Neural correlates of expected and perceived treatment efficacy concerning open-label placebos for reducing emotional distress.

Background: Treatment expectations for open-label placebos (OLPs) - placebos prescribed transparently - refer to what a person anticipates will happen as a result of taking the placebo. The actual outcome of OLP treatment may deviate from the initial expectation.

Method: A total of 108 participants received OLP treatment for reducing visually induced emotional distress during functional magnetic resonance imaging. They rated the expected effect of the OLP before the experiment, and evaluated the perceived effect after the experiment. Ratings reflecting the degree of outcome deviation from expectation were correlated with brain activity in regions of interest (dorsolateral/ventrolateral prefrontal cortex, anterior cingulate cortex (ACC), insula, inferior parietal cortex).

Results: Activity in the ACC, the insula, and parietal regions (region-of-interest findings), as well as the parahippocampus (whole-brain finding) was lower when the perceived treatment outcome met or even exceeded expectations.

Conclusions: A positive expectation-outcome evaluation for the OLP was associated with reduced activity in brain regions decoding the salience (insula, ACC) and context of stimuli (parahippocampus). These findings shed light on the mechanisms through which OLPs influence emotion regulation.