Mild Inflammation in Healthy Males Induces Fatigue Mediated by Changes in Effective Connectivity Within the Insula.
Allostasis
Dynamic causal models
Inflammation
Insula
Interoception
Sickness behavior
Journal
Biological psychiatry. Cognitive neuroscience and neuroimaging
ISSN: 2451-9030
Titre abrégé: Biol Psychiatry Cogn Neurosci Neuroimaging
Pays: United States
ID NLM: 101671285
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
11
02
2020
revised:
30
03
2020
accepted:
06
04
2020
pubmed:
14
6
2020
medline:
13
3
2021
entrez:
14
6
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 32532687
pii: S2451-9022(20)30098-7
doi: 10.1016/j.bpsc.2020.04.005
pii:
doi:
Substances chimiques
Salmonella Vaccines
0
Banques de données
ClinicalTrials.gov
['NCT02653235']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
865-874Informations de copyright
Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.