Dopaminergic medication increases motivation to exert cognitive control by reducing subjective effort costs in Parkinson’s patients

Bogdanov, Mario; LoParco, Sophia; Otto, A. Ross; Sharp, Madeleine

doi:10.1016/j.nlm.2022.107652

Cited by 4 publications

(5 citation statements)

References 74 publications

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“…But why does dopamine synthesis capacity promote reliance on WM? One idea is related to the emerging hypothesis that WM is effort-costly and stronger striatal dopamine signaling helps overcome those effort costs [24,27,38,[42][43][44][45][46][47][48][49][50][51][52]. In a prior study, we showed that people are more willing to accept offers to perform more demanding WM tasks for money if they have higher dopamine synthesis capacity and on methylphenidate versus placebo [24].…”

Section: Discussionmentioning

confidence: 99%

Striatal Dopamine Can Enhance Learning, Both Fast and Slow, and Also Make it Cheaper

Westbrook,

van den Bosch,

Hofmans

et al. 2024

Preprint

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Associations can be learned incrementally, via reinforcement learning (RL), or stored instantly in working memory (WM). While WM is fast, it is also capacity-limited and effortful. Striatal dopamine may promote RL plasticity, and WM, by facilitating updating and effort exertion. Yet, prior studies have failed to distinguish between dopamine's effects on RL versus WM. N = 100 participants completed a paradigm isolating these systems in a double-blind study measuring dopamine synthesis with [18F]-FDOPA imaging and manipulating dopamine with methylphenidate and sulpiride. Learning is enhanced among high synthesis capacity individuals and by methylphenidate, but impaired by sulpiride. Methylphenidate also blunts effort cost learning. Computational modeling reveals that individuals with high dopamine synthesis rely more on WM, while methylphenidate boosts their RL rates. The D2 antagonist sulpiride reduces accuracy due to diminished WM involvement and faster WM decay. We conclude that dopamine enhances both slow RL, and fast WM, by promoting plasticity and reducing effort sensitivity. These results also highlight the need to control for dopamine's effects on WM when testing its effects on RL.

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Section: Discussionmentioning

confidence: 99%

Striatal Dopamine Can Enhance Learning, Both Fast and Slow, and Also Make it Cheaper

Westbrook,

van den Bosch,

Hofmans

et al. 2024

Preprint

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“…Many studies have focused on the causal role of these catecholamines in motivating physical effort in humans (Wardle et al, 2011;Soder et al, 2021; for review, see Salamone et al, 2016;Walton and Bouret, 2019). The role of catecholamines in cognitive effort has been relatively less explored, but emerging data indicate a comparable effect (Cocker et al, 2012;McGuigan et al, 2019;Westbrook et al, 2020;Bogdanov et al, 2022). Importantly, no single study has directly compared the effects of catecholaminergic stimulation within participants across both domains.…”

Section: Discussionmentioning

confidence: 99%

“…In the broader neuroscience literature, dopamine and noradrenaline are known to play causal roles in motivated behavior. Lower levels of these catecholamines are associated with lower motivation to invest effort (Salamone et al, 2016;Borderies et al, 2020), and exogenous catecholamines facilitate both cognitive (Cocker et al, 2012;McGuigan et al, 2019;Westbrook et al, 2020;Bogdanov et al, 2022) and physical effort (Wardle et al, 2011;Chong et al, 2015;Yohn et al, 2016;Addicott et al, 2019;Soutschek et al, 2020;Soder et al, 2021). However, the mechanisms underlying cognitive and physical motivation are also partially dissociable, being subserved by a network of domain-general and domain-specific mechanisms (Schmidt et al, 2012;Hosking et al, 2015;Chong et al, 2017;Atkins et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Amphetamines Improve the Motivation to Invest Effort in Attention-Deficit/Hyperactivity Disorder

