Emotion regulation via conditioning placebo effects: The role of the dorsolateral prefrontal cortex in conditioning formation

doi:10.3724/SP.J.1041.2026.2008

Abstract

Abstract:

Can a purely conditioned placebo effect regulate emotion in the absence of an explicit regulatory goal, and does the dorsolateral prefrontal cortex (DLPFC) play a causal role in that process? To address these questions, we applied repetitive transcranial magnetic stimulation (rTMS) over the right DLPFC before conditioning and measured both subjective negative-emotion ratings and pupil diameter during conditioning and during the post-conditioning test 24 h later. During conditioning, participants in the DLPFC group showed greater pupil dilation to low-intensity cues than those in the control group, suggesting greater allocation of cognitive resources to those cues. They also reported lower negative-emotion ratings and showed smaller pupil responses to pictures following low- intensity cues, indicating more positive cue-outcome representations. At the post-conditioning test phase, both groups showed reliable placebo effects, but the effect was stronger in the DLPFC group, which again showed lower negative-emotion ratings and smaller pupil responses following low- intensity cues. Mediation analyses further showed that DLPFC activation strengthened the placebo effect indirectly by increasing resource allocation to low-intensity cues during conditioning and by widening the representational gap between high-and low-intensity cue-emotion associations. Together, these findings provide causal evidence that the DLPFC contributes to the formation of conditioned placebo effects and support the view that conditioning-based placebo can serve as an implicit form of emotion regulation.

Key words: emotion regulation, implicit emotion regulation, conditioned placebo effect, dorsolateral prefrontal cortex

TANG Yuyao, LI Yiwei, GUO Xinyu, ZHANG Dandan. (2026). Emotion regulation via conditioning placebo effects: The role of the dorsolateral prefrontal cortex in conditioning formation. Acta Psychologica Sinica, 58(10), 2008-2021.

Figures/Tables 5

Figure 1. Experimental procedure. A: Overall timeline of the experiment across 2 days. B: Simulated TMS-induced current distribution, with normalized electric-field strength shown in color. C: Meaning of the three cue shapes. For half of the participants in each group, the triangle predicted high-intensity negative pictures and the square predicted low-intensity negative pictures; for the other half, this mapping was reversed. D: Schematic trial structure for the pre-conditioning test, conditioning, and post-conditioning test phases. In the test phases, all three cues were paired with medium-intensity negative pictures. In the conditioning phase, the high- and low-intensity cues were probabilistically paired with high- and low-intensity negative pictures, respectively.

Figure 2. Results from the conditioning phase. A: Negative-emotion ratings for pictures. B: Mean cue-evoked changes in pupil diameter. C: Cue-evoked pupil-diameter waveforms; the shaded region indicates the time window used to compute the mean values in Panel B. D: Correlation between picture-evoked pupil diameter and negative-emotion ratings (p = 0.042), combining both groups. E: Mean picture-evoked changes in pupil diameter. F: Picture-evoked pupil-diameter waveforms; the shaded region indicates the time window used to compute the mean values in Panel E. Error bars represent SEM. Panels A, B, and E use the same legend, and Panels C and F use the same legend. * p < 0.05, ** p < 0.01.

Figure 3. Negative-emotion ratings during the post-conditioning test phase. A: Interaction between TMS group and cue type. B: Conditioned placebo and nocebo effects in the two groups. C: Pre- versus post-conditioning ratings in the DLPFC group. D: Pre- versus post- conditioning ratings in the control group. Error bars represent SEM. Panels A and B use the same legend. * p < 0.05, ** p < 0.01, *** p < 0.001.

Figure 4. Pupil-diameter responses during the post-conditioning test phase. A: Interaction between TMS group and cue type. B: Picture-evoked pupil-diameter waveforms; the shaded region indicates the time window used to compute the mean values in Panel A. C: Conditioned placebo and nocebo effects in the two groups. D: Correlation between pupil diameter and negative-emotion ratings (p = 0.022), combining both groups. Error bars represent SEM. Panels A and C use the same legend. * p < 0.05, ** p < 0.01.

Figure 5. Mediation analyses. A: Mediation model based on subjective ratings. B: Serial mediation model based on pupil diameter. Dashed paths indicate nonsignificant effects. * p < 0.05, ** p < 0.01, *** p < 0.001.

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