Alterations in static and dynamic topological properties of brain functional network after chronic high altitude exposure: a panel study

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Background: Long-term exposure to a high-altitude (HA) hypoxic environment induces cognitive impairments, but the underlying mechanisms remain unclear. Notably, the specific topological features of brain networks in this context have not been thoroughly explored. This study investigated graph-based topological characteristics of brain networks from static and dynamic perspectives, and examined how these alterations contribute to the chronic HA-induced cognitive changes. Methods: This longitudinal panel study enrolled 49 college freshmen who relocated from low altitude to a HA region in Tibet. Comprehensive cognitive assessments and brain magnetic resonance imaging (MRI) were performed at baseline, 2 years, and 4 years. Resting-state functional MRI data were used to characterize the topological organization of functional brain networks, encompassing both nodal and global network properties. Results: Behavioral assessments showed persistent impairments in cognitive functions following prolonged HA exposure. Neuroimaging analyses consistently identified the left superior parietal gyrus, left inferior parietal lobule, and right Heschl's gyrus as key nodes for both static and dynamic nodal properties. After 4 years of HA exposure, all dynamic global network metrics were elevated relative to baseline values, and these alterations were associated significantly with cognitive changes. Specifically, increased variances of characteristic path length (Lp) and global efficiency (Eglob) correlated with working memory decline. Conclusion: Our findings demonstrate that variances in Lp and Eglob contribute significantly to chronic hypoxia-induced cognitive impairment. Collectively, these results provide novel evidence that dynamic functional instability, as reflected by altered fluctuations in Lp and Eglob, plays a pivotal role in driving hypoxia-related cognitive decline.