title: Systemic inflammation and resting state connectivity of the default mode network.
abstract: The default mode network (DMN) encompasses brain systems that exhibit coherent neural activity at rest. DMN brain systems have been implicated in diverse social, cognitive, and affective processes, as well as risk for forms of dementia and psychiatric disorders that associate with systemic inflammation. Areas of the anterior cingulate cortex (ACC) and surrounding medial prefrontal cortex (mPFC) within the DMN have been implicated specifically in regulating autonomic and neuroendocrine processes that relate to systemic inflammation via bidirectional signaling mechanisms. However, it is still unclear whether indicators of inflammation relate directly to coherent resting state activity of the ACC, mPFC, or other areas within the DMN. Accordingly, we tested whether plasma interleukin (IL)-6, an indicator of systemic inflammation, covaried with resting-state functional connectivity of the DMN among 98 adults aged 30-54 (39% male; 81% Caucasian). Independent component analyses were applied to resting state fMRI data to generate DMN connectivity maps. Voxel-wise regression analyses were then used to test for associations between IL-6 and DMN connectivity across individuals, controlling for age, sex, body mass index, and fMRI signal motion. Within the DMN, IL-6 covaried positively with connectivity of the sub-genual ACC and negatively with a region of the dorsal medial PFC at corrected statistical thresholds. These novel findings offer evidence for a unique association between a marker of systemic inflammation (IL-6) and ACC and mPFC functional connectivity within the DMN, a network that may be important for linking aspects of immune function to psychological and behavioral states in health and disease.
authors.affiliation: Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, United States. Electronic address: marsland@pitt.edu.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Marsland
authors.affiliation: Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, United States.
authors.forename: Dora C-H
authors.initials: DC
authors.lastname: Kuan
authors.affiliation: Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, United States.
authors.forename: Lei K
authors.initials: LK
authors.lastname: Sheu
authors.affiliation: Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, United States.
authors.forename: Katarina
authors.initials: K
authors.lastname: Krajina
authors.affiliation: Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, United States; Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, Pittsburgh, PA 15213, United States.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Kraynak
authors.affiliation: Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, United States.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Manuck
authors.affiliation: Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, United States; Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, Pittsburgh, PA 15213, United States.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Gianaros
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000503:physiopathology; D001931:Brain Mapping; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000000981:diagnostic imaging* / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000000981:diagnostic imaging* / Q000503:physiopathology
chemical_list: D015850:Interleukin-6; D002097:C-Reactive Protein
keywords: Anterior cingulate cortex; CRP; Default mode network; IL-6; Inflammation; Prefrontal cortex; Resting state connectivity