Oxygen dependency of cognition: Neural mechanisms of reversible cognitive changes in Tibetan highlanders during altitudinal migration

Abstract

The dynamic changes occurring in the brain to adapt to the environment are crucial for human survival. Extensive research has demonstrated that the Tibetan population, indigenous to the plateau, has evolved unique physiological adaptations to hypoxia. However, the neurocognitive basis of these adaptive strategies remains incompletely understood. This study employs a multimodal approach (behavioral testing, event-related potentials, and time-frequency analysis) to systematically examine the effects of long-term high-altitude hypoxic exposure (3680 m) on working memory function in indigenous Tibetans. The aim is to determine whether this impact stems from energy-constrained adaptive functional adjustments or irreversible neurofunctional impairment. Participants included high-altitude native Tibetans, Tibetan migrants residing at plain for 1 and 3 years, and low-altitude Han Chinese controls. Results revealed that spatial working memory remained unaffected in native Tibetans, while verbal working memory accuracy (ACC) showed statistically significant decline. Following relocation to the plains, verbal working memory progressively recovered with increasing duration of residence, with the 3-year group reaching control levels. Neurophysiological data further revealed compensatory increases in late positive potential (LPP) amplitude and beta-band oscillatory power among high-altitude natives, both of which exhibited linear decline with residence duration in individuals relocated to the plains. These findings indicate that high-altitude hypoxia does not cause permanent impairment of verbal working memory function. Instead, it induces selective inhibition of energy-intensive verbal processing systems under energy-constrained conditions. This inhibition is environmentally dependent and reversibly restores upon improved oxygen supply. This study confirms at the cognitive neural mechanism level that functional changes induced by high-altitude hypoxia are fundamentally energy-optimization-driven adaptive reorganization, providing crucial empirical evidence for understanding human brain plasticity under extreme conditions.