Placebo and nocebo have been intensively explored in direct conditioning/ context learning paradigms. However, most learning in daily life and clinical settings takes place indirectly (e.g., observational / social learning) in response to higly relevant contextual cues and may induce placebo/nocebo effects not only consciously but also subconsciously. Despite the ubiquity of indirect learning and the potential promise of harnessing it, little is known about the brain mechanisms of indirectly learned cue-induced placebo/nocebo. The goal of this proposal is to investigate the neural mechanism of direct and indirect, conscious and subliminal placebo/nocebo learning and retrieval. By applying MEG, featuring millisecond resolution, we will be able to study 1) placebo/nocebo responses evoked with conscious and non-conscious cues; 2) brain networks involved in context learning and placebo / nocebo effect; 3) the oscillatory dynamics underlying the interaction between direct / indirect learning and conscious / non- conscious activation of contextual cues. The use of pseudo drug names as cues will further enhance our understanding of the influence of medication labels on placebo/nocebo response. All subjects will undergo both a classical conditioning (experiencing different cues with different levels of pain intensity) and social observation conditioning (observing others' response to cues and pain). We will then compare subjective pain ratings and MEG signal changes evoked by identical pain preceded by high or low directly or observationally learned pseudo drug names, perceived consciously or non-consciously. The results obtained will shed light on developing new methods of harnessing placebo/nocebo effects, as well as understanding the mechanisms of direct and indirect learning in a clinical setting. Revealing the modulation effects of 'unseen' cues learned through social observation will unveil general mechanisms of non-conscious observational learning, which can be extended to other fields of psychiatric research such as addiction and Post-Traumatic Stress Disorder, where cue-activation of unwanted memories or cravings is relevant.
Contextual influence in a clinical setting is often described in terms of placebo and nocebo effects. The goal of this study is to investigate how direct/observational learned context could modulate our pain experience consciously and non-consciously using magnetoencephalography. The result obtained will significantly improve our understanding on the neural dynamic of placebo and nocebo effects.
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