Methylphenidate enhances or impairs the cognitive control of Pavlovian bias depending on working memory capacity

Value-based decision-making is regulated by a delicate interplay of instrumental and Pavlovian controllers. Here we assessed the role of catecholamines in this interplay. We investigated the effects of the catecholamine reuptake inhibitor methylphenidate (MPH) in 100 healthy subjects using a combined appetitive and aversive Pavlovian to instrumental transfer (PIT) paradigm including approach and withdrawal actions. By administering the drug after learning, our design allowed us to establish that MPH can also bias action outside a learning context by directly modulating the expression of motivational bias on instrumental action rather than by only modulating instrumental learning bias. In line with previous results, the effect of MPH on bias varied across individuals as a function of their working memory span capacity. By assessing both approach and withdrawal actions, we revealed that MPH enhanced not only the invigorating effect of appetitive Pavlovian cues on active approach, but also the inhibitory effect of appetitive cues on active withdrawal, the invigorating effect of aversive cues on active withdrawal, and the inhibitory effect of aversive cues on active approach. Thus, in participants with high working memory capacity, MPH boosted both approach and withdrawal PIT. Taken together, this pattern of effects is most consistent with the hypothesis that MPH modulates the cognitive control of Pavlovian biasing in a baseline-state-dependent manner, in line with the well-established inverted-U shaped relationship between catecholamine receptor stimulation in prefrontal cortex, and cognitive control.