The DOI matches its Crossref record; 96 of the 96 references it cites were found in a registry or an index.
Predicting Individual Differences in Placebo Analgesia: Contributions of Brain Activity during Anticipation and Pain Experience
Open accessAbstract
Recent studies have identified brain correlates of placebo analgesia, but none have assessed how accurately patterns of brain activity can predict individual differences in placebo responses. We reanalyzed data from two fMRI studies of placebo analgesia (N= 47), using patterns of fMRI activity during the anticipation and experience of pain to predict new subjects' scores on placebo analgesia and placebo-induced changes in pain processing. We used a cross-validated regression procedure, LASSO-PCR, which provided both unbiased estimates of predictive accuracy and interpretable maps of which regions are most important for prediction. Increased anticipatory activity in a frontoparietal network and decreases in a posterior insular/temporal network predicted placebo analgesia. Patterns of anticipatory activity across the cortex predicted a moderate amount of variance in the placebo response (∼12% overall, ∼40% for study 2 alone), which is substantial considering the multiple likely contributing factors. The most predictive regions were those associated with emotional appraisal, rather than cognitive control or pain processing. During pain, decreases in limbic and paralimbic regions most strongly predicted placebo analgesia. Responses within canonical pain-processing regions explained significant variance in placebo analgesia, but the pattern of effects was inconsistent with widespread decreases in nociceptive processing. Together, the findings suggest that engagement of emotional appraisal circuits drives individual variation in placebo analgesia, rather than early suppression of nociceptive processing. This approach provides a framework that will allow prediction accuracy to increase as new studies provide more precise information for future predictive models.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Pain relief produced by these cognitive techniques are associated with significant reductions in pain-related brain activation (i.e., SI, SII, posterior insula, parietal operculum) and activation in higher-order brain regions, such as the ACC, PFC, and insula.86, 89, 98–110”
From Mindfulness meditation-based pain relief: a mechanistic account (2016) · cites this paper as [103]
In the citing paper
“and a recent study found that vmPFC activity was correlated with the strength of both expectations of analgesia and pain relief [62].”
From Ventromedial prefrontal–subcortical systems and the generation of affective meaning (2012) · cites this paper as [62]
In the citing paper
“While placebo studies often involve conditioning procedures, these may often serve primarily to alter expectations and the meaning of pain in context [60,61], and a recent study found that vmPFC activity was correlated with the strength of both expectations of analgesia and pain relief [62].”
From Ventromedial prefrontal–subcortical systems and the generation of affective meaning (2012) · cites this paper as [62]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Regression shrinkage and selection via the lasso
Tibshirani, R. (1996) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1996.tb02080.x · Cited by 51,482
The Elements of Statistical Learning
Hastie, T., Tibshirani, R., & Friedman, J. (2009) · Springer Series in Statistics · doi:10.1007/978-0-387-84858-7 · Cited by 25,970
Book Review: Pattern Recognition and Machine Learning
Nasrabadi, N. M. (2007) · Journal of Electronic Imaging · doi:10.1117/1.2819119 · Cited by 22,066
A Study of Cross-Validation and Bootstrap for Accuracy Estimation and Model Selection
Kohavi, R. (1995) · Zenodo · doi:10.5281/zenodo.19712698 · Cited by 10,909
Finding the missing heritability of complex diseases
Manolio, T. A., Collins, F. S., Cox, N. J., Goldstein, D. B., Hindorff, L. A., Hunter, D. J., McCarthy, M. I., Ramos, E. M., Cardon, L. R., Chakravarti, A., et al. (2009) · Nature · doi:10.1038/nature08494 · Cited by 8,336
Distributed and overlapping representations of faces and objects in ventral temporal cortex
Haxby, J. V., Gobbini, M. I., Furey, M. L., Ishai, A., Schouten, J. L., & Pietrini, P. (2001) · Science · doi:10.1126/science.1063736 · Cited by 3,940
Pain Affect Encoded in Human Anterior Cingulate But Not Somatosensory Cortex
Rainville, P., Duncan, G. H., Price, D. D., Carrier, B., & Bushnell, M. C. (1997) · Science · doi:10.1126/science.277.5328.968 · Cited by 2,629
(2013) · Springer eBooks · Cited by 2,625
Kirsch, I., Deacon, B. J., Huedo-Medina, T. B., Scoboria, A., Moore, T. J., & Johnson, B. T. (2008) · PLoS Medicine · doi:10.1371/journal.pmed.0050045 · Cited by 2,442
Reliability of the Visual Analog Scale for Measurement of Acute Pain
Bijur, P. E., Silver, W. G., & Gallagher, E. J. (2001) · Academic Emergency Medicine · doi:10.1111/j.1553-2712.2001.tb01132.x · Cited by 2,091
Research works printed but not linked: 1
- Bishop CM (2006) Pattern recognition and machine learning (Springer, New York).
