The neural processes of acquiring placebo effects through observation.

Learning through social observation is critical for humans. The present study investigates the neural processes underlying the acquisition of placebo effects through observational learning. We created a new functional magnetic resonance imaging (fMRI) paradigm where participants (n ​= ​38, healthy, both sexes) observed a demonstrator experiencing pain relief by a placebo treatment cream and experiencing pain without a treatment (control cream), and subsequently performed the same procedure themselves. Participants demonstrated placebo hypoalgesia while they performed the procedure themselves, confirming that observational learning can lead to placebo effects. During the observational learning phase, fMRI analysis showed a modulation of the amygdalae, periaqueductal grey, temporoparietal junctions (TPJ), and dorsolateral prefrontal cortex (DLPFC). Connectivity between the DLPFC and TPJ during the observational learning task was modulated by the placebo treatment and predicted subsequent placebo effects. Mediation analysis further confirmed that the DLPFC-TPJ connectivity formally mediated the effect of the observed treatment condition on subsequent placebo effects. Additionally, pre-recorded resting state connectivity between the DLPFC and TPJ also predicted observationally-learned placebo effects. Our findings provide an understanding of the neural processes during the acquisition of placebo effects through observation and indicate a critical role for DLPFC-TPJ integration processes during observational learning of therapeutic outcomes.