Intrinsic functional connectivity of insular cortex and symptoms of sickness during acute experimental inflammation

Mats Lekander*, Bianka Karshikoff, Emilia Johansson, Anne Soop, Peter Fransson, Johan N. Lundström, Anna Andreasson, Martin Ingvar, Predrag Petrovic, John Axelsson, Gustav Nilsonne

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)


Task-based fMRI has been used to study the effects of experimental inflammation on the human brain, but it remains unknown whether intrinsic connectivity in the brain at rest changes during a sickness response. Here, we investigated the effect of experimental inflammation on connectivity between areas relevant for monitoring of bodily states, motivation, and subjective symptoms of sickness. In a double-blind randomized controlled experiment, 52 healthy volunteers were injected with 0.6 ng/kg LPS (lipopolysaccharide) or placebo, and participated in a resting state fMRI experiment after approximately 2 h 45 min. Resting state fMRI data were available from 48 participants, of which 28 received LPS and 20 received placebo. Bilateral anterior and bilateral posterior insula sections were used as seed regions and connectivity with bilateral orbitofrontal and cingulate (anterior and middle) cortices was investigated. Back pain, headache and global sickness increased significantly after as compared to before LPS, while a non-significant trend was shown for increased nausea. Compared to placebo, LPS was followed by increased connectivity between left anterior insula and left midcingulate cortex. This connectivity was significantly correlated to increase in back pain after LPS and tended to be related to increased global sickness, but was not related to increased headache or nausea. LPS did not affect the connectivity from other insular seeds. In conclusion, the finding of increased functional connectivity between left anterior insula and middle cingulate cortex suggests a potential neurophysiological mechanism that can be further tested to understand the subjective feeling of malaise and discomfort during a sickness response.

Original languageEnglish
Pages (from-to)34-41
Number of pages8
JournalBrain, Behavior, and Immunity
Publication statusPublished - 1 Aug 2016
Externally publishedYes


  • Endotoxin
  • fMRI
  • Inflammation
  • Insular cortex
  • Interoception
  • Intrinsic connectivity
  • Lipopolysaccharide
  • Resting state
  • Sickness behavior
  • Spontaneous pain


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