Biology subjects

Hofmans, L.

Publications and source records attributed to Hofmans, L..

6 recordsLinked to original sources

bioRxiv2024

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

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 dopamines 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 dopamines effects on WM when testing its effects on RL.

animal behavior and cognition↗

bioRxiv2022

Evidence for absence of links between striatal dopamine synthesis capacity and working memory capacity, spontaneous eye-blink rate, and trait impulsivity

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.

neuroscience↗

bioRxiv2020

Does dopamine synthesis capacity predict individual variation in curiosity?

Curiosity, which can be defined as "intrinsically motivated information-seeking", is an important driving force in our everyday lives. Based on previous evidence demonstrating a link between information prediction errors and dopamine neuronal firing rates, we asked whether the drive to seek information varies with individual differences in dopamine synthesis capacity. In order to investigate this, we let participants perform a lottery task in which we independently manipulated outcome uncertainty, outcome valence (gains versus losses) and expected value, and asked participants to indicate their curiosity for each presented lottery. In a separate session, participants underwent an [18F]DOPA PET scan to quantify their dopamine synthesis capacity. We replicate previous behavioral results, showing that curiosity is a function of outcome uncertainty as well as outcome valence (gain versus loss). However, we found no evidence that curiosity or the sensitivity to outcome uncertainty, outcome valence and expected value was related to participants dopamine synthesis capacity in the ventral striatum, the caudate nucleus or the putamen. These findings stress the need for further studies into the role of dopamine in (different types of) curiosity.

neuroscience↗

bioRxiv2020

The cognitive effects of a promised bonus do not depend on dopamine synthesis capacity

Reward motivation is known to enhance cognitive control. However, detrimental effects have also been observed, which have been attributed to overdosing of already high baseline dopamine levels by further dopamine increases elicited by reward cues. Aarts et al. (2014) indeed demonstrated, in 14 individuals, that reward effects depended on striatal dopamine synthesis capacity, measured with [18F]FMT-PET: promised reward improved Stroop control in low-dopamine individuals, while impairing it in high-dopamine individuals. Here, we aimed to assess this same effect in 44 new participants, who had previously undergone an [18F]DOPA-PET scan to quantify dopamine synthesis capacity. This sample performed the exact same rewarded Stroop paradigm as in the prior study. However, we did not find any correlation between reward effects on cognitive control and striatal dopamine synthesis capacity. The discrepancy between the current and our previous findings might reflect the use of different radiotracers for indexing dopamine synthesis capacity. STATEMENT OF RELEVANCEReward motivation is generally thought to enhance cognitive control, but paradoxical negative effects of rewards on cognitive control have also been observed. A previous PET study demonstrated that reward effects on Stroop control depended on baseline striatal dopamine synthesis capacity, indexed by uptake of the radiotracer [18F]FMT. The sample size is this study was very small for a between-subject correlational design. Replicating the exact same Stroop paradigm within a larger sample is therefore crucial to robustly establish the mechanistic link between incentive motivation and cognitive control and advancing our understanding of who chokes under pressure and why, a topic of great societal relevance today. The present study did not reveal any correlation between reward effects on cognitive control and striatal dopamine synthesis capacity, indexed with [18F]FDOPA-PET. Future studies might consider putative differential sensitivity of the radiotracer [18F]FMT and [18F]FDOPA, while also addressing other indices of dopamine transmission.

neuroscience↗

bioRxiv2019

Baseline dopamine predicts individual variation in methylphenidate's effects on cognitive motivation

The cognitive enhancing effects of methylphenidate are well established, but the mechanisms remain unclear. We recently demonstrated that methylphenidate boosts cognitive motivation by enhancing the weight on the benefits of a cognitive task in a manner that depended on striatal dopamine. Here we considered the complementary hypothesis that methylphenidate might also act by changing the weight on the opportunity cost of a cognitive task. To this end, fifty healthy participants (25 women) completed a novel cognitive effort discounting task that was sensitive to opportunity cost, and required choices between task and leisure. They were tested on methylphenidate, sulpiride or placebo and also underwent an [18F]DOPA PET scan to quantify baseline dopamine synthesis capacity. Methylphenidate boosted choices of cognitive effort over leisure across the group, and this effect was greatest in participants with more striatal dopamine at baseline. The effects of sulpiride did not reach significance. This study strengthens the motivational account of methylphenidates effects on cognition and suggests that methylphenidate reduces the cost of mental labor by increasing striatal dopamine.

neuroscience↗

bioRxiv2019

Dopamine Promotes Cognitive Effort by Biasing the Benefits Versus Costs of Cognitive Work

Stimulants like methylphenidate are increasingly used for cognitive enhancement, but precise mechanisms are unknown. We found that methylphenidate boosts willingness to expend cognitive effort by altering the benefit-to-cost ratio of cognitive work. Willingness to expend effort was greater for participants with higher striatal dopamine synthesis capacity, while methylphenidate and sulpiride - a selective D2 receptor antagonist - increased cognitive motivation more for participants with lower synthesis capacity. A sequential sampling model informed by momentary gaze revealed that decisions to expend effort are related to amplification of benefit-versus-cost information attended early in the decision process, while the effect of benefits is strengthened with higher synthesis capacity and by methylphenidate. These findings demonstrate that methylphenidate boosts the perceived benefits-versus-costs of cognitive effort by modulating striatal dopamine signaling. One Sentence SummaryStriatal dopamine increases cognitive effort by respectively amplifying and attenuating the subjective benefits and costs of cognitive control.

neuroscience↗