VR-based quantitative oculomotor analysis and association with regional brain atrophy in MSA

Background The quantitative assessment of the oculomotor system has emerged as a promising biomarker for neurodegenerative disorders. Although oculomotor impairments are commonly observed in multiple system atrophy (MSA) patients, the specific abnormalities and underlying neural structural changes remain poorly understood. Objectives To explore oculomotor abnormalities and associated brain changes in MSA, evaluating their potential as biomarkers for diagnosis and disease monitoring. Methods A total of 100 MSA patients and 50 healthy controls (HCs) were included in this study. All subjects underwent comprehensive evaluations, including clinical assessments, virtual reality (VR)-based ocular-tracking tasks and structural magnetic resonance imaging (MRI). Results Compared with HCs, MSA patients showed significantly impaired smooth pursuit (SP) with increased number of deviations (13.33 [29.33] vs. 5.67 [7.67], p < 0.001); reduced prosaccadic (PS) average velocity (194.80 ± 82.45 °/s vs. 263.07 ± 68.17 °/s, p < 0.001); and reduced antisaccade (AS) average velocity (165.82 ± 85.75 °/s vs. 257.05 ± 74.39 °/s, p < 0.001). A combination of PS and AS average velocities with SP number of deviations effectively distinguished MSA patients from HCs with an AUC of 0.814. PS average velocity was negatively correlated with UMSARS total scores (r = -0.354, p < 0.001), whereas AS accuracy was positively correlated with MoCA scores (r = 0.375, p = 0.001). Voxel-based morphometry revealed significant associations between these oculomotor parameters and atrophy in the cerebellum and frontal gyrus ( p < 0.05, family-wise error correction). Conclusions Our study provides comprehensive insights into the VR-based quantitative oculomotor analysis and its association with regional brain atrophy in MSA, contributing to novel biomarkers identification and therapeutic targets exploration.