Cited by
Sorted by citations
Items 301–327 of 327
Willems, A. L., Oudenhove, L. V., & Vervliet, B. (2023) · eLife · doi:10.7554/elife.91400.1.sa1
Willems, A. L., Oudenhove, L. V., & Vervliet, B. (2023) · eLife · doi:10.7554/elife.91400.1.sa0
Neural signatures of emotional inference and experience align during social consensusPreprint
Reddan, M. C., Ong, D. C., Wager, T. D., Mattek, S., Kahhalé, I., & Zaki, J. (2023) · Research Square · doi:10.21203/rs.3.rs-3487248/v1
Self-citationVariability in neural representations of fear: insights from computational modeling
Wang, Y. (2023) · Digital Repository Service (Northeastern University) · doi:10.17760/d20537507
eLife Assessment: The neural dynamics of positive and negative expectations of pain
Manresa, J. A. B. (2024) · eLife · doi:10.7554/elife.97793.1.sa2
Fregni, F., Ortega-Márquez, J., González-González, L. F., Sosa, W., & Pacheco‐Barrios, K. (2024) · Research Square · doi:10.21203/rs.3.rs-4656968/v1
A distributed brain response predicting the facial expression of acute nociceptive painPreprint
Picard, M.-È., Miriam Kunz, A., Chen, J.-I., Coll, M., Vachon‐Presseau, É., Wager, T. D., & Rainville, P. (2024) · eLife · doi:10.7554/elife.87962.2
Self-citationThe neural dynamics of positive and negative expectations of painPreprint
Wittkamp, C. A., Wolf, M., & Rose, M. (2024) · eLife · doi:10.7554/elife.97793.2
Placebowirkungen bei Magen-Darm-Erkrankungen
Weimer, K. (2024) · Springer eBooks · doi:10.1007/978-3-662-68436-8_30
Palmisani, F., THIYAGARAJAN, J. S. P., Horsey, J., Hughes, S., & Medina, S. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.30.635687
Long-term effects on functional brain networks in adolescents treated for lumbar disc herniation
Blomé, S., Kastrati, G., Pontén, S., Jonsjö, M. A., Lagerbäck, T., Skorpil, M., Möller, H., Lalouni, M., Fransson, P., Gerdhem, P., et al. (2025) · Molecular Pain · doi:10.1177/17448069251376189
Lee, J., & Woo, C. (2025) · Cambridge University Press eBooks · doi:10.1017/9781009342919.016
Emotion Perception and Elicitation
Armony, J., & Vuilleumier, P. (2025) · Cambridge University Press eBooks · doi:10.1017/9781009342919.012
A Neural Signature of Similarity Assessment between a Face and One’s Own FacePreprint
Knyazev, G. G., Savostyanov, A. N., Bocharov, A. V., Saprigyn, A. E., Levin, E. A., & Lebedkin, D. A. (2025) · Research Square · doi:10.21203/rs.3.rs-7570992/v1
Brain-immune correlates of quality of life in adolescents with chronic musculoskeletal pain
Pascual‐Diaz, S., Suñol, M., Hoeppli, M., Biggs, E. E., King, C. D., Aghaeepour, N., Angst, M. S., Ganio, E. A., Cambriel, A. I. F., Feyaerts, D., et al. (2025) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.106225
Wiech, K., Vanderkerckhove, J., Zaman, J., Tuerlinckx, F., Vlaeyen, J. W. S., & Tracey, I. (2013) · Lirias · doi:10.13140/2.1.4814.1766
The Endocannabinoid System’s Contribution to Placebo AnalgesiaPreprint
