A Systems Neuroscience Approach for the Study of General Anesthesia

全身麻醉是一种药物诱导的可逆状态，包括五种行为状态：催眠(意识丧失)、健忘(记忆丧失)、止痛(痛觉丧失)、静止(静止)和血流动力学稳定，并控制应激反应。麻醉药导致全身麻醉状态的机制仍然是现代医学最大的谜团之一。关于神经学的研究 负责全身麻醉五种行为状态的回路是系统神经科学正在研究的一个基本问题，但并不是为了理解麻醉。我建议使用系统神经科学的范式来建立一个跨学科的项目来解决一般的 麻醉。该计划将包括一组在人类、猴子和大鼠身上使用相同麻醉剂的协调研究，此外还将使用动态系统建模研究麻醉剂对神经回路的影响，并开发新的信号处理算法以实时跟踪麻醉的动态 全身麻醉下的大脑状态。动物研究将使用已建立的行为模式、功能磁共振成像和多电极方法来跟踪大脑活动，并使用显微注射和新颖的纳米颗粒方法来特定部位地给药。人体研究将使用功能磁共振成像跟踪麻醉下的大脑状态 同时记录脑电。调查人员将合作将这些信息整合到 不同的系统和规模。这个项目将导致更精确的，以神经生理学为基础的 对全身麻醉的了解，麻醉药物开发的更安全的方案，特定部位的方法 用于麻醉药物输送和设计更好的、基于神经生理学的深度测量方法 麻醉剂的作用。因此，这项研究将通过降低麻醉相关风险来改善人类健康 外科或内科治疗需要全身麻醉的患者的发病率。这项研究还将 通过更多地强调系统神经科学，对麻醉师的培训产生广泛影响。

General anesthesia is a drug-induced, reversible condition comprised of five behavioral states: hypnosis (loss of consciousness), amnesia (loss of memory), analgesia (loss of pain sensation), akinesia (immobility), and hemodynamic stability with control of the stress response. The mechanisms by which anesthetic drugs induce the state of general anesthesia remain one of the biggest mysteries of modern medicine. Study of the neural circuitry responsible for each of the five behavioral states of general anesthesia is a fundamental question being investigated in systems neuroscience but not for the purpose of understanding anesthesia. I propose to use systems neuroscience paradigms to establish an interdisciplinary program to solve the mystery of general anesthesia. The program will consist of a set of coordinated studies in humans, monkeys and rats using the same anesthetic agents, in addition to use of dynamical systems modeling studies of anesthetic effects on neural circuits and the development of new signal processing algorithms to track in real-time the dynamics of brain states under general anesthesia. The animal studies will use established behavioral paradigms, fMRI, and multielectrode methods to track brain activity, and microinjection and novel nanoparticle methods for sitespecific delivery of anesthetic drugs. The human studies will track brain states under anesthesia using fMRI and simultaneously recorded EEG. The investigators will collaborate to integrate this information across the different systems and scales. This project will lead to a more precise, neurophysiologically-based understanding of general anesthesia, safer protocols for anesthetic drug-development, site-specific methods for anesthetic drug delivery and the design of better, neurophysiologically-based methods for measuring depth of anesthesia. Therefore, this research will improve human health by reducing the risk of anesthesia-related morbidity for patients whose surgical or medical therapies require general anesthesia. This research will also have broad impact on the training of anesthesiologists by placing greater emphasis on systems neuroscience.