Biology subjects

van den Bosch, R.

Publications and source records attributed to van den Bosch, R..

11 recordsLinked to original sources

bioRxiv2026

Dopamine modulates striatal activity when controlling the output of working memory

Cognitive control depends on capacity-limited mechanisms that require selection. Working memory (WM) therefore relies on an input-gate to filter information into WM and an output-gate to transform current WM representations into a prioritised state to guide behaviour. According to current theory, such WM gating processes are modulated by dopamine in the striatum, yet empirical evidence for this hypothesis remains sparse. We fill this gap by directly testing the role of dopamine for both WM input-and output-gating in a double-blind, placebo-controlled within-subject fMRI study (N = 34; 23 female, 11 male human subjects), using a 400 mg oral dose of the dopamine D2 receptor antagonist sulpiride. In our cued delayed-response task, which separated input-from output-gating, sulpiride altered neural activity in the striatum during output-gating. This effect was accompanied by a sulpiride-induced de-crease in the neural stimulus selectivity of gated sensory representations in visual association cortex, with greater decreases in stimulus selectivity correlating with reduced behavioural accuracy in the task. Together, the results establish a role for striatal dopamine during the control of cortical outflow of WM. Significance StatementTo act on a goal, the brain holds information in mind and brings the important parts into focus to guide what we do next. Scientists believe that this "selection" process involves dopamine, a chemical messenger, in a brain area called the striatum. We tested this by giving people a drug that alters dopamine activity in the brain. The drug changed how the striatum reacted when people selected information from memory. It also made the brains visual areas represent this information less clearly, and this change affected peoples behaviour. Therefore, we conclude that dopamine in the striatum plays a role when our brain controls which information in working memory is sent to other parts of the brain to guide actions.

neuroscience↗

bioRxiv2026

Low-grade inflammation in obesity causes low-effort food choice

Inflammation relates to decreased effortful behaviour and altered effort-related responses in brain regions, such as the dorsomedial prefrontal cortex (dmPFC). Inflammation is prevalent in obesity, but its effects on effortful versus more convenient food choices are unknown. We investigated the role of low-grade inflammation in effortful food choice using functional MRI in a cross-sectional study (n=150 women, BMI>27 kg/m{superscript 2}) and a 12-week randomized controlled trial (n=59 women, BMI>30 kg/m{superscript 2}, CRP>3 mg/L; colchicine 0.5 mg/d vs. placebo). Inflammation was related to less high-effort choices (OR=0.27, p=0.004) and higher effort-related dmPFC signal ({beta}=0.23, p=0.025, Rpartial{superscript 2}=0.039), and mediated the association between BMI and dmPFC signal. Colchicine decreased systemic inflammation (i.e. INFLA-score) as expected ({beta}=-0.10 SD, p<0.001, Rpartial{superscript 2}=0.030), increased high-effort choices (OR=1.32, p=0.044), and marginally decreased effort-related dmPFC signal ({beta}=-0.13, p=0.053, Rpartial{superscript 2}=0.037). These findings show a causal role for inflammation in choosing convenience foods in obesity via increased effort aversion and associated dmPFC processing.

neuroscience↗

bioRxiv2025

Validating molecular target-enriched fMRI for disentangling drug effects on dopamine

The psychostimulant methylphenidate may exert its effects on cognition and associated brain signals via action on the dopamine or noradrenaline transporter (DAT/NET). A recently developed and increasingly popular dual-regression approach (REACT; Dipasquale et al. (2019)) attempts to hone in on the molecular mechanisms underlying (drug-induced) changes in fMRI signal by enriching the analysis with information about the spatial distribution of molecular targets of interest. This method has great potential, but hitherto lacked validation of its molecular specificity and functional relevance. Here we leverage a unique pharmaco-fMRI dataset with established dopamine-dependent methylphenidate effects on neural reward prediction error (RPE) signaling, the canonical functional signature of dopamine. Using REACT we found that methylphenidate significantly modulated both DAT and NET-related functional connectivity networks, but only the effect on the DAT network varied with interindividual differences in striatal dopamine synthesis capacity, as measured with [18F]FDOPA PET. Furthermore, methylphenidate affected DAT-related connectivity in the prefrontal cortex in the same location where it affected neural RPE signaling. Together, these findings firmly establish the validity of REACT as a tool for isolating the role of dopamine from that of noradrenaline in methylphenidates effects on brain function.

