Dopaminergic modulation of neural mechanisms underlying dynamical cost-benefit valuations and (dysfunctional) motivational processes

动机导致代理人从事体力要求高的活动，并付出更大的努力，以获得奖励或加强结果。然而，要决定一项行动是否值得发起并坚持下去，个人需要权衡一项行动的努力成本和潜在收益。相当多的证据表明，神经递质多巴胺在这一关键的成本效益评估中起着关键作用。与此相一致的是，患有帕金森病的多巴胺缺乏的患者通常表现为缺乏动力。然而，关于多巴胺能对潜在（功能失调）动机行为的神经机制影响的人类数据很少。一方面，参与努力行为的意愿可能基于成本效益评估，在假设的情况下，高估行动的成本或低估资源可能在病理学上是不正常的。另一方面，在行动执行过程中，实际的努力感知也可能被夸大，导致先前计算的成本效益评估更新不足或主观疲劳的高估。为此，多巴胺如何在行动开始前影响成本和收益的整合，以及在实际行动执行过程中如何动态地影响成本和收益的整合，仍有待阐明。在我们的研究项目中，我们将使用行为和功能磁共振成像数据的计算模型来研究基于即将发生的动作的明确信息的预期调整如何影响实际动作执行过程中成本和收益的动态整合。此外，我们将探讨多巴胺如何影响努力行为和偶然结果的预期和评估的神经机制，以及这些过程如何与帕金森病患者的临床相关动机缺陷相关。此外，我们将使用脑磁图的高时间分辨率来表征多巴胺如何在大脑活动和连接的机制水平上调节动态成本效益评估过程中的动机活力和奖励敏感性。最后，我们的项目旨在解开（功能失调）动机过程的神经和药理学机制，以提高对临床人群动机缺陷的理解和治疗。

Motivation leads to agents engaging in physically demanding activity and expending greater effort in order to obtain rewarding or reinforcing outcomes. However, to determine if an action is worth initiating and persevering with, individuals need to weigh effort costs and potential benefits of an action. Considerable evidence points to a pivotal role of the neurotransmitter dopamine in this critical cost-benefit valuation. In line with that, patients suffering from a lack of dopamine as in Parkinson`s disease often present with impoverished motivational vigour. However, human data regarding the dopaminergic impact on neural mechanisms underlying (dysfunctional) motivated behaviour are sparse. On the one hand, willingness to engage in effortful behaviour could be based on a cost-benefit valuation where overestimated costs of an action or underestimation of resources in hypothetical scenarios might be dysfunctional in pathology. On the other hand, actual effort perception could also be exaggerated during action execution, leading to deficient updating of previously computed cost-benefit valuations or overestimation of subjective fatigue. To this end, it remains to be elucidated how dopamine affects the integration of costs and benefits prior to action initiation, but also dynamically during actual action execution. In our research project, we will use computational modelling of both behavioural and functional magnetic resonance imaging data to investigate how anticipatory adjustments based on explicit information about upcoming actions impact on the dynamical integration of costs and benefits during actual movement execution. Moreover, we will explore how dopamine affects neural mechanisms underlying the anticipation and valuation of effortful behaviour and contingent outcomes, and how these processes relate to clinically relevant motivational deficits in patients suffering from Parkinson's disease. Additionally, we will use the high temporal resolution of magnetoencephalography to characterize how dopamine modulates motivational vigour and reward sensitivity during dynamical cost-benefit valuations at a mechanistic level of brain activity and connectivity. Finally, our project aims at disentangling neural and pharmacological mechanisms of (dysfunctional) motivational processes in order to improve the understanding and treatment of motivational deficits in clinical populations.