Causal role of higher-order thalamo-cortical oscillations in sustained attention

高阶丘脑皮质振荡在持续注意力中的因果作用

基本信息

批准号：
10199754
负责人：
Wei Huang
金额：
$ 3.68万
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：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2022-05-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10199754
关键词：
Anatomy Animal Model Animals Attention Attention deficit hyperactivity disorder Attentional deficit Behavior Behavioral Bipolar Disorder Cognition Cognitive Cognitive deficits Communication Communities Computers Conflict (Psychology)Couples Data Dorsal Electrophysiology (science)Exhibits Ferrets Foundations Frequencies Functional disorder Impairment Implant Impulsivity Investigation Lasers Lateral Lateral posterior nucleus of thalamus Length Link Machine Learning Maps Mediating Mental disorders Methods Microelectrodes Modeling Neurons Parietal Parietal Lobe Performance Periodicity Phase Physiologic pulse Prefrontal Cortex Process Psyche structure Reaction Time Research Resources Rewards Role Schizophrenia Signal Transduction Statistical Models Stimulus Structure Techniques Testing Thalamic structure Therapeutic Time Touch sensation Training Visual Visual Cortex Work area striata base behavioral outcome calmodulin-dependent protein kinase II cognitive control cognitive function functional disability innovation neurotransmission novel optogenetics recruit relating to nervous system sensor sensory cortex signal processing sustained attention theories tool visual stimulus

项目摘要

PROPOSAL SUMMARY/ABSTRACT Sustained attention – the continuous allocation of cognitive resources to respond to infrequent but behaviorally relevant stimuli – is impaired in many psychiatric disorders and represents an important aspect of cognitive control. Sustained attention requires top-down control and engagement with the external world, which is linked to both frontoparietal and thalamic controlling signals on primary sensor cortices. Despite the extensive behavioral characterization of sustained attention in animal models using the five-choice serial reaction time task (5-CSRTT), very little is known about the oscillatory interaction between the dorsal attention network and thalamo-cortical dynamics and its potential as a stimulation target for enhancing sustained attention. The objective of this project is to dissect the causal role of higher-order thalamo-cortical oscillations in sustained attention via temporally-precise rhythmic stimulation. I will focus on three regions in the visual thalamo-cortical network: higher-order visual thalamus (lateral aspect of lateral posterior nucleus, LPl), posterior parietal cortex (PPC), and primary visual cortex (V1). I will test the central hypothesis that LPl-cortical theta (4-7 Hz) functional connectivity causally coordinates PPC-V1 functional connectivity to facilitate sustained attention. The rationale of this work is that the proposed temporally-precise rhythmic optogenetic perturbations will directly test the causal role of thalamo-cortical functional connectivity in sustained attention. Accordingly, the two specific aims are: (1) Delineate the functional role of higher-order thalamo-cortical oscillations in sustained attention, (2) Determine the causal role of thalamo-cortical functional connectivity in sustained attention via temporally-precise rhythmic optogenetics. This work is significant because it will causally test a convergent model in which higher-order visual thalamus coordinates the parietal top-down control signals onto visual cortex that is crucial for developing circuit- based therapies to enhance sustained attention. The work is innovative due to its integration of closed-loop optogenetics circuit interrogation, multisite electrophysiology, freely-moving sustained attention task, and machine-learning tools for the investigation of the causal role of oscillatory synchronization. The overall positive impact of the proposed study is to provide a more comprehensive map of how the higher-order visual thalamus interacts with the frontoparietal control signal to modulate V1, and thus mediates sustained attention, a transdiagnostic cognitive function that shows impairment in many psychiatric disorders including attention deficit hyperactivity disorder, bipolar disorder, and schizophrenia. The implication of this study is that it may reveal a general mechanism underlying the interaction between two higher-order processing structures signaling to lower sensory cortices during cognitive processing.

提案摘要/摘要持续注意力——持续分配认知资源以应对不常见但行为上的情况相关刺激——在许多精神疾病中受到损害，代表了认知的一个重要方面持续的注意力需要自上而下的控制和与外部世界的接触，这是相互联系的。尽管有广泛的影响，但初级传感器皮质上的额顶叶和丘脑控制信号。使用五选择串行反应时间任务对动物模型中持续注意力的行为进行表征（5-CSRTT），关于背侧注意网络和背侧注意网络之间的振荡相互作用知之甚少。丘脑皮质动力学及其作为增强持续注意力的刺激目标的潜力。该项目的目标是剖析高阶丘脑皮质振荡在持续性通过时间上精确的节律刺激来集中注意力。我将重点关注视觉丘脑皮质的三个区域。网络：高阶视觉丘脑（外侧后核外侧部分，LPl）、后顶叶皮层 (PPC) 和初级视觉皮层 (V1) 我将测试 LPl 皮质 theta (4-7 Hz) 功能的中心假设。连接性因果性地协调 PPC-V1 功能连接性以促进持续关注。这项工作的重点是，所提出的时间精确的节律光遗传学扰动将直接测试因果关系丘脑皮质功能连接在持续注意力中的作用因此，两个具体目标是：（1）描述高阶丘脑皮质振荡在持续注意力中的功能作用，（2）确定丘脑皮质功能连接通过时间精确的节律在持续注意力中的因果作用这项工作意义重大，因为它将因果测试一个收敛模型，其中高阶视觉丘脑将顶叶自上而下的控制信号协调到视觉皮层，这对于开发电路至关重要这项工作由于其闭环的整合而具有创新性。光遗传学电路询问、多部位电生理学、自由移动持续注意力任务，以及用于研究振荡同步的因果作用的机器学习工具总体上是积极的。拟议研究的影响是提供一个更全面的图谱来说明高阶视觉丘脑如何与额顶叶控制信号相互作用来调节 V1，从而介导持续注意力，跨诊断认知功能显示许多精神疾病（包括注意力缺陷）受损这项研究的意义在于它可能揭示了多动症、双相情感障碍和精神分裂症。两个高阶处理结构之间相互作用的一般机制，向低阶处理结构发出信号认知处理过程中的感觉皮层。