Plasma interleukin-6 correlates with connectivity of the default mode network in midlife adults

Abstract

The default mode network (DMN) is a group of brain systems that exhibit correlated activity at rest. Functional variation within the DMN is implicated in social, cognitive, and affective processes, as well as psychiatric and neurological disorders that associate with systemic inflammation. A major DMN hub, the ventromedial prefrontal cortex (vmPFC), connects with autonomic and neuroendocrine mechanisms that proximally influence inflammation. We tested whether plasma interleukin (IL)-6 covaried with functional DMN connectivity among 98 adults aged 30–54 (39% male; 81% Caucasian). DMN connectivity maps were derived using independent component analyses (MELODIC; ( http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/MELODIC )). Voxel-wise linear regression analyses tested IL-6 and DMN associations controlling for age, sex, and BMI at a whole-brain corrected false discovery rate threshold of q = 0.05 with an extent threshold of 20 voxels. Within the vmPFC, IL-6 covaried positively with connectivity of the subgenual anterior cingulate cortex and negatively with a portion of Brodmann area 11; while subcortically, IL-6 covaried negatively with connectivity of the medial thalamus and dorsal pons (all t ’s >3.4). It is possible that (1) higher peripheral inflammation through afferent visceral pathways influences connectivity within vmPFC and subcortical regions or (2) vmPFC connectivity, potentially via subcortical pathways, modulates peripheral autonomic and neuroendocrine mechanisms that upregulate inflammation. A link between DMN and peripheral inflammation provides a novel brain-body pathway that may be relevant to understanding depression and dementia.