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

• 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
• 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

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 持续关注 - 认知资源的持续分配，以应对罕见但行为上的反应 相关刺激 - 在许多精神疾病中受到损害，代表认知的重要方面 控制。持续的关注需要自上而下的控制和与外部世界的互动，这是联系的 在主要传感器皮层上的额叶和丘脑控制信号。尽管很广泛 使用五个选择的串行反应时间任务在动物模型中持续注意的行为表征 （5-CSRTT），关于背注意网络和 丘脑皮质动力学及其作为增强持续关注的刺激目标的潜力。这 该项目的目的是剖析持续的高阶丘脑 - 皮层振荡的因果关系 通过暂时精确的节奏刺激注意。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（侧后核的侧面，LPL），后顶皮层 （PPC）和一级视觉皮层（V1）。我将测试中心假设，即LPL皮质theta（4-7 Hz）功能 连接性可以将PPC-V1功能连接与持续注意力进行协调。理由 这项工作的是，提出的暂时精确的节奏光学遗传扰动将直接测试因果关系 丘脑 - 皮质功能连通性在持续关注中的作用。根据：（1）的两个具体目的是：（1） 描述高阶丘脑 - 皮层振荡在持续注意力中的功能作用，（2）确定 Thalamo-cortical功能连通性在持续关注中的因果作用，通过暂时精确的节奏 光遗传学。这项工作很重要，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上，这对于发展电路至关重要 - 基于增强持续关注的疗法。由于闭环的整合，这项工作具有创新性 光遗传学电路询问，多站点电生理学，自由移动的持续注意任务和 用于投资振荡同步因果作用的机器学习工具。总体积极 拟议的研究的影响是提供更全面的地图，以了解高阶视觉丘脑如何 与额叶控制信号相互作用以调节V1，从而介导持续的注意力，A 经诊断的认知功能显示出许多精神疾病（包括注意力缺陷）的损害 多动症，躁郁症和精神分裂症。这项研究的含义是它可能揭示 两个高阶处理结构之间相互作用的一般机制信号传导至较低 认知处理过程中的感觉皮质。