Machine learning with multitype functional connectivity uncovers whole-brain network disruption in primary angle-closure glaucoma.

Primary angle-closure glaucoma (PACG), an irreversible blinding disease characterized by retinal ganglion cell damage and optic nerve atrophy, exerts significant effects on brain functional networks. Using resting-state functional magnetic resonance imaging (rs-fMRI) data from 34 PACG patients and 34 matched healthy controls (HCs), we extracted four types of connectivity features-voxel-wise static functional connectivity (FC), dynamic functional connectivity (dFC), effective connectivity (EC), and dynamic effective connectivity (dEC)-via the AAL90 (Automated Anatomical Labeling 90) atlas following preprocessing. Elastic net feature selection was applied independently to each connectivity type to retain the top 10% most discriminative features. We evaluated the classification performance of ten machine learning models using individual feature types as well as their combined features, with the FC-based logistic regression (LR) model achieving optimal diagnostic efficacy (accuracy = 0.92, AUC = 0.96). SHapley Additive exPlanations (SHAP) of the model identified 20 critical connections, revealing abnormal patterns at both the region of interest (ROI)-level and network-level within brain networks such as the visual network (VSN), dorsal attention network (DAN), and sensorimotor network (SMN). Statistical group comparisons validated reduced connectivity (e.g., VSN-SMN, VSN-DAN) and enhanced DAN-thalamus connectivity in patients, while voxel-wise analyses of key regions confirmed diminished connectivity to visual areas. The results provide insights into how machine learning can be effectively employed to detect PACG-specific brain network disruptions and highlight potential neuroimaging biomarkers.