Neural markers of nociceptive input and pain intensity coding: a signal detection approach

The N2 and P2 vertex waves are the largest electroencephalographic (EEG) responses evoked by transient nociceptive stimuli. N2 and P2 amplitudes often correlate with both stimulus energy and pain intensity. However, studies using paradigms that dissociated afferent input from stimulus salience suggested the N2 and P2 waves primarily reflect supramodal salience, rather than being selective for nociception or pain. Here we investigated how well EEG responses to nociceptive laser stimuli discriminate stimulus intensities and subjective pain in healthy human volunteers. Specifically, we applied signal detection theory (SDT) to calculate how well single-trial amplitudes of stimulus-related EEG responses (contralateral N1 wave, vertex N2 and P2 waves, and gamma-band oscillations) discriminate between two laser energies (neuro-d’obj), and between participants’ reports of “high” or “low” pain intensity (neuro-d’subj). As a control, we applied the same procedure to similar brain potentials evoked by non-painful electrical stimulation. Participants’ perceptual sensitivity to stimulus intensity (d’) was similar between modalities, indicating that laser and electrical stimulus discriminations were similarly difficult. Laser-evoked N1, N2 and P2 waves were sensitive to stimulus intensity, whereas the same waves evoked by electrical stimulation showed minimal sensitivity. Inter-individual differences in laser-evoked N1, N2 and P2 neuro-d’obj also predicted inter-individual variability in nociceptive sensitivity (d’). Together, these findings show that the laser-evoked potential—elicited by stimuli at long, variable intervals—reflects nociceptive intensity discrimination. Further, the laser-evoked N2 wave captured trial-by-trial variability in pain perception that was unrelated to stimulus intensity. This indicates that the N2 carries particular information about subjective pain intensity.