Isolating causal roles of norepinephrine neuromodulation in mediating distinct components of attention control

分离去甲肾上腺素神经调节在介导注意力控制的不同组成部分中的因果作用

• 批准号: 10667842
• 负责人: Supriya Ghosh
• 金额: $ 24.6万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-03 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10667842
• 关键词: Adaptive Behaviors; Animals; Anterior; Area; Arousal; Attention; Attention deficit hyperactivity disorder; Behavior; Behavior Control; Behavioral; Brain; Brain Stem; Cerebral cortex; Classification; Clinical; Cognitive; Conflict (Psychology); Contralateral; Data; Diagnosis; Disease; Dissociation; Elements; Feedback; Functional disorder; Goals; Human; Individual; Intervention; Link; Measures; Mediating; Methods; Monitor; Monkeys; Motor; Nervous System; Neurobiology; Neurons; Noise; Norepinephrine; Pattern; Performance; Phase; Play; Prefrontal Cortex; Process; Psychology; Regulation; Research; Resources; Response to stimulus physiology; Role; Sensory; Stimulus; Structure; System; Testing; Therapeutic Intervention; Training; Uncertainty; Wakefulness; Work; attentional control; cingulate cortex; cognitive control; environmental change; executive function; flexibility; improved; insight; locus ceruleus structure; neurobiological mechanism; neurophysiology; neuroregulation; optogenetics; response; selective attention; sensory input; sensory stimulus; success; therapeutic target; visual stimulus

PROJECT SUMMARY/ABSTRACT When faced with environmental uncertainty, optimum top-down control facilitates attention shifts and improves performance. Several functionally distinct stages of attention are well stablished in psychology. Recent studies have associated some of these cognitive constructs with specific brain structures. However, less is known about the neurobiological mechanisms that transform contextual information into distinct components of attention control such as selection of relevant sensory inputs, perceptual decision and motor action responsible for adaptive behaviors in humans. Lack of appropriate attention control leads to various attention disorders such as attention-deficit/hyperactivity disorder (ADHD). Our long-term goal is to dissociate distinct neuronal processes underlying adaptive behavior, particularly neuromodulatory contributions to cognitive control within interacting brain structures. Neuronal activity in the anterior cingulate cortex (ACC) and dorso-lateral prefrontal cortex (dLPFC), two crucial brain areas involved in cognitive control are strongly regulated by norepinephrine (NE) neuromodulation from the locus coeruleus (LC) in the brainstem. The LC-NE neuromodulatory system projects throughout the cerebral cortex, and has been linked to sensory processing regulation, arousal and attention. Our preliminary data in monkeys show that spatially selective attention strongly modulates spiking dynamics of NE neurons in the LC including an increased spiking to attended visual stimuli. Moreover, optogenetic activation of these LC-NE neurons enhanced attentional performance. Our central hypothesis is that: 1) the LC receives contextual information about behavioral performance from the ACC, and is activated with increased performance errors; 2) LC-NE neuromodulation differentially regulates neuronal activity in the ACC and dLPFC respectively to mediate motor selection, and sensory and perceptual decision selections of attention control. To test these hypotheses, we will isolate neurophysiological correlates of performance errors, and attentional shifts in sensory relevance, perceptual decision criterion and motor criterion within the LC, ACC and dLPFC in monkeys. We will optogenetically activate LC-NE neurons while simultaneously record from the ACC and dLPFC to test which aspects of LC-NE activity dynamics (tonic and stimulus-locked phasic burst spiking) causally regulate ACC and dLPFC to mediate distinct components of attention control. The results from this proposed study will provide a direct, detailed neurobiological understanding of specialized neuromodulatory contributions that transform contextual information into different stages of attention control in improving adaptive behavioral performance in humans. This will further expedite progress in better classification and identifying potential therapeutic targets for various attention disorders associated with functionally specific deficits.

项目摘要/摘要 当面临环境不确定性时，最优的自上而下控制有助于注意力转移和改进 性能。在心理学中，注意力的几个不同的功能阶段是很稳定的。最新研究 将其中一些认知结构与特定的大脑结构联系起来。然而，人们对此知之甚少 将背景信息转化为注意力的不同组成部分的神经生物学机制 控制，如选择相关的感觉输入、感知决定和负责运动的动作 人类的适应性行为。缺乏适当的注意力控制会导致各种注意力障碍，例如 注意力缺陷/多动障碍(ADHD)。我们的长期目标是分离不同的神经元突起 潜在的适应行为，特别是相互作用中对认知控制的神经调节作用 大脑结构。前扣带回皮质和背外侧前额叶皮质的神经元活动 (DLPFC)，参与认知控制的两个关键脑区受到去甲肾上腺素(NE)的强烈调节。 脑干蓝斑(LC)的神经调节作用。LC-NE神经调节系统项目 贯穿大脑皮层，并与感觉处理调节、唤醒和注意力有关。我们的 在猴子身上的初步数据表明，空间选择性注意强烈地调制了去甲肾上腺素的放电动力学 LC中的神经元包括对视觉刺激的刺激增加的棘波。此外，光遗传激活 这些LC-NE神经元增强了注意行为。我们的中心假设是：1)LC接收 来自ACC的有关行为性能的上下文信息，并随着性能的提高而激活 2)LC-NE神经调制对ACC和DLPFC神经元活动的不同调节作用 调节运动选择，以及注意控制的感官和知觉决策选择。为了测试这些 假设，我们将分离出表现错误和感官注意力转移的神经生理学相关性。 猕猴LC、ACC和DLPFC内的相关性、知觉决策标准和运动标准。我们会 光遗传学激活LC-NE神经元，同时从ACC和DLPFC记录 LC-NE活动动力学的各个方面(紧张性和刺激性锁定的相位爆发峰电位)因果地调节ACC和 DLPFC来调节注意力控制的不同组成部分。这项拟议研究的结果将提供一个 对特定神经调节作用的直接、详细的神经生物学理解 注意控制的不同阶段对提高儿童适应行为绩效的影响 人类。这将进一步加快更好的分类和确定潜在治疗靶点的进展 治疗与特定功能缺陷相关的各种注意力障碍。