Multimodal brain structural and functional analysis in systemic lupus erythematosus patients without overt neuropsychiatric manifestations: associations with disease duration, organ damage, and neurocognitive function

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that often affects the central nervous system (CNS), leading to structural and functional brain alterations. Although neuroimaging studies have reported significant cortical and white matter changes in SLE, findings remain inconsistent, particularly regarding disease duration and organ damage. This study aimed to comprehensively investigate multimodal brain alterations in SLE using structural and functional neuroimaging. This cross-sectional study included 30 SLE patients without overt neuropsychiatric manifestations and 34 age-matched healthy controls (HCs). Neuroimaging data were acquired using a 3 T magnetic resonance imaging (MRI) scanner. Structural analyses included cortical and subcortical volume measurements via FreeSurfer (30 SLE, 34 HC) and white matter connectometry based on diffusion tensor imaging (DTI) using DSI Studio (29 SLE, 28 HC). Interhemispheric functional connectivity was assessed using resting-state fMRI in the CONN toolbox (27 per group). Clinical assessments included the SLEDAI-2 K, SLICC Damage Index, and SLICC Frailty Index, along with neurocognitive tests that assessed working memory, psychomotor speed, and executive function. Statistical analyses involved ANCOVA adjusted for age and intracranial volume, along with correlation analyses to explore associations between neuroimaging findings and clinical or neurocognitive measures. SLE patients exhibited significantly reduced volumes in the right occipital lobe (F = 11.274, η2 = 0.153, corrected p = .008) and left thalamus (F = 10.502, η2 = 0.140, corrected p = .028). DTI revealed reduced fractional anisotropy (FA) in the corpus callosum, right cingulum, and brainstem. FA values negatively correlated with disease duration, especially in the left and right inferior fronto-occipital fasciculi and the left cingulum. Patients with organ damage exhibited further FA reductions in the brainstem and left cingulum. FA decreases were also associated with poorer cognitive performance. While global interhemispheric functional connectivity was preserved, patients with moderate disease activity showed reduced connectivity in the frontal operculum and insula. Even in the absence of overt neuropsychiatric symptoms, SLE patients demonstrated structural brain changes—specifically reduced occipital and thalamic volumes and widespread white matter disruptions—associated with disease duration, organ damage, and neurocognitive dysfunction. Functional interhemispheric connectivity was globally preserved but impaired in the moderate activity subgroup.