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

 描述（由申请人提供）：尽管麻醉学领域在促进患者安全方面发挥了领导作用，但对于全身麻醉的目标器官：大脑，仍然没有标准的监测器。缺乏可靠的神经生理学监测可能导致患者并发症，因为麻醉不足（例如，意识和创伤后应激障碍）以及过度麻醉（例如，延迟苏醒、谵妄、神经毒性）。目前在手术室中使用了许多市售的脑监测器，但这些设备的实用性有限，并且通常基于专有或经验算法。神经生物学的最新进展预示着一个更复杂的大脑监测时代和改善患者安全的可能性。我们所需要的是识别由意识的神经生物学所告知的全身麻醉的可测量的神经生理学特征。我们已经收集了令人信服的数据，在人类手术患者的额叶到顶叶连接在大脑中被所有主要类别的麻醉剂抑制。然而，重要的问题仍然是关于大脑中信息传递的测量，这种抑制连接的潜在神经机制以及这些发现的临床相关性。此应用程序的目标是更深入地了解 在意识和麻醉过程中皮层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。我们将通过使用计算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，以及在整个围手术期对手术患者进行临床研究来实现这一目标。这些研究将通过推进麻醉机制的神经生物学，推进网络科学，并为手术和重症监护患者的新型脑监测策略迈出关键的一步，产生积极的影响。

 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.