Plos Biol
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Randomized Controlled Trial
Brain Connectivity Predicts Placebo Response across Chronic Pain Clinical Trials.
Placebo response in the clinical trial setting is poorly understood and alleged to be driven by statistical confounds, and its biological underpinnings are questioned. Here we identified and validated that clinical placebo response is predictable from resting-state functional magnetic-resonance-imaging (fMRI) brain connectivity. This also led to discovering a brain region predicting active drug response and demonstrating the adverse effect of active drug interfering with placebo analgesia. ⋯ Moreover, the approach led to discovering that right parahippocampus gyrus connectivity predicts drug analgesia after correcting for modeled placebo-related analgesia. Our evidence is consistent with clinical placebo response having biological underpinnings and shows that the method can also reveal that active treatment in some patients diminishes modeled placebo-related analgesia. Trial Registration ClinicalTrials.gov NCT02903238 ClinicalTrials.gov NCT01558700.