Anesthestic modulation of human memory during acute pain

急性疼痛期间人类记忆的麻醉调节

• 批准号: 9892230
• 负责人: Keith Michael Vogt
• 金额: $ 19万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9892230
• 关键词: Acute Pain; Adrenergic Antagonists; Adult; Affect; Age; Amnesia; Amygdaloid structure; Analgesics; Anesthesia procedures; Anesthesiology; Anesthetics; Animals; Anxiety; Attenuated; Aversive Stimulus; Awareness; Behavior; Behavioral; Brain; Brain imaging; Brain region; Characteristics; Clinical; Clinical Research; Cognitive; Conscious; Data; Data Set; Development; Development Plans; Dexmedetomidine; Dose; Emotions; Evaluation; Event; Fentanyl; Fright; Functional Magnetic Resonance Imaging; General Anesthesia; Goals; Heart Rate; Hippocampus (Brain); Human; Image; Incidence; Individual; Individual Differences; Insula of Reil; Investigation; Lead; Machine Learning; Magnetic Resonance Imaging; Measurable; Measurement; Measures; Mediating; Memory; Mentors; Methodology; Methods; Motivation; Neuroanatomy; Neurosciences; Pain; Pattern; Performance; Periodicity; Pharmaceutical Preparations; Pharmacology; Physicians; Physiological; Placebos; Post-Traumatic Stress Disorders; Process; Propofol; Protocols documentation; Psychology; Psychometrics; Psychophysiology; Randomized; Reaction Time; Research; Research Personnel; Research Technics; Running; Scientist; Sedation procedure; Single-Blind Study; Sleep; Statistical Data Interpretation; Stimulus; Stress; Structure; Subconscious; System; Techniques; Translational Research; Universities; Variant; Work; anxiety spectrum disorders; arm; base; behavior measurement; career development; clinically relevant; cognitive neuroscience; cognitive task; complement C2a; conditioning; design; direct application; experience; hands on research; human subject; hypnotic; imaging study; implicit memory; indexing; medical schools; meetings; memory encoding; multidisciplinary; neuroimaging; pain perception; pain processing; patient oriented; prevent; psychologic; receptor; relating to nervous system; response; sedative

Project Summary (abstract): Despite routine use of sedative-hypnotic and analgesic agents (anesthetics) to prevent or ease suffering during aversive conditions, the effects of these agents on behavior and the neural systems that form memories, respond to threat, and process pain are poorly understood. This project will determine the memory-modulating effects of propofol, dexmedetomidine, and fentanyl in the context of periodic pain stimulation. It is a randomized, placebo- controlled, single-blind, parallel arm fMRI study in healthy adults (under age 40). Subjects will perform a memory encoding task while receiving periodic acute pain stimulation. Explicit and implicit memory will be quantified using response time and physiologic responses, including heart rate and electrodermal activity. Neuroimaging will localize brain activity and connectivity. Psychometric data relevant to pain and anxiety will be used to account for inter-individual differences. The central hypothesis is that, when forming memory during concomitant painful stimulation, three anesthetic agents, with different receptor pharmacology, will have distinct behavioral and physiologic response patterns, which are mediated by different activity within and interactions between the neural systems responsible for memory encoding, threat response, and pain processing. There are three scientific research goals of this patient-oriented career development proposal. The first is to determine how behavioral and physiologic measures of explicit and implicit memory are modulated by pain and the individual effects of the three anesthetics under investigation. The second aim is to determine the brain structures differentially engaged in memory encoding under pain and drug conditions, using task-related functional MRI and functional connectivity analyses. The third aim is to determine brain changes correlated to subject psychometric measures of anxiety, stress, sleep, and pain through multivariate psychophysiological interaction analysis. The scientific framework for this project has a direct application in better understanding the impact of memories formed during sedation with anesthetics while experiencing noxious stimuli. Additionally, further extension of this pharmacologic modulation technique to other cognitive neuroscience paradigms could provide a multidisciplinary framework for basic studies of memory formation, the genesis of dysregulated memories, and the necessary conditions for anesthetic-induced amnesia. In addition to the hands-on research experience of running a trial, achieved through the research aims, this project will advance the applicant into an independent physician scientist in anesthesiology through specific career-development activities. This will be accomplished through a combination of mentoring and evaluation meetings, national scientific/professional meetings, formal didactics, and local seminars/presentations. As part of professional development, coursework in multivariate statistical analysis techniques and cognitive and behavioral neuroscience is planned. The project will be conducted at the University of Pittsburgh, in the School of Medicine, which has outstanding support for clinical and translational research and an established record of developing physician scientists into independent investigators.

项目摘要（abstract）： 尽管常规使用镇静催眠药和镇痛药（麻醉药）来预防或减轻疼痛， 厌恶的条件，这些代理人对行为和形成记忆的神经系统的影响， 对威胁和处理痛苦的认识很少。这个项目将确定记忆调节的影响， 丙泊酚、右美托咪定和芬太尼在周期性疼痛刺激的情况下。它是随机的安慰剂- 在健康成人（40岁以下）中进行的对照、单盲、平行臂fMRI研究。受试者将进行一次记忆 编码任务，同时接受周期性急性疼痛刺激。外显记忆和内隐记忆将被量化， 反应时间和生理反应，包括心率和皮肤电活动。神经成像将 定位大脑活动和连接。与疼痛和焦虑相关的心理测量数据将用于解释 个体间的差异。中心假设是，当在伴随疼痛的过程中形成记忆时， 刺激，三种麻醉剂，具有不同的受体药理学，将有不同的行为和 生理反应模式，由神经系统内的不同活动和神经系统之间的相互作用介导。 负责记忆编码、威胁反应和疼痛处理的系统。有三个科学的 本研究的目标是以病人为导向的职业发展建议。首先是确定行为如何 外显记忆和内隐记忆的生理学测量受到疼痛的调节， 三种麻醉剂正在调查中第二个目的是确定大脑结构的差异， 在疼痛和药物条件下的记忆编码中，使用任务相关的功能性MRI和功能性 连通性分析。第三个目的是确定大脑的变化与主题的心理测量措施 焦虑，压力，睡眠和疼痛通过多变量心理生理相互作用分析。科学 这个项目的框架有一个直接的应用程序，更好地理解记忆形成的影响， 在经历有害刺激时用麻醉剂镇静。此外，进一步扩展这种药理学 调制技术与其他认知神经科学范式的结合可以为 记忆形成的基础研究，失调记忆的起源，以及记忆形成的必要条件。 麻醉引起的失忆除了运行试验的实践研究经验外，还通过 研究目标是，该项目将使申请人晋升为独立的医生科学家， 通过具体的职业发展活动麻醉学。这将通过以下方式实现： 指导和评估会议、国家科学/专业会议、正式教学法和地方 研讨会/介绍会。作为专业发展的一部分，多元统计分析课程 技术以及认知和行为神经科学的研究。该项目将在大学进行 匹兹堡大学医学院，对临床和转化研究有着杰出的支持 以及将医生科学家培养成独立研究者的既定记录。