Psychostimulants such as methylphenidate are widely used for enhancing learning and decision making across a variety of mental disorders and healthy states, but the mechanisms of these effects remain unclear. The effects may reflect direct action on dopamine and noradrenaline transmission in the prefrontal cortex, or modulation of dopamine in the striatum. Unraveling this is key for the individual and contextual tailoring of treatment strategies. I will present recent work in which we combined [18F]DOPA positron emission tomography with pharmacological fMRI of reversal learning in 100 young healthy volunteers to examine the mechanisms of enhancing learning and decision making. Results suggest that psychostimulants boost either a striatal or an orbitofrontal learning strategy, depending on individual differences in baseline levels of striatal dopamine. Specifically, methylphenidate enhanced action-outcome prediction error signals in striatum in participants with low striatal dopamine synthesis capacity. Conversely, methylphenidate enhanced stimulus-reward prediction error signals in orbitofrontal cortex in participants with high striatal dopamine synthesis capacity. These observations illustrate how dopaminergic drugs regulate tradeoffs between distinct behavioral strategies depending on the state of the internal environment, thus counteracting pre-existent biases towards one strategy at the expense of another.










Roshan Cools
Professor of Cognitive Neuropsychiatry
Donders Institute
Radboud University

Roshan Cools – Mechanisms of enhancing learning and decision making with dopamine: Who benefits and why?