Prediction and action in cortical pain processing.

Predicting that a stimulus is painful facilitates action to avoid harm. But how distinct are the neural processes underlying the prediction of upcoming painful events vis-à-vis those taking action to avoid them? Here, we investigated brain activity as a function of current and predicted painful or nonpainful thermal stimulation, as well as the ability of voluntary action to affect the duration of upcoming stimulation. Participants performed a task which involved the administration of a painful or nonpainful stimulus (S1), which predicted an immediately subsequent very painful or nonpainful stimulus (S2). Pressing a response button within a specified time window during S1 either reduced or did not reduce the duration of the upcoming stimulation. Predicted pain increased activation in several regions, including anterior cingulate cortex (ACC), midcingulate cortex (MCC), and insula; however, activation in ACC and MCC depended on whether a meaningful action was performed, with MCC activation showing a direct relationship with motor output. Insula's responses for predicted pain were also modulated by potential action consequences, albeit without a direct relationship with motor output. These findings suggest that cortical pain processing is not specifically tied to the sensory stimulus, but instead, depends on the consequences of that stimulus for sensorimotor control of behavior.