Altered functional connectivity density in primary angle-closure glaucoma patients at resting-state

Background: Primary angle-closure glaucoma (PACG) is a neurodegenerative disease. Previous structural and functional studies of functional magnetic resonance imaging (fMRI) have demonstrated widespread dysfunction of spontaneous activity in the PACG brain. In this study, we applied a data-driven graph theory approach of functional connectivity density (FCD) mapping to investigate the altered local and global functional connectivity (FC) of the cortex in PACG. Methods: Forty-five PACG patients (53.28 +/- 10.79 years, 17 males/28 females) and 46 well-matched healthy controls (HCs) (52.67 +/- 11.01 years, 18 males/28 females) received resting-state fMRI scans. All PACG patients finished complete ophthalmologic examinations, including retinal nerve fiber layer thickness (RNFLT), intraocular pressure (IOP), average cup to disc ratio (A-C/D), and vertical cup to disc ratio (V-C/D). We calculated the between-group FCD difference for short-range and long-range in each voxel. Then, we generated the intrinsic FC of the seed region with the whole brain. Finally, correlations were investigated between FCD value of the altered regions and clinical variables. Results: PACG patients showed increased short-range FCD in the left inferior frontal gyrus (IFG)/insula/parahippocampal gyrus and right IFG/insula (P<0.05, corrected), compared with the HCs. Simultaneously, the decreased regions in short-range FCD map were the occipital/cuneus/precuneus/superior parietal/postcentral lobe (P<0.05, corrected). In the PACG groups, decreased long-range FCD was observed in the left middle frontal gyrus compared to the HC (P<0.05, corrected). RNFLT was positively correlated with decreased short-range FCD value of the occipital/cuneus/precuneus/superior parietal/postcentral lobes, and the A-C/D was negatively correlated with the increased short-range FCD value of the left IFG/insula/parahippocampal gyrus, and the right IFG/insula. Conclusions: Our findings suggest that PACG can induce extensive brain dysfunction, and showed different spatial distribution in short- and long-range FCD.