Experimental endotoxemia induces increased functional connectivity between the thalamus and the default mode network in healthy men

Abstract

While functional MRI studies revealed altered task-related BOLD responses during experimental endotoxemia, little is known how systemic inflammation affects resting state activity of the brain. In this randomized, placebo-controlled study, healthy men received either low-dose (0.4 ng/kg) lipopolysaccharide (LPS) (N = 20) or saline (N = 25). Resting state activity was measured at baseline and 3.5 h post-injection. In multi-subject independent component analysis (ICA), 13 out of 30 components were identified which displayed the common networks assigned to resting state brain activity. Dual regression analyses revealed that LPS-treated subjects exhibited distinct patterns of connectivity within multiple resting state networks, including the somatosensory network compared to baseline and the fronto-parietal network compared to placebo. Seed based resting state analysis showed greater functional connectivity between left thalamus and right posterior insula, left posterior cingulate cortex (BA 31), left precuneus, and cerebellum (bilateral) after LPS injection compared to placebo. Together, our data indicate that resting state activity of the brain is altered during systemic inflammation, including an increased functional connectivity between the thalamus and other brain regions which are part of the default mode network. This may reflect an increased integrative processing of interoceptive input arising from the vagus/brainstem, aiming to maintain homeostasis, and to promote a more internally focused self-reflection during states of inflammation. It remains to be determined if LPS-induced alterations in resting state parameters are associated with immune-mediated mood impairments.