Functional and structural magnetic resonance imaging correlates of fatigue in patients with rheumatoid arthritis

Neil Basu* (Corresponding Author), Chelsea M. Kaplan, Eric Ichesco, Tony Larkin, Andrew Schrepf, Alison D. Murray, Daniel J. Clauw, Gordon D. Waiter, Richard E. Harris

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)
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Fatigue is a major burden among patients with RA, yet is poorly understood. We sought to conduct the first imaging study to investigate the neurobiological correlates of fatigue in RA and to improve upon the methodological limitations of previous neuroimaging studies that have investigated this symptom in other populations.

Chronically fatigued RA patients were clinically characterized before undertaking a combined functional and structural mode MRI brain scan. The functional sequences were acquired during a fatigue-evoking task, then network-to-whole-brain analyses were undertaken. The structural analyses employed voxel-based morphometry in order to quantify regional grey matter volume. The scan was repeated 6 months later to test reproducibility.

Fifty-four participants attended both scans [n = 41 female; baseline mean (S.D.) age 54.94 (11.41) years]. A number of significant functional and structural neural imaging correlates of fatigue were identified. Notably, patients who reported higher levels of fatigue demonstrated higher levels of functional connectivity between the Dorsal Attention Network and medial prefrontal gyri, a finding that was reproduced in the repeat scans. Structurally, greater putamen grey matter volumes significantly correlated with greater levels of fatigue.

Fatigue in RA is associated with functional and structural MRI changes in the brain. The newly identified and reproduced neural imaging correlates provide a basis for future targeting and stratification of this key patient priority.
Original languageEnglish
Pages (from-to)1822-1830
Number of pages9
Issue number10
Early online date28 Apr 2019
Publication statusPublished - Oct 2019

Bibliographical note

The authors wish to thank all of the patient volunteers. We also thank Mariella D’Allesandro for supporting recruitment and data collection. N.B., C.M.K., E.I., A.S., T.L., G.W., A.M., R.E.H. and D.J.C. were involved in designing the study and interpreting the data, drafting the article and revising it critically for important intellectual content. All authors approved the final version to be published. N.B. and C.M.K. analysed the data, and N.B. and R.E.H. wrote the first draft. E.I., T.L. and G.W. contributed to the data analysis. N.B. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Funding: This work was supported by Pfizer. The funder had no role in study design, data collection, analysis, decision to publish or preparation of the manuscript. The content is solely the responsibility of the authors.


  • fatigue
  • rheumatoid arthritis
  • neural imaging correlates
  • functional connectivity
  • voxel-based morphometry


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