Imaging the placebo response: a neurofunctional review.

An emerging literature has started to document the neuronal changes associated with the placebo phenomenon. This has altered placebo from being considered a nuisance factor in clinical research to a target of scientific investigation per se. This paper reviews the neuroimaging literature on the placebo effect, and illustrates how imaging tools can improve current understanding of brain mechanisms underlying the placebo response. Imaging studies provide evidence of specific, predictable and replicable patterns of neural changes associated with placebo administration. In general, placebo responses seem mediated by "top-down" processes dependent on frontal cortical areas that generate and maintain cognitive expectancies. Dopaminergic reward pathways may underlie these expectancies. Placebo-induced clinical benefits also involve disorder-specific neuronal responses, yielding neurofunctional or neurochemical alterations similar to those produced by pharmacological treatments.