Transient nociceptive stimuli elicit robust phase-locked local field potentials (LFPs) in the human insula. However, these responses are not preferential for nociception, as they are also elicited by transient non-nociceptive vibrotactile, auditory, and visual stimuli. Here, we investigated whether another feature of insular activity, namely gamma-band oscillations (GBOs), is preferentially observed in response to nociceptive stimuli. Although nociception-evoked GBOs have never been explored in the insula, previous scalp electroencephalography and magnetoencephalography studies suggest that nociceptive stimuli elicit GBOs in other areas such as the primary somatosensory and prefrontal cortices, and that this activity could be closely related to pain perception. Furthermore, tracing studies showed that the insula is a primary target of spinothalamic input. Using depth electrodes implanted in 9 patients investigated for epilepsy, we acquired insular responses to brief thermonociceptive stimuli and similarly arousing non-nociceptive vibrotactile, auditory, and visual stimuli (59 insular sites). As compared with non-nociceptive stimuli, nociceptive stimuli elicited a markedly stronger enhancement of GBOs (150-300 ms poststimulus) at all insular sites, suggesting that this feature of insular activity is preferential for thermonociception. Although this activity was also present in temporal and frontal regions, its magnitude was significantly greater in the insula as compared with these other regions.

Thermosensation is crucial for humans to probe the environment and detect threats arising from noxious heat or cold. Over the last years, EEG frequency-tagging using long-lasting periodic radiant heat stimulation has been proposed as a means to study the cortical processes underlying tonic heat perception. This approach is based on the notion that periodic modulation of a sustained stimulus can elicit synchronized periodic activity in the neuronal populations responding to the stimulus, known as a steady-state response (SSR). In this paper, we extend this approach using a contact thermode to generate both heat-and coldevoked SSRs. Furthermore, we characterize the temporal dynamics of the elicited responses, relate these dynamics to perception, and assess the effects of displacing the stimulated skin surface to gain insight on the heat-and cold-sensitive afferents conveying these responses. Two experiments were conducted in healthy volunteers. In both experiments, noxious heat and innocuous cool stimuli were applied during 75 seconds to the forearm using a Peltier-based contact thermode, with intensities varying sinusoidally at 0.2 Hz. Displacement of the thermal stimulation on the skin surface was achieved by independently controlling the Peltier elements of the thermal probe. Continuous intensity ratings to sustained heat and cold stimulation were obtained in the first experiment with 14 subjects, and the EEG was recorded in the second experiment on 15 subjects. Both contact heat and cool stimulation elicited periodic EEG responses and percepts. Compared to heat stimulation, the responses to cool stimulation had a lower magnitude and shorter latency. All responses tended to habituate along time, and this response attenuation was most pronounced for cool compared to warm stimulation, and for stimulation delivered using a fixed surface compared to a variable surface.

This pilot study shows that VNS causes an increase in breathing frequency and a decrease in tidal volume and heart rate in the majority of patients, during both rest and exercise.

Brief thermo-nociceptive stimuli elicit low-frequency phase-locked local field potentials (LFPs) and high-frequency gamma-band oscillations (GBOs) in the human insula. Although neither of these responses constitute a direct correlate of pain perception, previous findings suggest that insular GBOs may be strongly related to the activation of the spinothalamic system and/or to the processing of thermal information. To disentangle these different features of the stimulation, we compared the insular responses to brief painful thermonociceptive stimuli, non-painful cool stimuli, mechano-nociceptive stimuli, and innocuous vibrotactile stimuli, recorded using intracerebral electroencephalograpic activity in 7 epileptic patients (9 depth electrodes, 58 insular contacts). All four types of stimuli elicited consistent low-frequency phase-locked LFPs throughout the insula, possibly reflecting supramodal activity. The latencies of thermo-nociceptive and cool low-frequency phase-locked LFPs were shorter in the posterior insula compared to the anterior insula, suggesting a similar processing of thermal input initiating in the posterior insula, regardless of whether the input produces pain and regardless of thermal modality. In contrast, only thermo-nociceptive stimuli elicited an enhancement of insular GBOs, suggesting that these activities are not simply related to the activation of the spinothalamic system or to the conveyance of thermal information.

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