Anesthestic modulation of human memory during acute pain

急性疼痛期间人类记忆的麻醉调节

基本信息

批准号：
10017055
负责人：
Keith Michael Vogt
金额：
$ 18.95万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
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/10017055
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 Functional Magnetic Resonance Imaging General Anesthesia Goals Heart Rate Hippocampus (Brain)Human Image Incidence Individual Individual Differences Insula of Reil Investigation Lead Magnetic Resonance Imaging Measurable Measurement Measures Mediating Memory Mentors Methodology Methods Motivation Neuroanatomy Neurosciences Opioid 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 conditioned fear 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 statistical learning

项目摘要

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.

项目概要（摘要）：尽管常规使用镇静催眠剂和镇痛剂（麻醉剂）来预防或减轻手术期间的痛苦厌恶条件，这些因素对行为和形成记忆的神经系统的影响，反应人们对威胁和过程痛苦知之甚少。该项目将确定以下物质的记忆调节作用：异丙酚、右美托咪定和芬太尼用于周期性疼痛刺激。它是一种随机安慰剂对健康成年人（40 岁以下）进行的对照、单盲、平行臂功能磁共振成像研究。受试者将进行记忆在接受周期性急性疼痛刺激的同时编码任务。显性和隐性记忆将使用以下方法进行量化反应时间和生理反应，包括心率和皮肤电活动。神经影像学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对于个体之间的差异。中心假设是，在伴随痛苦的过程中形成记忆时三种麻醉剂在刺激下，具有不同的受体药理作用，会产生不同的行为和反应。生理反应模式，由神经元内部的不同活动和神经元之间的相互作用介导负责记忆编码、威胁响应和疼痛处理的系统。科学的有三点这项以患者为导向的职业发展提案的研究目标。首先是确定行为方式外显记忆和内隐记忆的生理测量受到疼痛和个体影响的调节正在研究三种麻醉剂。第二个目标是确定差异参与的大脑结构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。第三个目标是确定与受试者心理测量相关的大脑变化通过多变量心理生理学相互作用分析来了解焦虑、压力、睡眠和疼痛。科学的该项目的框架可直接应用于更好地理解期间形成的记忆的影响经历有害刺激时使用麻醉剂镇静。此外，进一步扩展该药理学其他认知神经科学范式的调制技术可以提供一个多学科框架记忆形成、失调记忆的起源以及记忆形成的必要条件的基础研究麻醉引起的失忆症。除了进行试验的实践研究经验外，还通过研究目标是，该项目将使申请人成为一名独立的医师科学家通过特定的职业发展活动进行麻醉学。这将通过组合来完成指导和评估会议、国家科学/专业会议、正式教学和地方会议研讨会/演讲。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已计划进行。该项目将在大学进行匹兹堡医学院，为临床和转化研究提供出色的支持以及将医师科学家培养成独立研究者的既定记录。