Elevating understanding: Linking high-altitude hypoxia to brain aging through EEG functional connectivity and spectral analyses

Abstract

High-altitude hypoxia triggers brain function changes reminiscent of those in healthy aging and Alzheimer's disease, compromising cognition and executive functions. Our study sought to validate high-altitude hypoxia as a model for assessing brain activity disruptions akin to aging. We collected EEG data from 16 healthy volunteers during acute high-altitude hypoxia (at 4,000 masl) and at sea level, focusing on relative changes in power and aperiodic slope of the EEG spectrum due to hypoxia. Additionally, we examined functional connectivity using wPLI, and functional segregation and integration using graph theory tools. High altitude led to slower brain oscillations, that is, increased δ and reduced α power, and flattened the 1/f aperiodic slope, indicating higher electrophysiological noise, akin to healthy aging. Notably, functional integration strengthened in the θ band, exhibiting unique topographical patterns at the subnetwork level, including increased frontocentral and reduced occipitoparietal integration. Moreover, we discovered significant correlations between subjects' age, 1/f slope, θ band integration, and observed robust effects of hypoxia after adjusting for age. Our findings shed light on how reduced oxygen levels at high altitudes influence brain activity patterns resembling those in neurodegenerative disorders and aging, making high-altitude hypoxia a promising model for comprehending the brain in health and disease.

Keywords: 1/f aperiodic activity; Aging; EEG; Functional connectivity; High-altitude hypoxia; Oxygen supply; Power spectrum.

Figure 1.

Changes in power spectrum by altitude. (A) Relative power, to broadband 0.5–30 Hz spectrum, in each frequency band. (B) Regional differences in nodal relative power (altitude minus sea level). (C) Power spectrum and 1/f slope averaged across channels; 1/f slope topography is also shown. Data points in violin plots correspond to subjects in both conditions: sea level and altitude. Box plots were built using the 1st and 3rd quartiles, the median, and the maximum and minimum values of distributions. All p values were FDR-corrected. ***p < 0.001, **p < 0.01, *p < 0.05, ∼p < 0.1.

Figure 2.

Functional connectivity (FC) strength in high-altitude hypoxia. (A) Overall FC, computed as the average of wPLI FC matrices per subject and for each frequency band. (B) Regional differences in nodal strength (altitude minus sea level). (C) Pairwise difference (altitude minus sea level) between FCs at each frequency band. Data points in violin plots correspond to subjects in both conditions: sea level and altitude. Box plots were built using the 1st and 3rd quartiles, the median, and the maximum and minimum values of distributions. All p values were FDR-corrected. ***p < 0.001, **p < 0.01, *p < 0.05, ∼p < 0.1.

Figure 3.

Global and local changes in integration by altitude. (A) Global efficiency, computed by numerical integration of network metric as function of the threshold. (B) Regional differences in nodal efficiency (altitude minus sea level). Data points in violin plots correspond to subjects in both conditions: sea level and altitude. Box plots were built using the 1st and 3rd quartiles, the median, and the maximum and minimum values of distributions. All p values were FDR-corrected. ***p < 0.001, **p < 0.01, *p < 0.05, ∼p < 0.1.

Figure 4.

Global and local changes in segregation by altitude. (A) Transitivity, computed by numerical integration of network metric as function of the threshold. (B) Regional differences in nodal clustering coefficient (altitude minus sea level). Data points in violin plots correspond to subjects in both conditions: sea level and altitude. Box plots were built using the 1st and 3rd quartiles, the median, and the maximum and minimum values of distributions. All p values were FDR-corrected. ***p < 0.001, **p < 0.01, *p < 0.05, ∼p < 0.1.

Figure 5.

Effect of aging on brain activity. (A) Correlation of single subject age with α band relative power, 1/f slope, δ band overall FC (computed as the average of wPLI FC matrices), and θ band global efficiency (functional integration). Pearson’s r coefficients and p values are shown in the above figures. (B) Residuals obtained regressing out the effect of age from the set of EEG-related metrics. Data points in violin plots and scatter plots correspond to subjects in both conditions: sea level and altitude. Box plots were built using the 1st and 3rd quartiles, the median, and the maximum and minimum values of distributions. All p values were FDR-corrected. ***p < 0.001, **p < 0.01, *p < 0.05, ∼p < 0.1.