Multiple Brain Networks Mediating Stimulus-Pain Relationships in Humans.

Author: Geuter S1,2,3, Reynolds Losin EA4, Roy M5, Atlas LY6,7,8, Schmidt L9, Krishnan A10, Koban L2,9,11,12, Wager TD2,11,13, Lindquist MA1
Affiliation: <sup>1</sup>Department of Biostatistics, Johns Hopkins University, Baltimore, MD, USA. <sup>2</sup>Institute of Cognitive Science, University of Colorado Boulder, Boulder, CO, USA. <sup>3</sup>Vorwerk International &amp; Co. KmG, Zurich, Switzerland. <sup>4</sup>Department of Psychology, University of Miami, Coral Gables, FL, USA. <sup>5</sup>Department of Psychology, McGill University, Montreal, Quebec, Canada. <sup>6</sup>National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD, USA. <sup>7</sup>National Center on Drug Abuse, National Institutes of Health, Bethesda, MD, USA. <sup>8</sup>National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. <sup>9</sup>Control-Interoception-Attention Team, Institute du Cerveau et de la Moelle épinière, INSERM UMR 1127, CNRS UMR 7225, Sorbonne University, Paris, France. <sup>10</sup>Department of Psychology, Brooklyn College of the City University of New York, Brooklyn, NY, USA. <sup>11</sup>Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA. <sup>12</sup>Marketing Area, INSEAD, Fontainebleau, France. <sup>13</sup>Presidential 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.

© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

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