title: Exposure to an inflammatory challenge enhances neural sensitivity to negative and positive social feedback.
abstract: Inflammation, part of the body's innate immune response, can lead to "sickness behaviors," as well as alterations in social and affective experiences. Elevated levels of pro-inflammatory cytokines have been associated with increased neural sensitivity to social rejection and social threat, but also decreased neural sensitivity to rewards. However, recent evidence suggests that inflammation may actually enhance sensitivity to certain social rewards, such as those that signal support and care. Despite a growing interest in how inflammation influences neural reactivity to positive and negative social experiences, no known studies have investigated these processes in the same participants, using a similar task. To examine this issue, 107 participants were randomly assigned to receive either placebo or low-dose endotoxin, which safely triggers an inflammatory response. When levels of pro-inflammatory cytokines were at their peak, participants were scanned using fMRI while they received positive, negative, and neutral feedback from an "evaluator" (actually a confederate) about how they came across in an audio-recorded interview. In response to negative feedback (vs. neutral), participants in the endotoxin condition showed heightened neural activity in a number of threat-related neural regions (i.e., bilateral amygdala, dorsal anterior cingulate cortex) and a key mentalizing-related region (i.e., dorsomedial PFC), compared to placebo participants. Interestingly, when receiving positive feedback (vs. neutral), endotoxin (vs. placebo) led to greater neural activity in the ventral striatum and ventromedial PFC, regions often implicated in processing reward, as well as greater activity in dorsomedial PFC. Together, these results reveal that individuals exposed to an inflammatory challenge are more "neurally sensitive" to both negative and positive social feedback, suggesting that inflammation may lead to a greater vigilance for both social threats and social rewards.
authors.affiliation: Department of Psychology, University of California, Berkeley, United States. Electronic address: kmuscatell@berkeley.edu.
authors.forename: Keely A
authors.initials: KA
authors.lastname: Muscatell
authors.affiliation: Department of Psychology, University of California, Los Angeles, United States.
authors.forename: Mona
authors.initials: M
authors.lastname: Moieni
authors.affiliation: Department of Psychology, University of Pittsburgh, United States.
authors.forename: Tristen K
authors.initials: TK
authors.lastname: Inagaki
authors.affiliation: Department of Psychology, University of California, Los Angeles, United States.
authors.forename: Janine M
authors.initials: JM
authors.lastname: Dutcher
authors.affiliation: Department of Psychology, University of California, Los Angeles, United States.
authors.forename: Ivana
authors.initials: I
authors.lastname: Jevtic
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, United States; Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, United States.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Breen
authors.affiliation: Department of Psychology, University of California, Los Angeles, United States; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, United States; Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, United States.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Irwin
authors.affiliation: Department of Psychology, University of California, Los Angeles, United States. Electronic address: neisenbe@ucla.edu.
authors.forename: Naomi I
authors.initials: NI
authors.lastname: Eisenberger
mesh_terms: D000328:Adult; D000679:Amygdala / Q000000981:diagnostic imaging / Q000503:physiopathology*; D016207:Cytokines / Q000097:blood*; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D030141:Feedback, Psychological / Q000502:physiology*; D005260:Female; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000139:chemically induced; D007398:Interpersonal Relations; D008279:Magnetic Resonance Imaging; D008297:Male; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D012201:Reward; D055815:Young Adult
chemical_list: D016207:Cytokines; D004731:Endotoxins
keywords: Cytokines; Endotoxin; Inflammation; Reward; Social feedback; Threat; fMRI