Altered resting-state functional connectivity density in patients with neuromyelitis optica-spectrum disorders

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune, demyelinating disorder, accompanied by abnormal spontaneous activity of the brain and impairment of the retina and optic nerve. Functional connectivity density (FCD) map, a graph theory method, was applied to explore the functional connectivity alterations of brian in NMOSD patients and investigate the alterations of FCD to the structural and microvascular changes around the optic nerve head (ONH).

Methods: Nineteen NMOSD patients and 22 healthy controls (HCs) were included in our study. All participants underwent resting-state functional magnetic resonance imaging (fMRI) scans of the brain, and ophthalmological examinations included optical coherence tomographic angiography (OCT-A) imaging, visual acuity (VA), and intraocular pressure (IOP). The long- and short-range FCD was calculated by the fMRI graph theory method and two-sample t-tests were performed to compare the discrepancy of FCD between NMOSD and HCs. OCT-A imaging was used to obtain the structure (peripapillary retinal nerve fiber layer, pRNFL) and microvessels (radial peripapillary capillary, RPC) details around the ONH. The association between the long- and short-range FCD values with the structural and microvascular variation around the ONH were evaluated using Spearman's correlation.

Results: Significantly decreased (corrected p < 0.05) long-range FCD was seen in the right superior parietal gyrus (SPG) in patients with NMOSD when compared to HCs. Increased long-range FCD was seen in the right fusiform gyrus (FFG), left orbital part of superior frontal orbital gyrus (ORBsup) and left anterior cingulum and paracingulate gyri (ACG) in NMOSD patients (corrected p < 0.05). The regions with reduced short-range FCD in NMOSD were the left angular gyrus (ANG) and right SPG (corrected p < 0.05). Increased short-range FCD was shown (corrected p < 0.05) in the right FFG of NMOSD. The pRNFL thickness and RPC density in all participants were negatively correlated with the long-range FCD values in the right FFG, left ORBsup, and left ACG as well as short-range FCD values in the right FFG, besides, both were positively correlated with the long-range FCD values in the right SPG and short-range FCD values in the left ANG and right SPG (p < 0.05).

Conclusion: Our study demonstrates that patients with NMOSD have widespread brain dysfunction after optic neuritis attacks which shows as impairment of widespread spatial distribution in long- and short-range FCD. Structural and microvascular changes around the ONH are associated with neural changes in the brain.