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

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.

Removal of reinforcement improves instrumental performance in humans by decreasing a general action bias rather than unmasking learnt associations.

Performance during instrumental learning is commonly believed to reflect the knowledge that has been acquired up to that point. However, recent work in rodents found that instrumental performance was enhanced during periods when reinforcement was withheld, relative to periods when reinforcement was provided. This suggests that reinforcement may mask acquired knowledge and lead to impaired performance. In the present study, we investigated whether such a beneficial effect of removing reinforcement translates to humans. Specifically, we tested whether performance during learning was improved during non-reinforced relative to reinforced task periods using signal detection theory and a computational modelling approach. To this end, 60 healthy volunteers performed a novel visual go/no-go learning task with deterministic reinforcement. To probe acquired knowledge in the absence of reinforcement, we interspersed blocks without feedback. In these non-reinforced task blocks, we found an increased d', indicative of enhanced instrumental performance. However, computational modelling showed that this improvement in performance was not due to an increased sensitivity of decision making to learnt values, but to a more cautious mode of responding, as evidenced by a reduction of a general response bias. Together with an initial tendency to act, this is sufficient to drive differential changes in hit and false alarm rates that jointly lead to an increased d'. To conclude, the improved instrumental performance in the absence of reinforcement observed in studies using asymmetrically reinforced go/no-go tasks may reflect a change in response bias rather than unmasking latent knowledge.

Neuro-Cognitive Effects of Acute Tyrosine Administration on Reactive and Proactive Response Inhibition in Healthy Older Adults.

The aging brain is characterized by altered dopamine signaling. The amino acid tyrosine, a catecholamine precursor, is known to improve cognitive performance in young adults, especially during high environmental demands. Tyrosine administration might also affect catecholamine transmission in the aging brain, thereby improving cognitive functioning. In healthy older adults, impairments have been demonstrated in two forms of response inhibition: reactive inhibition (outright stopping) and proactive inhibition (anticipatory response slowing) under high information load. However, no study has directly compared the effects of a catecholamine precursor on reactive and load-dependent proactive inhibition. In this study we explored the effects of tyrosine on reactive and proactive response inhibition and signal in dopaminergically innervated fronto-striatal regions. Depending on age, tyrosine might lead to beneficial or detrimental neurocognitive effects. We aimed to address these hypotheses in 24 healthy older human adults (aged 61-72 years) using fMRI in a double blind, counterbalanced, placebo-controlled, within-subject design. Across the group, tyrosine did not alter reactive or proactive inhibition behaviorally but did increase fronto-parietal proactive inhibition-related activation. When taking age into account, tyrosine affected proactive inhibition both behaviorally and neurally. Specifically, increasing age was associated with a greater detrimental effect of tyrosine compared with placebo on proactive slowing. Moreover, with increasing age, tyrosine decreased fronto-striatal and parietal proactive signal, which correlated positively with tyrosine's effects on proactive slowing. Concluding, tyrosine negatively affected proactive response slowing and associated fronto-striatal activation in an age-dependent manner, highlighting the importance of catecholamines, perhaps particularly dopamine, for proactive response inhibition in older adults.