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 WM, by facilitating WM updating and effort exertion and also RL, by boosting plasticity. Yet, prior studies have failed to distinguish between the effects of dopamine manipulations on RL versus WM. N = 100 participants completed a paradigm isolating these systems in a double-blind study measuring dopamine synthesis with [¹⁸F]-FDOPA PET imaging and manipulating dopamine with methylphenidate and sulpiride. We find that learning is enhanced among high synthesis capacity individuals and by methylphenidate, but impaired by sulpiride. Methylphenidate also blunts implicit effort cost learning. Computational modeling reveals that individuals with higher dopamine synthesis capacity rely more on WM, while methylphenidate boosts their RL rates. The D2 receptor 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 implicit effort sensitivity. This work was completed as part of a registered trial with the Overview of Medical Research in the Netherlands (NL-OMON43196).

Interaction between Pavlovian and instrumental control systems is key for adaptive motivated behavior, but also plays an important role in various neuropsychiatric disorders, including depression, addiction, and anxiety. Here, we employed the flouorodopa positron emission tomography ([¹⁸F]-DOPA PET) in healthy participants (N = 100) to assess whether dopamine synthesis capacity (Ki), specifically in the ventral striatum, accounts for individual variation in Pavlovian-to-instrumental transfer (PIT). Surprisingly, this was not the case. Rather, the relationship of ventral striatal Ki with PIT depended on working memory (WM) capacity. Ventral striatal dopamine boosted the effects of Pavlovian cues on instrumental responding to a greater degree in participants with higher WM capacity. Caution is warranted to interpret this post hoc four-way interaction given the modest sample size. Nonetheless, these results chime with prior findings demonstrating that dopaminergic drugs boost Pavlovian biases to a greater degree in participants with greater WM capacity and highlight the importance of interactions between striatal dopamine and WM capacity. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Individual differences in striatal dopamine synthesis capacity have been associated with working memory capacity, trait impulsivity, and spontaneous eye-blink rate (sEBR), as measured with readily available and easily administered, ‘off-the-shelf’ tests. Such findings have raised the suggestion that individual variation in dopamine synthesis capacity, estimated with expensive and invasive brain positron emission tomography (PET) scans, can be approximated with simple, more pragmatic tests. However, direct evidence for the relationship between these simple trait measures and striatal dopamine synthesis capacity has been limited and inconclusive. We measured striatal dopamine synthesis capacity using [¹⁸F]-FDOPA PET in a large sample of healthy volunteers (N = 94) and assessed the correlation with simple, short tests of working memory capacity, trait impulsivity, and sEBR. We additionally explored the relationship with an index of subjective reward sensitivity. None of these trait measures correlated significantly with striatal dopamine synthesis capacity, nor did they have out-of-sample predictive power. Bayes factor analyses indicated the evidence was in favour of absence of correlations for all but subjective reward sensitivity. These results warrant caution for using these off-the-shelf trait measures as proxies of striatal dopamine synthesis capacity.

Catecholamine-enhancing psychostimulants, such as methylphenidate have long been argued to undermine creative thinking. However, prior evidence for this is weak or contradictory, stemming from studies with small sample sizes that do not consider the well-established large variability in psychostimulant effects across different individuals and task demands. We aimed to definitively establish the link between psychostimulants and creative thinking by measuring effects of methylphenidate in 90 healthy participants on distinct creative tasks that measure convergent and divergent thinking, as a function of individuals’ baseline dopamine synthesis capacity, indexed with 18F-FDOPA PET imaging. In a double-blind, within-subject design, participants were administered methylphenidate, placebo or selective D2 receptor antagonist sulpiride. The results showed that striatal dopamine synthesis capacity and/or methylphenidate administration did not affect divergent and convergent thinking. However, exploratory analysis demonstrated a baseline dopamine-dependent effect of methylphenidate on a measure of response divergence, a creativity measure that measures response variability. Response divergence was reduced by methylphenidate in participants with low dopamine synthesis capacity but enhanced in those with high dopamine synthesis capacity. No evidence of any effect of sulpiride was found. These results show that methylphenidate can undermine certain forms of divergent creativity but only in individuals with low baseline dopamine levels.