Dynamic functional connectivity variability may explain hypoxia-induced cognitive impairment at high-altitude
Siyao Zeng1, Sijia Guo1, Yang Zhou1
1The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environments, Shaanxi Provincial Key Laboratory of Environmental Health Hazard Assessment and Protection, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Iscience
|August 14, 2026
Summary
High-altitude hypoxia causes long-term cognitive impairments. Elevated dynamic functional connectivity (dFC) variability in specific brain regions is a key factor contributing to these chronic cognitive deficits.
Area of Science:
- Neuroscience
- Environmental Medicine
- Cognitive Science
Background:
- Long-term exposure to high-altitude (HA) hypoxic environments is known to cause cognitive impairments.
- The precise temporal mechanisms underlying these cognitive changes in response to chronic hypoxia remain unclear.
Purpose of the Study:
- To investigate the longitudinal brain functional alterations associated with cognitive changes in individuals exposed to high-altitude hypoxia.
- To identify specific neuroimaging markers correlating with cognitive deficits over time.
Main Methods:
- A longitudinal study involving 49 college freshmen relocated from sea level to Tibet.
- Comprehensive cognitive assessments and magnetic resonance imaging (MRI) were conducted at baseline, 2-year, and 4-year follow-ups.
- Resting-state fMRI techniques, including regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF)/fractional ALFF (fALFF), static functional connectivity (sFC), and dynamic functional connectivity (dFC), were employed.
Main Results:
- Behavioral data confirmed persistent cognitive deficits throughout the 4-year study period.
- Neuroimaging revealed biphasic patterns in ReHo, ALFF/fALFF, and sFC, characterized by initial suppression followed by partial or full recovery.
- Significantly, dynamic functional connectivity (dFC) variability in the right orbital middle frontal gyrus (ORBmid.R) and Heschl's gyrus (HES.R) increased at 2 years and remained elevated, correlating strongly with cognitive changes.
Conclusions:
- Elevated dFC variability in the ORBmid.R and HES.R is a critical neuroimaging indicator associated with chronic hypoxia-induced cognitive impairments.
- These findings elucidate the temporal brain functional alterations contributing to cognitive deficits in high-altitude environments.
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