Author: Geuter S^1,^2,³, Reynolds Losin EA⁴, Roy M⁵, Atlas LY^6,^7,⁸, Schmidt L⁹, Krishnan A¹⁰, Koban L^2,^9,^11,¹², Wager TD^2,^11,¹³, Lindquist MA¹
Affiliation: 1Department of Biostatistics, Johns Hopkins University, Baltimore, MD, USA. 2Institute of Cognitive Science, University of Colorado Boulder, Boulder, CO, USA. 3Vorwerk International & Co. KmG, Zurich, Switzerland. 4Department of Psychology, University of Miami, Coral Gables, FL, USA. 5Department of Psychology, McGill University, Montreal, Quebec, Canada. 6National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD, USA. 7National Center on Drug Abuse, National Institutes of Health, Bethesda, MD, USA. 8National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. 9Control-Interoception-Attention Team, Institute du Cerveau et de la Moelle épinière, INSERM UMR 1127, CNRS UMR 7225, Sorbonne University, Paris, France. 10Department of Psychology, Brooklyn College of the City University of New York, Brooklyn, NY, USA. 11Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA. 12Marketing Area, INSEAD, Fontainebleau, France. 13Presidential Cluster in Neuroscience and Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH, USA.
Conference/Journal: Cereb Cortex.
Date published: 2020 Mar 26
Other: Pages: bhaa048 , Special Notes: doi: 10.1093/cercor/bhaa048. [Epub ahead of print] , Word Count: 204

The brain transforms nociceptive input into a complex pain experience comprised of sensory, affective, motivational, and cognitive components. However, it is still unclear how pain arises from nociceptive input and which brain networks coordinate to generate pain experiences. We introduce a new high-dimensional mediation analysis technique to estimate distributed, network-level patterns that formally mediate the relationship between stimulus intensity and pain. We applied the model to a large-scale analysis of functional magnetic resonance imaging data (N = 284), focusing on brain mediators of the relationship between noxious stimulus intensity and trial-to-trial variation in pain reports. We identify mediators in both traditional nociceptive pathways and in prefrontal, midbrain, striatal, and default-mode regions unrelated to nociception in standard analyses. The whole-brain mediators are specific for pain versus aversive sounds and are organized into five functional networks. Brain mediators predicted pain ratings better than previous brain measures, including the neurologic pain signature (Wager et al. 2013). Our results provide a broader view of the networks underlying pain experience, as well as novel brain targets for interventions.

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KEYWORDS: brain networks; fMRI; mediation analysis; pain; pattern analysis

PMID: 32219311 PMCID: PMC7264706 DOI: 10.1093/cercor/bhaa048

Multiple Brain Networks Mediating Stimulus-Pain Relationships in Humans.