Differential Neural Activity Predicts the Long-term Stability of the Effects of Positive and Negative Expectations on Pain

Abstract Expectations modulating pain perception is a well-researched phenomenon, but less is known about the persistence of expectation effects over longer time courses. In this preregistered study, we examined the persistence of positive (placebo) and negative (nocebo) expectation effects over one week and investigated whether neural activity on day 1 (fMRI) can predict the stability of these effects one week later (n = 41). We further tested whether expectations were reflected in EEG oscillatory activity. Both positive and negative expectations persisted over the tested time-period and did not undergo extinction. Expectations of higher pain led to larger theta-to-alpha EEG activity. Most interestingly, differential neural activity was predictive for persistent positive and negative expectations. Individual differences in the persistence of positive expectation effects were predicted by reduced amygdala activity and enhanced activity in the anterior insula and in the dorsolateral prefrontal cortex (DLPFC) in the first session, while the persistence of negative expectation effects was predicted by enhanced activity in the thalamus. Our findings indicate that placebo and nocebo effects are relatively stable over longer time courses, but this persistence is based on different neural areas for positive and negative expectations within larger neural networks that are observed during the actual processing.