Methylphenidate boosts choices of mental labor over leisure depending on baseline striatal dopamine

• Published in: bioRxiv
• Main Authors: Hofmans, Lieke, Papadopetraki, Danae, Van Den Bosch, Ruben, Määttä, Jessica I, Froböse, Monja Isabel, Zandbelt, Bram B, Westbrook, Andrew, Robbert-Jan Verkes, Cools, Roshan
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 23.04.2020
• Subjects: Cognitive ability; Dihydroxyphenylalanine; Dopamine; Dopamine D2 receptors; Impulsive behavior; Impulsivity; Mental task performance; Mesencephalon; Methylphenidate; Motivation; Positron emission tomography; Short term memory; Sulpiride
• DOI: 10.1101/859637

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 methylphenidate's effects on cognition and suggests that methylphenidate reduces the cost of mental labor by increasing striatal dopamine. Competing Interest Statement The authors have declared no competing interest. Footnotes * After having discovered a mistake in our measure of impulsivity (BIS-11), we reanalyzed our results and revised the manuscript. The manuscript has also been adjusted to incorporate a recent publication from our group (Westbrook et al., 2020, Science): differences between that publication and the current manuscript are discussed. NB: the results in the earlier version pertaining to impulsivity are not valid anymore. New analyses revealed NO correlations between BIS-11 scores and effects of methylphenidate on cognitive motivation or response latency.