Altered coupling of cerebral blood flow and functional connectivity strength in visual and higher order cognitive cortices in primary open angle glaucoma

Primary open-angle glaucoma (POAG) has been suggested to be a neurodegenerative disease associated with altered cerebral vascular hemodynamics and widespread disruption of neuronal activity within the visual, working memory, attention and executive networks. We hypothesized that disturbed neurovascular coupling in visual and higher order cognitive cortices exists in POAG patients and correlates with glaucoma stage and visual field defects. Through multimodal magnetic resonance imaging, we evaluated the cerebral blood flow (CBF)-functional connectivity strength (FCS) correlations of the whole gray matter and CBF/FCS ratio per voxel for all subjects. Compared with normal controls, POAG patients showed reduced global CBF-FCS coupling and altered CBF/FCS ratios, predominantly in regions in the visual cortex, salience network, default mode network, and dorsal attentional network. The CBF/FCS ratio was negatively correlated with glaucoma stage, and positively correlated with visual field defects in the lingual gyrus in POAG patients. Moreover, early brain changes were detected in early POAG. These findings indicate neurovascular coupling dysfunction might exist in the visual and higher order cognitive cortices in POAG patients and its clinical relevance. The results may contribute to the monitoring of POAG progression and provide insight into the pathophysiology of the neurodegenerative process in POAG.