Altered hippocampal subfield functional connectivity and its association with back pain in axial spondyloarthritis: a...

To investigate hippocampal subfield volumes and resting-state functional connectivity (rsFC) in patients with axial spondyloarthritis (axSpA), and to assess their clinical relevance. In this cross-sectional study, 39 patients with axSpA and 41 healthy controls (HCs) underwent 3-T structural T1-weighted and resting-state functional MRI. Hippocampal subfields were segmented using FreeSurfer, and seed-based rsFC maps were computed for 12 subfields per hemisphere. Group differences were assessed with general linear models (FDR-corrected) for volumes and permutation-based family-wise error correction with threshold-free cluster enhancement for rsFC. Partial correlations adjusted for age, sex, and education tested associations between rsFC and clinical parameters (FDR-corrected). No hippocampal subfield volume differed significantly between groups after FDR correction, although patients with axSpA showed nominally larger right CA4 and bilateral GC-ML-DG volumes. Increased rsFC between the left presubiculum and left precentral gyrus/supplementary motor area (PreCG/SMA) was observed in patients relative to HCs (permutation-based FWER-corrected p < 0.05). Presubiculum-PreCG/SMA rsFC was negatively associated with overall back pain (partial r = -0.52, p = 0.001, FDR-corrected q = 0.028), the only association surviving FDR correction across all clinical parameters. No significant associations were observed with inflammatory markers or disease activity indices. axSpA is associated with hippocampal-motor cortical connectivity, with increased presubiculum-PreCG/SMA rsFC linked to lower back pain severity, whereas hippocampal subfield volumes are largely preserved. These findings support reconceptualizing axSpA as a systemic disease with measurable central nervous system involvement and pain-related network reorganization. Clinical trials register number: ChiCTR2500111024 (October 23th 2025).