Neuroimaging Placebo Effects: New Tools Generate New Questions

Placebos were historically defined as inert substances (e.g., sugar or bread pills) that cause symptom improvement but are now characterized more broadly to include contextual aspects of both active and inactive treatments that contribute to symptom improvement in therapeutic settings. These contexts may be associated with the environment, including the size and color of a pill, a doctor’s demeanor, or the invasiveness and cost of a treatment. The context may also be generated by the patient’s prior experience or expectations about the efficacy of a treatment. Placebo effects are cognitive, behavioral, or biological responses to these contextual aspects of treatment. Although placebo effects may be a nuisance for clinical trials, they remain an important tool for clinicians and often prove beneficial for patients. Despite their efficacy, the scientific community has tended to regard placebo effects as noise rather than a potential topic of research. However, a major paradigm shift has generated renewed interest in investigating neurocognitive and neurochemical mechanisms that drive placebo effects. The timing of this renewed interest overlaps with increasing access to neuroimaging tools, allowing for investigation of these underlying mechanisms that cannot be readily assessed via self-report or observation alone.