The Neuroeconomics of Behavioral Therapies for Adolescent Substance Abuse

描述（由申请人提供）：青少年神经发育在青少年药物滥用治疗结果中的作用知之甚少。青少年药物滥用治疗的发展和评估很少包括考虑不同的认知能力及其神经表征作为治疗反应个体差异的决定因素。本R21项目将通过确定参与两项正在进行的青少年药物滥用随机临床试验的青少年的决策、任务相关神经处理和治疗结果之间的联系来解决这一差距。增加我们对青少年大麻和酒精使用者决策背后的神经过程的理解，将为未来干预和预防工作的发展提供信息。这个补充项目将从两项正在进行的调查基于应急管理（CM）治疗的研究——“青少年大麻滥用的行为治疗”（DA015186）和“青少年酒精滥用的基于家庭的应急管理”（AA016917）——中抽取研究对象。两项试验都比较了一种独特的CM干预，包括基于戒断的强化计划和一种标准的、最先进的认知行为干预。分析将分别对两个样本进行，首先使用大麻样本测试假设，然后使用酒精样本评估复制/特异性。拟议的项目将探索对CM干预反应的新的神经生物学预测因子。在R21项目期间，大麻试验（n=69，每个治疗组23人）和酒精试验（n=54，每个治疗组27人）招募的青少年将参加神经成像会议。在神经成像过程中，青少年会在延迟折扣任务中做出跨期选择决策。大麻试验的初步数据表明，在行为延迟折扣任务上的表现与治疗期间取得的戒断之间存在显著的关联，这超出了治疗条件的显著影响。我们试图了解在这项实验室任务中表现的神经过程，以及这些神经过程的变化与青少年药物滥用治疗结果的关系和预测的程度。拟议项目的概念框架是一个竞争性神经系统模型，该模型假设在理解物质依赖个体的次优决策模式时，“冲动”（或“反射”）神经系统和“执行”（或“反射”）神经系统之间存在偏见竞争。一个重要的假设是，对不同治疗方法（CM vs. CBT）的不同反应取决于这些相互竞争的神经系统内部和之间的激活模式或功能连接。具体来说，我们将确定在实验室延迟贴现任务中的表现与冲动和/或执行神经系统的活动相关的程度。我们还将确定在实验室延迟贴现任务和神经处理上的表现预测青少年药物滥用治疗结果的程度，而不是治疗条件的影响。最后，我们将探讨对CM的反应与延迟折扣相关的神经处理之间的相互作用。这个神经影像项目将为这个新成立的跨学科团队未来项目的发展提供一个跳板。在对照临床试验的背景下进行拟议的影像学研究有可能指导开发/改进针对个体的更有效的治疗方法，并且可能对预防研究和干预也有很强的意义。我们对最常见的门诊干预措施之一（即MET/CBT）和最有希望改善MET/CBT结果的干预措施之一（即CM）的反应的神经预测因子的研究，增强了这一具体建议的重要性。最后，对奖励的时间折扣的关注代表了对驱动成瘾过程的主要理论结构的重要测试。决策和激励评估是未来治疗干预的新目标。

DESCRIPTION (provided by applicant): Little is known about the role of adolescent neurodevelopment in adolescent substance abuse treatment outcomes. The development and evaluation of adolescent substance abuse treatments rarely includes consideration of varying cognitive capacities and their neural representations as determinants of individual variation in treatment response. This proposed R21 project would address this gap by identifying associations among decision making, task-related neural processing, and treatment outcome among adolescents participating in two ongoing randomized clinical trials for adolescent substance abuse. Increasing our understanding of neural processes that underlie decision making in adolescent marijuana and alcohol users would inform the development of future intervention and prevention efforts. This complementary project would draw subjects from two ongoing studies investigating contingency- management (CM) based treatments "Behavioral Treatment of Adolescent Marijuana Abuse" (DA015186), and "Family Based Contingency Management for Adolescent Alcohol Abuse" (AA016917). Both trials compare a unique CM intervention that involves an abstinence-based reinforcement program to a standard, state of the art cognitive behavioral intervention. Analyses would be performed separately for the two samples, with hypotheses tested first using the Marijuana sample, and assessed for replication/specificity using the Alcohol sample. The proposed project would explore novel neurobiological predictors of response to CM interventions. Adolescents recruited into the Marijuana Trial (n=69; 23 per treatment arm) and the Alcohol Trial (n=54; 27 per treatment arm) during the period of this R21 project would participate in a neuroimaging session. During the neuroimaging session, adolescents would make intertemporal choice decisions in a Delay Discounting task. Preliminary data from the Marijuana trial demonstrates significant association between performance on this behavioral delay discounting task and abstinence achieved during treatment over and above the significant effect of treatment condition. We seek to understand the neural processes that underlie performance on this laboratory task, and the degree to which variation in these neural processes relate to and predict adolescent substance abuse treatment outcomes. The conceptual framework for the proposed project is a competing neural systems model which hypothesizes a biased competition between an "impulsive" (or ''reflexive") neural system and the "executive" (or "reflective") neural system in understanding patterns of suboptimal decision making among substance-dependent individuals. An overarching hypothesis is that differing responses to distinct treatment approaches (CM vs. CBT) depend on the pattern of activation or functional connectivity within and across these competing neural systems. Specifically, we will determine the degree to which performance on a laboratory delay discounting task correlates with activity in impulsive and/or executive neural systems. We will also determine the degree to which performance on a laboratory delay discounting task and neural processing predict adolescent substance abuse treatment outcome over and above the effects of treatment condition. Finally, we will explore interactions between response to CM and delay discounting-related neural processing. This neuroimaging project will provide a springboard for the development of future projects with this newly formed interdisciplinary team. Conducting the proposed imaging study in the context of a controlled clinical trial has potential to guide the development/refinement of more efficacious treatments tailored to the individual, and may have strong implications for prevention research and intervention as well. The significance of this specific proposal is enhanced by our proposed investigation of neural predictors of response to one of the most common outpatient interventions (i.e., MET/CBT) and one of the most promising interventions for improving outcomes of MET/CBT (i.e., CM). Last, the focus on temporal discounting of rewards represents a significant test of a major theoretical construct thought to drive the addiction process. Decision making and incentive valuation represent novel targets of future treatment interventions. PUBLIC HEALTH RELEVANCE: This study will measure the brain activity of adolescent substance abusers while they make decisions about their preferences to receive smaller, immediate rewards vs. larger delayed rewards. We expect that patterns of brain activity while engaged in this decision making task will predict response to treatment among adolescent substance users. We expect to use the results of this study to develop more effective treatments for adolescent substance abuse.