title: Frontal-Brainstem Pathways Mediating Placebo Effects on Social Rejection.
abstract: Placebo treatments can strongly affect clinical outcomes, but research on how they shape other life experiences and emotional well-being is in its infancy. We used fMRI in humans to examine placebo effects on a particularly impactful life experience, social pain elicited by a recent romantic rejection. We compared these effects with placebo effects on physical (heat) pain, which are thought to depend on pathways connecting prefrontal cortex and periaqueductal gray (PAG). Placebo treatment, compared with control, reduced both social and physical pain, and increased activity in the dorsolateral prefrontal cortex (dlPFC) in both modalities. Placebo further altered the relationship between affect and both dlPFC and PAG activity during social pain, and effects on behavior were mediated by a pathway connecting dlPFC to the PAG, building on recent work implicating opioidergic PAG activity in the regulation of social pain. These findings suggest that placebo treatments reduce emotional distress by altering affective representations in frontal-brainstem systems.SIGNIFICANCE STATEMENTPlacebo effects are improvements due to expectations and the socio-medical context in which treatment takes place. Whereas they have been extensively studied in the context of somatic conditions such as pain, much less is known of how treatment expectations shape the emotional experience of other important stressors and life events. Here, we use brain imaging to show that placebo treatment reduces the painful feelings associated with a recent romantic rejection by recruiting a prefrontal-brainstem network and by shifting the relationship between brain activity and affect. Our findings suggest that this brain network may be important for nonspecific treatment effects across a wide range of therapeutic approaches and mental health conditions.
authors.affiliation: Institute of Cognitive Science and leonie.koban@colorado.edu.|Department of Psychology and Neuroscience, University of Colorado, Boulder, Colorado 80309.
authors.forename: Leonie
authors.identifier: 0000-0002-3121-6491
authors.initials: L
authors.lastname: Koban
authors.affiliation: Department of Psychology, University of Michigan, Ann Arbor, Michigan 48109, and.
authors.forename: Ethan
authors.identifier: 0000-0002-8664-2711
authors.initials: E
authors.lastname: Kross
authors.affiliation: Center for Neuroscience Imaging Research, Institute for Basic Science and.|Department of Biomedical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Choong-Wan
authors.identifier: 0000-0002-7423-5422
authors.initials: CW
authors.lastname: Woo
authors.affiliation: Institute of Cognitive Science and.|Department of Psychology and Neuroscience, University of Colorado, Boulder, Colorado 80309.
authors.forename: Luka
authors.initials: L
authors.lastname: Ruzic
authors.affiliation: Institute of Cognitive Science and.|Department of Psychology and Neuroscience, University of Colorado, Boulder, Colorado 80309.
authors.forename: Tor D
authors.identifier: 0000-0002-1936-5574
authors.initials: TD
authors.lastname: Wager
mesh_terms: D000293:Adolescent; D000328:Adult; D000339:Affect; D000698:Analgesia / Q000523:psychology*; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D058748:Pain Perception / Q000187:drug effects / Q000502:physiology*; D015990:Placebo Effect; D010919:Placebos / Q000008:administration & dosage; D012929:Psychological Distance; D013404:Suggestion; D055815:Young Adult
chemical_list: D010919:Placebos
keywords: emotion regulation; nociception; opioid; placebo; resilience; social