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Consistent differences in brain structure and functional connectivity in high-altitude native Tibetans and immigrants

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Abstract

It has been well-established that high-altitude (HA) environments affect the human brain; however, the differences in brain structural and functional networks between HA natives and acclimatized immigrants have not been well clarified. In this study, native HA Tibetans were recruited for comparison with Han immigrants (average of 2.3 ± 0.3 years at HA), with lowland residents recruited as controls. Cortical gray matter volume, thickness, and functional connectivity were investigated using magnetic resonance imaging data. In addition, reaction time and correct score in the visual movement task, hematology, and SpO2 were measured. In both Tibetans and HA immigrants vs. lowlanders, decreased SpO2, increased hematocrit and hemoglobin, and increased reaction time and correct score in the visual movement task were detected. In both Tibetans and HA immigrants vs. lowlanders, gray matter volumes and cortical thickness were increased in the left somatosensory and motor cortex, and functional connectivity was decreased in the visual, default mode, subcortical, somatosensory-motor, ventral attention, and subcortical networks. Furthermore, SpO2 increased, hematocrit and hemoglobin decreased, and gray matter volumes and cortical thickness increased in the visual cortex, left motor cortex, and right auditory cortex in native Tibetans compared to immigrants. Movement time and correct score in task were positively correlated with the thickness of the visual cortex. In conclusion, brain structural and functional network difference in both Tibetan natives and HA immigrants were largely consistent, with native Tibetans only showing more intense brain modulation. Different populations acclimatized to HA develop similar brain mechanisms to cope with hostile HA environmental factors.

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All data and materials generated or used during the study are available from the corresponding author by request.

References

  • Barbier, E. L., Lamalle, L., & Decorps, M. (2001). Methodology of brain perfusion imaging. Journal Of Magnetic Resonance Imaging, 13, 496–520.

    Article  CAS  PubMed  Google Scholar 

  • Beall, C. M. (2007). Two routes to functional adaptation: tibetan and andean high-altitude natives. Proc Natl Acad Sci U S A, 104(Suppl 1), 8655–8660.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bianba, B. S., Andersen, L. B., Stigum, H., Ouzhuluobu, Nafstad, P., Wu, T., & Bjertness, E. (2014). Exercise capacity and selected physiological factors by ancestry and residential altitude: cross-sectional studies of 9-10-year-old children in Tibet. High Altitude Medicine & Biology, 15, 162–169.

    Article  CAS  Google Scholar 

  • Billaut, F., Gore, C. J., & Aughey, R. J. (2012). Enhancing team-sport athlete performance: is altitude training relevant? Sports Medicine (Auckland, N. Z.), 42, 751–767.

    Article  PubMed  Google Scholar 

  • Boroujerdi, A., & Milner, R. (2015). Defining the critical hypoxic threshold that promotes vascular remodeling in the brain. Experimental Neurology, 263, 132–140.

    Article  PubMed  Google Scholar 

  • Chen, J., Fan, C., Li, J., Han, Q., Lin, J., Yang, T., & Zhang, J. (2016a). Increased intraregional synchronized neural activity in adult brain after prolonged adaptation to High-Altitude Hypoxia: a resting-state fMRI study. High Altitude Medicine & Biology, 17, 16–24.

    Article  Google Scholar 

  • Chen, J., Li, J., Han, Q., Lin, J., Yang, T., Chen, Z., & Zhang, J. (2016b). Long-term acclimatization to high-altitude hypoxia modifies interhemispheric functional and structural connectivity in the adult brain. Brain Behav, 6, e00512.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen, J., Lin, I. T., Zhang, H., Lin, J., Zheng, S., Fan, M., & Zhang, J. (2016c). Reduced cortical thickness, surface area in patients with chronic obstructive pulmonary disease: a surface-based morphometry and neuropsychological study. Brain Imaging Behav, 10, 464–476.

    Article  PubMed  Google Scholar 

  • Chen, Q. H., Ge, R. L., Wang, X. Z., Chen, H. X., Wu, T. Y., Kobayashi, T., & Yoshimura, K. (1997). Exercise performance of Tibetan and Han adolescents at altitudes of 3,417 and 4,300 m. J Appl Physiol (1985) 83:661–667.

