The influence of variability of prior experience and pain on placebo responses

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Although previous neuroimaging studies have identified cortical (rACC, PFC), subcortical (RVM, PAG), and spinal (dorsal horn) sites involved in placebo analgesia, the mechanism of how expectation and prior experience can shape pain perception is currently unknown. In analogy to multisensory integration we hypothesize that the brain integrates prior experience and expectation with incoming pain stimuli in a Bayesian sense. In this framework prior experience and expectation are considered as a ‘prior’ that is then combined with a likelihood (i.e., pain stimulus). Importantly, this framework takes uncertainty of the initial experience/expectation into account and therefore makes predictions about the posterior, i.e., the effect size of the placebo response. In essence, if the prior experience is kept at a similar mean strength but with different degrees of variance, the incoming data will gain more weight in the case of a highly variable expectation and thus result in a weaker placebo response. Conversely, if the experience is kept constant, but the incoming stimulus has a high level of variability, the experience will gain more weight, which will result in a stronger placebo effect.We will test this model in two experimental series. In the first series we will vary the variance of prior experience and in the second series we will vary the variance of the experienced data (i.e., likelihood). Using a novel cortico-spinal fMRI protocol, we will be able not only to assess cortical and spinal responses to painful stimuli in the context of placebo analgesia, but will also be in a position to investigate the connectivity between cortical, subcortical, and spinal areas.