Emotion-specific nocebo effects: an fMRI study

The neurobiological mechanisms of nocebos are still poorly understood. Thirty-eight women participated in a 'smell study' using functional magnetic resonance imaging. They were presented with an odorless stimulus (distilled water) together with the verbal suggestion that this fluid has an aversive odor which enhances disgust feelings. The nocebo was presented while the participants viewed disgusting, fear-inducing, and neutral images. Participants' affective and neuronal responses during nocebo administration were compared with those in a control condition without nocebo. Twenty-nine women (76%) reported perceiving a slightly unpleasant and arousing odor. These 'nocebo responders' experienced increased disgust during the presentation of disgusting images in combination with the nocebo and showed enhanced left orbitofrontal cortex (OFC) activation. It has been suggested that the OFC is involved in the generation of placebo/nocebo-related expectations and appraisals. This region showed increased functional connectivity with areas involved in interoception (insula), autobiographical memories (hippocampus), and odor imagery (piriform cortex) during nocebo administration. The nocebo-induced change in brain activation was restricted to the disgust condition. Implications for psychotherapy are discussed.