Direct evidence of nociceptive input to human anterior cingulate gyrus and parasylvian cortex

Many lines of evidence implicate the anterior cingulate cortex (ACC, Brodmann’s area [BA] 24) and parasylvian cortex in pain perception. Clinical studies demonstrate alterations in pain and temperature sensation after lesions of these structures. Imaging studies reveal increased blood flow in ACC and parasylvian cortex, both ipsilateral and contralateral to painful stimuli. Additionally, painful stimuli evoke potentials that seem t arise from these cortical structures. Short-duration cutaneous stimulation with a CO2 laser evokes painrelated potentials (LEPs) with a vertex maximum and an initial negative peak followed by a positive wave. The cutaneous laser stimulus evokes a pure pain sensation due to selective activation of cutaneous nociceptors. Electrical source modeling has suggested that the vertex maximum of the scalp LEP arises, in part, from generators in the cingulate gyrus and parasylvian cortex. Thus, imaging and electrophysiologic studies suggest that these cortical structures are activated by painful stimuli. However, these studies incorporate multiple assumptions and therefore do not establish the presence of nociceptive inputs to ACC and parasylvian cortex. We review our recent reports of intracranial potentials evoked by painful stimuli. These studies provide direct evidence of nociceptive inputs to the human ACC and parasylvian cortex