Nociceptive local field potentials recorded from the human insula are not specific for nociception

Introduction. Insular lesions can alter pain perception, and direct electrical stimulation of the insula can generate pain-related sensations. Furthermore, direct intracerebral recordings have shown that nociceptive stimulation can elicit robust local field potentials (LFPs) in the insula, interpreted as reflecting activity specifically involved in the encoding of pain and temperature sensations. Aims. Taking advantage of the high spatial resolution of direct intracerebral recordings performed in humans, our aim was to assess whether the insula exhibits responses that are specific to nociceptive stimulation. Methods. Six patients were investigated using depth electrodes implanted at different locations, comprising the anterior and posterior insula, for a total of 62 insular sites. Participants received brief stimuli belonging to each of the following four modalities: nociceptive laser stimuli, non-nociceptive tactile stimuli, auditory stimuli, and visual stimuli. The stimuli were delivered in blocks, both on the right and on the left side of the body. Results. All four types of stimuli elicited consistent LFPs in the posterior and anterior insula, appearing as large biphasic waves. The spatial distribution of the responses elicited by nociceptive stimulation at the different insular contacts was indistinguishable from the spatial distribution of the responses elicited by non-nociceptive tactile, auditory and visual stimulation. Conclusions Our results indicate that, in both the posterior and the anterior insula, LFPs elicited by transient nociceptive stimuli reflect cortical activities that are unspecific for pain. Importantly, this conclusion is not incompatible with the possible involvement of the insula in pain perception

Stimulus-evoked gamma-band oscillations recorded from the human insula may reflect early and nociceptive-specific stages of cortical processing

Introduction. Gamma-band oscillations (GBOs, 30-100 Hz) are considered to represent a mechanism for integrating low-level cortical processing of basic stimulus features with high-level cognitive processes. Several studies have shown that nociceptive stimuli elicit a transient enhancement of GBOs in the primary somatosensory (SI) and motor (MI) cortices whose magnitude relates to perceived pain intensity. GBOs may therefore constitute a specific and clinically relevant biomarker for the perception of pain. To this date, no study has ever investigated the presence of GBOs in the insula, a region considered to have a major role in pain representation. Aims. Using direct intracerebral recordings performed in humans, we investigate whether nociceptive stimulation elicits nociceptive-specific GBOs in the anterior and posterior insula. Methods. Six patients with deep multicontact electrodes implanted for the presurgical evaluation of focal epilepsy took part in the study. Insular activity was recorded from a total of 62 insular contacts. Patients received stimuli belonging to each of the following four sensory modalities: nociceptive somatosensory, non-nociceptive somatosensory, auditory, and visual. Results. In all patients, nociceptive stimuli consistently elicited GBOs at one or more insular electrodes, but not at other cortical and subcortical locations. In contrast, non-nociceptive somatosensory, auditory, and visual stimuli did not elicit such high frequency activities at any of the recorded contacts. Conclusions. Nociceptive stimuli elicit consistent GBOs in the insula. Because non-nociceptive stimuli do not elicit a similar response, these responses could reflect activity specific for nociception, possibly involved in the integration of stimulus-driven and top-down determinants of pain perception