Dopamine restores cognitive motivation in Parkinson's disease

McGuigan, Sara, Zhou, Shou-Han, Brosnan, Méadhbh B., Thyagarajan, Dominic, Bellgrove, Mark A., and Chong, Trevor T-J. (2019) Dopamine restores cognitive motivation in Parkinson's disease. Brain, 142 (3). pp. 719-732.

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Disorders of motivation, such as apathy, are common in Parkinson’s disease, and a key feature of such disorders is a greater aversion to effort. In humans, the experience of cognitive effort is ubiquitous, and cognitive apathy has traditionally been considered distinct and separable from other subtypes. Surprisingly, however, the neurobiology of cognitive motivation is poorly understood. In particular, although dopamine has a well-characterized role in incentivizing physically effortful behaviour, a critical, unresolved issue is whether its facilitatory role generalizes to other domains. Here, we asked how dopamine modulates the willingness of patients with Parkinson’s disease to invest cognitive effort in return for reward. We tested 20 patients with idiopathic Parkinson’s disease across two counterbalanced sessions—ON and OFF their usual dopaminergic medication—and compared their performance to 20 healthy age-matched controls. We applied a novel task in which we manipulated cognitive effort as the number of rapid serial visual presentation streams to which participants had to attend. After training participants to ceiling performance, we then asked them to choose between a low-effort/low-reward baseline option, and a higher-effort/higher-reward offer. Computational models of choice behaviour revealed four key results. First, patients OFF medication were significantly less cognitively motivated than controls, as manifest by steeper cognitive effort discounting functions in the former group. Second, dopaminergic therapy improved this deficit, such that choices in patients ON medication were indistinguishable from controls. Third, differences in motivation were also accompanied by independent changes in the stochasticity of individuals’ decisions, such that dopamine reduced the variability in choice behaviour. Finally, choices on our task correlated uniquely with the subscale of the Dimensional Apathy Scale that specifically indexes cognitive motivation, which suggests a close relationship between our laboratory measure of cognitive effort discounting and subjective reports of day-to-day cognitive apathy. Importantly, participants’ choices were not confounded by temporal discounting, probability discounting, physical demand, or varying task performance. These results are the first to reveal the central role of dopamine in overcoming cognitive effort costs. They provide an insight into the computational mechanisms underlying cognitive apathy in Parkinson’s disease, and demonstrate its amenability to dopaminergic therapy. More broadly, they offer important empirical support for prominent frameworks proposing a domain-general role for dopamine in value-based decision-making, and provide a critical link between dopamine and multidimensional theories of apathy.

Item ID: 68406
Item Type: Article (Research - C1)
ISSN: 1460-2156
Keywords: dopamine, Parkinson’s disease, apathy, cognitive effort, decision-making
Copyright Information: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.
Funders: Australian Research Council (ARC), Judith Jane Mason and Harold Stannett Williams Memorial Foundation, Brain Foundation (BF), Rebecca L Cooper Medical Research Foundation (RCMRF), Society for Mental Health Research (SMHR), Bethlehem Griffiths Foundation, National Health and Medical Research Council (NHMRC)
Projects and Grants: ARC DP 180102383, ARC DP DE 180100389
Date Deposited: 22 Jun 2021 21:38
FoR Codes: 52 PSYCHOLOGY > 5204 Cognitive and computational psychology > 520402 Decision making @ 80%
40 ENGINEERING > 4003 Biomedical engineering > 400309 Neural engineering @ 20%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280121 Expanding knowledge in psychology @ 80%
28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280110 Expanding knowledge in engineering @ 20%
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