Neuroeconomic investigation of craving in opioid addiction

阿片类药物成瘾渴望的神经经济学研究

• 批准号: 9323365
• 负责人: Anna Borisova Konova
• 金额: $ 5.71万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9323365
• 关键词: Alcohols; Arousal; Behavior; Behavior Therapy; Behavioral; Biological; Brain; Brain region; Categories; Clinical; Cocaine Dependence; Cognitive; Corpus striatum structure; Crossover Design; DSM-V; Decision Making; Development; Disease; Dopamine; Drug Addiction; Drug Metabolic Detoxication; Drug usage; Economics; Emotional; Emotions; Event; Fellowship; Food; Functional Magnetic Resonance Imaging; Future; Gambling; Human; Hybrids; Individual; Intervention; Investigation; Link; Maintenance; Measurement; Measures; Methods; Modeling; Monitor; Moods; Neurobiology; Neurosciences; Neurosciences Research; Nicotine; Obesity; Opiate Addiction; Opioid; Organism; Patient Self-Report; Persons; Pharmaceutical Preparations; Pharmacology; Physiological; Play; Prefrontal Cortex; Process; Psychologist; Randomized; Reporting; Research; STEM research; Signal Transduction; Smoker; Specificity; Stimulus; Stress; Supervision; Symptoms; System; Testing; Time; Training; Treatment outcome; Work; addiction; base; behavior influence; cognitive task; contingency management; craving; design; experience; experimental study; improved; indexing; neural circuit; neural correlate; neuroeconomics; neurofeedback; neurotransmission; new therapeutic target; novel; opioid use disorder; programs; public health relevance; relating to nervous system; therapeutic target; therapy development; tool; treatment strategy

 DESCRIPTION (provided by applicant): This application describes a focused 3-year training plan that will enable me, a psychologist with background in functional magnetic resonance imaging (fMRI) of cocaine addiction, to initiate clinical neuroscience research employing tools from neuroeconomics, an emerging field that combines neuroscience and economics to understand how people or the brain make decisions. Supervised by neuroeconomics (Dr. Glimcher) and addiction (Dr. Ross) experts, the current proposal aims to test how craving might bias addicted individuals' decisions toward drug use and away from other courses of action. Craving is the intense desire for a specific drug and is thought to increase behavioral indices of its subjective value (SV). The underlying mechanism of this influence, however, has not been determined. The overlap in the neural circuits that represent craving and those involved in the computation and comparison of SVs when making a choice, such as the striatum and ventromedial prefrontal cortex, raises the possibility that craving might bias decisions towards the drug by increasing neural activity in this circuit specifically associated with the drug's SV. n alternative view stemming from research on incidental emotions suggests that craving could also influence decisions by nonspecific effects in this circuit, such that mood states that accompany craving or perhaps craving itself, might modify category- independent SVs (those related as well as unrelated to the drug of choice). To test which of these mechanisms is at play and its underlying neurobiological basis, opioid users undergoing a detoxification program, in whom craving and mood states are expected to be particularly variable, will first complete repeated testing sessions where they will rate their level of craving and mood, provide physiological measures of arousal, and make hypothetical decisions on tasks designed to establish the SV of drug-related (e.g., different amounts of the drug, drug paraphernalia) and drug-unrelated items (e.g., consumer goods such as event tickets, DVDs, accessories, etc. and food). This design will allow for testing the specificity of craving's influence on SVs [as compare with other mood states and as a function of the types of items being evaluated (drug-related, drug-unrelated)]. Detoxified subjects will then complete fMRI following experimentally induced craving or a neutral condition in a randomized, crossover design. During fMRI, subjects will perform a novel "hybrid" decision making task that intersperses craving (symptom-capture) and similar decision (cognitive-task-based) trials. Given that craving will be manipulated directly, ths latter component will allow for testing, in a causal manner, how real-time craving influences neural signals that track the two types of SVs. If successful, results of this proposal may help advance our understanding of drug addiction by linking a specific neural computation to the occurrence of a specific symptom. Results may also help identify new therapeutic targets (drug-related SVs and their neural correlates) amenable to pharmacological and behavioral interventions and inform treatment development aimed at reversing the specific decision biases caused by fluctuations in craving.

 描述(申请人提供)：此申请描述了一个有重点的三年培训计划，将使我，一个在可卡因成瘾的功能磁共振成像(FMRI)方面有背景的心理学家，利用神经经济学的工具启动临床神经科学研究，神经经济学是一个结合神经科学和经济学来理解人或大脑如何做出决定的新兴领域。在神经经济学(Glimcher博士)和成瘾(Ross博士)专家的监督下，当前的提案旨在测试渴望可能如何使成瘾个人的决定倾向于药物使用，而不是其他行动方案。渴求是对特定药物的强烈渴望，被认为可以增加其主观价值(SV)的行为指数。然而，这种影响的潜在机制尚未确定。代表渴望的神经回路与做出选择时参与计算和比较SVS的神经回路(如纹状体和前额叶腹内侧皮质)的重叠，增加了这样一种可能性，即渴望可能会通过增加该回路中与药物SV特定相关的神经活动而使决定倾向于药物。来自对偶发情绪的研究的另一种观点表明，渴望也可以通过这个回路中的非特定效应来影响决策，比如伴随着渴望或也许是渴望本身的情绪状态，可能会修改类别无关的SVS(那些与所选药物相关或无关的)。为了测试这些机制中的哪一种正在发挥作用及其潜在的神经生物学基础，正在接受戒毒计划的阿片类药物使用者将首先完成重复的测试过程，在该过程中，他们将对他们的渴望和情绪水平进行评级，提供唤醒的生理测量，并对旨在建立与药物相关的任务(例如，不同数量的药物、药物用具)和与药物无关的物品(例如，诸如活动门票、DVD、配件等和食物的消费品)的SV做出假设决定。这一设计将允许测试渴望对SVS影响的特异性[与其他情绪状态相比，以及作为被评估项目类型(与药物相关的、与药物无关的)的函数]。然后，戒毒的受试者将在随机交叉设计中，在实验诱导的渴望或中性条件下完成fMRI。在功能磁共振成像中，受试者将执行一项新颖的“混合”决策任务，其中穿插着渴望(症状捕获)和类似的决策(基于认知任务)试验。考虑到渴望将被直接操纵，后一部分将允许以因果方式测试实时渴望如何影响跟踪这两种类型的SVS的神经信号。如果成功，这项提议的结果可能会通过将特定的神经计算与特定症状的发生联系起来，帮助我们加深对药物成瘾的理解。结果还可能有助于确定新的治疗靶点(药物相关的SVS及其神经关联)，适合于药物和行为干预，并为旨在扭转欲望波动引起的特定决策偏差的治疗开发提供信息。