Nociceptive Intra-epidermal Electric Stimulation Evokes Steady-State Responses in the Secondary Somatosensory Cortex

Abstract

Recent studies have established the presence of nociceptive steady-state evoked potentials (SSEPs), generated in response to thermal or intra-epidermal electric stimuli. This study explores cortical sources and generation mechanisms of nociceptive SSEPs in response to intra-epidermal electric stimuli. Our method was to stimulate healthy volunteers (n = 22, all men) with 100 intra-epidermal pulse sequences. Each sequence had a duration of 8.5 s, and consisted of pulses with a pulse rate between 20 and 200 Hz, which was frequency modulated with a multisine waveform of 3, 7 and 13 Hz (n = 10, 1 excluded) or 3 and 7 Hz (n = 12, 1 excluded). As a result, evoked potentials in response to stimulation onset and contralateral SSEPs at 3 and 7 Hz were observed. The SSEPs at 3 and 7 Hz had an average time delay of 137 ms and 143 ms respectively. The evoked potential in response to stimulation onset had a contralateral minimum (N1) at 115 ms and a central maximum (P2) at 300 ms. Sources for the multisine SSEP at 3 and 7 Hz were found through beamforming near the primary and secondary somatosensory cortex. Sources for the N1 were found near the primary and secondary somatosensory cortex. Sources for the N2-P2 were found near the supplementary motor area. Harmonic and intermodulation frequencies in the SSEP power spectrum remained below a detectable level and no evidence for nonlinearity of nociceptive processing, i.e. processing of peripheral firing rate into cortical evoked potentials, was found.

How to make calibration less painful—A proposition for an automatic, reliable and time‐efficient procedure

“…In the present study, we incorporate intraepidermal electric stimulation (IES) that is widely used in neurophysiological studies (Paul et al., 2021; Perchet et al., 2012; van den Berg et al., 2020; van den Berg, Hijma, et al., 2022; van den Berg, Manoochehri, et al., 2022; Vecchio & De Pascalis, 2021) owing to its documented capacity to preferentially activate nociceptive afferent nerve fibers in the epidermis when the stimulus intensity is kept below twice the sensation threshold ( t ) (Motogi et al., 2016; Mouraux et al., 2010; Poulsen et al., 2020). Such stimulation can be elicited via a one‐needle WASP electrode that operates on a similar principle to the classical Inui (Inui et al., 2002; Inui & Kakigi, 2012) electrode and a five‐microneedle electrode (Jansen et al., 2021; Steenbergen et al., 2012; van den Berg & Buitenweg, 2021; van den Berg, Hijma, et al., 2022; van den Berg, Manoochehri, et al., 2022). Discrepancies in electrode attributes (e.g., needle length and outer ring radius) and the type of the stimulation (e.g., pulse train stimulation vs single long duration stimulation) warrant distinct calibration procedures.…”

“…These involve repetitive measurements of t , in the form of yes/no responses, which are then used as arguments in a mathematical function to estimate the level of painful stimulation delivered as a pulse train. Specifically, such procedures combine selection stimuli procedures (e.g., minimum entropy procedure; Doll et al., 2013; adapted probing procedure (Doll et al., 2013, 2015; van den Berg et al., 2021) with specific estimation methods (e.g., logistic regression or Bayesian estimation) or other procedures that implement a threshold tracking technique, designed to estimate detection thresholds that may potentially drift over time (Doll et al., 2015, 2016; van den Berg et al., 2021; van den Berg, Hijma, et al., 2022; van den Berg, Manoochehri, et al., 2022). Unlike train stimulation, there is still a need for further development of stimuli estimation methods for other electric stimulation, including single‐pulse IES.…”