A new perspective on the literature about pain and emotion processing in the cingulate gyrus is provided by the four-region neurobiological model and its associated subregions. Indeed, linkages can be made directly on the basis of numerous studies rather than attempting a single group analysis and this provides added confidence in the conclusions. Furthermore, both matches and mismatches with expected parallels between processing in these two distributed networks become more apparent in this context. Amazingly, the most common acute pain and simple emotion plots suggest there are complex relationships between these cortical functions rather than a simple overlap of negative emotions and pain affect as predicted from the dual-cognitive model of pain processing. Of course, it needs to be reiterated that these plots are of peak voxel activity from many studies, they do not represent the full extent of activation, and the studies employed were only those reporting cingulate activations. In spite of these caveats, the following observations appear to be justified.
First, the fear and pain sites overlap in aMCC and validate the general conclusion of this region in avoidance behaviours. This match between the two systems occurs in the context of heavy MITN inputs to it.
Second, it is surprising that pMCC has no consistent emotion activations yet robust nociceptive responses. Assuming that nociceptive responses are generally short-latency, it seems reasonable to conclude that these evoke skeletomotor, body orientation to the noxious stimulus without affective (autonomic) or emotional (valenced) content. This would likely be mediated via the caudal cingulate motor area that appears to operate more as a skeletomotor integrator rather than in the assessment of behavioural outcomes using valence-coded information.
Third, visceral nociceptive activity is associated mainly with the pACC yet this is not an autonomic integrative center like sACC. Indeed, although this region is most often associated with happiness in studies of simple emotion, amplification of unpleasantness during noxious stimulation enhances the activity in the caudal part of pACC and not sACC32
. The four-region model would have predicted preferential sACC activation during noxious stimulation of skin and viscera and this is one of the most striking incongruities (mismatches) in these observations and requires further explanation. Although sACC is sensitive to susceptibility artifacts with high field strength magnets, many studies of acute pain were done with PET in which this was not an issue. It is also true that pain anticipation can reduce cerebral blood flow in sACC51, 52
and this could contribute to a general lack of signal in this region during acute pain. Finally, sad events that evoked sACC activity tended to be associated with personally relevant events and not a simple, external, noxious stimulus. It is possible that pain could engage sACC is a person-specific manner and the currently used stimulation paradigms are not relevant to the internal states of individual subjects. Another way of expressing this concern is to say that the unpleasantness of a noxious thermal stimulus does not generate an adequately negative emotional event to drive sACC.
Fourth, acute nociceptive stimulation does not activate vPCC as part of a generalized self-relevance assessment. It appears that the MITN-mediated nociceptive signal bypasses processing in vPCC and this latter system is primarily involved in visual stimulus assessment. Indeed, nociceptive stimulation actually shuts off much of PCC activity.33, 35
Thus, emotion activations of vPCC have little or nothing to do with pain affect because this subregion does not receive MITN inputs and there may be a cognitively mediated mechanism whereby activity in this area is inactivated during noxious stimulation. Inactivation of vPCC could be one mechanism of reducing the overall perception of noxious stimulation and reduce suffering.
Fifth, the dPCC does not appear to have a specific role in pain processing because it can be activated with noxious and innocuous stimulation. Importantly, this region and adjacent pMCC likely dominate activity in the caudal cingulate motor area and mediate rapid, body orientation to somatic stimuli and they both have little or nothing to do with emotion.
It appears that the four-region neurobiological model of the cingulate gyrus and its subregions are a productive way to assess interchanges between pain and emotion networks in the cingulate gyrus. We predict that this will be true for many of its other essential functions of this region. Surprisingly, the cingulate cortex is not uniformly involved in emotion and not all pain-activation sites are associated with affect or emotion – facts that should lead to a better understanding of how each is processed. Although the MITN provide direct circuits to each cingulate region, this projection differs in density to each subregion and each subregion employs this information differently for pain processing. In conclusion, the cingulate gyrus mediates three main aspects of pain processing: fear-avoidance in aMCC, unpleasantness in pACC, and skeletomotor orientation of the body to the noxious stimulus in pMCC and dPCC. The MCC and dPCC are generally engaged in premotor planning and may have little to do with sensation. Even the fear signal in aMCC might be more closely associated with predicting behavioural outcomes than sensory affect per se.