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1. Two experiments were aimed at investigating the functional organization of the human anterior cingulate cortex (ACC) in relation to higher-order motor control. 2. The 15O-labeled H2O bolus method was used to measure relative changes of regional cerebral blood flow (rCBF) in 18 healthy human subjects as they performed oculomotor, manual, or speech tasks. 3. Task-specific rCBF changes were obtained in distinct subregions of the ACC, depending on the output system employed. The oculomotor and the manual task-related foci were found in the rostral and caudal regions of the ACC, respectively, whereas the speech foci were localized within two cingulate subregions, the intermediate dorsal and the rostral ACC. 4. In the manual tasks, two groups of activation foci could be distinguished, one just behind and the other just in front of the vertical plane traversing the anterior commissure. 5. The above pattern of rCBF changes was observed only if there was concomitant activation within the lateral prefrontal cortex (except for the posterior group of foci obtained in the manual tasks). 6. The localization of output-specific rCBF changes within the human ACC is consistent with the known somatotopic organization of the cingulate cortex in the monkey. 7. It is tentatively proposed that the ACC participates in motor control by facilitating the execution of the appropriate responses and/or suppressing the execution of the inappropriate ones. Such a modulatory effect would be of particular importance when behavior has to be modified in new and challenging situations.

Pain is a diverse sensory and emotional experience that likely involves activation of numerous regions of the brain. Yet, many of these areas are also implicated in the processing of nonpainful somatosensory information. In order to better characterize the processing of pain within the human brain, activation produced by noxious stimuli was compared with that produced by robust innocuous stimuli. Painful heat (47-48 degrees C), nonpainful vibratory (110 Hz), and neutral control (34 degrees C) stimuli were applied to the left forearm of right-handed male subjects. Activation of regions within the diencephalon and telencephalon was evaluated by measuring regional cerebral blood flow using positron emission tomography (15O-water-bolus method). Painful stimulation produced contralateral activation in primary and secondary somatosensory cortices (SI and SII), anterior cingulate cortex, anterior insula, the supplemental motor area of the frontal cortex, and thalamus. Vibrotactile stimulation produced activation in contralateral SI, and bilaterally in SII and posterior insular cortices. A direct comparison of pain and vibrotactile stimulation revealed that both stimuli produced activation in similar regions of SI and SII, regions long thought to be involved in basic somatosensory processing. In contrast, painful stimuli were significantly more effective in activating the anterior insula, a region heavily linked with both somatosensory and limbic systems. Such connections may provide one route through which nociceptive input may be integrated with memory in order to allow a full appreciation of the meaning and dangers of painful stimuli. These data reveal that pain-related activation, although predominantly contralateral in distribution, is more widely dispersed across both cortical and thalamic regions than that produced during innocuous vibrotactile stimulation. This distributed cerebral activation reflects the complex nature of pain, involving discriminative, affective, autonomic, and motoric components. Furthermore, the high degree of interconnectivity among activated regions may account for the difficulty of eliminating pathological pain with discrete CNS lesions.