Associations between peripheral inflammation and resting state functional connectivity in adolescents

Abstract

Relatively little is known about associations between peripheral inflammation and neural function in humans. Neuroimaging studies in adults have suggested that elevated peripheral inflammatory markers are associated with altered resting state functional connectivity (rsFC) in several brain networks associated with mood and cognition. Few studies have examined these associations in adolescents, yet scarce data from adolescents point to different networks than adult studies. The current study examined the associations between peripheral inflammation and rsFC in a community sample of adolescents (n = 70; age, 12-15 years; 32 female, 36 male, 2 nonbinary). After blood sampling, an fMRI scan was performed to assess rsFC. Assay for serum inflammatory markers, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP), was performed. Results indicated that higher TNF-α was associated with altered rsFC between the right amygdala and left striatum and between the right inferior frontal gyrus and left parietal cortex (p < 0.05 whole-brain corrected). Associations with IL-6 and CRP were not significant. In contrast with findings in adults, inflammation may have unique links with the connectivity of the developing adolescent brain. Results have implications for understanding how peripheral inflammation may influence connectivity during adolescence, when neural networks are undergoing major developmental changes.

Keywords: Adolescence; Amygdala; Brain; Inflammation; Resting state connectivity; fMRI.

Fig. 1.

Regions of interest for seed-to-whole brain resting state functional connectivity analysis. Note: Regions of interest were obtained from the CONN toolbox atlas, which is derived from the Harvard-Oxford atlas. Coronal and sagittal views of the middle frontal gyrus are both shown to better depict this ROI.

Fig. 2.

Association between TNF-α and right amygdala connectivity. Note: Region where TNF-α is significantly associated with resting state connectivity using right amygdala as seed. Cluster in red depicts right amygdala seed ROI and cluster in blue depicts the striatal region where a significant effect was observed, thresholded at p < 0.05 whole-brain corrected using the 3dClustSim correction.

Fig. 3.

Association between TNF-α and right inferior frontal gyrus connectivity. Note: Region where TNF-α is significantly associated with resting state connectivity using right inferior frontal gyrus as seed. Cluster in red depicts right inferior frontal gyrus seed ROI and cluster in blue depicts the parietal cortex region where a significant effect was observed, thresholded at p < 0.05 whole-brain corrected using the 3dClustSim correction.