Frontoparietal functional connectivity is related to active disease and processing speed in adolescents with childhood-onset lupus

To evaluate brain functional connectivity (FC) with resting-state magnetic resonance imaging (rs-fMRI) in adolescents with childhood-onset systemic lupus erythematosus (cSLE) compared to healthy controls (HCs) and to evaluate associations among FC, disease characteristics, and cognitive performance. Patients with cSLE aged 11 to 17 years, and age- and sex-matched HCs, underwent rs-fMRI at 3T and clinical (current and cumulative cSLE activity and glucocorticoid dose, anti-dsDNA positivity, nephritis diagnosis) and cognitive (attention, working memory, processing speed, inhibition) data collection. Group differences in FC between brain regions of interest (ROI) within/across resting-state networks as well as associations between FC and clinical and cognitive variables were evaluated with age-adjusted general linear models. Analyses were corrected for multiple comparisons with family-wise error (FWE) methods (threshold-free cluster enhancement P-FWE < .05, individual pairs of ROI connections P < .01). Participants included 60 patients (14.9 ± 1.84 years, 52 females) with cSLE and 59 HCs. Patients had lower FC compared to HCs in frontoparietal connections that were exacerbated in subgroups with active cSLE features (all P-FWE ≤ .049). In cSLE patients, lower FC in frontocerebellar connections were associated with higher cumulative disease activity and glucocorticoid use (P-FWE ≤ .018). Positive associations were found between FC in frontoparietal-occipital connections and processing speed scores in cSLE patients (P-FWE = .010) but not in HCs. Adolescents with cSLE, compared to HCs, exhibited lower brain FC in frontoparietal regions of the dorsal attention and somatosensory regions, which was associated with greater disease activity. Higher FC in frontoparietal-occipital regions, critical for visual attention, was associated with better processing speed, which could be compensatory to disease effects.