Hirschbichler, Stephanie Theresa; (2021) Motivation in motor and cognitive control: Effects of dopamine and monetary reward and penalty. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Dopamine has been identified as a key player in reward signalling and motivational processes and has been linked to apathy in Parkinson’s disease (PD), its hallmark being dopamine depletion. Direct characterisation of how dopamine modulates reward sensitivity especially in the presence of aversive stimuli is, however, still a matter of controversy. Saccadic eye movements have long been considered reward insensitive due to their high level of stereotypy, but in recent years have been recognised as a precise tool to study motor and cognitive control processes and measure reward sensitivity. This thesis investigates how oculomotor properties are influenced by different dopamine levels and motivation through both reward anticipation and penalty avoidance. Thereby I seek to shed light on the underlying pathomechanisms responsible for motor and non-motor symptoms in diseases characterized by dopamine depletion (e.g., PD). Data from the first experimental chapter suggest a common “net-value” for both incentive valences and confirms similar effects of both incentives on saccadic properties in healthy participants. The second part investigates the role of dopamine in signalling incentive values, which indicates a similar role of dopamine in both rewarding and aversive incentives. Both drugs (haloperidol and levodopa) decreased motor vigour, while having different effects on preparatory and inhibitory processes, which ultimately led to antagonistic effects on precision. Most intriguingly we also found increased reward sensitivity after a single dose of levodopa independent of incentive valence. As some of these effects might reflect motor effects of dopamine, I next examined the high-level cognitive effects using a visual working memory task. This was assessed in health as well as in a cohort of patients who had undergone VTA DBS surgery. No effect of Madopar or motivation was found on working memory in a tablet-based task, while haloperidol was detrimental to memory precision. DBS stimulation in the VTA improved performance potentially by increasing dopamine levels in the mesocorticolimbic pathway. In conclusion, this thesis aims provide a comprehensive picture of the role of nigrostriatal as well as mesolimibic dopamine on motor and cognitive control potentially aiding early diagnosis and optimising treatment strategies in disease.

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