Brain network representations of placebo analgesia

BACKGROUND: Prior neuroimaging studies and meta-analyses investigating brain correlates of placebo analgesia (PA) have yielded neuroanatomically heterogeneous findings, which may be reconciled from a connectomics perspective. The objective of this study was to examine network localization of brain functional alterations related to PA. METHODS: We initially identified PA-induced brain activation alterations (hyper-activation and hypo-activation separately) during experimental pain from 29 published studies with 674 individuals. By combining these implicated dysfunctional brain regions with large-scale discovery (N = 1113) and validation (N = 1093) resting-state functional magnetic resonance imaging datasets, we then employed a novel functional connectivity network mapping approach to construct PA hyper-activation and hypo-activation networks, respectively. RESULTS: The PA hyper-activation network manifested as a pattern of circumscribed brain regions mainly involving the limbic, default, and frontoparietal networks. By contrast, the PA hypo-activation network comprised a broadly distributed set of brain regions primarily implicating the ventral attention, somatomotor, and subcortical networks. CONCLUSIONS: Our findings regarding the brain network representations of PA may contribute to a deeper understanding of its action mechanisms and provide a neural framework that may inform future clinical translation.