Fronto-cerebellar features associate with cognitive dysfunction in childhood-onset systemic lupus erythematosus

Cognitive dysfunction (CD) is a prevalent symptom in childhood-onset systemic lupus erythematosus (cSLE). This study aimed to investigate the neurobehavioral basis of CD in cSLE.

Patients with cSLE (N=20) and age- and sex-matched healthy controls (HCs, N=20) completed questionnaires and multiple neurocognitive tests. The Systemic Lupus Erythematosus Disease Activity Index 2000 and laboratory markers were used to monitor patients' clinical status. Neuroimaging assessments included functional near-infrared spectroscopy (fNIRS), functional magnetic resonance imaging (fMRI), and structural MRI.

cSLE patients demonstrated moderate disease activity with high inflammation and immune dysregulation, alongside low medication adherence. Relative to HCs, cSLE patients showed worse cognitive functioning, higher emotional distress and more physical symptoms. fNIRS revealed higher prefrontal cortex activity in cSLE vs. HCs during the color-word Stroop task, suggesting impaired cognitive flexibility. fMRI performed during the N-back working memory task revealed altered frontal cortex and cerebellum activity, while modulations in resting-state fronto-cerebellar connectivity in the cSLE cohort were observed. Patients with cSLE were characterized by reduced gray matter morphological properties in frontal cortex and cerebellar subdivisions (e.g., crus II) alongside altered white matter structural connectivity among these cognitive processing hubs. K-means clustering analysis delineated three subgroups within the cSLE cohort based on neuroimaging profiles, where subgroups varied based on cognitive and emotional health.

This study provides evidence of fronto-cerebellar abnormalities and their associations with CD in cSLE. This investigation underscores the need for multidisciplinary research efforts to further elucidate the neurobiological underpinnings of CD in cSLE.