Stimulus novelty, and not neural refractoriness, explains the repetition suppression of laser-evoked potentials

Brief radiant laser pulses selectively activate skin nociceptors and elicit transient brain responses (laser-evoked potentials [LEPs]). When LEPs are elicited by pairs of stimuli (S1-S2) delivered at different interstimulus intervals (ISIs), the S2-LEP is strongly reduced at short ISIs (250 ms) and progressively recovers at longer ISIs (2,000 ms). This finding has been interpreted in terms of order of arrival of nociceptive volleys and refractoriness of neural generators of LEPs. However, an alternative explanation is the modulation of another experimental factor: the novelty of the eliciting stimulus. To test this alternative hypothesis, we recorded LEPs elicited by pairs of nociceptive stimuli delivered at four ISIs (250, 500, 1,000, 2,000 ms), using two different conditions. In the constant condition, the ISI was identical across the trials of each block, whereas in the variable condition, the ISI was varied randomly across trials and single-stimulus trials were intermixed with paired trials. Therefore the time of occurrence of S2 was both less novel and more predictable in the constant than in the variable condition. In the constant condition, we observed a significant ISI-dependent suppression of the biphasic negative-positive wave (N2-P2) complex of the S2-LEP. In contrast, in the variable condition, the S2-LEP was completely unaffected by stimulus repetition. The pain ratings elicited by S2 were not different in the two conditions. These results indicate that the repetition-suppression of the S2-LEP is not due to refractoriness in nociceptive afferent pathways, but to a modulation of novelty and/or temporal predictability of the eliciting stimulus. This provides further support to the notion that stimulus saliency constitutes a crucial determinant of LEP magnitude and that a significant fraction of the brain activity time-locked to a brief and transient sensory stimulus is not directly related to the quality and the intensity of the corresponding sensation, but to bottom-up attentional processes