Differential neural activity predicts the long-term stability of the effects of positive and negative expectations on pain

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 tested whether expectations were reflected in EEG oscillatory activity at the second measurement. Both positive and negative pain modulation effects persisted over the tested time-period and did not undergo extinction. Expectations of higher compared to lower pain led to larger theta-to-alpha EEG activity. Most interestingly, differential neural activity in fMRI was correlated with persistent expectations. Individual differences in the persistence of positive expectation effects were related to reduced amygdala activity and enhanced activity in the anterior insula and dorsolateral prefrontal cortex (DLPFC) during the first session. In contrast, persistence of negative expectation effects was predicted by enhanced thalamus activity. Our findings indicate relatively stable placebo and nocebo effects over longer time courses, but this persistence is based on different neural areas for positive and negative expectations.