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

动态成本效益评估和（功能失调）动机过程背后的神经机制的多巴胺能调节

基本信息

批准号：
317080338
负责人：
Dr. Jochen Michely
金额：
--
依托单位：
Klinik für Psychiatrie und Psychotherapie (CCM)
依托单位国家：
德国
项目类别：
Research Fellowships
财政年份：
2016
资助国家：
德国
起止时间：
2015-12-31 至 2019-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/317080338?language=en
关键词：
Dopaminergic modulation neural mechanisms underlying

项目摘要

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.

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，以获得奖励或加强的结果。然而，为了确定一个行动是否值得开始并坚持下去，个人需要权衡一个行动的努力成本和潜在收益。大量证据表明，神经递质多巴胺在这一关键的成本效益评估中发挥着关键作用。与此相一致的是，患有帕金森氏症的多巴胺缺乏症的患者往往表现出缺乏动力的活力。然而，关于多巴胺能影响神经机制（功能障碍）动机行为的人类数据很少。一方面，参与努力行为的意愿可以基于成本效益评估，在假设情景中高估行动成本或低估资源可能会在病理学中起作用。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，导致之前计算的成本效益估值更新不足或主观疲劳的高估。为此，它仍然有待阐明多巴胺如何影响成本和效益的整合之前，行动启动，但也动态地在实际行动执行。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建模来研究基于即将到来的行动的明确信息的预期调整如何影响实际运动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神经机制的预期和评价的努力的行为和偶然的结果，以及这些过程如何与临床相关的动机缺陷患有帕金森氏病的患者。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械水平上在动态成本效益评估过程中调节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机制，以提高对临床人群中动机缺陷的理解和治疗。