title: Alterations in functional connectivity of resting state networks during experimental endotoxemia - An exploratory study in healthy men.
abstract: Systemic inflammation impairs mood and cognitive functions, and seems to be involved in the pathophysiology of psychiatric disorders. Functional magnetic resonance imaging (fMRI) studies revealed altered task-related blood-oxygen-level-dependent (BOLD) responses during experimental endotoxemia, but little is known about effects of systemic inflammation on resting-state activity of the brain. Thus, we conducted a randomized, placebo-controlled study in healthy men receiving an intravenous injection of either low-dose (0.4 ng/kg) lipopolysaccharide (LPS) (N=20) or placebo (N=25). Resting state activity was measured at baseline and 3.5h post-injection. Based on a two (condition) × two (group) design, we used multi-subject independent component analysis (ICA) to decompose and estimate functional connectivity within resting-state networks (RSNs). Seed-based analyses were applied to investigate the effect of LPS on the functional coupling for a priori-defined regions-of-interest (ROIs). ICA analyses identified 13 out of 35 components displaying common RSNs. Seed based analysis revealed greater functional connectivity between the left thalamus and the cerebellum after LPS compared to placebo administration, while the functional coupling between seeds within the amygdala, insula, and cingulate cortex and various brain regions including parieto-frontal networks was significantly reduced. Within the LPS group, endotoxin-induced increases in Interleukin (IL)-6 were significantly associated with resting-state connectivity between the left thalamus and left precuneus as well as the right posterior cingulate cortex. In summary, this exploratory study provides first evidence that systemic inflammation affects the coupling and regulation of multiple networks within the human brain at rest.
authors.affiliation: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Labrenz
authors.affiliation: Department of Neurosurgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Wrede
authors.affiliation: Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Forsting
authors.affiliation: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Engler
authors.affiliation: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Schedlowski
authors.affiliation: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Elsenbruch
authors.affiliation: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. Electronic address: sven.benson@uk-essen.de.
authors.forename: Sven
authors.initials: S
authors.lastname: Benson
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001931:Brain Mapping / Q000379:methods; D063132:Connectome / Q000379:methods*; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010100:Oxygen / Q000097:blood
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D010100:Oxygen
keywords: Endotoxemia; Functional connectivity; LPS; Resting state; Sickness behavior; Systemic inflammation; fMRI