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 持续的注意力-认知资源的持续分配，以应对不频繁，但行为 相关刺激-在许多精神疾病中受损，代表认知障碍的一个重要方面， 控制持续的注意力需要自上而下的控制和与外部世界的接触， 额顶叶和丘脑控制初级感觉皮层的信号。尽管广泛 使用五选择系列反应时任务的动物模型中持续注意的行为表征 （5-CSRTT），很少有人知道的振荡之间的相互作用的背注意网络和 丘脑-皮层动力学及其作为增强持续注意力的刺激靶点的潜力。的 本项目的目的是剖析高阶丘脑-皮层振荡在持续性脑缺血中的因果作用。 注意力通过时间上精确的节奏刺激。我将集中在视觉丘脑皮层的三个区域 网络：高级视觉丘脑（外侧后核的外侧面，LPl），后顶叶皮层 (PPC)初级视皮层（V1）。我将测试中心假设，即LPI-皮质θ（4-7 Hz）功能 连接性因果地协调PPC-V1功能连接性以促进持续的注意。的理由 这项工作的一个重要方面是，所提出的时间精确的节律性光遗传学扰动将直接测试因果关系。 丘脑-皮层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-皮层振荡在持续注意中的功能作用，（2）确定 丘脑-皮层功能连接在持续性注意中因果作用 光遗传学。这项工作是有意义的，因为它将因果测试收敛模型，其中高阶视觉 丘脑协调顶叶自上而下的控制信号，将其传递到视觉皮层，这对发展回路至关重要， 基础疗法，以提高持续的注意力。该工作是创新的，因为它的闭环集成 光遗传学电路询问，多位点电生理学，自由移动持续注意力任务， 机器学习工具的振荡同步的因果作用的调查。总阳性 这项研究的影响是提供一个更全面的地图，说明高阶视觉丘脑是如何 与额顶叶控制信号相互作用以调节V1，从而介导持续注意， 在许多精神疾病（包括注意力缺陷）中表现出损害的跨诊断认知功能 多动症、双相情感障碍和精神分裂症。这项研究的含义是，它可能揭示了一个 作为两个较高阶处理结构之间相互作用的基础的一般机制， 在认知过程中的感觉皮层。