Pain and emotion interactions in subregions of the cingulate gyrus

Abstract

The cingulate gyrus participates in pain and emotion processing. Although Brodmann identified two regions without knowledge of their functional activity, recent cytoarchitectural, connection and functional imaging studies show that the cingulate gyrus actually has four regions, with associated subregions, and that each makes a qualitatively unique contribution to brain functions. These regions and subregions are the subgenual and pregenual anterior cingulate cortex (sACC and pACC), the anterior and posterior midcingulate cortex (aMCC and pMCC), the dorsal and ventral posterior cingulate cortex (dPCC and vPCC), and the retrosplenial cortex (RSC). Pain processing is usually conceived in terms of two cognitive domains with sensory-discriminative and affective-motivational components. The ACC and MCC are thought to mediate the latter of these components. The nociceptive properties of cingulate neurons include large somatic receptive fields and a predominance of nociceptive activations, with some that even respond to an innocuous tap. These responses are predicted by the properties of midline and intralaminar thalamic neurons that project to the cingulate cortex, including the parafascicular, paraventricular and reuniens nuclei that derive their nociceptive information from the spinal cord, the subnucleus reticularis dorsalis and the parabrachial nuclei. Human functional imaging studies of activity during acute noxious stimulation of cutaneous, muscular and visceral tissues show that cutaneous activity is greatest throughout the MCC, whereas the pACC, and to a lesser extent the aMCC, are active during noxious deep tissue stimulation. In addition, electroencephalographic findings indicate that a short-latency nociceptive response can be generated by noxious and innocuous stimuli from the pMCC and dPCC. To investigate the hypothesis that the cingulate cortex mediates pain affect, we localized the simple emotions of sadness, happiness, anger and fear in the framework of cingulate subregions. Amazingly, it failed to show a simple overlap of pain affect sites and sadness as predicted. The five main outcomes of this study are as follows. First, the sACC is involved in negatively valenced memories. Second, the pACC is involved in happy emotions. Third, the aMCC is involved in fear. Fourth, the pMCC and dPCC have little or no involvement in emotion. Fifth, the vPCC is involved in emotion but not in a specific way, as it is also activated by control conditions without emotional valence. Rather than having a simple role in pain affect, the cingulate gyrus seems to have three roles in pain processing. First, the pACC is involved in unpleasant experiences and directly drives autonomic outputs. Second, the aMCC is involved in fear, prediction of negative consequences and avoidance behaviours through the rostral cingulate motor area. Third, the pMCC and dPCC are not involved in emotion but are driven by short-latency somatosensory signals that mediate orientation of the body in space through the caudal cingulate motor area. In addition to these functions, nociceptive stimuli reduce activity in the vPCC and, therefore, activity in a subregion that normally evaluates the self-relevance of incoming visual sensations. So, there is a complex interaction between pain and emotion. Moreover, hypnoanalgesia and opioid and acupuncture placebos indicate mechanisms whereby the cingulate subregions can be engaged for therapeutic intervention.