Tomin, R., Murray, K., Hadjis, G. E., Khalil, O., Sexton, C. A., Bourke, S. L., Khan, J. S., Finn, D. P., Atlas, L. Y., & Moayedi, M. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.25.707676
Self-citationDiverging influences of punishment motivation and negative affect on cognitive control
Brough, R. E., Spurbeck, C., & Chiew, K. S. (2026) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-026-01421-5
Cerebellar activation in human placebo analgesia: Bridging findings from mice to humansPreprint
Wei, Z., Spisák, T., Timmann, D., Scherrer, G., Bingel, U., & Wager, T. D. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.07.717067
Self-citationDean, J. G., Allen, A., Barrows, D., Birenbaum, J., Castellanos, J. P., Chakravarthy, K. V., Chen, C., Cruanes, G. F., Dhillon, S., Esshaki, Y., et al. (2026) · Contemporary Clinical Trials Communications · doi:10.1016/j.conctc.2026.101665
Effects of prefrontal transcranial direct current stimulation on open-label placebo responses
Brehm, B. L., Macha, A.-M., Denk, P. A., Weigand, A., & Schaefer, M. (2026) · Neuropsychopharmacology · doi:10.1038/s41386-026-02516-w
How is facial similarity to one’s own face encoded in the brain?
Knyazev, G. G., Савостьянов, А. Н., Bocharov, A. V., Saprigyn, A. E., Levin, E. A., & Lebedkin, D. A. (2026) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-026-02054-4
Lyndon, S., & Nedeljkovic, S. (2026) · Pain · doi:10.1097/j.pain.0000000000004123
Metadata
- Authors
- Wager, T. D., Atlas, L. Y., Leotti, L. A., & Rilling, J. K.
- Affiliations
- University of Colorado Boulder (US)
- Columbia University (US)
- Rutgers, The State University of New Jersey (US)
- Emory University (US)
- Corresponding author
- Wager, Tor D.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-01-12
- Volume
- 31
- Issue
- 2
- Pages
- 439-452
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3735131
- OpenAlex
- W2158440149
- Cited by
- 328
- References
- 96
- Citations by year
- 2026: 11 · 2025: 19 · 2024: 25 · 2023: 26 · 2022: 13 · 2021: 16 · 2020: 22 · 2019: 18 · 2018: 20 · 2017: 27 · 2016: 18 · 2015: 24 · 2014: 23 · 2013: 29 · 2012: 24
- FWCI
- 14.28
- 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)
- Europe PMC (PubMed Central) (acceptedVersion)
- Journal of Neuroscience Nursing
- Funders
- John D. and Catherine T. MacArthur Foundation
- Kohlberg Foundation
- National Institutes of Health (MH076136)
- National Institute of Mental Health (MH076136, R01MH076136, R37MH076136)
- National Institute on Drug Abuse (RC1DA028608, R01DA027794)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- placebo analgesia, individual differences, pain experience, emotional appraisal, frontoparietal network, posterior insula, paralimbic regions, pain processing, nociception
- MeSH terms
- Analgesia, Analgesics, Brain, Cerebral Cortex, Data Interpretation, Statistical, Humans, Individuality, Magnetic Resonance Imaging, Nerve Net, Pain, Regression Analysis, Placebo Effect, Cluster Analysis, Anticipation, Psychological
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
