Computational and Neural Modeling of Cue Reactivity in Addiction

摘要 物质使用障碍(SUD)和肥胖都是美国主要的公共卫生问题， 据估计，2015年有2080万美国人患有至少一种肥胖症，7860万成年人和1270万人 一百万肥胖儿童。暗示引发的渴望是吸毒成瘾和酗酒的中心症状 进食和复发的强烈预测。与其他sud症状相比，渴求也要多得多。 对治疗有抗药性。不幸的是，我们对线索诱导渴望的神经生物学基础的理解是 仍然有限，特别是与现有的丰富的人类神经成像数据相比。这部分是由于 也缺乏大数据集合(即功能磁共振研究大多是彼此独立进行的) 因为在成瘾和肥胖的神经成像研究中缺乏基于模型的计算分析。这个 这个项目的总体目标是使用多层次的、基于模型的计算方法来重新分析六个 现有的fMRI数据集，检查了总共954名有物质的个体的线索反应性和渴望 暴饮暴食(59名吸烟者、254名吸食大麻者、598名酗酒者和43名暴饮者)。 我们将使用新的计算建模方法解决三个及时的目标：1)进行贝叶斯模型- 基于分析来检验药物和食物渴望的共同和不同的计算机制 跨不同组；2)使用动态因果模型来量化神经区域之间的定向耦合 参与不同物质使用和暴食群体共有或独特的线索反应；3)探索 暗示引发的渴望模型是如何受到物质使用和暴食的严重程度的影响的。发现 将极大地提高我们对神经和计算机制的理解 吸毒成瘾和暴饮暴食的潜在渴望和线索反应。这些结果的含义可能是 影响深远，因为1)渴望是不同物质使用和使用的共同和核心表型 2)这些先进的建模方法可以应用于许多其他相关的病理学 与功能失调的渴求和奖赏加工有关；以及3)这些机制在更严重的 (例如，SUD)和不太严重(例如，非SUD)的个人可以提供可能保护 来自发育迟缓的个体。

Abstract Substance use disorders (SUD) and obesity are both major public health concerns in the United States, with an estimated 20.8 million Americans struggling with at least one SUD in 2015 and 78.6 million adults and 12.7 million children who are obese. Cue-elicited craving is a central symptom of both drug addiction and binge eating and a strong predictor of relapse. Compared to other SUD symptoms, craving is also much more resistant to treatment. Unfortunately, our understanding of the neurobiological basis of cue-induced craving is still limited, especially compared to the wealth of existing human neuroimaging data. This is partially due to the lack of big data collectives (i.e. fMRI studies have mostly been conducted in isolation from each other) as well as the scarcity of model-based computational analysis in neuroimaging studies on addiction and obesity. The overarching goal of this project is to use multi-level, model-based computational methods to re-analyze six existing fMRI datasets that examine cue reactivity and craving across a total of 954 individuals with substance use or binge eating (59 tobacco smokers, 254 cannabis users, 598 binge drinkers, and 43 binge eating adults). We will address three timely aims using novel computational modeling methods: 1) conduct Bayesian model- based analyses to examine the common and distinct computational mechanisms of drug and food craving across different groups; 2) use dynamic causal modeling to quantify directed coupling between neural regions involved in cue reactivity shared by or unique to different substance using and binge eating groups; 3) explore how models of cue-elicited craving are modulated by the severity of substance use and binge eating. Findings from this project will greatly enhance our understanding of the neural and computational mechanisms underlying craving and cue reactivity in drug addiction and binge eating. The implication of these results could be far-reaching, because 1) craving is a common and core phenotype across different substance use and binge eating groups; 2) these advanced modeling methods could be applied to many other pathologies related to dysfunctional craving and reward processing; and 3) how these mechanisms differ between more severe (e.g. SUD) and less severe (e.g. non-SUD) individuals could provide mechanisms that might protect an individual from developing SUD.