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（丧失 意识丧失）、健忘症（记忆丧失）、痛觉缺失（痛觉丧失）、运动不能（不动），以及 血液动力学稳定性与应激反应的控制。麻醉药物诱导的机制 全身麻醉状态仍然是现代医学最大的谜团之一。研究神经 负责全身麻醉的五种行为状态中的每一种的电路是一个基本问题 在系统神经科学中被研究，但不是为了理解麻醉。我建议 使用系统神经科学范式建立一个跨学科的计划，以解决一般的神秘 麻醉该计划将包括一系列在人类，猴子和大鼠中进行的协调研究， 相同的麻醉剂，除了使用动力学系统建模研究麻醉剂对 神经电路和新的信号处理算法的发展，以实时跟踪的动态 在全身麻醉下的大脑状态。动物研究将使用已建立的行为范例，功能磁共振成像， 和多电极方法来跟踪大脑活动，以及显微注射和新的纳米粒子方法， 麻醉药物的特异性递送。人类研究将使用功能磁共振成像技术跟踪麻醉下的大脑状态 同时记录脑电图调查人员将合作整合这些信息， 不同的系统和规模。这个项目将导致一个更精确的，基于神经生理学的 了解全身麻醉，麻醉药物开发的更安全方案，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。因此，这项研究将通过减少麻醉相关风险来改善人类健康。 手术或药物治疗需要全身麻醉的患者的发病率。这项研究也将 通过更加强调系统神经科学，对麻醉师的培训产生了广泛的影响。

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 site- specific 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.