Abstract
Purpose :
Glaucoma is a widespread neurodegenerative disease affecting the retinal ganglion cells, optic nerve, distal visual pathways and beyond. Recent studies suggest that cerebrospinal fluid (CSF) plays a role in clearing wastes from the brain and that CSF dynamics may be altered in neurodegenerative diseases. Since CSF dynamics can be facilitated by the global brain activity, in the present study, we investigated how the dynamics of CSF and its coupling with global brain activity may be altered in glaucoma using functional magnetic resonance imaging (fMRI).
Methods :
19 early glaucoma patients (62.3±1.7 yrs) (mean±SEM), 19 advanced glaucoma patients (64.7±2.4 yrs), and 19 healthy subjects (59±2.4 yrs) underwent anatomical MRI and resting-state fMRI with eyes closed. Age did not differ across groups (P=0.188). We extracted the CSF signal time profiles from the fourth ventricle (Fig. 1A) and the global brain activity [blood-oxygenation-level-dependent signal time profiles] from the entire gray matter (Fig. 1B). Following previous literature (Han F, et al. PLOS Biol 2021;19), the coupling between the CSF signals and the global brain activity (CSF-BOLD coupling) was examined via cross correlation at the 4s time lag, where more negative values indicate stronger coupling. We also associated these correlations with the volumes of the anterior visual pathway in anatomical MRI.
Results :
A significant group difference was observed in the power (i.e., strength) of the low frequency (0.01-0.03Hz) in the CSF signals (P=0.013; Fig.1C). Specifically, early glaucoma patients showed significantly greater power than advanced glaucoma patients (Bonferroni P=0.010). The power of the global brain activity showed similar trends but did not reach significance (P=0.390; Fig.1D).
The CSF-BOLD coupling at the 4s lag differed significantly across groups (P=0.007; Fig. 1E). Early glaucoma patients had significantly stronger coupling than advanced glaucoma patients (Bonferroni P=0.025) and healthy controls (Bonferroni P=0.013).
Further, CSF-BOLD coupling was correlated with the volumes of optic nerve (right: R=-0.342, P=0.009; left: R=-0.344, P=0.009, Fig. 2D,E) and optic chiasm (R=0.264, P=0.047, Fig. 2F).
Conclusions :
Our observations of the altered CSF dynamics and CSF-BOLD coupling provide physiological evidence to support the recent hypothesis of widespread brain involvements in the early stage of glaucoma.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.