Decision Neuroscience of Craving

渴望的决策神经科学

• 批准号: 10473874
• 负责人: Anna Borisova Konova
• 金额: $ 57.99万
• 依托单位: RUTGERS BIOMEDICAL/HEALTH SCIENCES-RBHS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10473874
• 关键词: Address; Algorithms; Amygdaloid structure; Architecture; Area; Behavior; Behavioral; Biological; Biometry; Brain; Clinical; Corpus striatum structure; Crossover Design; Cues; Decision Making; Dorsal; Drug Regulations; Drug usage; Economics; Emotions; Evidence based treatment; Food; Functional Magnetic Resonance Imaging; Gold; Health; Human; Image; Individual; Insula of Reil; Knowledge; Link; Mathematics; Measures; Mental disorders; Methods; Modality; Modeling; Neurobiology; Neurosciences; Opioid; Outcome; Participant; Patient-Focused Outcomes; Patients; Pattern; Persons; Pharmaceutical Preparations; Precipitating Factors; Prefrontal Cortex; Procedures; Process; Psychology; Public Health; Relapse; Research; Rewards; Role; Symptoms; Testing; Time; Work; addiction; base; behavior change; behavioral study; cognitive control; craving; design; drug craving; experience; food craving; human imaging; imaging study; implementation intervention; improved; improved outcome; indexing; neural circuit; neural correlate; neuroeconomics; neurofeedback; non-drug; novel; opioid epidemic; opioid use disorder; personalized intervention; pre-clinical; prevent; relating to nervous system; societal costs; standard care

Project Summary/Abstract The current opioid epidemic is a pressing public health crisis. A key precipitating factor of reuse and relapse among people with opioid use disorders (OUD) is craving, or the intense, specific desire for the drug. While craving has been extensively studied, and is known to predict drug use, we still lack an explanatory and algorithmically-precise model that can directly link craving neurobiology to its observed consequences: the decision to pursue drugs over other valuable alternatives. Given that typical treatments for OUD do not adequately address craving and fail to prevent reuse in many patients, clarifying the precise, decision-relevant, mechanism of craving may critically inform more targeted ways to treat craving and improve clinical outcome. To address these important questions, we developed an experimental paradigm to study craving based on methods widely used in decision neuroscience to assess value-based decision-making. Decision neuroscience (or neuroeconomics) integrates concepts and methods from psychology, economics, and neuroscience to understand the neural architecture for decision-making, and has been increasingly applied in mechanistic studies of psychiatric disorders including addiction. Our paradigm constitutes a novel application of this framework by quantifying a subject’s in-the-moment (i.e., state-dependent) decision process during craving15. In pilot behavioral studies in healthy and opioid addicted subjects, we find that this paradigm captures 1) how value—the key determinant of the decision to pursue a particular option versus another—changes under craving, and 2) the selectivity of this effect to the object of craving. It also 3) provides an algorithmically-specific process (a mathematical description) of this change that can be used to tie behavior to its neural substrate. In the present study we aim to elucidate this neural substrate by identifying the specific neural computations through which craving modulates the value of drug and nondrug alternatives and thereby drug use decisions in human OUD. We propose to identify the neural substrate of opioid craving in N=89 OUD patients who will complete our paradigm during fMRI in a within-subjects cross-over design following a brief craving induction or a control manipulation16. Because decision circuits encode value in a reward-identity specific manner, our design will enable us to isolate the computations associated with drug-related value from those of nondrug value. Our study will for the first time determine whether and how experimentally-induced craving dynamically shifts such “identity-specific” neural encoding of drug-related value (Aim 1), and the parts of a putative ‘craving circuit’ involved in this shift (Aim 2). To test whether this mechanism is unique and reward-identity specific, we will also measure brain activity associated with experimentally-induced food craving and specific food-value in the same patients and N=89 healthy controls (Aim 3). If successful, this integrative approach will uncover precise targets for selectively mitigating craving-induced increases in drug-value that promote opioid reuse, laying the groundwork for precision interventions to treat craving in treatment unresponsive individuals.

项目概要/摘要 当前的阿片类药物流行是一场紧迫的公共卫生危机。重用和复发的关键促成因素 患有阿片类药物使用障碍 (OUD) 的人对这种药物的渴望或强烈的、特定的渴望。尽管 渴望已被广泛研究，并且已知可以预测药物使用，但我们仍然缺乏解释和解释 算法精确的模型可以直接将渴望神经生物学与其观察到的后果联系起来： 决定寻求药物而不是其他有价值的替代品。鉴于 OUD 的典型治疗方法并不 充分解决了许多患者的渴望，但未能防止重复使用，澄清了精确的、与决策相关的、 渴望的机制可能会为治疗渴望和改善临床结果的更有针对性的方法提供重要信息。 为了解决这些重要问题，我们开发了一个实验范式来研究基于的渴望 决策神经科学中广泛使用的方法来评估基于价值的决策。决策神经科学 （或神经经济学）整合了心理学、经济学和神经科学的概念和方法 了解决策的神经架构，并已越来越多地应用于机械 对包括成瘾在内的精神疾病的研究。我们的范例构成了这种方法的新颖应用 通过量化受试者在渴望期间的即时（即依赖于状态的）决策过程来构建框架15。 在健康和阿片类药物成瘾受试者的试点行为研究中，我们发现这种范式捕获了 1）如何 价值——决定选择某种特定选择而不是另一种选择的关键决定因素——变化 贪爱，以及 2）此效应对贪爱对象的选择性。它还 3) 提供了特定于算法的 这种变化的过程（数学描述）可用于将行为与其神经基础联系起来。在 本研究的目的是通过识别特定的神经计算来阐明这种神经基质 通过这种渴望调节药物和非药物替代品的价值，从而调节药物使用决策 人类 OUD。我们建议确定 N=89 名 OUD 患者对阿片类药物渴求的神经基质，这些患者将 在短暂的渴望诱导后，在功能磁共振成像期间以受试者内交叉设计完成我们的范式或 控制操作 16.因为决策电路以奖励身份特定的方式编码价值，我们的 设计将使我们能够将与药物相关价值相关的计算与非药物相关价值的计算分开 价值。我们的研究将首次确定实验是否以及如何动态地诱发渴望 改变药物相关价值的这种“特定于身份”的神经编码（目标 1），以及假定的“渴望”的部分 电路”参与了这一转变（目标 2）。为了测试这种机制是否独特且特定于奖励身份，我们 还将测量与实验诱发的食物渴望相关的大脑活动以及特定食物价值 相同的患者和 N=89 名健康对照（目标 3）。如果成功的话，这种综合方法将揭示 选择性减轻因渴望而导致的药物价值增加的精确目标，从而促进阿片类药物的再利用， 为精准干预奠定基础，以治疗治疗无反应个体的渴望。