Binocular Integrated Visual Field Deficits Are Associated With Changes in Local Network Function in Primary Open-Angle Glaucoma: A Resting-State fMRI Study

Abstract

In glaucoma participants, both structural and functional brain changes have been observed, but we still have insufficient understanding of how these changes also affect the integrity of cortical functional networks, and how these changes relate to visual function. This is relevant, as functional network integrity may affect the applicability of future treatments, as well as the options for rehabilitation or training. Here, we compare global and local functional connectivity in local and global brain networks between glaucoma and control participants. Moreover, we study the relationship between functional connectivity and visual field (VF) loss. For our study, 20 subjects with primary open-angle glaucoma (POAG) and 24 age-similar healthy participants were recruited to undergo an ophthalmic assessment followed by two resting-state (RS) (f)MRI scans. For each scan and for each group, the ROIs with eigenvector centrality (EC) values higher than the 95th percentile were considered the most central brain regions ("hubs"). Hubs for which we found a significant difference in EC in both scans between glaucoma and healthy participants were considered to provide evidence for network changes. In addition, we tested the notion that a brain region's hub function in POAG might relate to the severity of a participant's VF defect, irrespective of which eye contributed mostly to this. To determine this, for each participant, eye-independent scores were derived for: (1) sensitivity of the worse eye - indicating disease severity, (2) sensitivity of both eyes combined - with one eye potentially compensating for loss in the other, or (3) difference in eye sensitivity - potentially requiring additional network interactions. By correlating each of these VF scores and the EC values, we assessed whether VF defects could be associated with centrality alterations in POAG. Our results show that no functional connectivity disruptions were found at the global brain level in POAG participants. This indicates that in glaucoma global brain network communication is preserved. Furthermore, for the Lingual Gyrus, identified as a brain hub, we found a positive correlation between the EC value and the VF sensitivity of both eyes combined. The fact that reduced local network functioning is associated with reduced binocular VF sensitivity suggests the presence of local brain reorganization that has a bearing on functional visual abilities.

Keywords: HFA; POAG; eigenvector centrality; functional connectivity; functional networks; resting-state fMRI; visual field defects.