Distinct prefrontal lateralization in Placebo and Reappraisal mechanisms: An ALE meta-analysis

Cognitive reappraisal is an emotional regulation strategy by which the individual changes the perspective on a situation to alter its emotional impact. Similar reinterpretation mechanisms have been associated with the placebo effect in which beliefs about the efficacy of a treatment modulate subjective experience and physiological responses. This analogy raises the hypothesis that reappraisal and placebo may share neural networks. However, despite previous efforts to identify these networks separately, there has been no recent systematic comparison using a whole-brain meta-analytic approach. To fill this gap, in the current study, we performed a coordinate-based ALE meta-analysis of task-based fMRI studies investigating reappraisal and placebo. Results show that both processes recruit the dorsolateral prefrontal cortex (DLPFC), highlighting the shared cognitive control mechanisms by which they modify the emotional response. However, reappraisal primarily engages the left portion of the DLPFC, along with the ventrolateral PFC and dorsomedial PFC, while placebo primarily engages the right portion of the DLPFC. These results show that despite common general aspects, reappraisal and placebo are different in nature and rely on different neuropsychological mechanisms. We discuss possible explanations and their implications for clinical practice and future research.