Human ventromedial prefrontal cortex lesions enhance the effect of expectations on pain perception

Pain is strongly modulated by expectations and beliefs. Across species, subregions of ventromedial prefrontal cortex (VMPFC) are implicated in a variety of functions germane to pain, predictions, and learning. Human fMRI studies show that VMPFC activity tracks expectations about pain and mediates expectancy effects on pain-related activity in other brain regions. Prior lesion studies suggest that VMPFC may instead play a more general role in generating affective responses to painful stimuli. To test whether VMPFC is required to generate affective responses to pain or is more specifically involved in expectancy-based pain modulation, we studied responses to heat stimuli in five adults with bilateral surgical lesions of VMPFC and twenty healthy adults without brain damage. All participants underwent a quantitative sensory testing procedure followed by a pain expectancy task in which cues predicting either low or high pain were followed by intermittent medium intensity heat stimuli. Compared to adults without brain damage, individuals with VMPFC lesions reported larger differences in expected pain based on predictive cues and failed to update expectations following the covert introduction of unexpected medium temperature stimuli. Consistent with observed expectancy differences, subjective pain unpleasantness ratings in the VMPFC lesion group were more strongly modulated by cue during thermal stimulation. We found no group differences in overall pain sensitivity, nor in relationships between pain and autonomic arousal, suggesting that VMPFC damage specifically enhances the effect of expectations on pain processing, likely driven by impaired integration of new sensory feedback to update expectations about pain. These results provide essential new data regarding the specific functional contribution of VMPFC to pain modulation.