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Brain Behav Immun. 2016 Aug;56:34-41. doi: 10.1016/j.bbi.2015.12.018. Epub 2015 Dec 28.

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

Author information

1
Stress Research Institute, Stockholm University, Stockholm, Sweden; Osher Center for Integrative Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. Electronic address: Mats.Lekander@ki.se.
2
Stress Research Institute, Stockholm University, Stockholm, Sweden; Osher Center for Integrative Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
3
Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
4
Department of Anaesthesiology and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
5
Osher Center for Integrative Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
6
Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Monell Chemical Senses Center, Philadelphia, PA, United States; Department of Psychology, University of Pennsylvania, Philadelphia, PA, United States.
7
Stress Research Institute, Stockholm University, Stockholm, Sweden; Osher Center for Integrative Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Division of Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
8
Stress Research Institute, Stockholm University, Stockholm, Sweden; Osher Center for Integrative Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Abstract

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 0.6ng/kg LPS (lipopolysaccharide) or placebo, and participated in a resting state fMRI experiment after approximately 2h 45min. 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.

KEYWORDS:

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

PMID:
26732827
DOI:
10.1016/j.bbi.2015.12.018
[Indexed for MEDLINE]

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