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Brain connectivity predicts placebo response across chronic pain clinical trials

Placebo response is extensively studied in healthy subjects and for experimental manipulations. However, in the clinical setting it has been primarily relegated to statistical confounds. Here, for the first time we examine predictability of future placebo response in the clinical setting in patients with chronic osteoarthritis pain. We examine resting state fMRI brain connectivity prior to start of clinical trial, and in the setting of neutral instructions regarding treatment. Our results show that clinical placebo pill ingestion shows stronger analgesia than no treatment, is predictable from resting state BOLD fMRI, and right mid-frontal gyrus degree count (extent of functional connectivity) identifies placebo pill responders in one trial and can be validated (95% correct) in the placebo group of a second trial but not in the active drug treatment (duloxetine) group. By modeling the expected placebo response in subjects receiving active drug treatment, we uncover a placebo-corrected drug response predictive brain signal, and show that in some subjects active drug tends to enhance, while in others interferes, with predicted placebo response. Together, these results provide evidence for clinical placebo being predetermined by brain biology, and show that brain imaging may also identify a placebo-corrected prediction of response to active treatment.


  • Marwan N. Baliki
  • A. Vania Apkarian
  • Thomas J. Schnitzer
  • Etienne Vachon-Presseau
  • Ali Mansour
  • Pascal Tétreault

Contact Information:

Name: Pascal Tetreault

Acknowledgements and Funding:

Contributors: P.T. collected, analyzed and interpreted the data and prepared and wrote the manuscript, A.M. and E.V.-P., contributed to data collection and analysis. T.J.S. designed the study, assessed patients for eligibility, and interpreted the data. A.V.A. designed the study, interpreted the data and wrote the manuscript. M.N.B analyzed and interpreted the data and wrote the manuscript. All authors reviewed and edited the manuscript. Acknowledgements: We thank the staff and faculty of Center of Translational Imaging at Northwestern University and students and staff of Apkarian Lab and all study participants. Funding: Eli Lilly Pharmaceuticals funded study 2 (IIT number: F1J-US-XO61). This research was partially also supported by grants from National Institute of Neurological Disorders and Stroke (NS035115), and National Center for Complementary and Integrative Health (AT007987) of U.S. National Institutes of Health. P.T. and E.V.-P. were supported by the Canadian Institutes of Health Research.

External Publication Links:

Brain Connectivity Predicts Placebo Response across Chronic Pain Clinical Trials

Sample Size:


Scanner Type:

3T Siemens Trio whole-body scanner with echo-planar imaging (EPI) capability



Accession Number:


How to cite this dataset:

In addition to any citation requirements in the dataset summary please use the following to cite this dataset:

This data was obtained from the OpenfMRI database. Its accession number is ds000208



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Revision: 1.0.0 Date Set: Sept. 22, 2016, 5:12 a.m.


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