Learning and decision making as predictors of treatment outcome in alcohol use disorder

项目2将检查130名戒毒的酒精依赖患者和40名年龄和性别匹配的对照组。所有受试者都将接受变焦操纵杆任务(ZJT)训练，以改变习惯性的酒精提示接近偏差。这个项目的主要目的是评估1)ZJT治疗会改变哪些与基于奖励的学习相关的行为和神经成像改变(见项目1和3)，以及哪些改变可以预测6个月的随访期间的治疗结果(主要结果：复发，次要结果：饮酒量)，2)这些改变如何与可以改变复发风险的临床和心理社会因素相互作用，以及3)为遗传和成像分析和建模提供数据。此外，我们还将探讨性别对学习功能成像参数的影响。患者将在住院环境中戒毒，在随机安慰剂对照设计中接受6次ZJT治疗，并将使用Time-Line随访程序进行为期6个月的跟踪。临床评估、学习行为范式和脑成像将在任何精神药物治疗后至少四个半衰期内进行。受试者将接受如前所述的医疗管理，每两周进行一次随访，并预定义纳入和排除标准。我们将应用功能成像范式评估1)巴甫洛夫-工具迁移，2)习惯性真性目标定向行为和3)工作记忆。我们将学习的模型参数与功能激活和预期摄入量相关联，以控制共病、心理社会和神经生物学疾病严重程度标志。

Project 2 will examine 130 detoxified alcohol-dependent patients and 40 age- and gender matched controls. All subjects will be treated with Zooming Joystick Task (ZJT) training to alter a habitual alcohol cue approach bias. The primary aim of this project is to assess 1) which behavioural and neuroimaging alterations (fMRI) associated with reward-based learning (see Projects 1 &3) are altered by ZJT treatment and which alterations predict treatment outcome (primary outcome: relapse, secondary outcome: amount of alcohol intake) within the follow-up period of 6 months, 2) how these alterations interact with clinical and psychosocial factors that can modify relapse risk, and 3) to provide data for genetic and imaging analyses and modelling. Furthermore, we will explore gender effects on functional imaging parameters of learning. Patients will be detoxified in an inpatient setting, receive six sessions of the ZJT in a randomized placebo controlled design and will be followed for six months using the Time-Line Follow-Back Procedure. Clinical assessments, behavioural paradigms of learning, and brain imaging will be carried out within at least four half-lives after any psychotropic medication. Subjects will undergo medical management with biweekly follow-ups and predefined inclusion and exclusion criteria as previously described. We will apply functional imaging paradigms assessing 1) Pavlovian-to-instrumental transfer, 2) habitual verus goal directed behaviour and 3) working memory. We will associate model parameters of learning with functional activation and prospective intake controlling for comorbidity, psychosocial and neurobiological disease severity markers.