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

基本信息

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
项目类别：
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

项目摘要

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，弗洛希里奇持续的关注是认知控制的基本维度，并指分配过程认知资源适当地应对不频繁但与任务相关的刺激。持续的关注与由于缺乏能力限制和竞赛。持续注意力的缺陷在精神病中很常见，包括注意力缺陷多动症疾病，躁郁症和精神分裂症。因此，了解持续关注的网络基质将会显着提高了我们发展基于电路的理论的能力，该理论有选择地参与和恢复活动引起持续关注的模式。两个高阶网络中的同步已成为神经亚一般来说，持续关注和认知控制的策略。首先，额叶网络充当自上而下的控制信号。其次，丘脑后丘脑 - 皮层网络门的输入处理和展示任务 - 持续关注期间的调节。然而，目前尚不清楚这两个是否通过振荡进行同步网络在持续关注和认知控制方面更广泛地发挥了因果关系。针对性的大脑刺激具有逻辑图案模拟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绩效变化，以确立目标活动模式。高阶脑功能的这种因果神经科学将从根本上推动我们的了解认知是由大脑中的大规模电活动模式产生的。总体目标是确定振荡功能相互作用在节奏光学遗传刺激持续注意中的因果关系 tion。我们将在动物中采用广泛使用的持续关注范式任务（5-CSRTT），与雪貂中的节奏光遗传学刺激和多作用电生理学结合使用。我们使用雪貂（而不是更常用的啮齿动物物种）进行认知的振荡底物功能以来，由于我们以前发现雪貂与人类有两个基本的自上而下的脑部节奏：额叶theta振荡可控制后顶叶皮层和后α振荡视觉感知。拟议的项目建立在我们发表的这两个网络中发表的振荡互动工作的基础上作为与雪貂中的5-CSRTT和感觉输入的互动的函数，以及我们的成功数据 fre-fre-fre-fre-fre-fre-fre-fre-fre-fre-fre-fre-n of-fre-n of-fre-调制的调节敏感特异性的节奏光遗传学模拟。我们假设这两个中的振荡功能相互作用网络受到动态调节，以引起此任务中的持续关注。完成这三个目标的完成视频对持续的额叶和后丘脑 - 皮质网络的因果作用有深入的了解注意力。该项目的理由是，在高阶中推进同步的因果投资认知控制中的大脑结构将为开发新的诊断和治疗开发新的途径认知控制中防御能力的策略。因此，拟议的工作具有很高的翻译意义和广泛的意义由于许多精神病疾病会损害持续的关注，因此影响。