Thermosensory predictive coding underpins an illusion of pain

Jesper Fischer Ehmsen; Niia Nikolova; Daniel Elmstrøm Christensen; Leah Banellis; Rebecca A. Böhme; Malthe Brændholt; Arthur S. Courtin; Camilla E. Krænge; Alexandra G. Mitchell; Camila Sardeto Deolindo; Christian Holm Steenkjær; Melina Vejlø; Christoph Mathys; Micah G. Allen; Francesca Fardo

doi:10.1126/sciadv.adq0261

Thermosensory predictive coding underpins an illusion of pain

Jesper Fischer Ehmsen, Niia Nikolova, Daniel Elmstrøm Christensen, Leah Banellis, Rebecca A. Böhme, Malthe Brændholt, Arthur S. Courtin, Camilla E. Krænge, Alexandra G. Mitchell, Camila Sardeto Deolindo, Christian Holm Steenkjær, Melina Vejlø, Christoph Mathys, Micah G. Allen, Francesca Fardo^*

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

The human brain has a remarkable ability to learn and update its beliefs about the world. Here, we investigate how thermosensory learning shapes our subjective experience of temperature and the misperception of pain in response to harmless thermal stimuli. Through computational modeling, we demonstrate that the brain uses a probabilistic predictive coding scheme to update beliefs about temperature changes based on their uncertainty. We find that these expectations directly modulate the perception of pain in the thermal grill illusion. Quantitative microstructural brain imaging further revealed that individual variability in computational parameters related to uncertainty-driven learning and decision-making is reflected in the microstructure of brain regions such as the precuneus, posterior cingulate gyrus, cerebellum, as well as basal ganglia and brainstem. These findings provide a framework to understand how the brain infers pain from innocuous thermal inputs, with important implications for the etiology of thermosensory symptoms under chronic pain conditions.

Original language	English
Article number	eadq0261
Journal	Science Advances
Volume	11
Issue	11
ISSN	2375-2548
DOIs	https://doi.org/10.1126/sciadv.adq0261
Publication status	Published - Mar 2025

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Ehmsen, J. F., Nikolova, N., Christensen, D. E., Banellis, L., Böhme, R. A., Brændholt, M., Courtin, A. S., Krænge, C. E., Mitchell, A. G., Deolindo, C. S., Steenkjær, C. H., Vejlø, M., Mathys, C., Allen, M. G., & Fardo, F. (2025). Thermosensory predictive coding underpins an illusion of pain. Science Advances, 11(11), Article eadq0261. https://doi.org/10.1126/sciadv.adq0261

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title = "Thermosensory predictive coding underpins an illusion of pain",

abstract = "The human brain has a remarkable ability to learn and update its beliefs about the world. Here, we investigate how thermosensory learning shapes our subjective experience of temperature and the misperception of pain in response to harmless thermal stimuli. Through computational modeling, we demonstrate that the brain uses a probabilistic predictive coding scheme to update beliefs about temperature changes based on their uncertainty. We find that these expectations directly modulate the perception of pain in the thermal grill illusion. Quantitative microstructural brain imaging further revealed that individual variability in computational parameters related to uncertainty-driven learning and decision-making is reflected in the microstructure of brain regions such as the precuneus, posterior cingulate gyrus, cerebellum, as well as basal ganglia and brainstem. These findings provide a framework to understand how the brain infers pain from innocuous thermal inputs, with important implications for the etiology of thermosensory symptoms under chronic pain conditions.",

author = "Ehmsen, {Jesper Fischer} and Niia Nikolova and Christensen, {Daniel Elmstr{\o}m} and Leah Banellis and B{\"o}hme, {Rebecca A.} and Malthe Br{\ae}ndholt and Courtin, {Arthur S.} and Kr{\ae}nge, {Camilla E.} and Mitchell, {Alexandra G.} and Deolindo, {Camila Sardeto} and Steenkj{\ae}r, {Christian Holm} and Melina Vejl{\o} and Christoph Mathys and Allen, {Micah G.} and Francesca Fardo",

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doi = "10.1126/sciadv.adq0261",

language = "English",

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T1 - Thermosensory predictive coding underpins an illusion of pain

AU - Ehmsen, Jesper Fischer

AU - Nikolova, Niia

AU - Christensen, Daniel Elmstrøm

AU - Banellis, Leah

AU - Böhme, Rebecca A.

AU - Brændholt, Malthe

AU - Courtin, Arthur S.

AU - Krænge, Camilla E.

AU - Mitchell, Alexandra G.

AU - Deolindo, Camila Sardeto

AU - Steenkjær, Christian Holm

AU - Vejlø, Melina

AU - Mathys, Christoph

AU - Allen, Micah G.

AU - Fardo, Francesca

PY - 2025/3

Y1 - 2025/3

N2 - The human brain has a remarkable ability to learn and update its beliefs about the world. Here, we investigate how thermosensory learning shapes our subjective experience of temperature and the misperception of pain in response to harmless thermal stimuli. Through computational modeling, we demonstrate that the brain uses a probabilistic predictive coding scheme to update beliefs about temperature changes based on their uncertainty. We find that these expectations directly modulate the perception of pain in the thermal grill illusion. Quantitative microstructural brain imaging further revealed that individual variability in computational parameters related to uncertainty-driven learning and decision-making is reflected in the microstructure of brain regions such as the precuneus, posterior cingulate gyrus, cerebellum, as well as basal ganglia and brainstem. These findings provide a framework to understand how the brain infers pain from innocuous thermal inputs, with important implications for the etiology of thermosensory symptoms under chronic pain conditions.

AB - The human brain has a remarkable ability to learn and update its beliefs about the world. Here, we investigate how thermosensory learning shapes our subjective experience of temperature and the misperception of pain in response to harmless thermal stimuli. Through computational modeling, we demonstrate that the brain uses a probabilistic predictive coding scheme to update beliefs about temperature changes based on their uncertainty. We find that these expectations directly modulate the perception of pain in the thermal grill illusion. Quantitative microstructural brain imaging further revealed that individual variability in computational parameters related to uncertainty-driven learning and decision-making is reflected in the microstructure of brain regions such as the precuneus, posterior cingulate gyrus, cerebellum, as well as basal ganglia and brainstem. These findings provide a framework to understand how the brain infers pain from innocuous thermal inputs, with important implications for the etiology of thermosensory symptoms under chronic pain conditions.

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VL - 11

JO - Science Advances

JF - Science Advances

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Thermosensory predictive coding underpins an illusion of pain

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