Elisabeth Colon

Nociceptive steady-state evoked potentials elicited by rapid periodic thermal stimulation of cutaneous nociceptors

The periodic presentation of a sensory stimulus induces, at certain frequencies of stimulation, a sustained electroencephalographic response known as steady-state evoked potential (SS-EP). In the somatosensory, visual, and auditory modalities, SS-EPs are considered to constitute an electrophysiological correlate of cortical sensory networks resonating at the frequency of stimulation. In the present study, we describe and characterize, for the first time, SS-EPs elicited by the selective activation of skin nociceptors in humans. The stimulation consisted of 2.3-s-long trains of 16 identical infrared laser pulses (frequency, 7 Hz), applied to the dorsum of the left and right hand and foot. Two different stimulation energies were used. The low energy activated only C-nociceptors, whereas the high energy activated both Aδ- and C-nociceptors. Innocuous electrical stimulation of large-diameter Aβ-fibers involved in the perception of touch and vibration was used as control. The high-energy nociceptive stimulus elicited a consistent SS-EP, related to the activation of Aδ-nociceptors. Regardless of stimulus location, the scalp topography of this response was maximal at the vertex. This was noticeably different from the scalp topography of the SS-EPs elicited by innocuous vibrotactile stimulation, which displayed a clear maximum over the parietal region contralateral to the stimulated side. Therefore, we hypothesize that the SS-EPs elicited by the rapid periodic thermal activation of nociceptors may reflect the activation of a network that is preferentially involved in processing nociceptive input and may thus provide some important insight into the cortical processes generating painful percepts.

Steady-state evoked potentials to tag specific components of nociceptive cortical processing.

Studies have shown that the periodic repetition of a stimulus induces, at certain stimulation frequencies, a sustained electro-cortical response of corresponding frequency, referred to as steady-state evoked potential (SSEP). Using infrared laser stimulation, we recently showed that SSEPs can be used to explore nociceptive cortical processing. Here, we implemented a novel approach to elicit such responses, using a periodic intra-epidermal electrical stimulation of cutaneous Aδ-nociceptors (Aδ-SSEPs). Using a wide range of frequencies (3-43 Hz), we compared the scalp topographies and temporal dynamics of these Aδ-SSEPs to the Aβ-SSEPs elicited by non-nociceptive transcutaneous electrical stimulation, as well as to the transient ERPs elicited by the onsets of the 10-s stimulation trains, applied to the left and right hand. At 3 Hz, we found that the topographies of Aβ- and Aδ-SSEPs were both maximal at the scalp vertex, and resembled closely that of the late P2 wave of transient ERPs, suggesting activity originating from the same neuronal populations. The responses also showed marked habituation, suggesting that they were mainly related to unspecific, attention-related processes. In contrast, at frequencies >3 Hz, the topographies of Aβ- and Aδ-SSEPs were markedly different. Aβ-SSEPs were maximal over the contralateral parietal region, whereas Aδ-SSEPs were maximal over midline frontal regions, thus indicating an entrainment of distinct neuronal populations. Furthermore, the responses showed no habituation, suggesting more obligatory and specific stages of sensory processing. Taken together, our results indicate that Aβ- and Aδ-SSEPs offer a unique opportunity to study the cortical representation of nociception and touch.

Steady-state evoked potentials to study the processing of tactile and nociceptive somatosensory input in the human brain

The periodic presentation of a sensory stimulus induces, at certain frequencies of stimulation, a sustained electroencephalographic response of corresponding frequency, known as steady-state evoked potentials (SS-EP). In visual, auditory and vibrotactile modalities, studies have shown that SS-EP reflect mainly activity originating from early, modality-specific sensory cortices. Furthermore, it has been shown that SS-EP have several advantages over the recording of transient event-related brain potentials (ERP), such as a high signal-to-noise ratio, a shorter time to obtain reliable signals, and the capacity to frequency-tag the cortical activity elicited by concurrently presented sensory stimuli. Recently, we showed that SS-EP can be elicited by the selective activation of skin nociceptors and that nociceptive SS-EP reflect the activity of a population of neurons that is spatially distinct from the somatotopically-organized population of neurons underlying vibrotactile SS-EP. Hence, the recording of SS-EP offers a unique opportunity to study the cortical representation of nociception and touch in humans, and to explore their potential crossmodal interactions. Here, (1) we review available methods to achieve the rapid periodic stimulation of somatosensory afferents required to elicit SS-EP, (2) review previous studies that have characterized vibrotactile and nociceptive SS-EP, (3) discuss the nature of the recorded signals and their relationship with transient event-related potentials and (4) outline future perspectives and potential clinical applications of this technique.

Eeg frequency tagging to dissociate the cortical responses to nociceptive and nonnociceptive stimuli

Whether the cortical processing of nociceptive input relies on the activity of nociceptive-specific neurons or whether it relies on the activity of neurons also involved in processing nonnociceptive sensory input remains a matter of debate. Here, we combined EEG “frequency tagging” of steady-state evoked potentials (SS-EPs) with an intermodal selective attention paradigm to test whether the cortical processing of nociceptive input relies on nociceptive-specific neuronal populations that can be selectively modulated by top–down attention. Trains of nociceptive and vibrotactile stimuli (Experiment 1) and trains of nociceptive and visual stimuli (Experiment 2) were applied concomitantly to the same hand, thus eliciting nociceptive, vibrotactile, and visual SS-EPs. In each experiment, a target detection task was used to focus attention toward one of the two concurrent streams of sensory input. We found that selectively attending to nociceptive or vibrotactile somatosensory input indistinctly enhances the magnitude of nociceptive and vibrotactile SS-EPs, whereas selectively attending to nociceptive or visual input independently enhances the magnitude of the SS-EP elicited by the attended sensory input. This differential effect indicates that the processing of nociceptive input involves neuronal populations also involved in the processing of touch, but distinct from the neuronal populations involved in vision.

Frequency tagging of steady-state evoked potentials to explore the crossmodal links in spatial attention between vision and touch

The sustained periodic modulation of a stimulus induces an entrainment of cortical neurons responding to the stimulus, appearing as a steady-state evoked potential (SS-EP) in the EEG frequency spectrum. Here, we used frequency tagging of SS-EPs to study the crossmodal links in spatial attention between touch and vision. We hypothesized that a visual stimulus approaching the left or right hand orients spatial attention toward the approached hand, and thereby enhances the processing of vibrotactile input originating from that hand. Twenty-five subjects took part in the experiment: 16-s trains of vibrotactile stimuli (4.2 and 7.2 Hz) were applied simultaneously to the left and right hand, concomitantly with a punctate visual stimulus blinking at 9.8 Hz. The visual stimulus was approached toward the left or right hand. The hands were either uncrossed (left and right hands to the left and right of the participant) or crossed (left and right hands to the right and left of the participant). The vibrotactile stimuli elicited two distinct SS-EPs with scalp topographies compatible with activity in the contralateral primary somatosensory cortex. The visual stimulus elicited a third SS-EP with a topography compatible with activity in visual areas. When the visual stimulus was over one of the hands, the amplitude of the vibrotactile SS-EP elicited by stimulation of that hand was enhanced, regardless of whether the hands were uncrossed or crossed. This demonstrates a crossmodal effect of spatial attention between vision and touch, integrating proprioceptive and/or visual information to map the position of the limbs in external space.