neuroscience↗

bioRxiv2024

Fatigue >12 weeks after coronavirus disease (COVID) is associated with reduced reward sensitivity during effort-based decision making

BackgroundFatigue and depressive mood is inherent to acute disease, but a substantial group of people report persisting disabling fatigue and depressive symptoms long after a COVID infection. Acute infections have shown to change decisions to engage in effortful and rewarding activities, but it is currently unclear whether fatigue and depressive symptoms similarly affect decision making during acute and persistent phases of a COVID infection. Here, we investigated whether fatigue and depressive mood are associated with altered weighting of effort and reward in decision-making during different timepoints after COVID infection. MethodsWe conducted an online cross-sectional study between March 2021 and March 2022. 242 Participants (18-65 years) with COVID <4 weeks ago (n=62), COVID >12 weeks ago (n=81), or no prior COVID (self-reported) (n=90) performed an effort-based decision-making task, in which they decided whether they wanted to exert physical effort (ticking boxes on screen, 5 levels) for reward (money to be gained in a voucher-lottery, 5 levels). State fatigue and depressive mood was measured by the Profile of Mood States (POMS) prior to the task. We used multilevel binomial regression analysis to test whether fatigue and depressive mood were related to acceptance rates for effort and reward levels and whether this differed between the groups. ResultsCompared with no COVID and COVID <4 weeks groups, the COVID >12 weeks group reported higher state fatigue scores (mean{+/-}SD: 20{+/-}7 vs. 14{+/-}7 and 12{+/-}6 POMS-score, respectively; both p<0.001) and was less sensitive to rewards (Reward*Group: OR: 0.35 (95%CI 0.20, 0.62), p<0.001 and OR: 0.38 (95%CI 0.20, 0.72), p=0.003). In the COVID >12 weeks group, fatigue was more negatively associated with reward sensitivity compared with the COVID <4 weeks group (Reward*Fatigue*Group: OR 0.47 (95%CI 0.25, 1.13), p=0.022) and the no COVID group (Reward*Fatigue*Group: OR 0.48 (95%CI 4.01, 0.92), p=0.029). No group differences were observed for the relationship between fatigue and effort sensitivity. No group differences were observed for the relationship between depressive mood and effort or reward sensitivity. Higher age, lower BMI, unhealthy lifestyle, and worrying during the acute phase of COVID each predicted decreased reward sensitivity in the >12 weeks group (Age*Reward: OR 0.30 (95%CI 0.19, 0.48), p<0.001; BMI*Reward: OR 1.43 (95%CI 1.01, 2.00), p=0.047); Lifestyle*Reward: OR 1.50 (95%CI 1.06, 2.14), p=0.022; Worrying*Reward: OR 0.59 (95%CI 0.38, 0.94), p=0.025, respectively). ConclusionThe finding that fatigue is related to lower reward sensitivity >12 weeks after COVID, suggesting potential reward deficits in post-covid fatigue. These findings are in line with previous observations that long-term inflammation can induce dysregulations in neural reward processing, which should be further investigated in future studies. HighlightsO_LIWe tested if fatigue and mood were related to altered decision making post-COVID C_LIO_LIParticipants post-COVID >12wks ago were more fatigued and less reward sensitive C_LIO_LIPost-COVID-related fatigue was associated with reduced reward sensitivity C_LIO_LIPost-COVID-related depressive mood was not associated with altered decision making C_LIO_LIHigher age, unhealthy lifestyle, and worrying predicted reward deficits C_LI

neuroscience↗

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↗

bioRxiv2020

Striatal dopamine synthesis capacity reflects smartphone social activity

Striatal dopamine has been implicated in social behavior across humans, rodents, and non-human primates in artificial laboratory settings with highly-practiced tasks and fixed reward contingencies. Whether striatal dopamine drives naturalistic, spontaneous social behavior remains unclear. Here, we leverage day-to-day logs of unconstrained smartphone behavior and establish a novel link between smartphone social activity and individual differences in striatal dopamine synthesis capacity using [18F]-DOPA PET in (N=22) healthy adult humans. We find a strong relationship such that a higher proportion of social app interactions correlates with lower dopamine synthesis capacity in the bi-lateral putamen. Permutation tests and penalized regressions provide evidence that this link between dopamine synthesis capacity and social versus non-social smartphone taps is specific. These observations provide a key empirical grounding for current speculations about dopamines role in digital social behavior.

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↗