Reinforcer-specific value-based decision-making in persistence of and recovery from alcohol use disorder

酒精给社会带来了相当大的负担；2019年，它导致了英格兰2.5万多人死亡和100多万人住院。与酒精有关的伤害的大部分负担可以归因于最重度的饮酒者，在英国有50万人(患有酒精使用障碍的人；AUD)。在英国，大多数患有AUD的人没有接受治疗，而那些接受治疗的人中，大多数人并没有从中受益。在我们对AUD和其他成瘾的理解以及寻找新的循证治疗方法方面，科学进展一直很缓慢。这在一定程度上是因为许多成瘾科学家认为，成瘾是强迫性和习惯性的，这意味着饮酒和吸毒是对其后果变得不敏感的行为。然而，有证据表明，所有有动机的行为，包括吸毒者表面上的非理性行为，都是由人们的目标及其背后的价值观决定的。行为经济学将这一观点应用于成瘾研究，并积累了大量证据和连贯的理论，可以解释成瘾是如何发展和持续的，治疗是如何起作用的，以及即使没有接受治疗，人们也是如何从成瘾中恢复过来的。尽管有这些重要的进展，但成瘾扰乱基于价值的决策(VBDM)所依据的心理和神经过程的机制在很大程度上还不清楚。因此，需要神经科学知识的方法来描述决定酒精选择和其他奖励(特别是与饮酒不相容的活动)的内部过程，并证明这些过程如何与AUD的持久性、康复和治疗反应有关。为此，我们开发了一个计算机化的VBDM任务，并使用计算方法来解释参与者对任务的反应。我们的初步发现表明，这项任务可以区分目前有毒瘾的人和已经康复的人，而且它对强烈的酒精渴望很敏感。在这个项目中，我们将应用这些方法来系统地描述澳元基于价值的选择的内在机制。主要目的是展示VBDM的扭曲如何有助于AUD的重要特征，特别是AUD患者和康复患者的特征，强烈的饮酒欲望对饮酒行为的影响，以及对治疗的反应。为实现这些目标，我们将完成以下一揽子工作。首先，我们将尝试根据他们的VBDM来区分目前患有AUD的人、已经从AUD中恢复的人，以及一组轻度饮酒者。其次，我们将进行一项实验室研究，在测量AUD患者的VBDM并记录他们自愿饮酒量之前，我们将试验性地增加AUD患者的酒精渴望。这将告诉我们VBDM在渴望发作期间是如何变化的，以及VBDM的哪些特定方面可以预测饮酒。第三，我们将跟踪VBDM在为期三周的基于社区的AUD行为经济治疗过程中的变化，在该治疗中，参与者将获得与他们能够减少饮酒(应急管理)程度成比例的经济激励。这将确定VBDM的哪些特定方面可以预测后续饮酒的减少。该项目的重要成果包括通过证实基于价值的酒精选择与替代增强剂的驱动因素的新框架，促进了对成瘾的概念性理解。我们还将验证一种新的测量工具，用于衡量认知动机结构中的个体差异，该工具可以区分哪些人正在摆脱毒瘾的轨道上，哪些人需要额外的支持；这个工具可以在未来的工作中加以利用。

Alcohol places a considerable burden on society; it was responsible for more than 25,000 deaths and over one million hospital admissions in England in 2019. Much of the burden of alcohol-related harm can be attributed to the heaviest drinkers, of whom there are half a million (people with Alcohol Use Disorder; AUD) in the United Kingdom. The majority of people with AUD in the UK do not receive treatment and of those that do, most do not benefit from it. Scientific progress in our understanding of AUD and other addictions, and the search for new evidence-based treatments, has been slow. This is partly because many addiction scientists believe that addiction is compulsive and habitual, meaning that drinking and drug use are behaviors that become insensitive to their consequences. However, there is evidence that all motivated behaviour, including the apparently irrational behaviour of people with addiction, is determined by the goals that people have, and the values that underlie their goals. Behavioural economics has applied this idea to the study of addiction, and has amassed a large body of evidence and coherent theories that can explain how addictions develop and persist, how treatments work, and how people recover from addiction even if they do not receive treatment. Despite these important advances, the mechanisms through which addiction disrupts the psychological and neural processes that underlie value-based decision-making (VBDM), are largely unknown. Therefore, there is a need for neuroscience-informed methods that can characterise the internal processes that determine choice for alcohol and other rewards (particularly activities that are incompatible with drinking alcohol), and demonstrate how those processes are implicated in the persistence of AUD, recovery, and treatment response. To this end, we developed a computerized VBDM task and used computational methods to interpret participants' responses on the task. Our preliminary findings suggest that the task can discriminate people who currently have addictions from people who have recovered, and it is sensitive to intense alcohol cravings. In this project we will apply these methods to systematically characterise the internal mechanics of value-based choice in AUD. The overarching aim is to demonstrate how distortions in VBDM contribute to important features of AUD, specifically characterisation of people with AUD versus people who have recovered, the influence of powerful cravings on drinking behaviour, and the response to treatment. To achieve these aims we will complete the following package of work. First, we will attempt to distinguish people who currently have AUD, people who have recovered from AUD, and a control group of light drinkers, on the basis of their VBDM. Second, we will conduct a laboratory study in which we will experimentally increase alcohol craving in people with AUD before measuring their VBDM and recording how much alcohol they voluntarily consume. This will tell us how VBDM changes during craving episodes, and which specific aspects of VBDM are predictive of alcohol consumption. Third, we will track changes in VBDM over the course of a three-week community-based behavioural economic treatment for AUD in which participants receive financial incentives proportional to the extent that they are able to reduce their drinking (contingency management). This will identify which specific aspects of VBDM are predictive of reductions in drinking at follow-up. Important outcomes from the project include advancing the conceptual understanding of addiction by corroborating a novel framework of the drivers of value-based choice of alcohol versus alternative reinforcers. We will also validate a new measurement tool of individual differences in the cognitive-motivational constructs that distinguish people who are on track to recover from their addictions, and those who require additional support; this tool can be exploited in future work.