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Relationships between cerebrovascular reactivity, visual-evoked functional activity, and resting-state functional connectivity in the visual cortex and basal forebrain in glaucoma

Glaucoma is primarily considered an eye disease with widespread involvements of the brain. Yet, it remains unclear how cerebrovasculature is regulated in glaucoma and how different brain regions coordinate functionally across disease severity. To address these questions, we applied a novel whole-brain relative cerebrovascular reactivity (rCVR) mapping technique using resting-state functional magnetic resonance imaging (fMRI) without gas challenges to 38 glaucoma patients and 21 healthy subjects. The relationships between rCVR, visual-evoked fMRI response, and resting-state functional connectivity in glaucoma were then established. In the visual cortex, rCVR has a decreasing trend with glaucoma severity (p<0.05), and is coupled with visual-evoked response and functional connectivity in both hemispheres (p<0.001). Interestingly, rCVR in the basal forebrain (BF) has an increasing trend with glaucoma severity (p<0.05). The functional connectivity between right diagonal band of Broca (a sub-region of BF) and lateral visual cortex decreases with glaucoma (p<0.05), while such connectivity is inversely coupled with rCVR in the BF (p<0.05), but not the visual cortex. Overall, we demonstrate opposite trends of rCVR changes in the visual cortex and BF in glaucoma patients, suggestive of compensatory actions in vascular reserve between the two brain regions. The neurovascular coupling within the visual cortex appears deteriorated in glaucoma, whereas the association between BF-visual cortex functional connectivity and rCVR of BF indicates the functional and vascular involvements in glaucoma beyond the primary visual pathway.