Structural and Functional Characterization of Gray Matter Alterations in Female Patients With Neuropsychiatric Systemic Lupus

OBJECTIVE: To investigate morphological and functional alterations within gray matter (GM) in female patients with neuropsychiatric systemic lupus (NPSLE) and to explore their clinical significance. METHODS: 54 female patients with SLE (30 NPSLE and 24 non-NPSLE) and 32 matched healthy controls were recruited. All subjects received a quantitative MRI scan (FLAIR, 3DT1, resting-state functional MRI). GM volume (GMV), fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and degree of centrality (DC) were obtained. Between-group comparison, clinical correlation, and discrimination of NPSLE from non-NPSLE were achieved by voxel-based analysis, cerebellar seed-based functional connectivity analysis, regression analysis, and support vector machine (SVM), respectively. RESULTS: Patients with NPSLE showed overt subcortical GM atrophy without significantly abnormal brain functions in the same region compared with controls. The dysfunction within the left superior temporal gyri (L-STG) was found precede the GM volumetric loss. The function of the nodes in default mode network (DMN) and salience network (SN) were weakened in NPSLE patients compared to controls. The function of the cerebellar posterior lobes was significantly activated in non-NPSLE patients but attenuated along with GM atrophy and presented higher connectivity with L-STG and DMN in NPSLE patients, while the variation of the functional activities in the sensorimotor network (SMN) was the opposite. These structural and functional alterations were mainly correlated with disease burden and anti-phospholipid antibodies (aPLs) (r ranges from -1.53 to 1.29). The ReHos in the bilateral cerebellar posterior lobes showed high discriminative power in identifying patients with NPSLE with accuracy of 87%. CONCLUSION: Patients with NPSLE exhibit both structural and functional alterations in the GM of the brain, which especially involved the deep GM, the cognitive, and sensorimotor regions, reflecting a reorganization to compensate for the disease damage to the brain which was attenuated along with pathologic burden and cerebral vascular risk factors. The GM within the left temporal lobe may be one of the direct targets of lupus-related inflammatory attack. The function of the cerebellar posterior lobes might play an essential role in compensating for cortical functional disturbances and may contribute to identifying patients with suspected NPSLE in clinical practice.