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: 9404200
• 负责人: Anna Borisova Konova
• 金额: $ 0.18万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9404200
• 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（由申请人提供）：本申请描述了一个为期3年的集中培训计划，该计划将使我，一名具有可卡因成瘾功能性磁共振成像（fMRI）背景的心理学家，能够使用神经经济学的工具启动临床神经科学研究，神经经济学是一个新兴领域，结合神经科学和经济学来了解人们或大脑如何做出决策。在神经经济学（Glimcher博士）和成瘾（Ross博士）专家的监督下，目前的提案旨在测试渴望如何使成瘾者的决定偏向药物使用而远离其他行动。渴望是对特定药物的强烈渴望，并被认为会增加其主观价值（SV）的行为指数。然而，这种影响的潜在机制尚未确定。在做出选择时，代表渴望的神经回路与参与SV计算和比较的神经回路（如纹状体和腹内侧前额叶皮层）的重叠，增加了渴望可能会通过增加与药物SV特别相关的神经活动而使决策偏向药物的可能性。另一种来自对附带情绪的研究的观点表明，渴望也可以通过该回路中的非特异性效应影响决策，例如伴随渴望或渴望本身的情绪状态可能会改变类别独立的SV（与所选药物相关或不相关的SV）。为了测试这些机制中的哪一个在起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，其中渴望和情绪状态预计特别可变，将首先完成重复的测试会话，其中他们将评估他们的渴望和情绪水平，提供唤醒的生理测量，并对旨在建立药物相关SV的任务做出假设决定（例如，不同量的药物，药物用具）和与药物无关的物品（例如，消费品，如活动门票、DVD、配件等和食品）。这种设计将允许测试渴望对SV的影响的特异性[与其他情绪状态相比，并作为评估项目类型的函数（药物相关，药物无关）]。然后，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。在功能磁共振成像期间，受试者将执行一种新的“混合”决策任务，该任务将渴望（捕获）和类似的决策（基于认知任务）试验穿插其中。考虑到渴望将被直接操纵，后一个组件将允许以因果关系的方式测试实时渴望如何影响跟踪两种类型SV的神经信号。如果成功的话，这个建议的结果可能有助于通过将特定的神经计算与特定症状的发生联系起来来促进我们对药物成瘾的理解。研究结果还可能有助于确定新的治疗靶点（药物相关的SV及其神经相关物），这些靶点适用于药理学和行为干预，并为旨在逆转由渴望波动引起的特定决策偏差的治疗开发提供信息。