Long-term acclimatization to high-altitude hypoxia modifies interhemispheric functional and structural connectivity in the adult brain

Background: Structural and functional networks can be reorganized to adjust to environmental pressures and physiologic changes in the adult brain, but such processes remain unclear in prolonged adaptation to high-altitude (HA) hypoxia. This study aimed to characterize the interhemispheric functionally and structurally coupled modifications in the brains of adult HA immigrants. Methods: We performed resting-state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) in 16 adults who had immigrated to the Qinghai-Tibet Plateau (2300-4400 m) for 2 years and in 16 age-matched sea-level (SL) controls. A recently validated approach of voxel-mirrored homotopic connectivity (VMHC) was employed to examine the interhemispheric resting-state functional connectivity. Areas showing changed VMHC in HA immigrants were selected as regions of interest for follow-up DTI tractography analysis. The fiber parameters of fractional anisotropy and fiber length were obtained. Cognitive and physiological assessments were made and correlated with the resulting image metrics. Results: Compared with SL controls, VMHC in the bilateral visual cortex was significantly increased in HA immigrants. The mean VMHC value extracted within the visual cortex was positively correlated with hemoglobin concentration. Moreover, the path length of the commissural fibers connecting homotopic visual areas was increased in HA immigrants, covarying positively with VMHC. Conclusions: These observations are the first to demonstrate interhemispheric functional and structural connectivity resilience in the adult brain after prolonged HA acclimatization independent of inherited and developmental effects, and the coupled modifications in the bilateral visual cortex indicate important neural compensatory mechanisms underlying visual dysfunction in physiologically well-acclimatized HA immigrants. The study of human central adaptation to extreme environments promotes the understanding of our brain's capacity for survival.