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

项目总结/摘要 当面对环境的不确定性时，最佳自上而下的控制有助于注意力转移和改善 性能注意力的几个功能上不同的阶段在心理学中得到了很好的确立。最近的研究 将这些认知结构与特定的大脑结构联系起来。然而，人们对 将上下文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，知觉决定和运动动作负责 人类的适应行为。缺乏适当的注意力控制会导致各种注意力障碍，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过程 潜在的适应性行为，特别是神经调节对相互作用中认知控制的贡献， 大脑结构前扣带皮层（ACC）和背外侧前额叶皮层的神经元活动 去甲肾上腺素（NE）强烈调节dLPFC，这两个参与认知控制的关键脑区 脑干中蓝斑（LC）的神经调节。LC-NE神经调节系统 在整个大脑皮层，并已联系到感觉处理调节，唤醒和注意力。我们 猴子的初步数据表明，空间选择性注意强烈地调节NE的尖峰动态 LC中的神经元，包括增加的尖峰出席视觉刺激。此外， 这些LC-NE神经元增强注意力表现。我们的中心假设是：1）LC接收 来自ACC的关于行为表现的上下文信息，并且随着表现的提高而被激活 2）LC-NE神经调节分别对ACC和dLPFC中的神经元活动进行差异调节 调节注意控制的运动选择、感觉和知觉决策选择。测试这些 假设，我们将隔离神经生理相关的性能错误，和注意力转移的感觉 相关性，知觉决策标准和运动标准内LC，ACC和dLPFC的猴子。我们将 光遗传学激活LC-NE神经元，同时记录ACC和dLPFC，以测试 LC-NE活性动力学的方面（紧张性和刺激锁定的相位爆发尖峰）因果地调节ACC， dLPFC介导注意力控制的不同成分。这项研究的结果将提供一个 直接，详细的神经生物学理解的专门神经调节的贡献， 情境信息到不同阶段的注意力控制，提高适应性行为表现， 人类这将进一步加快在更好的分类和确定潜在治疗靶点方面的进展 治疗与特定功能缺陷相关的各种注意力障碍。

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.