The effects of stress on decision-making in alcohol use disorder: A translational approach

摘要 这个翻译项目的目的是测试急性应激诱导对认知灵活性的影响 与对照组相比，AUD患者的习惯学习。为了阐明 酒精和压力之间复杂的相互作用，阐明大脑回路和机制至关重要， 揭示了酒精和压力如何在一系列领域相互作用。到目前为止，我们对 这种机制仅限于临床前水平的分析。为了提高翻译的影响， 关于压力和AUD的科学，本申请提出了对具有AUD的临床样品的研究， 仔细的实验操作的压力感应，功能性磁共振成像（fMRI），和一个 对决策制定的明确评估。我们建议测试急性应激诱导对 认知灵活性（即，威斯康星州卡片排序任务; WCST）和习惯学习（即，序贯决策 任务; SDMT）在64名个体的样本中，32名非寻求治疗的AUD个体和32名匹配的 对照组（无AUD）。所有参与者将完成一个慢性压力知情电池。基线措施 认知灵活性和习惯学习（WCST和SDMT）将被收集。合资格的参与者将完成一个 基于神经成像的压力诱导任务，在此之前和之后立即进行认知评估 灵活性和习惯学习（WCST和SDMT）。总体目标是测试是否对急性 压力诱导与认知灵活性的降低和习惯学习的增加有关， 与对照组相比，AUD患者。如果研究假设得到支持， 与对照组相比， 对照组，我们将进行大规模（R 01级）研究，其中压力/神经条件和决策- 使用神经成像范例完成测量， 和决策都可以被审问。

ABSTRACT The objective of this translational project is to test the effects of acute stress induction on cognitive flexibility and habit learning among individuals with AUD compared to matched controls. Towards elucidating the complex interplay between alcohol and stress, it is crucial to elucidate brain circuitry and mechanisms that underlie how alcohol and stress interact across a range of domains. To date, much of our understanding of such mechanisms is confined to the preclinical level of analysis. To advance the translational impact of the science of stress and AUD, this application proposes an investigation in a clinical sample with AUD, combining careful experimental manipulations of stress induction, functional magnetic resonance imaging (fMRI), and a well-defined assessment of decision making. We propose to test the effects of acute stress induction on cognitive flexibility (i.e., Wisconsin Card Sort Task; WCST) and habit learning (i.e., Sequential Decision-Making Task; SDMT) in a sample of 64 individuals, 32 non-treatment seeking individuals with AUD and 32 matched controls (no AUD). All participants will complete a chronic stress-informed battery. Baseline measures of cognitive flexibility and habit learning (WCST and SDMT) will be collected. Eligible participants will complete a neuroimaging-based stress-induction task, immediately preceded and followed by assessments of cognitive flexibility and habit learning (WCST and SDMT). The overarching goal is to test whether response to an acute stress induction is associated with decreases on cognitive flexibility and increases in habit learning in individuals with AUD compared to matched controls. If the study hypotheses are supported and acute stress decreases cognitive flexibility and enhances habit learning in individuals with AUD, compared to matched controls, we will undertake large scale (R01-level) studies in which both stress/neural conditions and decision- making measures are completed using neuroimaging paradigms so that neurocircuitry of both stress response and decision-making can be interrogated.