The role of metacognitive functions in placebo analgesia - An Activation Likelihood Estimation meta-Analysis.

Background and aims: Understanding placebo analgesia (PA) by studying the neuropsychological-related-network modulated by expectation is an endeavour that has strong clinical implications. Indeed a patient´s expectancy of improvement influences outcomes in placebo response. Up till now we have a limited understanding of the neuropsychological factors that influence patients' response to placebo treatment. We recently used Activation Likelihood Estimation meta-analysis (ALE) to search for the cortical areas involved in PA in human experimental pain models. The expectation-placebo-related analgesic mechanisms were found in the left anterior cingulate, right precentral, lateral prefrontal cortex and in the left periaqueductal gray (Amanzio et al., 2013). Since anterior cingulate is part of the medial prefrontal cortex (MPFC), it would be interesting to study the role of executive-metacognitive functions in PA and the functional network on the basis of this phenomenon. Methods: Following a forward inference between PA in human experimental pain and selected metacognitive functions (monitoring, response-inhibition and set-shifting), we used focused ALE meta-analysis to estimate related consistent activation. To test whether these results differed statistically, we performed subtraction analyses using a contrast studies procedure. Results: We found an effective overlap between these two functional networks with a particularly important role of MPFC, thus emphasizing the relation between PA and metacognitive functions. Conclusions: Our results demonstrate how the PA response arises as a result of cognitive abilities emphasizing the role of specific metacognitive functions in order to achieve a more comprehensive approach compared to previous studies in this field.