Evaluation of potential therapies for neurological disease has been challenging due to beneficial responses in patients receiving the sham/placebo treatment. Placebo effects are especially prominent in Parkinson’s disease (PD), which has become a useful model for studying the neurobiology of placebo responses. In this issue of the JCI, Ko and colleagues identify a neural circuit associated with the placebo response in a PD patient cohort. The observed placebo effect–associated pattern involved metabolic activity increases that corresponded with long-term motor improvements after sham surgery. Presurgery activity in this network was inversely related to sham response, suggesting that this network has potential for identifying sham responders and thus reducing placebo-related variance in surgical trials.