Changes in brain functional connectivity and clinical correlations in neuromyelitis optica spectrum disorder: a...

Neuromyelitis Optica Spectrum Disorder (NMOSD) affects the optic nerves and spinal cord, but its longitudinal effects on brain function remain unclear. This study aims to examine changes in brain functional connectivity over time in NMOSD patients and assess their correlation with clinical outcomes, and explore whether shifts in connectivity, especially within the default-mode hub Brodmann area 23 (BA23), are indicative of changes in clinical status.

Clinical assessments and resting-state fMRI data were analysed from 31 non-relapsing NMOSD patients at baseline and during one-year follow-up, and from 20 age- and gender-matched healthy controls (HCs) at baseline. We identified resting-state networks (RSNs) using independent component analysis (ICA). Functional connectivity (FC) was analyzed both within RSNs and between region-of-interest seeds and whole-brain voxels. Comparisons between groups (HCs vs. Baseline, HCs vs. Follow-up) and within the patient group (Baseline vs. Follow-up), as well as correlations with clinical evaluations, were conducted.

Significant FC changes were observed in NMOSD patients. At baseline, NMOSD patients exhibited significantly reduced FC in the lateral visual, sensorimotor, executive control, and left dorsal visual networks; however, these abnormalities showed partial recovery over time. Meanwhile, further decreases were noted in the medial visual and right dorsal visual networks at follow-up. Conversely, a significant increase in FC within the default mode network, particularly in the BA23 region, correlated with improvements in EDSS scores (r = 0.53, p < 0.01). Declines in connectivity between the BA23 region and both the lingual and fusiform gyri were associated with worsening Expanded Disability Status Scale (EDSS) scores (r =  - 0.38, p < 0.05) and reduced visual acuity (r =  - 0.45, p < 0.05).

NMOSD patients exhibit both compensatory and progressive changes in brain functional connectivity over time. Alterations in the BA23 region are closely associated with clinical outcomes, highlighting its potential as a functional biomarker. Highlights 1. Dynamic alterations in brain functional connectivity were observed in NMOSD patients during follow-up, reflecting both recovery and deterioration. 2. Increased connectivity within the default mode network, especially in the BA23 region, suggests compensatory neural adaptations. 3. Reduced connectivity between BA23 and visual processing regions (fusiform and lingual gyri) was linked to declines in visual acuity and neurological function.