Event-related brain potentials elicited by high-speed cooling of the skin: A robust and non-painful method to assess the spinothalamic system in humans

Abstract

Objective: To investigate whether cool-evoked potentials (CEP) elicited by brisk innocuous cooling of the skin could serve as an alternative to laser-evoked potentials (LEP), currently considered as the best available neurophysiological tool to assess the spinothalamic tract and diagnose neuropathic pain.

Methods: A novel device made of micro-Peltier elements and able to cool the skin at -300 °C/s was used to record CEPs elicited by stimulation of the hand dorsum in 40 healthy individuals, characterize the elicited responses, and assess their signal-to-noise ratio. Various stimulation surfaces (40 mm2 and 120 mm2), cooling ramps (-200 °C/s and -133 °C/s) and temperature steps (20 °C, 15 °C, 10 °C, 5 °C) were tested to identify optimal stimulation conditions.

Results: CEPs were observed in all conditions and subjects, characterized by a biphasic negative-positive complex maximal at the vertex (Cz), peaking 190-400 ms after stimulus onset, preceded by a negative wave over central-parietal areas contralateral to the stimulated hand. Their magnitude was modulated by stimulation surface, cooling ramp and temperature step.

Conclusion: Rapid innocuous skin cooling elicits robust CEPs at latencies compatible with the conduction velocity of Aδ-fibers.

Significance: CEPs can be a complementary tool to the recording of LEPS for assessing the function of small-diameter Aδ-fibers and the spinothalamic tract.

Keywords: A-delta fibers; Cool evoked potentials; Cool perception; Electroencephalogram; High speed cooling ramp.

Conflict of interest statement

Conflict of Interest

None declared.

Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Figures

Figure 1

A. Time-course of skin temperature cooling generated by the contact cold stimulator and measured by the thermocouple located at the centre of the stimulation surface for a requested decrease of 20°C relative to baseline at 200°C/s. Note that the ramp actually reaches 200°C/s, but with a small delay of approximately 20 ms. B. Surface of the stimulation probe containing micro-Peltier elements (white rectangles). The two circles depict the two stimulation surfaces used (40 mm2 and 120 mm2). C. Overview of the different stimulation profiles used in the two experiments.

Figure 2

Intensity of perception. A. The intensity of the cool percept elicited by brief cooling of the skin is dependent on stimulation surface. Stimulation with a large surface (120 mm2) is perceived as cooler than stimulation with a small surface (40 mm2). B. The intensity of cool perception also varies with the amplitude of the temperature step. All temperature steps greater than 5°C from baseline skin temperature are perceived as cooler than the sensation elicited by the 5°C step. C. Varying the steepness of the cooling ramp (-133°C/s vs. -200°C/s) does not influence the intensity of cool perception. Single-subject data is shown as thin lines with white connectors. Group-level averages are shown as thick lines with black connectors. * p<.05, *** p<.001 (paired-sample t-tests).

Figure 3

Effect of stimulation surface (40 mm2 vs. 120 mm2) on cool-evoked ERPs. The upper waveforms correspond to the group-level average CEPs recorded at Cz vs. M1M2. The lower waveforms correspond to the group-level average CEPs recorded at the contralateral centra-parietal electrode CPC vs. Fz. Larger N2 and P2 amplitudes were obtained for the large stimulation surface. The graphs shown on the right correspond to the individual (thin lines

Figure 4

Effect of the size of the temperature step on cool-evoked ERPs. The upper waveforms correspond to the group-level average CEPs recorded at Cz vs. M1M2. The lower waveforms correspond to the group-level average CEPs recorded at the contralateral centra-parietal electrode CPC vs. Fz. For temperature steps ranging between -5°C and -20°C, the amplitude of the temperature step had little effect on CEP magnitude. Nevertheless, the magnitude of the N2 wave elicited by the -20°C was significantly greater than the magnitude of the N2 wave elicited by the -5°C stimulus. The graphs shown on the right correspond to the individual (thin lines with white connectors) and group-level average (thick lines with black connectors) N1 amplitude, N2 amplitude, P2 amplitude and N2-P2 peak-to-peak amplitude. * p<.05>

Figure 5

Effect of cooling ramp (-133 vs. -200 °C/s) on cool-evoked ERPs. The upper waveforms correspond to the group-level average CEPs recorded at Cz vs. M1M2. The lower waveforms correspond to the group-level average CEPs recorded at the contralateral centra-parietal electrode CPC vs. Fz. At electrode Cz, larger P2 amplitudes were observed for the steeper cooling ramp (200°C/s). The graphs shown on the right correspond to the individual (thin lines with white connectors) and group-level average (thick lines with black connectors) of N1 amplitude, N2 amplitude, P2 amplitude and N2-P2 peak-to-peak amplitude. * p<.05.>

Figure 6

Signal-to-noise ratio (SNR) of cool-evoked ERPs elicited by the -20°C stimulus delivered at 200°C/s in Experiment 2, as a function of the number of trials used to compute the average waveforms. The black waveform corresponds to the average SNR across participants. The grey area corresponds to the standard error of the mean.

Figure 7

Individual cool-evoked ERP with the N2 indicated by a first red circle, and the P2 indicate by the second one. CEPs were identified in all subjects.

Figure 8

Group-level average scalp topography of the N1/P1, N2 and P2 waves of cool-evoked ERPs (averaged across all conditions in Experiment 2).