Alterations in functional connectivity of resting state networks during experimental endotoxemia – An exploratory study in healthy men

• Published in: Brain, behavior, and immunity Vol. 54; pp. 17 - 26
• Main Authors: Labrenz, Franziska, Wrede, Karsten, Forsting, Michael, Engler, Harald, Schedlowski, Manfred, Elsenbruch, Sigrid, Benson, Sven
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.05.2016
• Subjects: Adult; Allergy and Immunology; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain Mapping - methods; Connectome - methods; Endotoxemia; Endotoxemia - chemically induced; Endotoxemia - metabolism; Endotoxemia - pathology; fMRI; Functional connectivity; Humans; Interleukin-6 - metabolism; Lipopolysaccharides - administration & dosage; LPS; Magnetic Resonance Imaging - methods; Male; Membrane Potentials - drug effects; Membrane Potentials - physiology; Oxygen - blood; Psychiatry; Resting state; Sickness behavior; Systemic inflammation; Functional connectivity; fMRI; Sickness behavior; Resting state; Systemic inflammation; Endotoxemia; LPS
• ISSN: 0889-1591; 1090-2139; 1090-2139
• DOI: 10.1016/j.bbi.2015.11.010

•We tested effects of experimental endotoxemia on resting state brain activity.•Resting-state brain activity is altered during systemic inflammation.•Connectivity between the thalamus and the default mode network was increased.•Connectivity emanating from amygdala, insula, and cingulate cortex was reduced.•This may reflect central processes involved in restoring homeostasis. 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 (0.4ng/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.