, and regulate neuronal spiking activity. The objective of AIM 1 is to demonstrate the causal role of theta and alpha oscillations in selection and suppression, respectively. To accomplish this, theta and alpha frequency rhythmic transcranial magnetic stimulation is applied in healthy participants to frontal and parietal sites with simultaneous electroencephalography (EEG) during a working memory task with a retrospective cue that drives output-gating. The hypothesis of AIM 1 is that frontal theta activity coordinates the selection of relevant information, while parietal alpha activity coordinates the suppression of irrelevant information. The objective of AIM 2 is to spatially resolve the theta and alpha network dynamics that support selection and suppression, respectively. To achieve this objective, direct cortical stimulation combined with invasive EEG will be used in epilepsy patients with implanted electrodes for clinical purposes. The hypothesis of AIM 2 is that connectivity between frontal and parietal regions establishes oscillatory dynamics critical for selection and suppression. The objective of AIM 3 is to determine how oscillatory network dynamics regulate neuronal spiking activity. This is examined by applying theta and alpha frequency rhythmic optogenetic stimulation to frontal and parietal sites in the ferret with simultaneous electrophysiology recordings during an attentional task that modulates theta and alpha oscillations. The hypothesis of AIM 3 is that theta oscillations increase spiking and alpha oscillations decrease spiking activity. The proposed work is significant since it will provide a multi-scale mechanistic understanding of how theta and alpha oscillations coordinate output-gating. The proposed aims are innovative since they employ synergistic causal perturbations through targeted brain stimulation paradigms with concurrent electrophysiology, enabling the manipulation of oscillatory dynamics and the delineation of their role in coordinating neuronal spiking, network organization, and behavior. This work will provide the foundation for the future development of brain stimulation interventions that target impaired brain network oscillations for the restoration of cognitive deficits in psychiatric illnesses.

项目摘要 - 北卡罗来纳大学教堂山分校，弗罗利希 认知控制需要大脑动态分配有限的资源来操纵内部 作为行为需求函数的表征，这个过程被称为输出门控。输出门控 包括两个相互交织的认知过程：相关信息的选择和相关信息的抑制 不相关的信息。这两个认知过程与振荡神经元网络相关 两个不同频段和网络位置的活动：前额皮质中的 theta 振荡 (4-7 Hz) (PFC) 用于选择，而后顶叶皮质中的 α 振荡 (8-12 Hz) 用于抑制。然而， 这些振荡的因果作用及其在输出门控中的相互作用尚未确定。为了解决这个问题 间隙，该提案研究了 theta 和 alpha 振荡在多个尺度的输出门控中的因果作用 使用个性化的大脑刺激范例来提供这些振荡如何发生的机械描述 支持行为、协调网络活动并调节神经元尖峰活动。 AIM 1 的目标是 证明 theta 和 alpha 振荡分别在选择和抑制中的因果作用。到 为了实现这一目标，theta 和 alpha 频率节律性经颅磁刺激应用于健康 在工作期间对参与者的额叶和顶叶部位进行同步脑电图（EEG）检查 具有驱动输出门控的回顾性线索的记忆任务。 AIM 1 的假设是额叶 theta 活动协调相关信息的选择，而顶叶阿尔法活动协调抑制 的不相关信息。 AIM 2 的目标是在空间上解析 theta 和 alpha 网络动态， 分别支持选择和抑制。为了实现这一目标，直接皮层刺激结合 具有侵入性的脑电图将用于临床目的植入电极的癫痫患者。这 AIM 2 的假设是额叶和顶叶区域之间的连接建立了振荡动力学 对于选择和抑制至关重要。 AIM 3 的目标是确定振荡网络动态如何 调节神经元尖峰活动。这是通过应用 theta 和 alpha 频率节律光遗传学来检查的 刺激雪貂的额叶和顶叶部位，同时进行电生理学记录 调节 theta 和 alpha 振荡的注意力任务。 AIM 3 的假设是 theta 振荡 增加尖峰和阿尔法振荡减少尖峰活动。拟议的工作意义重大，因为它将 提供对 theta 和 alpha 振荡如何协调输出门控的多尺度机制理解。 所提出的目标具有创新性，因为它们通过目标大脑采用协同因果扰动 具有并发电生理学的刺激范例，能够操纵振荡动力学和 描述它们在协调神经元尖峰、网络组织和行为中的作用。这项工作将 为未来针对受损大脑的脑刺激干预措施的发展奠定基础 网络振荡用于恢复精神疾病中的认知缺陷。