High-altitude exposure alters the coupling among core large-scale brain networks: a multi-altitude rs-fMRI study

The impact of high-altitude environments on the three core large-scale brain networks (default mode network (DMN), executive control network (ECN), and salience network (SN)) remains poorly understood. This study included 64 ultra-high-altitude residents (U-HA, 3600 m), 51 high-altitude residents (HA, 1500 m), and 49 low-altitude residents (LA, 400 m). Large-scale networks (DMN, SN, and bilateral ECN) were identified by group independent component analysis. The within- and between-network functional connectivity (FC) was quantified. Groups were compared using one-way analysis of variance. Partial correlations assessed the associations between network FC and oxygen saturation and HA residence duration after controlling confounders. The HA and U-HA groups exhibited higher medial prefrontal cortex (mPFC)-left posterior parietal cortex (PPC)/right dorsolateral prefrontal cortex (dlPFC), posterior cingulate cortex (PCC)-right anterior insula (AI), left and right dlPFC, and left dlPFC-dorsal anterior cingulate cortex (dACC) FC than the LA group (FDR-corrected, LSD post hoc). The blood oxygen saturation negatively correlated with the above FC, surviving correction for age, sex, education, and motion. Our findings may indicate that HA hypoxia is associated with reduced functional segregation between the DMN and ECN, as well as enhanced coupling of the bilateral ECN and SN-ECN.