Effects of methylphenidate on reversal learning depend on working memory capacity

Brain catecholamines have long been implicated in cognitive flexibility, exemplified by catecholamine drug and genetic effects on probabilistic reversal learning. However, the mechanisms underlying such effects are unclear. Here we investigated effects of an acute catecholamine challenge with methylphenidate (20 mg, oral) on a novel probabilistic reversal learning paradigm with three options, which was designed to disentangle effects on punishment avoidance from effects on reward perseveration. Given the known large individual variability in methylphenidate’s effects, we stratified our effects by working memory capacity and trait impulsivity, putative proxies of baseline dopamine, in a large sample (n = 102) of healthy volunteers. Contrary to our prediction, methylphenidate did not alter performance in the reversal phase of the task. However, learning rates during the initial acquisition phase of the task were altered by methylphenidate, in a manner that depended on baseline working memory capacity. Participants with greater capacity exhibited greater adaptive reduction of the learning rate in this initial phase, in which outcome contingencies were stable. We hypothesize that the addition of a third choice option in this novel paradigm increased the demands for reinforcement learning, uncovering an effect of methylphenidate on initial learning rather than flexibility to reverse what was learnt.