Mild inflammation in healthy males induces fatigue mediated by changes in effective connectivity within the insula

Stefanov, K. , McLean, J., McColl, A., Basu, N. , Cavanagh, J. and Krishnadas, R. (2020) Mild inflammation in healthy males induces fatigue mediated by changes in effective connectivity within the insula. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 5(9), pp. 865-874. (doi: 10.1016/j.bpsc.2020.04.005) (PMID:32532687)

[img] Text
219158.pdf - Accepted Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

1MB

Abstract

Background: Systemic inflammation is associated with sickness behaviors such as low mood and fatigue. Activity patterns within the insula are suggested to coordinate these behaviors but have not been modeled. We hypothesized that mild systemic inflammation would result in changes in effective connectivity between the viscerosensory and the visceromotor regions of the insula. Methods: We used a double-blind, crossover design to randomize 20 male subjects to receive either a Salmonella typhi vaccine or a placebo saline injection at two separate sessions. All participants underwent a resting-state functional magnetic resonance scan 3 hours after injection. We determined behavioral and inflammatory changes, using the Profile of Mood States questionnaire and interleukin-6 levels. We extracted effective connectivity matrices between bilateral mid/posterior (viscerosensory) and anterior (visceromotor) insular cortices using spectral dynamic causal modeling. We applied parametric empirical Bayes and mediation analysis to determine a vaccination effect on effective connectivity and whether this mediated behavioral changes. Results: The vaccine condition was associated with greater interleukin-6 levels and greater fatigue 3 hours after the injection. Activity within the right mid/posterior insula increased the activity within the bilateral anterior insular regions. This connectivity was augmented by vaccination over a 99% posterior confidence threshold. The right mid/posterior insula-to-left anterior insula connectivity was significantly associated with fatigue and mediated the association between inflammation and increased fatigue scores. Conclusions: These results demonstrate that increased effective connectivity between specific nodes of the insula can model and mediate the association between inflammation and fatigue in males.

Item Type:Articles
Additional Information:This work was supported by an Academy of Medical Sciences Clinical Lecturer Starter Grant (to RK).
Keywords:Allostasis, dynamic causal models, inflammation, insula, interoception, sickness behavior.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cavanagh, Professor Jonathan and Basu, Professor Neil and Stefanov, Mr Kristian and McColl, Dr Alison and Krishnadas, Dr Rajeev
Authors: Stefanov, K., McLean, J., McColl, A., Basu, N., Cavanagh, J., and Krishnadas, R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Publisher:Elsevier
ISSN:2451-9022
ISSN (Online):2451-9030
Published Online:22 April 2020
Copyright Holders:Copyright © 2020 Society of Biological Psychiatry
First Published:First published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging 5(9):865-874
Publisher Policy:Reproduced in accordance with the publisher copyright policy

University Staff: Request a correction | Enlighten Editors: Update this record