Brain mediators of predictive cue effects on perceived pain
Open accessAbstract
Information about upcoming pain strongly influences pain experience in experimental and clinical settings, but little is known about the brain mechanisms that link expectation and experience. To identify the pathways by which informational cues influence perception, analyses must jointly consider both the effects of cues on brain responses and the relationship between brain responses and changes in reported experience. Our task and analysis strategy were designed to test these relationships. Auditory cues elicited expectations for barely painful or highly painful thermal stimulation, and we assessed how cues influenced human subjects' pain reports and brain responses to matched levels of noxious heat using functional magnetic resonance imaging. We used multilevel mediation analysis to identify brain regions that (1) are modulated by predictive cues, (2) predict trial-to-trial variations in pain reports, and (3) formally mediate the relationship between cues and reported pain. Cues influenced heat-evoked responses in most canonical pain-processing regions, including both medial and lateral pain pathways. Effects on several regions correlated with pretask expectations, suggesting that expectancy plays a prominent role. A subset of pain-processing regions, including anterior cingulate cortex, anterior insula, and thalamus, formally mediated cue effects on pain. Effects on these regions were in turn mediated by cue-evoked anticipatory activity in the medial orbitofrontal cortex (OFC) and ventral striatum, areas not previously directly implicated in nociception. These results suggest that activity in pain-processing regions reflects a combination of nociceptive input and top-down information related to expectations, and that anticipatory processes in OFC and striatum may play a key role in modulating pain processing.
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Automated meta-analyses of working memory, emotion, and pain converge markedly with previously published meta- or mega-analytic maps, both qualitatively and quantitatively.
“Comparison of automated meta-analyses of three broad psychological terms (‘working memory’, ‘emotion’, and ‘pain’) with previously published meta- or mega-analytic maps14-16 revealed a marked convergence between approaches both qualitatively (Fig. 2) and quantitatively (Supplementary Fig. 5).”
From Large-scale automated synthesis of human functional neuroimaging data. (2011) · cites this paper as [14]
The dorsolateral prefrontal cortex is implicated in integrating incoming nociceptive signals with the expectation of pain.
“the DLPFC has been implicated in integrating incoming nociceptive signals with the expectation of pain4”
From The dorsolateral prefrontal cortex in acute and chronic pain (2017) · cites this paper as [4]
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“However, an fMRI study using the same expectancy manipulation [6] found enhanced pre-stimulus activity with high pain cues in ventral striatum, and ventromedial prefrontal cortex, which have been associated with valuation processes but not with attention in the traditional sense (i.”
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“Most prior work on social and sensory cues has used reinforcement paradigms, in which cues are informative because they are paired with subsequent reinforcers [i.e., reward, punishment, or symbolic outcomes such as money (31, 32)].”
Self-citation
- Authors
- Atlas, L. Y., Bolger, N., Lindquist, M. A., & Wager, T. D.
- Affiliations
- Columbia University (US)
- University of Colorado Boulder (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-09-29
- Volume
- 30
- Issue
- 39
- Pages
- 12964-12977
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2966558
- OpenAlex
- W2008961184
- Cited by
- 389
- References
- 110
- Citations by year
- 2026: 12 · 2025: 21 · 2024: 21 · 2023: 20 · 2022: 34 · 2021: 28 · 2020: 20 · 2019: 29 · 2018: 35 · 2017: 32 · 2016: 16 · 2015: 33 · 2014: 23 · 2013: 23 · 2012: 27
- FWCI
- 12.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (0631637)
- National Institutes of Health (MH076136, RR009784)
- National Institute of Mental Health (R01MH076136)
- National Institute on Drug Abuse (R01DA027794)
- National Center for Research Resources (P41RR009784)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- pain anticipation, predictive cues, pain perception, anticipatory activity, medial orbitofrontal cortex, ventral striatum, anterior cingulate cortex, anterior insula, thalamus, nociception, thermal pain, pain processing, top-down expectations
- MeSH terms
- Adult, Brain, Cognition, Cues, Female, Hot Temperature, Humans, Male, Pain, Perception, Physical Stimulation, Pain Threshold
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