Evidence that the anterior cingulate and supplementary somatosensory cortices generate the pain-related negative difference potential

Objective: The pain-related negative difference potential (NDP) is derived by subtracting sural nerve-evoked somatosensory evoked potentials elicited at the pain threshold level from those elicited at supra-pain threshold levels. This experiment evaluated a hypothesis derived from our earlier work, namely that the NDP is generated by pain-related activity in the primary somatosensory (SI) cortex. Methods: The dipole source localization method was applied to NDPs evoked by electrical stimulation of the finger and of the sural nerve in 20 subjects. Results: Comparison of several one-, two- and three-source configurations demonstrated that both the finger-evoked NDP and the sural nerve-evoked NDP are best-fit by two sources, with one located in or near the anterior cingulate cortex and the other in or near the supplementary somatosensory area. Conclusions: Both the anterior cingulate cortex and the supplementary somatosensory area receive afferent projections from medial thalamic nuclei that receive nociceptive inputs, and both have been shown to respond to noxious stimulation. Hence, although the results of this experiment did not confirm our hypothesis that the NDP is generated in SI, they are consistent with the hypothesis that the NDP is generated in the supraspinal pain pathways.