Neural correlates of fatigue in granulomatosis with polyangiitis: a functional magnetic resonance imaging study

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OBJECTIVE: The aim of this study was to investigate the neurophysiological effects of fatigue among patients with granulomatosis with polyangiitis (GPA).

METHODS: A case-control functional MRI (fMRI) study was conducted. Stable GPA subjects were recruited according to fatigue status, with those reporting fatigue defined as cases and those not defined as controls. In addition, a control group of general population subjects with idiopathic fatigue were studied. During fMRI, all participants performed a fatigue-inducing cognitive task. Functional data were acquired with a 3 T MRI scanner during periods of task activity and rest. Analyses of the differences in blood oxygen level dependent (BOLD) signal were then performed using SPM8 software and comparisons were made between case and control groups.

RESULTS: GPA cases (n = 12) were demographically matched to GPA controls (n = 14) and were clinically similar apart from the higher reporting of fatigue, by design, and depressive symptoms (P = 0.0007). After adjusting for depressive symptoms, comparison of BOLD signals revealed significantly greater activation in the right thalamus, left paracentral lobule, left medial frontal gyrus and right medial globus pallidus among GPA cases. When compared with the similarly fatigued population control group (n = 13), GPA cases shared many overlapping areas of activation. However, in addition, the population control group revealed significantly greater activation elsewhere, principally the left precentral gyrus, right superior frontal gyrus and right cingulate gyrus.

CONCLUSION: fMRI has identified specific differences in the neurophysiology of fatigued GPA subjects. Future application of this promising biomarker may inform the precise mechanisms of this clinically important symptom.

Original languageEnglish
Pages (from-to)2080-2087
Number of pages8
Issue number11
Early online date13 Jun 2014
Publication statusPublished - Nov 2014

Bibliographical note

© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email:

Funding: This work was supported by NHS Grampian and
the Chief Scientist’s Office (ref: CAF/08/08)


  • granulomatosis with polyangiitis
  • vasculitis
  • fatigue
  • functional MRI


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