A neural mechanism of direct and observational conditioning for placebo and nocebo responses

• Published in: NeuroImage (Orlando, Fla.) Vol. 184; pp. 954 - 963
• Main Authors: Tu, Yiheng, Park, Joel, Ahlfors, Seppo P., Khan, Sheraz, Egorova, Natalia, Lang, Courtney, Cao, Jin, Kong, Jian
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2019; Elsevier Limited
• Subjects: Adult; Alpha band connectivity; Analgesia; Brain - physiology; Brain Waves; Conditioning; Conditioning, Psychological; Consciousness; Cortex (cingulate); Cortex (temporal); Experiments; Facial Recognition; Female; Heat; Humans; Hyperalgesia; Learning; Magnetoencephalography; Male; Narcotics; Neural networks; Neural Pathways - physiology; Nocebo Effect; Nocebos; Nociception - physiology; Pain; Pain Measurement; Pain perception; Placebo; Placebo Effect; Rostral anterior cingulate cortex; Sensory perception; Studies; Temporal gyrus; Visual cortex; Visual stimuli; Young Adult; Learning; Rostral anterior cingulate cortex; Alpha band connectivity; Conditioning; Consciousness; Placebo
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2018.10.020

Classical theories suggest placebo analgesia and nocebo hyperalgesia are based on expectation and conditioned experience. Whereas the neural mechanism of how expectation modulates placebo and nocebo effects during pain anticipation have been extensively studied, little is known about how experience may change brain networks to produce placebo and nocebo responses. We investigated the neural pathways of direct and observational conditioning for conscious and nonconscious conditioned placebo/nocebo effects using magnetoencephalography and a face visual cue conditioning model. We found that both direct and observational conditioning produced conscious conditioned placebo and nocebo effects and a nonconscious conditioned nocebo effect. Alpha band brain connectivity changes before and after conditioning could predict the magnitude of conditioned placebo and nocebo effects. Particularly, the connectivity between the rostral anterior cingulate cortex and middle temporal gyrus was an important indicator for the manipulation of placebo and nocebo effects. Our study suggests that conditioning can mediate our pain experience by encoding experience and modulating brain networks. •Direct and observational conditioning could produce placebo/nocebo effects•Direct and observational conditioning could modulate alpha band brain connectivity•Alpha band brain connectivity was predictive for placebo/nocebo responses•rACC-MTG connectivity was an indicator of placebo/nocebo response magnitude