Predicting individual differences in placebo analgesia: Contributions of brain activity during anticipation and pain experience

• Type of Material: Article
• Authors: Tor D. Wager, University of Colorado Boulder; Lauren Y. Atlas, Columbia University; Lauren A. Leotti, Rutgers University; James K Rilling, Emory University
• Language: English
• Date: 2011-01-12
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Final Published Version
• Copyright Statement: Copyright © 2011 the authors.
• Final Published Version (URL): http://dx.doi.org/10.1523/JNEUROSCI.3420-10.2011
• Title of Journal or Parent Work: Journal of Neuroscience Nursing
• ISSN: 0888-0395
• Volume: 31
• Issue: 2
• Start Page: 439
• End Page: 452
• Grant/Funding Information: This paper was made possible with the support of National Institutes of Health (NIH) Grants MH076136 and 1RC1DA028608 (T.D.W.); as well as support from the Mind Brain Body and Health Initiative, funded by the NIH; the John D. and Catherine T. MacArthur Foundation; the Rockefeller Family and Associates; and the Kohlberg Foundation.
• Keywords: Individuality; Analgesia; Regression Analysis; Pain; Humans; Nerve Net; Cluster Analysis; Data Interpretation, Statistical; Brain; Cerebral Cortex; Analgesics; Magnetic Resonance Imaging; Placebo Effect; Anticipation, Psychological
• Research Categories: Biology, Neuroscience; Psychology, Clinical; Psychology, Psychobiology

Abstract

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 β 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.