Integration of prior expectations and suppression of prediction errors during expectancy-induced pain modulation: the influence of anxiety and pleasantness

Abstract

Pain perception arises from the integration of prior expectations with sensory information. Although recent work has demonstrated that treatment expectancy effects (e.g., placebo hypoalgesia) can be explained by a Bayesian integration framework incorporating the precision level of expectations and sensory inputs, the key factor modulating this integration in stimulus expectancy-induced pain modulation remains unclear. In a stimulus expectancy paradigm combining emotion regulation in healthy male and female adults, we found that participants’ voluntary reduction in anticipatory anxiety and pleasantness monotonically reduced the magnitude of pain modulation by negative and positive expectations, respectively, indicating a role of emotion. For both types of expectations, Bayesian model comparisons confirmed that an integration model using the respective emotion of expectations and sensory inputs explained stimulus expectancy effects on pain better than using their respective precision. For negative expectations, the role of anxiety is further supported by our fMRI findings that (i) functional coupling within anxiety-processing brain regions (amygdala and anterior cingulate) reflected the integration of expectations with sensory inputs, and (ii) anxiety appeared to impair the updating of expectations via suppressed prediction error signals in the anterior cingulate, thus perpetuating negative expectancy effects. Regarding positive expectations, their integration with sensory inputs relied on the functional coupling within brain structures processing positive emotion and inhibiting threat responding (medial orbitofrontal cortex and hippocampus). In summary, different from treatment expectancy, pain modulation by stimulus expectancy emanates from emotion-modulated integration of beliefs with sensory evidence and inadequate belief updating.Significance StatementAlthough evidence indicates that human pain experiences stem from the integration of prior beliefs with sensory evidence, the key factor that biases this integration process as pain perception is affected by stimulus expectancy remains unclear. Using fMRI, we examine participants’ emotional reactions when they expect and then perceive incoming painful stimuli. We find that the elicited anxiety during pain enhancement by expectations of increased pain influences the integration of expectations with sensory inputs and appears to impair the updating of expectations. By contrast, this integration mainly involves pleasant emotion provoked during pain attenuation by expectations of decreased pain. This work highlights the important role of emotions when human experience of pain is shaped by stimulus expectancy.