Decision Neuroscience of Craving

渴望的决策神经科学

基本信息

批准号：
10655500
负责人：
Anna Borisova Konova
金额：
$ 57.99万
依托单位：
RUTGERS BIOMEDICAL AND HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10655500
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 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 Qualifying Relapse Research Rewards Role Symptoms Testing Time Work addiction behavior change behavioral study cognitive control craving design drug craving experience food craving human imaging imaging study implementation intervention improved improved outcome indexing neural neural circuit neural correlate neuroeconomics neurofeedback non-drug novel opioid epidemic opioid use disorder personalized intervention pre-clinical prevent societal costs standard care

项目摘要

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.

项目摘要/摘要当前的阿片类药物流行是一种紧迫的公共卫生危机。重用和退休的关键降水因素在患有阿片类药物使用障碍（OUD）的人中，是对药物的渴望，也是对药物的强烈渴望。尽管渴望已经广泛研究，众所周知可以预测吸毒，我们仍然缺乏爆炸性和可以将渴望神经生物学直接联系到其观察到的后果的算法模型：决定对其他有价值的替代品寻求毒品。鉴于Oud的典型治疗方法不适当地解决渴望，无法防止许多患者重复使用，从而确定了与决策相关的精确度，渴望的机制可能会批判性地为治疗渴望和改善临床结果的更有针对性的方法提供信息。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在决策神经科学中广泛使用的方法评估基于价值的决策。决定神经科学（或神经经济学）将心理学，经济学和神经科学中的概念和方法整合到了解决策的神经结构，并越来越多地应用于机械精神疾病在内的研究包括成瘾。我们的范式构成了这种新颖的应用通过量化受试者在渴望15期间的主题（即国家依赖）决策过程的框架。在健康和阿片类上瘾的受试者中的试点行为研究中，我们发现该范式捕获了1）价值 - 决定采取特定选项与另一种选择的决定的关键决定者，这改变了渴望和2）这种影响对渴望的对象的选择性。它也3）提供了特定于算法的该变化的过程（数学描述）可用于将行为与其神经底物联系起来。本研究我们旨在通过识别特定的神经元计算来阐明该神经元底物渴望通过它调节药物和非药物替代品的价值，从而在人乌德。我们建议在n = 89名OUD患者中确定阿片类药物渴望的神经底物在短暂渴望感应后，在fMRI期间完成我们的受试者内部设计范式或控制操作16。因为决策电路以奖励认同的方式编码价值，所以我们设计将使我们能够隔离与nondrug的计算相关值的计算价值。我们的研究将首次确定是否以及如何动态地诱导渴望转移与药物相关价值的“特定身份”神经编码（AIM 1）和推定的'渴望的部分电路参与了这一转变（AIM 2）。为了测试这种机制是否独特且特定于奖励认同，我们还将测量与实验引起的食物渴望和特定食品价值相关的大脑活动同一患者和n = 89个健康对照（AIM 3）。如果成功，这种综合方法将发现选择性缓解渴望引起的药物增长的精确靶标，促进阿片类药物再利用，为精确干预措施奠定基础，以治疗无响应的个体的渴望。