 In summary, the proposed research is novel with respect to design, technology, and its multi-level integration probing psychological and neurobiological constructs assumed to be crucially implicated in placebo response and has significant clinical and research implications for the future. Specifically, the future implications include: 1 identification of biomarkers and biosignatures of placebo responders, 2 new possibilities to understanding and manipulating the system, 3 possibly decreasing or eliminating a major confounder in clinical trials and drug development, and 4 refining treatments with novel drugs that decrease in clinical trial or increase in clinical practice the placebo response. 