Resting-state functional MRI analysis of the brain's adaptation to chronic hypoxia: disease and environment

The brain is highly sensitive to oxygen supply; however, it remains unclear whether chronic hypoxia resulting from disease or environmental exposure leads to similar or distinct patterns of brain adaptation. This study aimed to characterize and compare the structural and functional brain changes associated with chronic hypoxia induced by chronic obstructive pulmonary disease (COPD) and high-altitude residence.

A total of 110 participants were enrolled in the study, including 20 patients with COPD (aged 45-65 years) and 30 matched controls, as well as 30 high-altitude residents (aged 35-50 years, altitude >2,800 m for >30 years) and 30 matched low-altitude controls. Structural brain assessment was performed using three-dimensional (3D) T1-weighted imaging, with voxel-based morphometry (VBM) analysis conducted via statistical parametric mapping. Functional evaluation was performed using regional homogeneity (ReHo) analysis with the Data Processing and Analysis of Brain Imaging (DPABI) toolkit based on resting-state blood oxygen level-dependent (BOLD) data. Group comparisons were performed using two-sample t-tests, with statistical significance set at P<0.05.

Patients with COPD exhibited reduced gray matter volume in eight regions, predominantly located in emotion- and cognition-related regions, including the Temporal_inf_R (cluster size =194, t=3.50), Rectus_R (cluster size =145, t=3.72), ParaHippocampal_L (cluster size =158, t=3.68), and Insula_R (cluster size =201, t=4.38). The high-altitude residents showed gray matter changes primarily in visual regions, including the Cuneus_L (cluster size =162, t=2.79) and Occipital_Mid_L (cluster size =140, t=-2.82). ReHo analysis revealed increased ReHo in the bilateral caudate (R: cluster size =125, t=2.99; L: cluster size =89, t=2.34) and decreased ReHo in the Lingual_R (cluster size =94, t=-4.93) and Precuneus_R (cluster size =92, t=-4.78) in the COPD patients, while the high-altitude residents showed increased ReHo in the bilateral supplementary motor area (R: cluster size =164, t=3.80; L: cluster size =144, t=3.48) and decreased ReHo in the Precuneus_R (cluster size =82, t=-4.08). No significant differences in age or education were observed between the groups; however, the hemoglobin and oxygen saturation (SpO₂) levels differed significantly between the groups (P<0.01).

These findings indicate that COPD and high-altitude residence are associated with distinct structural brain changes, affecting emotion- and cognition-related regions in patients with COPD and visual regions in high-altitude residents, despite broadly similar functional (ReHo) alterations in motor and visual areas. These findings highlight the differential vulnerability of brain regions to distinct types of chronic hypoxia.