Abstract
According to the placebo-reward hypothesis, placebo is a reward-anticipation process that increases midbrain dopamine (DA) levels. Reward-based learning processes, such as reinforcement learning, involves a large part of the DA-ergic network that is also activated by the placebo intervention. Given the neurochemical overlap between placebo and reward learning, we investigated whether verbal instructions in conjunction with a placebo intervention are capable of enhancing reward learning in healthy individuals by using a monetary reward-based reinforcement-learning task. Placebo intervention was performed with non-invasive brain stimulation techniques. In a randomized, triple-blind, cross-over study we investigated this cognitive placebo effect in healthy individuals by manipulating the participants' perceived uncertainty about the intervention's efficacy. Volunteers in the purportedly low- and high-uncertainty conditions earned more money, responded more quickly and had a higher learning rate from monetary rewards relative to baseline. Participants in the purportedly high-uncertainty conditions showed enhanced reward learning, and a model-free computational analysis revealed a higher learning rate from monetary rewards compared to the purportedly low-uncertainty and baseline conditions. Our results indicate that the placebo response is able to enhance reward learning in healthy individuals, opening up exciting avenues for future research in placebo effects on other cognitive functions.