Laser-Evoked Potentials Are Graded and Somatotopically Organized Anteroposteriorly in the Operculoinsular Cortex of Anesthetized Monkeys

1 Institute of Physiology and Pathophysiology, Johannes Gutenberg University, Mainz, Germany; and 2 Atkinson Research Laboratory, Barrow Neurological Institute, Phoenix, Arizona Submitted 12 May 2006; accepted in final form 5 August 2006 The operculoinsular cortical region has a major role in the representation of noxious stimuli, based on functional imaging observations, clinical lesion studies, and EEG recordings of specifically pain-related laser-evoked potentials (LEPs) in humans. The source of LEPs has not been identified, and several somatic representations and cytoarchitectonic areas may be present in this complex region. To overcome the limitations of human studies, a primate model is needed in which the main LEP generator in this region can be localized and characterized using invasive methods. We obtained EEG recordings of evoked responses to noxious laser stimulation at different intensities and performed dipole source analyses in three anesthetized macaque monkeys. We show that LEPs can be recorded that 1 ) grade with stimulus intensity, 2 ) display two distinct responses corresponding to the "late" (A -fiber) and the "ultralate" (C-fiber) LEPs recorded in humans, and 3 ) originate deep within the operculoinsular region, thus establishing a valid primate model for experimental analysis of LEPs. Further, we found that LEPs elicited from the leg, arm, and ear display a global somatotopy organized in the posteroanterior direction (leg posterior and arm and ear anterior), which contrasts starkly with the mediolateral (leg to face) gradient of the somatotopic representations in primary and secondary somatosensory cortices. These results provide evidence that the main generator of pain-related activity in operculoinsular cortex may participate in both the somatic localization and the intensity discrimination of pain sensations, and they indicate that it may be distinct from the traditional somatosensory cortices. Address for reprint requests and other correspondence: A. D. Craig, Atkinson Research Laboratory, Barrow Neurological Institute, 350 West Thomas Rd., Phoenix, AZ 85013 (E-mail: bcraig{at}chw.edu )