The influence of arousal state on coordinated neural dynamics

 描述(申请人提供)：唤醒和大脑功能之间的相互作用已经建立得很好，特别是当它们与唤醒状态的极端相关时，如战斗/逃跑与放松，清醒与睡眠，以及专心与疏忽。然而，最近的研究表明，在正常和临床受影响的大脑中，唤醒对每一时刻、注意力集中的信息处理的影响要普遍得多，也更细微。对于导致这些更细微差异的影响的机制，人们知之甚少。部分基于最近将觉醒介导的信息处理调制与脑干蓝斑(LC)神经元向大脑其他大部分部位释放去甲肾上腺素(NE)联系起来的研究以及我们自己的初步数据，我们在这里测试了这一假设，即在注意加工过程中唤醒状态的时刻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。这项研究的三个关键特点将大大扩大其影响。首先，我们将研究在人类和动物研究中广泛使用的条件下，觉醒的波动对大脑功能的影响：在数百次试验中，一个专心的人执行一项需要信息处理和控制行为的任务。其次，我们将研究协调神经动力学，它特别容易受到大脑状态变化的影响，只有在考虑到这种影响时才能正确解释。第三，也许也是最关键的，我们将帮助确定几种现成的、非侵入性的唤醒生理测量方法，包括瞳孔测量、皮肤电导反应(SCR)、心率变异性(HRV)和脑电(EEG)，可以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。具体地说，我们将：1)确定唤醒测量(瞳孔、SCR、HRV和EEG)与注意力集中的猴子几个大脑区域内和跨大脑区域的协调神经动力学之间的关系；以及2)开发数学工具，将唤醒测量与大脑区域内和跨大脑区域的协调神经活动模式联系起来。总而言之，这些目标将提高关于这类唤醒效应的神经基础的科学知识，并为在解释大脑协调活动时考虑这些效应提供新的、实用的方法。

 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.