Learning to avoid pain: Computational mechanisms and application to methamphetami

学习避免疼痛：计算机制及其在甲基苯丙胺中的应用

基本信息

批准号：
7922059
负责人：
TOR D. WAGER
金额：
$ 34.68万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7922059
关键词：
Absence of pain sensation Abstinence Accounting Acute Address Affect Affective Amygdaloid structure Analgesics Anhedonia Animal Experimentation Animal Model Animals Anterior Area Association Learning Aversive Stimulus Avoidance Learning Base of the Brain Behavior Behavior Therapy Behavioral Bilateral Brain Brain Stem Brain region Choice Behavior Clinical Clinical Research Cognitive Comparative Study Computer Simulation Computing Methodologies Corpus striatum structure Cues Data Dependence Development Dopamine Drug Addiction Drug abuse Drug usage Drug user Event Expectancy Frequencies Fright Functional Magnetic Resonance Imaging Goals Health Care Costs Hippocampus (Brain)Human Image Imaging Techniques Individual Insula of Reil Interdisciplinary Study Intervention Lead Learning Life Link Literature Magnetic Resonance Imaging Measures Medial Mediating Memory Methamphetamine Methods Modeling Motivation Multivariate Analysis Neurobiology Neurosecretory Systems Opiates Opioid Opioid Receptor Outcome Pain Participant Pathology Pattern Performance Pharmaceutical Preparations Pharmacology Phase Physics Placebo Effect Placebos Population Population Study Preclinical Drug Evaluation Prefrontal Cortex Prevention Probability Process Property Psychological reinforcement Public Health Punishment Relapse Research Research Personnel Rewards Safety Scanning Signal Transduction Specificity Staging Stimulus Stress System Temporal Lobe Testing Time Urine Ventral Striatum Visual Work addiction avoidance behavior base behavior measurement brain behavior cognitive neuroscience computational neuroscience cost design drug abuser drug of abuse endogenous opioids expectation experience follow-up frontier hedonic insight long term memory methamphetamine abuse multiple drug use neural patterning neurobiological mechanism novel physical process prevent psychologic public health relevance relating to nervous system research study social theories treatment program

项目摘要

DESCRIPTION (provided by applicant): The persistent use of drugs in spite of costs in multiple areas of life is central to most definitions of drug dependence. A critical question is why individuals continue to choose to use drugs, rather than avoid them, despite increasing costs. Neurobiological research has begun to answer this question by investigating how drugs of abuse impact brain systems that underlie affect, motivation, and learning. Several major theories focus on sensitization in appetitive brain 'reward' systems. A growing body of evidence suggests that anhedonia and aversive learning are also critical, but relatively little work addresses how changes in human aversive learning systems are linked to drug abuse. Such work is critically needed to provide deeper and more specific links between animal and human research, and to link basic neurobiological mechanisms with human drug-taking behavior. That is the goal of this proposal. We combine a computational reinforcement learning approach, which has successfully characterized appetitive learning systems, with an experimental thermal pain model that has successfully characterized brain systems involved in generating and modulating pain and aversive expectancies. This novel combination of two successful research traditions is a powerful approach that can provide new measures of avoidance learning in healthy individuals and drug abusers and links with animal models of addiction. In Aim 1, we develop a normative model of human brain systems involved in learning to predict pain, their dynamics over time, and their relationship to avoidance behavior. Three experiments use functional magnetic resonance imaging (fMRI) to characterize brain systems involved in representing pain and avoidance learning. We focus on interactions between pain-processing and learning networks, multiple memory systems that may support complementary aspects of learning, and the effects of expectation on these processes. In Aim 2, we extend this work to characterize methamphetamine (MA) abusers, a growing but under-studied population that presents an increasing public safety and public health challenge. We will conduct a comparative study of MA abusers and controls to a) characterize differences in pain representation and avoidance learning systems; and b) use brain systems-based measures to prospectively predict patterns of drug use during a two-month follow up. Successful completion of these aims will help researchers to leverage theories and findings from animal models of addiction by linking them to human drug-use behavior. It will also provide new measures of aversive experience and aversive learning in both brain and behavior, which will provide important insights into the neurobiological causes of persistent drug abuse. Such findings can a) inform behavioral, cognitive, and pharmacological drug-abuse treatment programs; b) suggest new ways of preventing drug use from reaching the stage of clinical dependence, and c) identify sub-types of individuals that can help prevention and treatment programs be tailored more specifically to individuals. PUBLIC HEALTH RELEVANCE: Neurobiological studies of reward- and punishment-guided learning in the brain offer powerful explanations for why drug-dependent individuals continue to choose drugs in spite of substantial costs in many areas of life. Neurobiological accounts have provided theories that lead to the development of new behavioral, cognitive, and pharmacological interventions to help break the cycle of drug abuse. An important frontier in this effort is the study of how aversive brain processes and experience (physical or psychological pain) motivate continued drug use. We propose some of the first work to look at how pain-avoidance learning works at a mechanistic, computational level in the human brain, and how changes in these systems are linked to methamphetamine use patterns in abusers. Findings from these studies will inform the development of new models of drug abuse and new treatments for users, which will help to reduce the personal health costs to abusers and the public health burden.

