Direction-sensitive neural correlates of voluntary pain regulation: regional response attenuation during down-regulation and exploratory prefrontal-valuation coupling
- 1Department of Cognitive Neuroscience, Faculty of Education and Psychology, University of Tabriz, Tabriz, Iran
Abstract
Voluntary cognitive regulation can increase or decrease pain, but direction-sensitive neural correlates may emerge at different analytical levels. We reanalyzed 3,201 thermal-stimulation trials from 33 participants, integrating 0-200 warmth/pain ratings, regional fMRI activity, and trial-wise lagged coupling. Both instructions shifted ratings in the intended direction, with no reliable difference in mean success. Down-regulation was associated with lower bilateral S2/opercular and insular activity and higher left dlPFC/IFJ activity after FDR correction across 32 regions; run-matched comparisons were weaker and none survived the corresponding correction. Contrast-map Neurologic Pain Signature attenuation did not replicate in a rating-adjusted FWL-LSS trial-wise analysis despite strong temperature sensitivity. Up-regulation success covaried with an exploratory, post selection lagged dlPFC/IFJ-valuation composite (r = -0.546, 95% CI [-0.764, -0.270]). The association exceeded matched reverse-direction, zero-lag, and time-reversed controls, lay outside permutation and circular-shift nulls, and persisted after AR(1) prewhitening. A transition-level analysis across 297 up-regulation transitions preserved a negative success-by-source interaction (adjusted three-target mean beta = -0.163, cluster-bootstrap 95% CI [-0.290, -0.054], Freedman-Lane p = 0.010). Six session-wise DCM variants showed no consistent regulation-versus-passive effective-connectivity effect and did not independently validate an up-specific directed mechanism. These analyses identify a down-regulation-associated regional pattern and a candidate prefrontal-valuation coupling association requiring independent confirmation.
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BibTeX
@misc{kharghani2026directionsensitive,
title = {{Direction-sensitive neural correlates of voluntary pain regulation: regional response attenuation during down-regulation and exploratory prefrontal-valuation coupling}},
author = {M. Kharghani and E. Gholami},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.01.756083},
url = {https://www.biorxiv.org/content/10.64898/2026.10.01.756083v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Direction-sensitive neural correlates of voluntary pain regulation: regional response attenuation during down-regulation and exploratory prefrontal-valuation coupling
AU - M. Kharghani
AU - E. Gholami
PY - 2026
DA - 2026/10/01
PB - bioRxiv
DO - 10.64898/2026.10.01.756083
UR - https://www.biorxiv.org/content/10.64898/2026.10.01.756083v1
AB - Voluntary cognitive regulation can increase or decrease pain, but direction-sensitive neural correlates may emerge at different analytical levels. We reanalyzed 3,201 thermal-stimulation trials from 33 participants, integrating 0-200 warmth/pain ratings, regional fMRI activity, and trial-wise lagged coupling. Both instructions shifted ratings in the intended direction, with no reliable difference in mean success. Down-regulation was associated with lower bilateral S2/opercular and insular activity and higher left dlPFC/IFJ activity after FDR correction across 32 regions; run-matched comparisons were weaker and none survived the corresponding correction. Contrast-map Neurologic Pain Signature attenuation did not replicate in a rating-adjusted FWL-LSS trial-wise analysis despite strong temperature sensitivity. Up-regulation success covaried with an exploratory, post selection lagged dlPFC/IFJ-valuation composite (r = -0.546, 95% CI [-0.764, -0.270]). The association exceeded matched reverse-direction, zero-lag, and time-reversed controls, lay outside permutation and circular-shift nulls, and persisted after AR(1) prewhitening. A transition-level analysis across 297 up-regulation transitions preserved a negative success-by-source interaction (adjusted three-target mean beta = -0.163, cluster-bootstrap 95% CI [-0.290, -0.054], Freedman-Lane p = 0.010). Six session-wise DCM variants showed no consistent regulation-versus-passive effective-connectivity effect and did not independently validate an up-specific directed mechanism. These analyses identify a down-regulation-associated regional pattern and a candidate prefrontal-valuation coupling association requiring independent confirmation.
ER -