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

项目摘要-北卡罗来纳大学-查佩尔山，弗罗里希 认知控制需要大脑动态地分配有限的资源来操纵内部 表示作为行为需求的函数，这一过程称为输出门控。输出选通 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。 无关的信息这两种认知过程与振荡神经元网络有关 两个不同频带和网络位置的活动：前额叶皮层的θ振荡（4-7 Hz） (PFC)用于选择和后顶叶皮层中的α振荡（8-12 Hz）用于抑制。但 这些振荡及其相互作用在产出门控中的因果作用尚未确定。为了解决这个 间隙，该提案探讨了多尺度输出门控中θ和α振荡的因果作用 个性化的脑刺激范例，以提供这些振荡如何 支持行为、协调网络活动和调节神经元尖峰活动。AIM 1的目标是 分别证明了θ振荡和α振荡在选择和抑制中的因果作用。到 为了达到这一目的，将θ和α频率节律性经颅磁刺激应用于健康人， 参与者的额叶和顶叶的网站与同步脑电图（EEG）在工作期间， 记忆任务与回顾线索驱动输出门控。AIM 1的假设是， 活动协调相关信息的选择，而顶叶阿尔法活动协调抑制 不相关的信息。AIM 2的目标是在空间上解决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EEG将用于植入电极的癫痫患者，用于临床目的。的 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力学 调节神经元尖峰活动。这是通过应用θ和α频率节律光遗传学来检查的 刺激雪貂的额叶和顶叶部位，同时进行电生理记录， 调节θ和α振荡的注意力任务。AIM 3的假设是θ振荡 增加尖峰和α振荡降低尖峰活性。拟议的工作意义重大，因为它将 提供了一个多尺度的机械理解θ和α振荡如何协调输出门控。 所提出的目标是创新的，因为他们采用协同因果扰动，通过有针对性的大脑 刺激范例与并发电生理学，使操纵振荡动力学， 它们在协调神经元尖峰、网络组织和行为中的作用的描绘。这项工作将 为未来开发针对受损大脑的脑刺激干预提供基础 网络振荡用于恢复精神疾病中的认知缺陷。

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.