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: 10573308
• 负责人: Flavio Frohlich
• 金额: $ 38.95万
• 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/10573308
• 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 Lobe; Pattern; Performance; Periodicity; Play; Prefrontal Cortex; Process; Public Health; Publishing; Reaction Time; Research; Resources; Rodent; Role; Schizophrenia; Signal Transduction; Site; Stimulus; Structure; Task Performances; Testing; Thalamic structure; Therapeutic; United States National Institutes of Health; Universities; Visual; Visual Perception; Work; area striata; attentional control; cognitive control; cognitive function; design; improved; innovation; interest; neural; novel; novel diagnostics; novel therapeutic intervention; optogenetics; 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 - 北卡罗来纳大学教堂山分校，弗罗利希 持续注意力代表了认知控制的一个基本维度，是指分配注意力的过程。 对不常见但与任务相关的刺激做出适当反应的认知资源不同于持续注意力。 更常见的研究是转移或分散注意力，因为它缺乏能力限制的定义特征和 持续注意力缺陷在精神疾病中很常见，包括注意力缺陷多动症。 因此，了解持续注意力的网络基础将有助于理解精神障碍、双相情感障碍和精神分裂症。 显着提高我们开发基于回路的疗法的能力，选择性地参与和恢复活动 驱动持续注意力的模式已经作为神经子网络出现。 首先，额顶叶网络充当持续注意力和认知控制的发生器。 其次，后丘脑皮质网络控制输入的处理并表现出任务- 然而，目前尚不清楚这两者是否通过振荡进行同步。 网络在持续注意力和更广泛的认知控制中发挥着因果作用。 具有节奏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产生的行为表现变化，以确定该行为的因果作用 这种高阶大脑功能的因果神经科学将从根本上推动我们的进步。 了解认知如何从大脑中的大规模电活动模式产生。 通过节律性光遗传学刺激来确定振荡功能相互作用在持续注意力中的因果作用 我们将采用在动物中广泛使用的持续注意力范例，即五选择串行反应时间。 任务（5-CSRTT），结合雪貂的节律性光遗传学刺激和多部位电生理学。 使用雪貂（而不是更常用的啮齿类动物）来研究认知的振荡基质 因为我们之前发现雪貂与人类有两种基本的自上而下的大脑节律： 额叶θ振荡提供对后顶叶皮层的控制，而后α振荡则控制门控 所提出的项目建立在我们已发表的这两个网络中振荡相互作用的工作的基础上。 作为雪貂 5-CSRTT 和感觉输入参与的函数，以及我们成功的初步数据 通过 fre- 成功调节 5-CSRTT 中的神经尖峰、功能连接和行为表现 我们捕获了这两者中的振荡功能相互作用。 网络受到动态监管，以推动对这项任务的持续关注。这三个目标的完成将有利于- 深入了解额顶叶和后丘脑皮质网络在持续性 该项目的基本原理是推进高阶同步的研究。 认知控制中的大脑结构将为开发新型诊断和治疗开辟新途径 因此，拟议的工作具有高度的转化意义和广泛的意义。 由于许多精神疾病会损害持续注意力，因此会产生影响。