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

 描述（申请人提供）：虽然麻醉学领域在促进患者安全方面发挥了主导作用，但全身麻醉的目标器官：大脑仍然没有标准的监测仪。缺乏可靠的神经生理学监测可能会因麻醉不足（例如意识和创伤后应激障碍）以及麻醉过度（例如苏醒延迟、谵妄、神经毒性）而导致患者出现并发症。目前，手术室中使用了许多商用脑监视器，但此类设备的实用性有限，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更复杂的大脑监测时代的到来和改善患者安全的可能性。我们需要的是识别全身麻醉的可测量的神经生理学特征，这些特征是由意识神经生物学提供的。我们在人类外科手术患者中收集了令人信服的数据，表明所有主要类别的麻醉剂都会抑制大脑额叶到顶叶的连接。然而，关于大脑信息传递的测量、这种抑制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问题。此应用程序的目标是更深入地了解 意识和麻醉过程中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、非人类灵长类大脑的机械实验以及手术患者整个围手术期的临床研究进行创新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、总体上推进网络科学以及为手术和重症监护患者的新型大脑监测策略迈出关键的转化一步来产生积极影响。

 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.