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

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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.