Figure 1.

Experimental design and behavioral results. A, Each trial was initiated with a 1.5 s pain-predictive visual cue (a high-pain cue in this example). After a 3–5 s anticipation period, a 0.1 s electrical pain stimulus was applied to the dorsum of the left hand and, after a 3.9 s delay, participants reported subjective pain intensity on a VAS within 3.5 s. The intertrial interval was 4–6 s. B, Cue–stimulus contingencies. The conditioned visual cue was a compound image consisting of a square and a circle. The lower and upper part of the square brightened to constitute the low- and high-pain cue, respectively. Brightening of the inner circle denoted the medium-pain cue. On trials without a conditioned cue, the visual cue consisted of a question mark. The numbers in parentheses indicate the number of repetitions of each trial type in a single scanning session (totally 40 trials per session). C, Compared with a medium-pain cue and during the receipt of an identical medium pain stimulation, a low- and high-pain cue significantly reduced and increased subjective pain intensity, respectively (both p < 0.0001). D, The change in pain rating caused by a low-pain cue was positively correlated with that caused by a high-pain cue (p = 0.045). E, The low- and high-pain cue respectively elicited a significantly lower and higher expected pain intensity compared with that provoked by a medium-pain cue (both p < 0.0001). F, The cue-elicited subjective certainty about expected pain was not significantly different among the three cues (p > 0.065 for all pairwise comparisons). G, For both low- and high-pain cues, subjective certainty ratings were positively correlated with the extent of pain rating changes (p = 0.021 for the low-pain cue and p = 0.027 for the high-pain cue), with no significant difference between both correlations (p = 0.626). H, The subjective certainty elicited by a high-pain cue exhibited a significant negative correlation with the signed prediction error (PE) of pain (i.e., reported pain intensity − expected pain intensity) engendered in the HM condition (p = 0.009). The correlation associated with a low-pain cue was not significant (p = 0.159). I, The anxiety level elicited by a low- and high-pain cue was significantly lower (p = 0.009) and higher (p = 0.001) than that provoked by a medium-pain cue. J, For a low-pain cue, the level of provoked anxiety was negatively correlated with the corresponding change in pain rating (p = 0.0003). These relationships did not reach statistical significance for a high-pain cue (p = 0.052) and the correlation related to a low-pain cue was significantly stronger than that associated with a high-pain cue (p = 0.025). Error bars in C, E, F, and I represent SDs. *p < 0.05.