Chong,

Fortunato,

Bellgrove

2023

J. Neurosci.

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Prevailing frameworks propose that a key feature of attention-deficit/hyperactivity disorder (ADHD) is lower motivation. An important component of motivation is the willingness to engage in cognitively or physically effortful behavior. However, the degree to which effort sensitivity is impaired in ADHD has rarely been tested, and the efficacy of stimulant medication in ameliorating any such impairments is unclear. Here, we tested 20 individuals with ADHD (11 males, 9 females) who were managed with amphetamine-based medication (dexamfetamine, lisdexamfetamine), and 24 controls (8 males, 16 females). Individuals with ADHD were tested over two counterbalanced sessions, ON and OFF their usual amphetamine-based medication. In each session, participants performed an effort-based decision-making task, in which they were required to choose how much cognitive or physical effort they were willing to engage in return for reward. Our results revealed three main findings. First, individuals with ADHD had lower motivation relative to controls to invest effort in both the cognitive and physical domains. Second, amphetamine increased motivation uniformly across both domains. Finally, the net effect of amphetamine treatment was to mostly restore motivation across both domains of effort relative to healthy controls. These data provide clear evidence for a heightened sensitivity to both cognitive and physical effort in ADHD, and reveal the efficacy of amphetamine-based drugs in restoring effort sensitivity to levels similar to controls. These findings confirm the existence of reduced motivational drive in ADHD, and more broadly provide direct causal evidence for a domain-general role of catecholamines in motivating effortful behavior.SIGNIFICANCE STATEMENTA core feature of attention-deficit/hyperactivity disorder (ADHD) is thought to be a heightened aversion to effort. Surprisingly, however, the degree to which effort sensitivity is impaired in ADHD has rarely been tested. More broadly, the relative efficacy of catecholamines in motivating the investment of cognitive and physical effort is unclear. We tested 20 individuals with ADHD ON and OFF amphetamines, and compared their behavior on an effort-based decision-making task to 24 controls. When tested OFF medication, the ADHD group was less cognitively and physically motivated than controls. However, amphetamines led to a comparable increase in motivation across both domains. This demonstrates the efficacy of catecholamines in facilitating domain-general effort, and highlights the broader potential of such drugs to treat disorders of motivation.

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“…For effort-based decision-making, studies in both humans and rodents indicate that diminished dopamine transmission makes individuals less willing to exert physical effort in exchange for larger rewards [ 3 – 9 ]. Pharmacological studies consistently demonstrate that agents that enhance dopaminergic transmission in humans increase reward sensitivity and decrease effort sensitivity, while studies directly investigating the effects of selective D2-receptor antagonism in healthy humans are rare [ 10 – 12 ]. For delay discounting, the existing literature is somewhat more mixed.…”

Section: Introductionmentioning

confidence: 99%

Dopamine and acetylcholine have distinct roles in delay- and effort-based decision-making in humans

Erfanian Abdoust,

Froböse,

Schnitzler

et al. 2024

PLoS Biol

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In everyday life, we encounter situations that require tradeoffs between potential rewards and associated costs, such as time and (physical) effort. The literature indicates a prominent role for dopamine in discounting of both delay and effort, with mixed findings for delay discounting in humans. Moreover, the reciprocal antagonistic interaction between dopaminergic and cholinergic transmission in the striatum suggests a potential opponent role of acetylcholine in these processes. We found opposing effects of dopamine D2 (haloperidol) and acetylcholine M1 receptor (biperiden) antagonism on specific components of effort-based decision-making in healthy humans: haloperidol decreased, whereas biperiden increased the willingness to exert physical effort. In contrast, delay discounting was reduced under haloperidol, but not affected by biperiden. Together, our data suggest that dopamine, acting at D2 receptors, modulates both effort and delay discounting, while acetylcholine, acting at M1 receptors, appears to exert a more specific influence on effort discounting only.

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Dopaminergic medication increases motivation to exert cognitive control by reducing subjective effort costs in Parkinson’s patients

Cited by 4 publications

References 74 publications

Striatal Dopamine Can Enhance Learning, Both Fast and Slow, and Also Make it Cheaper

Striatal Dopamine Can Enhance Learning, Both Fast and Slow, and Also Make it Cheaper

Amphetamines Improve the Motivation to Invest Effort in Attention-Deficit/Hyperactivity Disorder

Dopamine and acetylcholine have distinct roles in delay- and effort-based decision-making in humans

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