Determinants of Laser-Evoked EEG Responses: Pain Perception or Stimulus Saliency?

1 Department of Physiology, Anatomy and Genetics, 2 Department of Engineering Science, and 3 Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford; and 4 Department of Anaesthesia, University of Cambridge, Cambridge, United Kingdom Submitted 28 January 2008; accepted in final form 31 May 2008 Although laser-evoked electroencephalographic (EEG) responses are increasingly used to investigate nociceptive pathways, their functional significance remains unclear. The reproducible observation of a robust correlation between the intensity of pain perception and the magnitude of the laser-evoked N1, N2, and P2 responses has led some investigators to consider these responses a direct correlate of the neural activity responsible for pain intensity coding in the human cortex. Here, we provide compelling evidence to the contrary. By delivering trains of three identical laser pulses at four different energies, we explored the modulation exerted by the temporal expectancy of the stimulus on the relationship between intensity of pain perception and magnitude of the following laser-evoked brain responses: the phase-locked N1, N2, and P2 waves, and the non-phase-locked laser-induced synchronization (ERS) and desynchronization (ERD). We showed that increasing the temporal expectancy of the stimulus through stimulus repetition at a constant interstimulus interval 1 ) significantly reduces the magnitudes of the laser-evoked N1, N2, P2, and ERS; and 2 ) disrupts the relationship between the intensity of pain perception and the magnitude of these responses. Taken together, our results indicate that laser-evoked EEG responses are not determined by the perception of pain per se, but are mainly determined by the saliency of the eliciting nociceptive stimulus (i.e., its ability to capture attention). Therefore laser-evoked EEG responses represent an indirect readout of the function of the nociceptive system. Address for reprint requests and other correspondence: G. Iannetti, Department of Physiology, Anatomy, and Genetics, University of Oxford, South Parks Road, OX1 3QX, Oxford, UK (E-mail: giandomenico.iannetti{at}dpag.ox.ac.uk )