The influence of arousal state on coordinated neural dynamics

 描述（由申请人提供）：唤醒和大脑功能之间的相互作用已经得到很好的建立，特别是当它们涉及极端的唤醒状态时，例如战斗/逃跑与放松，清醒与睡眠，以及注意与不注意。然而，最近的研究表明，在正常和临床受影响的大脑中，唤醒对每时每刻的注意力信息处理的影响更为普遍和微妙。对这些更微妙的影响的机制知之甚少。部分基于最近的研究，将唤醒介导的信息处理调制与脑干蓝斑核（LC）中的神经元释放去甲肾上腺素（NE）到大脑的大部分其他区域以及我们自己的初步数据联系起来，在这里，我们测试了以下假设：注意处理期间唤醒状态的每时每刻的变化调节了大脑区域内和跨大脑区域的协调神经元动力学。这项研究的三个主要特点将大大扩大其影响。首先，我们将在人类和动物研究中广泛使用的条件下研究唤醒波动对大脑功能的影响：一个专注的个体在数百次试验中执行一项需要信息处理和控制行为的任务。第二，我们将研究协调的神经动力学，这是特别容易受到大脑状态的变化，只有当这种影响被考虑在内，才能被正确解释。第三，也许是最重要的，我们将帮助确定几个现成的，非侵入性的生理指标，包括瞳孔测量，皮肤电导反应（SCR），心率变异性（HRV）和脑电图（EEG），可以用来有效地表征唤醒对同时测量的大脑活动和行为的持续影响。具体而言，我们将：1）确定唤醒措施（瞳孔，SCR，HRV和EEG）之间的关系和协调的神经元动力学内和跨几个大脑区域的注意猴子;和2）开发数学工具，唤醒措施与协调的神经活动模式内和跨大脑区域。总之，这些目标将提高关于这些唤醒效应的神经基础的科学知识，并提供新的实用方法，在解释协调的大脑活动时考虑这些效应。

 DESCRIPTION (provided by applicant): Interactions between arousal and brain function are well established, particularly as they relate to extremes of arousal state such as fight/flight versus relaxed, awake versus asleep, and attentive versus inattentive. However, recent studies suggest far more prevalent and nuanced effects of arousal on moment-by-moment, attentive information processing in the normal and clinically affected brain. Less is known about the mechanisms responsible for these more nuanced effects. Based in part on recent studies linking arousal- mediated modulations of information processing to release of norepinephrine (NE) from neurons in the brainstem nucleus locus coeruleus (LC) to much of the rest of the brain and our own preliminary data, here we test the hypothesis that moment-by-moment changes in arousal state during attentive processing modulate coordinated neuronal dynamics within and across brain regions. Three key features of this study will substantially broaden its impact. First, we wil study the effects of fluctuations of arousal on brain function under conditions that are in widespread use in human and animal studies: an attentive individual performing a task requiring information processing and controlled behaviors over many hundreds of trials. Second, we will study coordinated neural dynamics, which are particularly susceptible to changes in brain state and can only be interpreted correctly when such influences are taken into account. Third, and perhaps most critically, we will help to identify which of several readily available, non-invasive physiological measures of arousal, including pupillometry, skin conductance responses (SCR), heart rate variability (HRV), and electroencephalography (EEG), can be used to effectively characterize ongoing effects of arousal on simultaneously measured brain activity and behavior. Specifically, we will: 1) Determine relationships between arousal measures (pupil, SCR, HRV, and EEG) and coordinated neuronal dynamics within and across several brain regions in attentive monkeys; and 2) Develop mathematical tools to relate arousal measures to patterns of coordinated neural activity within and across brain regions. Together, these Aims will improve scientific knowledge about the neural basis of these kinds of arousal effects, and provide new, practical approaches for taking these effects into account when interpreting coordinated brain activity.