Neuroimaging to identify the neural correlates of anesthetic and analgesic action in humans

神经影像学可识别人类麻醉和镇痛作用的神经相关性

• 批准号: 10795475
• 负责人: Keith Michael Vogt
• 金额: $ 5.41万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10795475
• 关键词: Absence of pain sensation; Acute Pain; Address; Adult; Affect; Amnesia; Analgesics; Anesthesia procedures; Anesthesiology; Anesthetics; Behavior; Behavioral; Biomedical Engineering; Brain; Clinical; Clinical Trials; Combination Medication; Complex; Conscious; Data; Data Analyses; Dexmedetomidine; Dose; Drug Interactions; Electroencephalography; Engineering; Ensure; Environment; Fentanyl; Foundations; Functional Magnetic Resonance Imaging; Goals; Human; Image; Individual; Investigation; Ketamine; Knowledge; Lidocaine; Magnetic Resonance Imaging; Measures; Memory; Midazolam; Modeling; Neurosciences; Neurosciences Research; Operative Surgical Procedures; Pain; Patients; Perioperative; Pharmaceutical Preparations; Pharmacology; Physicians; Placebo Control; Polypharmacy; Procedures; Productivity; Propofol; Psychology; Randomized; Research; Single-Blind Study; System; Time; Work; arm; clinical practice; cognitive function; cognitive task; conditioned fear; drug action; experience; heart rhythm; human subject; improved; innovation; multimodal data; neural; neural correlate; neuroimaging; pain processing; pain relief; prevent; programs; response; sevoflurane; trial comparing; volunteer

Project Summary This ESI MIRA program of research, within the field of anesthesiology and perioperative pain, is aimed at better understanding how anesthetic and analgesic agents block memory formation, prevent conditioned fear responses, and relieve pain during otherwise unbearable experiences. Current provision of clinical anesthesia is not universally effective in achieving these goals because of a critical knowledge gap in understanding the systems-level neuroscience of how these drugs act and interact. The PI is a physician-anesthesiologist and bioengineer who has established a unique and innovative interdisciplinary framework to address this important problem. A team of senior collaborators, with expertise in psychology, functional MRI analysis, MRI engineering, and anesthetic pharmacology has been assembled to take advantage of an extremely productive academic environment. The project will determine how anesthetics from the seven major mechanistic classes of clinically- used agents act and interact to affect cognitive functions, including where in the brain changes occur. Steady- state concentrations of anesthetics will be delivered in a high-field MRI environment, while subjects perform cognitive tasks with precisely timed acute pain stimulation; electroencephalography, electrodermal, and cardiac rhythm data will simultaneously be acquired. The inclusion of acute pain, use of high-field functional MRI, multimodal data and broad characterization of behavior all represent increased rigor compared to prior human anesthetic neuroscience work, and builds on the PI’s recent studying midazolam and ketamine. The first planned project will complete the mechanistic clinical trial comparing propofol, dexmedetomidine, and fentanyl, which has begun under the PI’s K23. This is a randomized placebo-controlled single-blind parallel arm neuroimaging study in healthy adult volunteers (NCT04062123). The second set of projects will examine lidocaine and sevoflurane, to complete the individual investigation of representative examples from each major mechanistic class of commonly-used anesthetics. The third set of proposed projects will address an important barrier to progress by employing combinations of anesthetics across two or more of the previously characterized mechanistic classes. This will mark a shift in the paradigm to more realistically model the polypharmacy that is ubiquitous in clinical anesthesia practice. Combinations of anesthetics will be constrained to those that would be feasible to implement together in clinical practice and selection will be based on a broad quantitative analysis of data obtained for each agent studied individually, with the goal of leveraging key synergistic behavioral and neural interactions across mechanistically-different anesthetics. The overall goal of this substantive program of systems-level neuroscience research is to identify the key neural signatures that are both necessary and sufficient for anesthetic-induced inhibition of memory formation, fear conditioning, and pain processing. This will lay the foundation needed to progress towards the long-term vision of improving clinical practice, through more informed dosing combinations or enhanced intraoperative measures, to ensure amnesia and analgesia for all patients under anesthesia.

项目概要 该 ESI MIRA 研究计划涉及麻醉学和围手术期疼痛领域，旨在更好地 了解麻醉剂和镇痛剂如何阻止记忆形成，防止条件性恐惧 反应，并减轻当前难以忍受的经历中的疼痛。 由于在理解这些目标方面存在严重的知识差距，因此在实现这些目标方面并不普遍有效 这些药物如何发挥作用和相互作用的系统级神经科学 PI 是一名内科麻醉师， 生物工程师，他建立了独特且创新的跨学科框架来解决这一重要问题 一个由高级合作者组成的团队，拥有心理学、功能性 MRI 分析、MRI 工程、 麻醉药理学已经聚集在一起，以利用极其富有成效的学术成果 该项目将确定七个主要机械类别的麻醉剂如何在临床上使用。 使用的代理的作用和相互作用会影响认知功能，包括大脑中发生变化的位置。 麻醉剂的状态浓度将在高场 MRI 环境中进行，同时受试者进行 具有精确定时的急性疼痛刺激的认知任务； 将同时获取节律数据，包括急性疼痛、使用高场功能 MRI、 多模态数据和广泛的行为特征都代表了与之前的人类相比增加的 ligor 麻醉神经科学工作，并建立在 PI 最近研究咪达唑仑和氯胺酮的基础上。 项目将完成比较异丙酚、右美托咪定和芬太尼的机制临床试验，该试验已 这是一项随机安慰剂对照、单盲平行臂神经影像学研究，在 PI 的 K23 下开始。 第二组项目将检查利多卡因和七氟烷， 完成对每个主要机械类别的代表性实例的单独调查 第三组拟议项目将解决进展的一个重要障碍。 采用两种或多种先前描述的机械类别的麻醉剂组合。 这将标志着范式的转变，以更现实地模拟临床中普遍存在的复方用药 麻醉实践中的麻醉组合将仅限于可行的组合。 临床实践和选择中的共同努力将基于对每个项目获得的数据进行广泛的定量分析 单独研究代理，目的是利用关键的协同行为和神经相互作用 这个系统级神经科学实质性计划的总体目标是机械上不同的麻醉剂。 研究的目的是确定麻醉诱导的必要且充分的关键神经特征 抑制记忆形成、恐惧调节和疼痛处理，这将为这些奠定基础。 通过更明智的剂量组合，朝着改善临床实践的长期愿景取得进展 或加强术中措施，保证所有麻醉下患者的遗忘和镇痛。