Studies on the role of subcortical dopaminergic networks in decision-making

基于奖励的决策障碍是许多神经精神疾病的中心诊断标准，包括物质使用障碍和病理性赌博。在这些疾病的神经解释中，一个反复出现的中心主题是多巴胺能神经传递的不适应变化。从不同的角度来看，本项目解决了两个核心问题：皮层-基底神经节回路中异常的奖励处理如何导致成瘾的决策障碍？在这种情况下，神经递质多巴胺扮演了什么不同的角色？这些问题的解决使用高分辨率功能性磁共振成像皮质下网络（纹状体，杏仁核）与药理学，行为学和计算方法相结合。一组项目研究了巴甫洛夫食欲刺激在调节健康受试者、病态赌徒和吸烟者的目标导向决策（时间折扣）中的作用，并研究了多巴胺在调节这些相互作用中的作用。第二项研究考察了异常强化学习过程在赌博成瘾中所起的作用，并探讨了多巴胺在学习过程中的调节探索与利用中的作用。最后，结合这些不同研究的决策和学习任务，我们检查了多巴胺能药物对强化学习、时间折扣和工具反应的影响的个体差异。综上所述，这些项目将促进我们对与成瘾相关的学习和决策的不适应变化的理解，并阐明皮层下多巴胺能区域在调节这些变化中的功能作用。

Impairments in reward-based decision-making are central diagnostic criteria of many neuropsychiatric disorders, including substance use disorders and pathological gambling. A central recurring theme in neural accounts of these disorders is a maladaptive change in dopaminergic neurotransmission. From different angles, the present project addresses two central questions: How does aberrant processing of rewards in cortical-basal ganglia circuits contribute to decision-making impairments in addiction? What are the different roles played by the neurotransmitter dopamine in this context? These questions are addressed using a combination of high-resolution functional magnetic resonance imaging of subcortical networks (Striatum, Amygdala) with pharmacological, behavioral and computational approaches.One set of projects examines the role of Pavlovian appetitive stimuli in modulating goal-directed decision-making (temporal discounting) in healthy subjects, pathological gamblers and smokers, and investigates the role of dopamine in mediating these interactions. A second line of studies examines the role that aberrant reinforcement learning processes play in gambling addiction, and address the role of dopamine in regulation exploration vs. exploitation during learning. Finally, using a combination of decision-making and learning tasks from these different lines of studies, we then examine individual differences in the effects of dopaminergic medication on reinforcement learning, temporal discounting and instrumental responding. Taken together, these projects will advance our understanding of the maladaptive changes in learning and decision-making associated with addiction, and shed light on the functional roles of subcortical dopaminergic regions in mediating these changes.