Sources of cortical responses to painful CO 2 laser skin stimulation of the hand and foot in the human brain

Baumgärtner, Ulf, Wiebke Tiede, Rolf-Detlef Treede, and A. D. (Bud) Craig. Laser-evoked potentials are graded and somatotopically organized anteroposteriorly in the operculoinsular cortex of anesthetized monkeys. J Neurophysiol 96: [2802][2803][2804][2805][2806][2807][2808] 2006. First published August 9, 2006; doi:10.1152/jn.00512.2006. 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. I N T R O D U C T I O NThe operculoinsular cortex has been identified as an important nociceptive region in humans by several methods, including EEG recordings of laser-evoked potentials (LEPs) and functional imaging (Apkarian et al. 2005). To investigate the cortical representation of pain, the most specific stimulus available is a noxious heat pulse generated by brief infrared laser stimulation. Laser pulses activate nociceptive A␦-and C-fibers in humans and monkeys, without concomitant activation of tactile afferents, and generate prominent LEPs within the brain that can be recorded from the surface of the cortex or from the scalp in awake humans (Bromm et al. 1984;Treede et al. 1995). The earliest cortical LEP correlates with pain sensation in several ways, and dipole source reconstruction analyses indicate that its main source lies in the contralateral operculoinsular region (Garcia-Larrea et al. 2003;Iannetti et al. 2005;Vogel et al. 2003). This observation is consistent with clinical findings ...

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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

Baumgärtner

Tiede²,

Treede³

et al. 2006

“…Moreover, these LEP components, as modeled by dipole sources analysis, appeared in the S2/insula region both ipsilaterally and contralaterally. Such sources were also obtained by several other groups (Bromm and Chen 1995;Kanda et al 2000;Miyazaki et al 1994;Tarkka and Treede 1993;Valeriani et al 2000;Watanabe et al 1998 operculum (S2; see Eickhoff et al 2006a,b) and the INS, the sources revealed by the bivariate tvGCI approach might depict the driving activity of S2/INS networks (Garcia-Larrea et al 2003;Peyron et al 2000). Additionally, source localizations of the N2 component in S1 have been reported for scalp LEPs (Tarkka and Treede 1993), laser-evoked magnetic fields (LEFs; e.g., Kanda et al 2000), and subdural recordings (e.g., Ohara et al 2004b).…”

Section: Discussionsupporting

confidence: 55%

How Do Brain Areas Communicate During the Processing of Noxious Stimuli? An Analysis of Laser-Evoked Event-Related Potentials Using the Granger Causality Index

Weiß

Hesse²,

Ungureanu³

et al. 2008

Several imaging techniques have identified different brain areas involved in the processing of noxious stimulation and thus in the constitution of pain. However, only little is known how these brain areas communicate with one another after activation by stimulus processing and which areas directionally affect or modulate the activity of succeeding areas. One measure for the analysis of such interactions is represented by the Granger Causality Index (GCI). In applying time-varying bivariate and partial variants of this concept (tvGCI), the aim of the present study was to investigate the interaction of neural activities between a set of scalp electrodes that best represent the brain electrical neural activity of major cortical areas involved in the processing of noxious laser-heat stimuli and their variation in time. Bivariate and partial tvGCIs were calculated within four different intervals of laser-evoked event-related potentials (LEPs) including a baseline period prior to stimulus application and three intervals immediately following stimulus application, i.e., between 170 and 200 ms (at the N2 component), between 260 and 320 ms (P2 component), and between 320 and 400 ms (P3 component of LEPs). Results show some similarities, but also some striking differences between bivariate and partial tvGCIs. These differences might be explained by the nature of bivariate and partial tvGCIs. However, both tvGCI approaches revealed a directed interaction between medial and lateral electrodes of the centroparietal region. This result was interpreted as a directed interaction between the anterior cingulate cortex and the secondary somatosensory cortex and the insula, structures that are significantly involved in the constitution of pain.

“…Hence, also with laser stimulation of a proximal territory such as the skin of the back, the source analysis located the generator in the same region found with hand, foot, or face stimulation (Bromm and Chen 1995;Valeriani et al 1996Valeriani et al , 2000.…”

Section: Brain Structuresmentioning

confidence: 75%

“…Using a high number of trials and grand averages, some studies aimed at identifying the cerebral generators of the late LEPs (Bromm and Chen 1995;Valeriani et al 1996Valeriani et al , 2000, found early components (termed N1-P1) that probably originate in the somatosensory cortex, in agreement with functional imaging studies (Brooks et al 2002;Hofbauer et al 2001;Talbot et al 1991). Because of the relatively small number of trials at each stimulated site, we could not identify any components earlier than the main negative-positive complex (termed N2-P2) described in RESULTS.…”

Section: Brain Structuresmentioning

confidence: 99%

Evidence of a Specific Spinal Pathway for the Sense of Warmth in Humans

Iannetti

Truini

Romaniello

et al. 2003

122

Evidence of a specific spinal pathway for the sense of warmth in humans. J Neurophysiol 89: 562-570, 2003; 10.1152/jn.00393.2002. While research on human sensory processing shows that warm input is conveyed from the periphery by specific, unmyelinated primary sensory neurons, its pathways in the central nervous system (CNS) remain unclear. To gain physiological information on the spinal pathways that convey warmth or nociceptive sensations, in 15 healthy subjects, we studied the cerebral evoked responses and reaction times in response to laser stimuli selectively exciting A␦ nociceptors or C warmth receptors at different levels along the spine. To minimize the conduction distance along the primary sensory neuron, we directed CO 2 -laser pulses to the skin overlying the vertebral spinous processes. Using brain source analysis of the evoked responses with highresolution electroencephalography and a realistic model of the head based on individual magnetic resonance imaging scans, we also studied the cortical areas involved in the cerebral processing of warm and nociceptive inputs. The activation of C warmth receptors evoked cerebral potentials with a main positive component peaking at 470 -540 ms, i.e., a latency clearly longer than that of the corresponding wave yielded by A␦ nociceptive input (290 -320 ms). Spinal neurons activated by the warm input had a slower conduction velocity (2.5 m/s) than the nociceptive spinal neurons (11.9 m/s). Brain source analysis of the cerebral responses evoked by the A␦ input yielded a very strong fit for one single generator in the mid portion of the cingulate gyrus; the warmth-related responses were best explained by three generators, one within the cingulate and two in the right and left opercular-insular cortices. Our results support the existence of slowconducting second-order neurons specific for the sense of warmth.