Prefrontal rTMS modulates dynamic expectancy processes to shape subsequent pain experience
- 1Tech X Academy, Shenzhen Polytechnic University, Shenzhen, China
- 2School of Psychology, Shenzhen University, Shenzhen, China
Abstract
Pain expectancy is a major determinant of pain perception, and identifying effective approaches to modulate expectancy may provide new opportunities for pain intervention. High-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex (DLPFC) has been implicated in expectancy-related pain modulation. However, it remains unclear how DLPFC-rTMS influences distinct stages of expectancy processing and how these changes relate to subsequent pain experience. Thirty-three healthy participants completed a randomized, double-blind, sham-controlled crossover study. Participants received real or sham high-frequency DLPFC-rTMS and performed a pain expectancy paradigm before and after stimulation while EEG was recorded. The paradigm dissociated expectancy formation and maintenance under certain and uncertain predictive contexts. Behaviorally, DLPFC-rTMS reduced pain intensity and unpleasantness, accompanied by a reduction in expected pain, and mediation analysis identified an indirect effect through expected pain. At the neural level, DLPFC-rTMS increased contextual cue-evoked P2 responses relative to sham during expectancy formation but reduced anticipatory N1 and contingent negative variation (CNV) responses during expectancy maintenance. During pain experience, laser-evoked N1 responses showed a context-dependent pattern, with greater attenuation under uncertainty. Importantly, mediation analyses identified distinct stage-related indirect associations: stimulation-related changes in contextual P2 responses were linked to subsequent laser-evoked N1 responses, whereas changes in anticipatory CNV and anxiety were jointly associated with subsequent pain ratings. Together, these findings demonstrate that DLPFC-rTMS modulates dynamic expectancy processes across distinct stages of pain anticipation, with formation- and maintenance-related changes linked to different aspects of subsequent pain processing.
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BibTeX
@article{jin2026prefrontal,
title = {{Prefrontal rTMS modulates dynamic expectancy processes to shape subsequent pain experience}},
author = {Richu Jin and Zhouan Liu and Jia Li and Yinglin Guan and Guohui Wang and Xiaoyun Li and Weiwei Peng},
journal = {Neurotherapeutics},
year = {2026},
month = oct,
doi = {10.1016/j.neurot.2026.e01107},
url = {https://doi.org/10.1016/j.neurot.2026.e01107},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Prefrontal rTMS modulates dynamic expectancy processes to shape subsequent pain experience
AU - Richu Jin
AU - Zhouan Liu
AU - Jia Li
AU - Yinglin Guan
AU - Guohui Wang
AU - Xiaoyun Li
AU - Weiwei Peng
PY - 2026
DA - 2026/10/28
JO - Neurotherapeutics
DO - 10.1016/j.neurot.2026.e01107
UR - https://doi.org/10.1016/j.neurot.2026.e01107
AB - Pain expectancy is a major determinant of pain perception, and identifying effective approaches to modulate expectancy may provide new opportunities for pain intervention. High-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex (DLPFC) has been implicated in expectancy-related pain modulation. However, it remains unclear how DLPFC-rTMS influences distinct stages of expectancy processing and how these changes relate to subsequent pain experience. Thirty-three healthy participants completed a randomized, double-blind, sham-controlled crossover study. Participants received real or sham high-frequency DLPFC-rTMS and performed a pain expectancy paradigm before and after stimulation while EEG was recorded. The paradigm dissociated expectancy formation and maintenance under certain and uncertain predictive contexts. Behaviorally, DLPFC-rTMS reduced pain intensity and unpleasantness, accompanied by a reduction in expected pain, and mediation analysis identified an indirect effect through expected pain. At the neural level, DLPFC-rTMS increased contextual cue-evoked P2 responses relative to sham during expectancy formation but reduced anticipatory N1 and contingent negative variation (CNV) responses during expectancy maintenance. During pain experience, laser-evoked N1 responses showed a context-dependent pattern, with greater attenuation under uncertainty. Importantly, mediation analyses identified distinct stage-related indirect associations: stimulation-related changes in contextual P2 responses were linked to subsequent laser-evoked N1 responses, whereas changes in anticipatory CNV and anxiety were jointly associated with subsequent pain ratings. Together, these findings demonstrate that DLPFC-rTMS modulates dynamic expectancy processes across distinct stages of pain anticipation, with formation- and maintenance-related changes linked to different aspects of subsequent pain processing.
SN - 1933-7213
SN - 1878-7479
ER -