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.
Highlights
Transcranial direct current stimulation is the most frequently employed research tool in studies that use electrical current as a NIBS technique[3]
We investigated whether verbally manipulating the participants to be more or less certain about the effectiveness of the applied placebo NIBS would influence the performance of healthy individuals in a reinforcement-learning task, i.e., induce a cognitive placebo effect
The question of whether the placebo response is confined to placebo analgesia or patient-reported symptoms of various diseases has provoked a considerable debate in the placebo literature during the past years[52]
Summary
Transcranial direct current stimulation (tDCS) is the most frequently employed research tool in studies that use electrical current as a NIBS technique[3]. A prominent conceptual framework focusing on the dopamine (DA)-mediated placebo mechanisms suggests that the placebo response can be considered a special case of a reward anticipation process, characterized by a neural overlap between anticipating the putative beneficial effects of the treatment and anticipating rewards[14,15] In line with this hypothesis, substantial placebo-induced release of DA was detected both in the www.nature.com/scientificreports/. In the current study we examined whether placebo interventions associated with different verbal manipulations would be capable of enhancing reward learning in healthy individuals This active placebo intervention was applied using sham protocols of NIBS for the following reasons. The rationale for the application of tNILS was first to provide different treatment characteristics for the repeated-measures design both for the participants and the operator, and second, to avoid the possibility that participants or the operator would encounter earlier scientific publications on the effect of tDCS on cognitive functions that would contradict the verbal manipulation
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