描述（由申请人提供）：尽管在生命的多个领域中有成本，但仍持续使用药物，这对于大多数药物依赖的定义至关重要。一个关键的问题是，尽管成本增加了，为什么个人继续选择使用药物而不是避免使用药物。神经生物学研究已开始通过研究滥用药物如何影响影响，动机和学习的大脑系统来回答这个问题。几种主要理论着重于食用大脑“奖励”系统中的敏感性。越来越多的证据表明，阿尼多尼亚和厌恶学习也是至关重要的，但是相对较少的工作解决了人类厌恶学习系统的变化如何与滥用药物有关。需要至关重要的工作，以提供动物与人类研究之间的更深层次，更具体的联系，并将基本的神经生物学机制与人类吸毒行为联系起来。这就是该提议的目标。我们结合了一种计算增强学习方法，该方法已成功地表征了食欲的学习系统，并通过实验性热疼痛模型成功地表征了涉及产生和调节疼痛和厌恶期望的大脑系统。这两种成功的研究传统的这种新颖组合是一种强大的方法，可以为健康的个体和吸毒者提供新的回避学习措施，并与成瘾动物模型联系在一起。在AIM 1中，我们开发了一个人类脑系统的规范模型，涉及学习以预测痛苦，随着时间的流逝和避免行为的关系。三个实验使用功能磁共振成像（fMRI）来表征与表示疼痛和回避学习有关的脑系统。我们专注于痛苦处理和学习网络之间的相互作用，可能支持学习互补方面的多个内存系统以及期望对这些过程的影响。在AIM 2中，我们将这项工作扩展到甲基苯丙胺（MA）滥用者的特征，这是一个日益增长但研究不足的人口，呈现出越来越多的公共安全和公共卫生挑战。我们将对虐待者和对照组进行比较研究，以表征疼痛表示和回避学习系统的差异； b）使用基于大脑系统的措施预测在两个月的随访中预测药物使用模式。这些目标的成功完成将有助于研究人员通过将其与人类的药物使用行为联系起来来利用动物成瘾模型的理论和发现。它还将提供大脑和行为中厌恶经验和厌恶学习的新措施，这将为持续的药物滥用的神经生物学原因提供重要的见解。此类发现可以a）为行为，认知和药理药物滥用治疗计划提供信息； b）建议防止药物使用临床依赖阶段的新方法，c）确定可以更专门针对个人定制的可以帮助预防和治疗计划的个体的子类型。公共卫生相关性：大脑中奖励和惩罚引导学习的神经生物学研究提供了有力的解释，说明为什么依赖药物的人在许多生活领域都有大量成本，但仍选择毒品。神经生物学说明提供了导致新行为，认知和药理学干预措施的发展，以帮助破坏药物滥用的周期。这项工作的一个重要领域是研究厌恶大脑过程和经验（身体或心理疼痛）如何促进持续使用药物。我们提出了一些第一批工作，以研究避免疼痛的学习如何在人脑中的机理，计算水平上起作用，以及这些系统中的变化如何与滥用者中的甲基苯丙胺使用模式相关联。这些研究的发现将为用户的新型药物滥用模式和新的治疗方法的发展提供信息，这将有助于减少施虐者和公共健康负担的个人健康费用。