Computational and neural mechanisms for the effect of dopamine on effort and reward learning

激励自己或被激励的能力是生活质量和最佳决策的重要决定因素。这方面的损害与许多神经精神疾病有关。这一过程的基础是了解奖励的能力和实现奖励所需的努力。人们早就知道，多巴胺能预测误差信号和奖赏学习是有因果关系的(Steinberg等人，2013年)。最近的研究还发现，在不同的大脑区域中，努力预测错误和奖励预测错误是平行编码的，努力预测错误表现在背内侧前额叶皮质，奖励预测错误表现在腹侧纹状体。我们将在一项受试者间、双盲、安慰剂对照研究中调查多巴胺对这一过程的影响，研究对象为N=60名健康男性参与者(30名安慰剂，30名L多巴)。参与者将在完成努力学习任务的同时接受fMRI协议(类似于Hauser等人，2017年的报告)。参与者还将报告他们对任务中所需的必要努力和可能的回报的信念，并完成关于冷漠和抑郁的自我报告问卷。分析将包括努力和回报学习以及信念的影响的计算模型、fMRI ROI分析和动态因果模型。回归分析将用于评估行为和神经参数之间的关系，以及亚临床范围内的情绪和动机报告。这项研究构成了我的博士项目的基础，该项目旨在扩大我们对努力和奖励学习的精神药理学、行为和神经基础的理解，以及它们与冷漠和心理健康的关系。

The capacity to motivate oneself or be motivated is an important determinant of quality of life and optimal decision-making. Impairments in this are associated with many neuropsychiatric conditions. Fundamental to this process are the ability to learn about rewards and the effort required to achieve them. It has long been known that dopaminergic prediction error signals and reward learning are causally linked (Steinberg et al., 2013). Recent work has also identified parallel encoding of effort and reward prediction errors within distinct brain regions, with effort prediction errors expressed in dorsomedial prefrontal cortex and reward prediction errors in ventral striatum. We will investigate the effects of dopamine on this process in a between-subject, double-blind, placebo-controlled study of N=60, healthy male participants (30 placebo, 30 L-DOPA). Participants will undergo an fMRI protocol while completing an effort learning task (similar to that reported in Hauser et al., 2017). Participants will also report their beliefs about necessary effort required and likely rewards during the task, and complete self-reported questionnaires of apathy and depression. Analysis will include computational modelling of effort and reward learning and the impact of beliefs, fMRI ROI analysis and dynamic causal modelling. Regression analyses will be used to assess the relationship between behavioural and neural parameters and reports of mood and motivation in the subclinical range. This study forms the foundation of my PhD project which will aim to expand our understanding of the psychopharmacological, behavioural and neural basis of effort and reward learning and their relationship to apathy and mental health.