Uncertainty of treatment efficacy moderates placebo effects on reinforcement learning

The placebo-reward hypothesis postulates that positive effects of treatment expectations on health (i.e., placebo effects) and reward processing share common neural underpinnings. Moreover, experiments in humans and animals indicate that reward uncertainty increases striatal dopamine, which is presumably involved in placebo responses and reward learning. Therefore, treatment uncertainty analogously to reward uncertainty may affect updating from rewards after placebo treatment. Here, we address whether different degrees of uncertainty regarding the efficacy of a sham treatment affect reward sensitivity. In an online between-subjects experiment with N = 141 participants, we systematically varied the provided efficacy instructions before participants first received a sham treatment that consisted of listening to binaural beats and then performed a probabilistic reinforcement learning task. We fitted a Q-learning model including two different learning rates for positive (gain) and negative (loss) reward prediction errors and an inverse gain parameter to behavioral decision data in the reinforcement learning task. Our results yielded an inverted-U-relationship between provided treatment efficacy probability and learning rates for gain, such that higher levels of treatment uncertainty, rather than of expected net efficacy, affect presumably dopamine-related reward learning. These findings support the placebo-reward hypothesis and suggest harnessing uncertainty in placebo treatment for recovering reward learning capabilities.