A Computational, Neurobiological and Clinical Study of Cortical Connectivity During Consciousness & Anesthesia

 说明(申请人提供)：虽然麻醉学领域在促进患者安全方面发挥了领导作用，但对于全身麻醉的靶器官：大脑，仍然没有标准的监测。缺乏可靠的神经生理监测可能会导致患者并发症，原因是麻醉不足(例如，意识不足和创伤后应激障碍)以及过度麻醉(例如，苏醒延迟、精神错乱、神经毒性)。目前，许多商业上可用的大脑监测器正在手术室中使用，但此类设备显示出的实用性有限，而且往往基于专有或经验算法。神经生物学的最新进展预示着大脑监测和改善患者安全的更复杂时代的可能性。所需要的是识别全身麻醉的可测量的神经生理特征，这些特征是由意识的神经生物学提供信息的。我们已经收集了令人信服的数据，在人类手术患者中，大脑中的额叶到顶叶的连接被所有主要类别的麻醉剂抑制。然而，关于大脑中信息传递的测量、这种被抑制的连接的潜在神经机制以及研究结果的临床相关性，仍然存在重要的问题。本应用程序的目标是更深入地理解 清醒和麻醉期间皮质连接模式的神经生物学原理以及这些模式与临床护理的相关性。我们将通过计算大脑网络模型进行创新研究，在非人类灵长类动物大脑中进行机械实验，并在整个围手术期对手术患者进行临床研究，以实现这一目标。这些研究将产生积极的影响，推动麻醉机制的神经生物学，总体上促进网络科学，并向外科和危重护理患者的新型脑监测策略迈出关键的一步。

 DESCRIPTION (provided by applicant): Although the field of anesthesiology has played a leadership role in promoting patient safety, there is still no standard monitor for the target orga of general anesthesia: the brain. The lack of reliable neurophysiologic monitoring can result in patient complications because of insufficient anesthesia (e.g., awareness and post- traumatic stress disorder) as well as excessive anesthesia (e.g., delayed emergence, delirium, neurotoxicity). A number of commercially-available brain monitors are currently used in the operating room, but such devices have shown limited utility and are often based on proprietary or empirical algorithms. Recent advances in neurobiology herald the possibility of a more sophisticated era of brain monitoring and improved patient safety. What is needed is the identification of measurable neurophysiological features of general anesthesia that are informed by the neurobiology of consciousness. We have gathered compelling data in human surgical patients that frontal-to-parietal connectivity in the brain is suppressed by all major classes of anesthetics. However, important questions remain regarding the measurement of information transfer in the brain, the underlying neural mechanisms of this suppressed connectivity and the clinical relevance of the findings. The objective for this application is a deeper understanding of the neurobiological principles of cortical connectivity patterns during consciousness and anesthesia as well as the relevance of such patterns for clinical care. We will achieve this objective by conducting innovative studies with computational brain network models, mechanistic experiments in the non-human primate brain, and a clinical study of surgical patients throughout the perioperative period. These studies will have a positive impact by advancing the neurobiology of anesthetic mechanisms, advancing network science in general, and making a key translational step toward novel brain monitoring strategies for surgical and critical care patients.