Pain-specific gamma-band oscillations recorded from the human insula

Abstract

Introduction: Pain is a multi­dimensional experience, including sensory­discriminative, affective­motivational, and cognitive­evaluative components. How these different dimensions integrate into a unified and coherent percept remains an open question (Moayedi 2014). Gamma­band oscillations (GBOs, 30­100 Hz) are considered to represent a possible mechanism to integrate low­level cortical processing of basic stimulus features with high­level cognitive processes. Zhang et al. (2012) reported that nociceptive stimuli elicit an enhancement of GBOs which can be measured using surface electroencephalograpy (EEG), and has been hypothesized to originate from the primary somatosensory cortex (SI). Because its magnitude appears to be specifically related to perceived pain intensity, this stimulus­evoked enhancement of GBOs in SI has been suggested to represent a specific biomarker for pain perception. The insula, especially its posterior portion, is considered to play a major role in pain perception, because insular lesions can alter pain perception, and because electrical stimulation and epileptic seizures in this region can generate pain­related experiences (Garcia­Larrea 2012). In the present study, we used direct intracerebral recordings performed in humans to investigate whether nociceptive stimulation elicits nociceptive­specific GBOs in the anterior and posterior insula. Methods: Insular activity was recorded from a total of 70 insular contacts in five patients with deep multicontact electrodes implanted for the presurgical evaluation of focal epilepsy (2 females, mean age: 29). The experiments comprised two sessions of four blocks each, one session per side of stimulation (right and left side of the body). The order of the blocks was randomized across participants. Each block consisted of 40 single­pulse stimuli, each lasting 40 ms, belonging to one of four sensory modalities: nociceptive, tactile, auditory and visual. Nociceptive stimuli consisted of CO2 laser pulses applied to the hand dorsum. Vibrotactile stimuli were delivered via a recoil­type vibrotactile transducer applied to the index fingertip. Visual stimuli were generated using a light­emitting diode placed on the hand dorsum. Auditory stimuli were lateralized 800­Hz sounds delivered through earphones. Participants were instructed to press a button as soon as they perceived each stimulus, and to rate its intensity on a numerical scale ranging from 0 to 10. Results: There was no significant difference in ratings of intensity across modalities (repeated­measures ANOVA, p=0.7). In four out of five patients, nociceptive stimuli consistently elicited a clear enhancement of GBO power at insular contacts, peaking 245 ms ± 12 ms after stimulus onset (Fig. 1), but not at other intracerebral contacts. Vibrotactile, auditory, and visual stimuli did not elicit such high frequency responses at any of the recorded contacts. Conclusions: Nociceptive stimuli elicit consistent GBOs in the human insula. Because non­nociceptive stimuli do not elicit a similar response, these high frequency oscillations could reflect activity specific for nociception, possibly involved in the integration of stimulus­driven and top­down determinants of pain perception