The Brain Structural-Functional Vulnerability in Drug-Naive Children With Juvenile Idiopathic Arthritis: Insights From the Hippocampus

Abstract

Objective: Leveraging an integrative multimodal MRI paradigm to elaborate on the hippocampus-derived structural and functional changes in children and adolescents with juvenile idiopathic arthritis (JIA) and to explore potential correlations within the “joint-inflammation-brain” axis during the period of central neural system (CNS) development. Methods: Twenty-one patients with JIA all completed the multimodal MRI scanning, laboratory tests, and neuropsychological assessments; meanwhile, 23 matched controls were recruited. We then harnessed the spherical harmonics with a point distribution model (SPHARM-PDM) and the ROI-to-voxel functional connectivity (FC) to measure the hippocampal shape and hippocampo-cortical FC patterns. Correlation analysis was performed to explore the potential links in neuroimaging features with disease-related indices. Results: Compared to controls, JIA patients only presented an atrophic tendency in the posterior part of the bilateral hippocampus. The hippocampo-cortical FC revealed the between-group divergences mainly located at the pain matrix, striatum, and temporal lobe. Remarkably, the enhanced FC between the right hippocampus and postcentral cortex is positively correlated with the disability index, while the weakened FC of right anterior hippocampus with right insula and that of left posterior hippocampus with left superior temporal gyrus was inversely related to the erythrocyte sedimentation rate and anxiety status, separately. Conclusion: As with macroscopic damages, the altered functional-connectome patterns of the hippocampus in JIA patients might be more sensitive to detect the early neuropathological changes. Moreover, the functional disturbances were demonstrated associated with the physical disability, inflammation, and emotional status. These findings may enlighten us on the underlying neuropathological mechanism of CNS comorbidities in JIA.