Psychostimulants such as methylphenidate are widely used for their cognitive enhancing effects, but there is large variability in the direction and extent of these effects. We tested the hypothesis that methylphenidate enhances or impairs reward/punishment-based reversal learning depending on baseline striatal dopamine levels and corticostriatal gating of reward/punishment-related representations in stimulus-specific sensory cortex. Young healthy adults (N = 100) were scanned with functional magnetic resonance imaging during a reward/punishment reversal learning task, after intake of methylphenidate or the selective D2/3-receptor antagonist sulpiride. Striatal dopamine synthesis capacity was indexed with [18F]DOPA positron emission tomography. Methylphenidate improved and sulpiride decreased overall accuracy and response speed. Both drugs boosted reward versus punishment learning signals to a greater degree in participants with higher dopamine synthesis capacity. By contrast, striatal and stimulus-specific sensory surprise signals were boosted in participants with lower dopamine synthesis. These results unravel the mechanisms by which methylphenidate gates both attention and reward learning.
© 2022. The Author(s).