Background/Purpose: Fatigue is one of the most frequent constitutional symptoms in systemic lupus erythematosus (SLE), usually accompanied with impaired quality of life. Resting-state functional magnetic resonance imaging (rs-fMRI) has emerged as a powerful technique for mapping extensive neural networks in the human brain through blood-oxygen-level-dependent (BOLD) signal. The temporal synchronization between separate brain regions of interest (ROI) can be termed as functional connectivity (FC). Although several altered FCs have been confirmed to be associated with fatigue severity in diseases such as multiple sclerosis and chronic fatigue syndrome, specific FCs associated with fatigue in SLE remain unclear. In this study, we aim to identify the specific FCs linked to fatigue in patients with SLE.

Methods: Totally 16 patients with SLE and 16 healthy controls (HCs) were enrolled in this study. Rs-fMRI data from 32 subjects were acquired. The patients’ fatigue severity and psychiatric status were estimated by 11-item Chalder Fatigue Scale and Hospital Anxiety and Depression (HAD) Scale respectively, in addition to Visual Analogue Scale to rate pain (pain-VAS). The scores were collected at the same date of conducting fMRI. Demographic and clinical data were collected from medical records. We used functional connectivity multivariate pattern analysis (fc-MVPA) to identify the clusters distinguishing SLE patients from HCs, adjusted for age and sex. And seed-based connectivity (SBC) analysis was conducted to identify the FCs associated with fatigue severity. Finally, we used simple linear regression to calculate the correlations.

Results: A total of 16 SLE patients (93.75% female; median age: 46.5 years, IQR: 31.75–56.75) and 16 HCs (56.25% female; median age: 41 years, IQR: 33–45.75) were enrolled. In patients with SLE, the median Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was 4 (IQR: 2–8), the median prednisolone (PSL) dose was 6.0 mg/day (IQR: 2.875–13.75), and the median Chalder fatigue scale score was 18.5 (IQR:11.25–24). The fatigue severity showed no significant correlation with age (p=0.81), SLEDAI (p=0.3) or PSL dose (p=0.89), while it was positively correlated with HAD scores (p< 0.0001). We identified an alteration of FCs between the MVPA-identifying ROI centering on left superior frontal gyrus and SBC-identifying ROI containing atlas ROIs of left inferior lateral occipital cortex and left temporooccipital middle temporal gyrus. In patients of SLE, the FCs were significantly correlated with fatigue severity (p< 0.0001, R2=0.80), and separately, correlated with physical symptom scores (p< 0.0001, R2=0.70) and mental symptom scores (p< 0.0001, R2=0.75). Besides, these FCs were also significantly correlated with HAD scores (p=0.0006, R2=0.58). There was no significant correlation between FCs and SLEDAI or pain-VAS scores.

Conclusion: Altered connectivity involving the left inferior lateral occipital cortex and left temporooccipital middle temporal gyrus were associated with fatigue severity, reflecting the influence of anxiety and depression.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/resting-state-functional-magnetic-resonance-imaging-analysis-revealed-altered-functional-connectivity-associated-with-fatigue-in-systemic-lupus-erythematosus/