Altered Temporal Variance and Functional Connectivity of BOLD Signal is Associated with State Anxiety During Acute Systemic Inflammation

Systemic inflammation is accompanied by complex behavioral changes and disturbed emotion regulation that have been related to the pathophysiology of mood disorders including depression and anxiety. However, the causal role of systemic inflammation on mood disorders is still unclear. We herein investigated neural resting state patterns of temporal variance of the amygdala and functional connectivity within the salience network underlying changes in state anxiety during experimentally-induced systemic inflammation. In this randomized, double-blind study, N = 43 healthy men received an intravenous injection of either low-dose lipopolysaccharide (LPS, 0.4 ng/kg body weight) or saline. Resting state functional magnetic resonance imaging was assessed before and 3.5 h after injection. State anxiety, assessed with a standardized questionnaire, and plasma cytokine concentrations were repeatedly measured. LPS administration induced a transient systemic inflammatory response reflected in increases in plasma Interleukin (IL)-6 and Tumor Necrosis Factor (TNF)-α concentration. Compared to placebo, state anxiety and temporal variance in the amygdala significantly increased while functional connectivity in the salience network decreased during LPS-induced systemic inflammation. Together, these data indicate that acute systemic inflammation alters temporal variance of the BOLD signal as well as functional connectivity in brain regions and networks implicated in emotion processing and regulation. These results are of translational importance to encourage further research on the role of inflammatory pathways in the pathophysiology of neuropsychiatric conditions including anxiety disorders.