Decision Neuroscience of Craving

项目摘要/摘要 目前的阿片类药物流行是一个紧迫的公共卫生危机。重复使用和复发的关键诱因 在有阿片类药物使用障碍的人中，(OUD)是对药物的渴望或强烈的特定欲望。而当 渴求已经被广泛研究，并被认为可以预测药物使用，但我们仍然缺乏解释性和 算法上精确的模型，可以直接将渴望神经生物学与其观察到的后果联系起来： 决定追求药物而不是其他有价值的替代品。考虑到对OUD的典型治疗不是 充分解决渴望并未能防止许多患者重复使用，澄清了准确的、与决策相关的 渴求的机制可能为治疗渴求提供更有针对性的方法，并改善临床结果。 为了解决这些重要的问题，我们开发了一种实验范式来研究渴望，基于 在决策神经科学中广泛使用的评估基于价值的决策的方法。决策神经科学 (或神经经济学)融合了心理学、经济学和神经科学的概念和方法，以 了解用于决策的神经结构，并已越来越多地应用于机械学 对包括成瘾在内的精神障碍的研究。我们的范例构成了这一点的新应用 通过量化受试者在渴望过程中的瞬间(即，依赖于状态的)决策过程来构建框架15。 在健康和阿片成瘾受试者的先导性行为研究中，我们发现这一范式捕捉到了1 价值-决定选择一个特定选项还是另一个选项的关键决定因素-在以下情况下发生变化 渴望，以及2)这种效应对渴望的对象的选择性。它还提供了特定于算法的 这种变化的过程(一种数学描述)，可以用来将行为与其神经底物联系起来。在……里面 本研究旨在通过识别特定的神经计算来阐明这种神经底物 通过这种渴望调节药物和非药物替代品的价值，从而在 人类的声音。我们建议在N=89名患者中确定阿片类药物渴望的神经底物 在短暂的渴望诱导或渴望之后，在受试者内交叉设计的fMRI期间完成我们的范例 一种控制操作。因为决策电路以特定于奖励身份的方式编码价值，所以我们的 设计将使我们能够将与毒品相关的价值的计算与非药物相关的计算分开 价值。我们的研究将首次确定实验是否以及如何动态地诱导渴望 改变药物相关价值的“特定身份”神经编码(目标1)，以及推定的“渴望”的部分 参与这一转移的电路(目标2)。为了测试这一机制是否是唯一的和特定于奖励身份的，我们 还将测量与实验诱导的食物渴望和特定食物价值相关的大脑活动 相同的患者和N=89名健康对照(目标3)。如果成功，这种综合方法将揭示 有选择地减轻渴望引起的促进阿片类药物重复使用的药物价值增加的准确目标， 为精准干预治疗对治疗无反应的个体的渴求奠定基础。

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.