Multi-method signature of risk for compulsive substance use: Human translation of the incentive-sensitization model

强迫性物质使用风险的多方法签名：激励敏化模型的人工翻译

• 批准号: 10089428
• 负责人: Lora M. Cope
• 金额: $ 16.69万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-15 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10089428
• 关键词: Active Learning; Address; Adolescent; Adult; Alcohol consumption; Animal Behavior; Animal Model; Animals; Basic Science; Behavior assessment; Behavioral; Biological Markers; Brain; Clinical; Corpus striatum structure; Cues; Development; Diagnosis; Dorsal; Drug usage; Educational workshop; Elements; Emotions; Esthesia; Exposure to; Foundations; Frequencies; Functional Magnetic Resonance Imaging; Globus Pallidus; Goals; Health; Human; Impulsivity; Incentives; Individual; Individual Differences; Intervention; Knowledge; Literature; Logistic Regressions; Measures; Mentored Research Scientist Development Award; Mentors; Mentorship; Methods; Michigan; Modeling; Motivation; Neurobiology; Nucleus Accumbens; Outcome; Participant; Pattern; Pharmaceutical Preparations; Phenotype; Play; Positioning Attribute; Property; Psychometrics; Relapse; Research; Research Personnel; Research Training; Rewards; Risk; Role; Selection for Treatments; Signal Transduction; Site; Smell Perception; Statistical Methods; Substance Use Disorder; Techniques; Testing; Time; Training; Translating; Translational Research; Translations; Universities; Work; addiction; aged; alcohol measurement; base; behavior measurement; career; career development; cue reactivity; discounting; human subject; improved; incentive salience; independent component analysis; individual variation; innovation; marijuana use; meetings; neural circuit; neuroimaging; predictive signature; preference; putamen; relating to nervous system; response; statistics; substance use; substance use treatment; substance user; tenure track; theories; trait

PROJECT SUMMARY/ABSTRACT The purpose of this K01 award is to advance the career of the candidate (Dr. Lora Cope) by providing the specialized training she needs in key components of behavioral addiction research, neuroimaging, and statistics. In pursuit of this goal, Dr. Cope will work closely with her carefully selected mentorship team at the University of Michigan, who will provide mentorship in three critical training domains: 1) incentive- sensitization theory of addiction and Pavlovian conditioned approach, 2) neuroimaging study development and implementation, and 3) advanced multivariate statistics. Training will consist of courses, mentor meetings, workshops, scientific meetings, experiential learning, and other activities as described in the Plan for Career Development. Dr. Cope's short-term career goal is to study impulsive choice- and cue reactivity-based individual differences for addiction liability from an incentive-sensitization perspective (see Specific Aims) while receiving the training outlined in this proposal. Her long-term career goal is to hold a tenure-track academic position in the field of addiction neuroimaging, conducting important and clinically meaningful translational research on individual differences for addiction liability. The research proposed in this application will not only facilitate this training, but also advance understanding of compulsive substance use and substance use disorder liability in adolescents transitioning to adulthood. The incentive-sensitization framework developed at the University of Michigan draws a critical distinction between “sign tracking” and “goal tracking” responses. It is an extensively studied and supported animal model of addiction, and the proposed research builds on promising attempts to translate this framework to humans. This work will delineate the multi-method signature of incentive salience attribution in humans by measuring 1) sign- tracking and goal-tracking using a Pavlovian conditioned approach paradigm, 2) neurobiological circuitry involved in impulsive choice and cue reactivity using functional magnetic resonance imaging, 3) trait constructs correlated with substance use, and 4) substance use outcomes. The project will study 92 participants with low to moderate levels of alcohol and/or marijuana use, aged 16–18 at the time of baseline assessment. Participants will be followed over 2.5 years for detailed substance use and behavioral assessment. This work will address the following research aims: 1) Delineate the neural signature of incentive salience attribution, and 2) Identify longitudinal multi-method predictors of substance use outcomes. The long- term objective of this work is to use detailed understanding of the brain mechanisms of incentive salience to construct objective biomarkers to guide diagnosis and treatment of substance use disorders, with the ultimate goals of limiting transition to compulsive use, reducing relapse, and improving human health.

项目摘要/摘要 该K01奖的目的是通过提供候选人（Lora Cope博士）的职业。 她在行为成瘾研究，神经影像学和 统计数据。为了实现这一目标，Cope博士将与她精心挑选的指导团队紧密合作 密歇根大学将在三个关键培训领域提供心态：1）激励 - 成瘾和帕夫洛维亚条件方法的敏化理论，2）神经影像学研究 开发和实施，以及3）高级多元统计。培训将包括课程， Menor会议，讲习班，科学会议，专家学习和其他活动 计划发展计划。科普博士的短期职业目标是研究冲动选择和提示 从激励敏感的角度来看，基于反应性的成瘾责任的个体差异（请参阅 具体目标）在接受本提案中概述的培训时。她的长期职业目标是举行 在成瘾神经影像领域的统治轨道学位，进行重要和临床 关于成瘾责任个体差异的有意义的翻译研究。 本应用程序中提出的研究不仅将支持此培训，而且还会提高对 在过渡到成年的青少年中，强迫药物使用和物质使用障碍责任。这 密歇根大学开发的激励敏感框架在 “标志跟踪”和“目标跟踪”响应。这是一种广泛研究和支持的动物模型 成瘾和拟议的研究基于承诺将该框架转化为人类的诺言。 工作将通过测量来描述人类激励显着性属性的多方法签名1）签名 - 使用Pavlovian条件方法范式进行跟踪和目标跟踪，2）神经生物学回路 使用功能磁共振成像参与冲动选择和提示反应性，3）特质构建体 与药物使用相关，4）物质使用结果。该项目将研究92名参与者 在基线评估时，适度的酒精和/或大麻使用，年龄在16-18岁。 参与者将在2。5年以上，以详细使用药物使用和行为评估。这项工作 将解决以下研究的目的：1）描述激励显着性的神经标志 归因和2）确定物质使用结果的纵向多方法预测指标。长期 这项工作的术语目标是利用对激励显着性的大脑机制的详细理解 构建客观生物标志物来指导诊断和治疗物质使用障碍，并具有最终 限制过渡到强迫使用，减少继电器和改善人类健康的目标。