Targeted circuit modulation to delineate the causal role of oscillatory interactions in top-down networks of cognitive control

有针对性的电路调制来描述自上而下的认知控制网络中振荡相互作用的因果作用

• 批准号: 10360683
• 负责人: Flavio Frohlich
• 金额: $ 37.72万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10360683
• 关键词: Agreement; Animals; Area; Attention; Attention deficit hyperactivity disorder; Behavioral; Bipolar Disorder; Brain; Cognition; Cognitive; Communities; Cortical Synchronization; Data; Development; Dimensions; Electrophysiology (science); Exhibits; Ferrets; Fostering; Frequencies; Health; Human; Impairment; Individual; Investigation; Lateral; Lateral posterior nucleus of thalamus; Mental Depression; Mental disorders; Mission; Modeling; Neurons; Neurosciences; North Carolina; Parietal; Parietal Lobe; Pattern; Performance; Periodicity; Play; Prefrontal Cortex; Process; Public Health; Publishing; Reaction Time; Research; Resources; Rodent; Role; Schizophrenia; Signal Transduction; Stimulus; Structure; Task Performances; Testing; Thalamic structure; Therapeutic; United States National Institutes of Health; Universities; Visual; Visual Perception; Work; area striata; base; cognitive control; cognitive function; design; improved; innovation; interest; novel; novel diagnostics; novel therapeutic intervention; optogenetics; relating to nervous system; sensory input; sustained attention; treatment strategy

PROJECT SUMMARY – UNIVERSITY OF NORTH CAROLINA-CHAPEL HILL, FROHLICH Sustained attention represents a fundamental dimension of cognitive control and refers to the process of allocating cognitive resources to appropriately respond to infrequent but task-relevant stimuli. Sustained attention differs from the more commonly studied shifting or dividing attention since it lacks the defining features of capacity limitation and competition. Deficits in sustained attention are common in psychiatric illnesses including attention deficit hyperactivity disorder, bipolar disorder, and schizophrenia. Understanding the network substrate of sustained attention will thus significantly advance our ability to develop circuit-based therapeutics that selectively engage and restore the activity patterns that drive sustained attention. Synchronization in two higher-order networks have emerged as neural sub- strate of sustained attention and cognitive control in general. First, the frontoparietal network acts as a generator of top-down control signals. Second, the posterior thalamo-cortical network gates processing of input and exhibits task- modulation during sustained attention. Yet, it remains unclear if the synchronization through oscillations in these two networks plays a causal in sustained attention and more broadly in cognitive control. Targeted brain stimulation of individual network nodes with rhythmically patterned stimulation offers the opportunity to manipulate specific network oscillatory patterns and examine the resulting change in behavioral performance to establish a causal role of the targeted activity pattern. Such causal neuroscience of higher-order brain function will fundamentally advance our understanding of how cognition arises from large-scale electrical activity patterns in the brain. The overall objective is to identify the causal role of oscillatory functional interactions in sustained attention by rhythmic optogenetic stimula- tion. We will employ a widely used paradigm of sustained attention in animals, the five-choice serial reaction time task (5-CSRTT), in combination with rhythmic optogenetic stimulation and multisite electrophysiology in ferrets. We use the ferret (instead of more commonly used rodent species) for the study of the oscillatory substrate of cognitive function since we previously found that the ferret shares two fundamental top-down brain rhythms with humans: frontal theta oscillations that provide control of posterior parietal cortex and posterior alpha oscillations that gate visual perception. The proposed project builds on our published work of oscillatory interactions in these two networks as a function of engagement with both the 5-CSRTT and sensory input in ferrets, and our preliminary data of suc- cessful modulation of neuronal spiking, functional connectivity, and behavioral performance in the 5-CSRTT by fre- quency-specific rhythmic optogenetic stimulation. We hypothesize that oscillatory functional interaction in these two networks is dynamically regulated to drive sustained attention in this task. Completion of these three aims will pro- vide an in-depth understanding of the causal role of frontoparietal and posterior thalamo-cortical network in sustained attention. The rationale of this project is that advancing the causal investigation of synchronization in higher-order brain structures in cognitive control will open new avenues for the development of novel diagnostic and therapeutic strategies for deficits in cognitive control. The proposed work is thus of high translational significance and broad impact since sustained attention is impaired in numerous psychiatric illnesses.

项目摘要-北卡罗来纳大学-弗罗利希教堂山 持续注意代表了认知控制的一个基本维度，指的是分配注意力的过程 认知资源，以适当地对不常见但与任务相关的刺激做出反应。持续的关注不同于 更普遍研究的是转移或分散注意力，因为它缺乏能力限制和 竞争。持续注意力缺陷在包括注意力缺陷多动在内的精神疾病中很常见 精神障碍、双相情感障碍和精神分裂症。因此，了解持续关注的网络基础将 极大地提高了我们开发基于电路的疗法的能力，这种疗法可以选择性地参与和恢复活动 驱使持续关注的模式。两个高阶网络中的同步已作为神经子网络出现 一般情况下，持续注意力和认知控制策略。首先，额顶神经网络起着生成器的作用 自上而下的控制信号。第二，丘脑-皮质后部网络对输入进行门控处理，并表现出任务-- 持续注意期间的调制。然而，目前还不清楚这两者是否通过振荡来实现同步 网络在持续的注意力和更广泛的认知控制中起着因果作用。有针对性的脑刺激 具有有节奏的模式刺激的单个网络节点提供了操纵特定网络的机会 振荡模式，并检查由此导致的行为表现的变化，以确定 有针对性的活动模式。这种关于高级大脑功能的因果神经科学将从根本上促进我们的 理解认知是如何从大脑的大规模电活动模式中产生的。总体目标是 为了确定振荡功能相互作用在节律性光遗传刺激持续注意中的因果作用- 提顿。我们将在动物中使用一种广泛使用的持续注意范式，即五选一系列反应时 任务(5-CSRTT)，结合节律性光遗传刺激和雪貂多部位电生理。我们 用雪貂(而不是更常用的啮齿动物)来研究认知的振荡底物 因为我们之前发现雪貂和人类有两个基本的自上而下的大脑节律： 额叶theta振荡提供对后顶叶皮质的控制，后方α振荡提供门 视觉感知。建议的项目建立在我们发表的关于这两个网络中的振荡相互作用的工作的基础上 作为与5-CSRTT和感觉输入在雪貂中的接触的函数，以及我们的SUC-C的初步数据。 FRE对5-CSRTT中神经元放电、功能连接和行为表现的成功调节 特定频率的节律性光遗传刺激。我们假设这两者中的振荡性函数相互作用 网络是动态调节的，以在这项任务中引起持续的关注。完成这三个目标将有助于- 通过深入了解额顶顶叶和丘脑后皮质网络在慢性阻塞性肺疾病中的作用 请注意。这个项目的基本原理是在更高的阶数上推进同步的因果研究 认知控制中的大脑结构将为开发新的诊断和治疗开辟新的途径 应对认知控制缺陷的策略。因此，建议的工作具有很高的翻译意义和广泛的意义 影响，因为在许多精神疾病中，持续的注意力受到损害。