Altered Functional Brain Network in Systemic Lupus Erythematosus Patients Without Overt Neuropsychiatric Symptoms Based on Resting-State Functional Magnetic Resonance Imaging and Multivariate Pattern Analysis.

Yiling Wang,Lixuan Huang,Xiaoqi Pang,Shu Li,Xia Meng,Zisan Zeng,Muliang Jiang

doi:10.3389/fneur.2021.690979

Abstract

Objective: This study aims to investigate the alterations in functional brain network in systemic lupus erythematosus patients without overt neuropsychiatric symptoms [neuropsychiatric systemic lupus erythematosus (non-NPSLE)] from the perspective of degree centrality (DC) and functional connectivity (FC) using resting-state functional magnetic resonance imaging (MRI) and multivariate pattern analysis (MVPA) approach.Methods: DC analysis was performed based on the resting-state functional MRI data derived from 47 non-NPSLE patients and 47 healthy controls (HCs). Nodes with abnormal DC were utilized as seeds for further FC analysis. The correlation between MRI variables and clinical or neuropsychological data was analyzed using Pearson correlation analysis. Finally, MVPA classification based on DC was performed.Results: When compared with the HCs, the non-NPSLE patients exhibited remarkably higher DC in the bilateral hippocampus (HIP), right insula (INS), and lower DC in the left superior parietal gyrus. Furthermore, the patients displayed significantly higher FC between the left HIP and the left INS/left dorsolateral middle frontal gyrus/left supramarginal gyrus and higher FC between the right HIP and the right middle temporal gyrus/right dorsolateral middle frontal gyrus/right dorsolateral inferior frontal gyrus/right supramarginal gyrus (all imaging variables mentioned earlier underwent cluster-level false discovery rate corrections, the voxel threshold was p < 0.001, cluster threshold was p < 0.05). Correlation analysis revealed significantly negative correlations between DC values of the right INS and disease activity and the DC values of the right HIP and the Montreal Cognitive Assessment scores. The accuracy, sensitivity, and specificity of MVPA classification based on DC were 72.34, 63.83, and 80.85%, respectively. The most discriminative power brain regions were chiefly located within the temporal, parietal, and frontal regions.Conclusion: Patients with non-NPSLE exhibited abnormal DC and FC in the brain network. MVPA based on DC possessed commendable classification ability. Our study may provide a novel perspective on the neuropathological mechanisms underlying subclinical brain damage in non-NPSLE.

Highlights

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple systems, which may affect the nervous system, progressing to neuropsychiatric systemic lupus erythematosus (NPSLE)
Four brain regions that showed significant differences in Degree centrality (DC) between non-NPSLE patients and HCs were set as seed
When the bilateral hippocampus was set as seed, no decreased functional connectivity (FC) between these two seeds and other brain regions was found in this study

Summary

Introduction

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple systems, which may affect the nervous system, progressing to neuropsychiatric systemic lupus erythematosus (NPSLE). The American College of Rheumatology (ACR) has defined 19 neuropsychiatric symptoms in NPSLE patients [2]. Cognitive impairment is one of the most common symptoms, which significantly reduces the patients’ quality of life [3] and manifests subtly in SLE patients without overt neuropsychiatric symptoms (defined as non-NPSLE) [4]. Neuroimaging studies have found evidence of gray matter atrophy [5, 6], microstructure damage of white matter [7], and abnormal neurochemical metabolism in non-NPSLE [8], suggesting that subclinical brain damage may occur before it develops into NPSLE Identifying such brain damage and clarifying its mechanism would be clinically beneficial

Methods

Results

Discussion

Conclusion