Assessments of anterior cingulate cortex in experimental animals and humans have led to unifying theories of its structural organization and contributions to mammalian behaviour. The anterior cingulate cortex forms a large region around the rostrum of the corpus callosum that is termed the anterior executive region. This region has numerous projections into motor systems, however, since these projections originate from different parts of anterior cingulate cortex and because functional studies have shown that it does not have a uniform contribution to brain functions, the anterior executive region is further subdivided into 'affect' and 'cognition' components. The affect division includes areas 25, 33 and rostral area 24, and has extensive connections with the amygdala and periaqueductal grey, and parts of it project to autonomic brainstem motor nuclei. In addition to regulating autonomic and endocrine functions, it is involved in conditioned emotional learning, vocalizations associated with expressing internal states, assessments of motivational content and assigning emotional valence to internal and external stimuli, and maternal-infant interactions. The cognition division includes caudal areas 24' and 32', the cingulate motor areas in the cingulate sulcus and nociceptive cortex. The cingulate motor areas project to the spinal cord and red nucleus and have premotor functions, while the nociceptive area is engaged in both response selection and cognitively demanding information processing. The cingulate epilepsy syndrome provides important support of experimental animal and human functional imaging studies for the role of anterior cingulate cortex in movement, affect and social behaviours. Excessive cingulate activity in cases with seizures confirmed in anterior cingulate cortex with subdural electrode recordings, can impair consciousness, alter affective state and expression, and influence skeletomotor and autonomic activity. Interictally, patients with anterior cingulate cortex epilepsy often display psychopathic or sociopathic behaviours. In other clinical examples of elevated anterior cingulate cortex activity it may contribute to tics, obsessive-compulsive behaviours, and aberrent social behaviour. Conversely, reduced cingulate activity following infarcts or surgery can contribute to behavioural disorders including akinetic mutism, diminished self-awareness and depression, motor neglect and impaired motor initiation, reduced responses to pain, and aberrent social behaviour. The role of anterior cingulate cortex in pain responsiveness is suggested by cingulumotomy results and functional imaging studies during noxious somatic stimulation. The affect division of anterior cingulate cortex modulates autonomic activity and internal emotional responses, while the cognition division is engaged in response selection associated with skeletomotor activity and responses to noxious stimuli. Overall, anterior cingulate cortex appears to play a crucial role in initiation, motivation, and goal-directed behaviours.(ABSTRACT...

PrefaceAcute pain and emotion are processed in two forebrain networks and cingulate cortex is in both. Although Brodmann's cingulate gyrus had two divisions and was not based on any functional criteria, functional imaging reports the location of activity by this model. Recent cingulate cytoarchitectural studies support a four-region model with subregions based on connections and qualitatively unique functions. Although pain and emotion activity have been widely reported, some view these as emergent products of the brain rather than small aggregates of neurons. Here we assess pain and emotion in each cingulate subregion and assess whether pain is co-localized with negative affect. Amazingly, these activation patterns do not simply overlap. KeywordsNociception; affect; limbic cortex; neurocytology; midline thalamus; visceral pain; anterior cingulate cortex; midcingulate cortex Pain is evoked during noxious body stimulation or through negative emotional events and memories. To understand pain we need to consider how and where in the brain it hurts. In previous decades there has been an emphasis on pain "sensation", which involves assessing the location and intensity of noxious stimuli. Somatosensory localization and intensity coding, however, are not necessarily linked with emotional responses, if they are processed in different parts of the brain. Moreover, linkage of pain and its affective (autonomic) substrates in the brain was not a viable research target until the conscious reports of human subjects during noxious stimulation could be related to changes in the brain with functional imaging. Imaging psychophysics allows one to correlate brain changes with sensory stimulation parameters. In terms of pain, this meant that modulating the level of unpleasantness might provide insight into the substrate of affect. Just as important and in parallel over the past decade, there has been a significant series of studies on emotional modulation of brain circuits that are assessed with scripts, faces, or films with emotional or non-emotional content. This provides control conditions and subject reports that were not previously possible in experimental animals and methods of relating emotion to specific brain circuits. The value of human functional imaging is apparent in studies of the amygdala during fear conditioning. An integrated study of the nociceptive connections, emotional activation and behavioural conditioning has provided important insights into the sensory inputs to the amygdala and its projections to parts of what are generally termed the emotional motor systems and this has been pivotal to driving new research paradigms. 1,2 In spite of the wealth of information about the amygdalar substrates of Contact information: Brent A. Vogt,

The cingulate gyrus is a major part of the "anatomical limbic system" and, according to classic accounts, is involved in emotion. This view is oversimplified in light of recent clinical and experimental findings that cingulate cortex participates not only in emotion but also in sensory, motor, and cognitive processes. Anterior cingulate cortex, consisting of areas 25 and 24, has been implicated in visceromotor, skeletomotor, and endocrine outflow. These processes include responses to painful stimuli, maternal behavior, vocalization, and attention to action. Since all of these activities have an affective component, it is likely that connections with the amygdala are critical for them. In contrast, posterior cingulate cortex, consisting of areas 29, 30, 23, and 31, contains neurons that monitor eye movements and respond to sensory stimuli. Ablation studies suggest that this region is involved in spatial orientation and memory. It is likely that connections between posterior cingulate and parahippocampal cortices contribute to these processes. We conclude that there is a fundamental dichotomy between the functions of anterior and posterior cingulate cortices. The anterior cortex subserves primarily executive functions related to the emotional control of visceral, skeletal, and endocrine outflow. The posterior cortex subserves evaluative functions such as monitoring sensory events and the organism's own behavior in the service of spatial orientation and memory.