The anterior cingulate cortex contains distinct areas dissociating external from self-administered painful...

The anterior cingulate cortex (ACC) has a pivotal role in human pain processing by integrating sensory, executive, attentional, emotional, and motivational components of pain. Cognitive modulation of pain-related ACC activation has been shown by hypnosis, illusion and anticipation. The expectation of a potentially noxious stimulus may not only differ as to when but also how the stimulus is applied. These combined properties led to our hypothesis that ACC is capable of distinguishing external from self-administered noxious tactile stimulation. Thermal contact stimuli with noxious and non-noxious temperatures were self-administered or externally applied at the resting right hand in a randomized order. Two additional conditions without any stimulus-eliciting movements served as control conditions to account for the certainty and uncertainty of the impending stimulus. Calculating the differences in the activation pattern between self-administered and externally generated stimuli revealed three distinct areas of activation that graded with perceived stimulus intensity: (i) in the posterior ACC with a linear increase during external but hardly any modulation for the self-administered stimulation, (ii) in the midcingulate cortex with activation patterns independent of the mode of application and (iii) in the perigenual ACC with increasing activation during self-administered but decreasing activation during externally applied stimulation. These data support the functional segregation of the human ACC: the posterior ACC may be involved in the prediction of the sensory consequences of pain-related action, the midcingulate cortex in pain intensity coding and the perigenual ACC is related to the onset uncertainty of the impending stimuli.