Internally and externally driven arousal changes in neural activity and hemodynamics

项目摘要/摘要 我们的觉醒水平几乎影响到我们参与的所有认知和行为能力 与我们的环境有关。各种术语被用来描述与觉醒相关的认知变化， 包括清醒、内在状态、参与和警觉。尽管这种模棱两可，但很明显，唤醒 是一种影响大脑活动、系统生理和行为的全球现象。行为上的唤醒缺陷 而心率和瞳孔直径等系统标记物存在于许多神经系统疾病中，包括 阿尔茨海默氏症、精神分裂症和注意力缺陷障碍。为了使用这些非侵入性的系统性措施 作为诊断标志，我们需要了解唤醒水平是如何影响大脑活动的 神经典型认知，进而导致行为的变化。这项提案的目标是调查 随着觉醒水平的波动而发生的大脑活动的变化。具体地说，我们将研究在 同时检测皮质神经元群活动和脑血流动力学。我们将跟踪唤醒 使用瞳孔直径和心率的水平。我们最重要的假设是，我们可以将每一分钟的唤醒联系起来 神经种群活动和脑血流动力学变化缓慢的波动。在第一个目标中，我们将 研究唤醒水平的内部驱动变化，这种变化发生在几个小时内和整个昼夜周期。在 第二个目标，我们将使用外部刺激来探测唤醒水平，以评估我们是否可以调节唤醒- 神经群体活动和血流动力学的关联漂移。我们记录同步人口的策略 在系统参数和行为背景下的活动和血流动力学变化将使我们能够 全面探索唤醒相关的变化，整合大脑、身体和大脑的唤醒效应 行为。这项建议的结果将有助于理解如何通过行为测量唤醒偏差 和系统生理学，可以作为全球大脑活动变化的生物标志物 神经紊乱。 这项提议将在卡内基的跨学科和协作培训环境中完成 梅隆大学及其认知神经基础中心由一个庞大的社区组成 神经学家和工程师研究潜在的认知和大脑障碍的大脑活动。在.之下 系统神经科学专家Matt Smith博士和系统神经科学专家Jana Kainerstorfer博士的指导 生物医学光学，这项提议将为我提供电生理学、光学和 探索认知功能的心理物理学。这些技能将帮助我朝着成为一名 内科科学家，研究大脑、系统生理学和行为之间的相互作用，以识别 认知障碍的生物标志物。

PROJECT SUMMARY/ABSTRACT Our level of arousal influences almost all of the cognitive and behavioral abilities that allow us to engage with our environment. A variety of terminology has been used to describe arousal-related changes in cognition, including wakefulness, internal state, engagement, and alertness. Despite this ambiguity, it is clear that arousal is a global phenomenon that affects brain activity, systemic physiology, and behavior. Arousal deficits in behavior and systemic markers, such as heart rate and pupil diameter, are present in many neurologic disorders, including Alzheimer’s, schizophrenia, and attention deficit disorder. In order to use these non-invasive systemic measures of arousal as diagnostic markers, we need to understand how arousal level influences brain activity in neurotypical cognition and in turn leads to changes in behavior. The goal of this proposal is to investigate changes in brain activity that occur with fluctuations in arousal level. Specifically, we will study slow changes in simultaneously measured cortical neural population activity and cerebral hemodynamics. We will track arousal level using pupil diameter and heart rate. Our overarching hypothesis is that we can link minute-to-minute arousal fluctuations with slow changes in neural population activity and cerebral hemodynamics. In the first aim, we will study internally driven variations in arousal level that occur over hours and across the circadian cycle. In the second aim, we will probe arousal level using an external stimulus to assess whether we can modulate arousal- linked drifts in neural population activity and hemodynamics. Our strategy to record simultaneous population activity and hemodynamic changes in context of systemic parameters and behavior will allow us to comprehensively probe arousal-related changes and integrate arousal effects across the brain, body, and behavior. Results from this proposal will help to understand how deviations in arousal, measured via behavior and systemic physiology, could serve as biomarkers of changes in global brain activity that are present in neurologic disorders. This proposal will be completed in the interdisciplinary and collaborative training environment of Carnegie Mellon University and its Center for the Neural Basis of Cognition that consists of a large community of neuroscientists and engineers investigating brain activity underlying cognition and brain disorders. Under the guidance of Dr. Matt Smith, an expert in systems neuroscience, and Dr. Jana Kainerstorfer, an expert in biomedical optics, this proposal will provide me with a multimodal skill set in electrophysiology, optics, and psychophysics to probe cognitive function. These skills will help me progress towards my goal of becoming a physician scientist studying the interaction between the brain, systemic physiology, and behavior to identify biomarkers of cognitive disorders.