  • Chen, X., Li, H., Zhang, Q., Wang, J., Zhang, W., Liu, J., Li, B., Xin, Z., et al. (2019). Combined fractional anisotropy and subcortical volumetric abnormalities in healthy immigrants to high altitude: a longitudinal study. Human Brain Mapping, 40, 4202–4212.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen, X., Liu, J., Wang, J., Xin, Z., Zhang, Q., Zhang, W., Xi, Y., Zhu, Y., et al. (2021). Altered resting-state networks may explain the executive impairment in young health immigrants into high-altitude area. Brain Imaging Behav, 15, 147–156.

    Article  PubMed  Google Scholar 

  • Cho, J. I., Basnyat, B., Jeong, C., Di Rienzo, A., Childs, G., Craig, S. R., Sun, J., & Beall, C. M. (2017). Ethnically tibetan women in Nepal with low hemoglobin concentration have better reproductive outcomes. Evol Med Public Health, 2017, 82–96.

    Article  PubMed  PubMed Central  Google Scholar 

  • Fan, C., Zhao, Y., Yu, Q., Yin, W., Liu, H., Lin, J., Yang, T., Fan, M., et al. (2016). Reversible brain abnormalities in people without Signs of Mountain Sickness during High-Altitude exposure. Scientific Reports, 6, 33596.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gekeler, K., Schatz, A., Fischer, M. D., Schommer, K., Boden, K., Bartz-Schmidt, K. U., Gekeler, F., & Willmann, G. (2019). Decreased contrast sensitivity at high altitude. Br J Ophthalmol.

  • Glasser, M. F., Coalson, T. S., Robinson, E. C., Hacker, C. D., Harwell, J., Yacoub, E., Ugurbil, K., Andersson, J., et al. (2016). A multi-modal parcellation of human cerebral cortex. Nature, 536, 171–178.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo, Z., Fan, C., Li, T., Gesang, L., Yin, W., Wang, N., Weng, X., Gong, Q., et al. (2020). Neural network correlates of high-altitude adaptive genetic variants in Tibetans: a pilot, exploratory study. Human Brain Mapping, 41, 2406–2430.

    Article  PubMed  PubMed Central  Google Scholar 

  • Li, Y., Wang, M. Y., Xu, M., Xie, W. T., Zhang, Y. M., Yang, X. Y., Wang, Z. X., Song, R. (2022). High-Altitude Exposure and Time Interval Perception of Chinese Migrants in Tibet. Brain Sci 12.

  • Ma, H., Huang, X., Liu, M., Ma, H., & Zhang, D. (2018a). Aging of stimulus-driven and goal-directed attentional processes in young immigrants with long-term high altitude exposure in Tibet: an ERP study. Scientific Reports, 8, 17417.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ma, H., Li, X., Liu, M., Ma, H., & Zhang, D. (2018b). Mental Rotation Effect on adult immigrants with long-term exposure to high Altitude in Tibet: an ERP Study. Neuroscience, 386, 339–350.

    Article  CAS  PubMed  Google Scholar 

  • Ma, H., Wang, Y., Wu, J., Luo, P., & Han, B. (2015). Long-term exposure to high Altitude affects response inhibition in the conflict-monitoring stage. Scientific Reports, 5, 13701.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ma, H., Zhang, D., Li, X., Ma, H., Wang, N., & Wang, Y. (2019). Long-term exposure to high altitude attenuates verbal and spatial working memory: evidence from an event-related potential study. Brain Behav, 9, e01256.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ma, X., & Fan, R. (2015). Analysis of the effect of high altitude hypoxia environment on human adaptability. Journal of Chengdu Sport University, 03, 94–97.

    Google Scholar 

  • McGuire, S. A., Sherman, P. M., Brown, A. C., Robinson, A. Y., Tate, D. F., Fox, P. T., & Kochunov, P. V. (2012). Hyperintense white matter lesions in 50 high-altitude pilots with neurologic decompression sickness. Aviation, Space And Environmental Medicine, 83, 1117–1122.

    Article  PubMed  Google Scholar 

  • Pforte, C., Henrich-Noack, P., Baldauf, K., & Reymann, K. G. (2005). Increase in proliferation and gliogenesis but decrease of early neurogenesis in the rat forebrain shortly after transient global ischemia. Neuroscience, 136, 1133–1146.

    Article  CAS  PubMed  Google Scholar 

  • Power, J. D., Cohen, A. L., Nelson, S. M., Wig, G. S., Barnes, K. A., Church, J. A., Vogel, A. C., Laumann, T. O., et al. (2011). Functional network organization of the human brain. Neuron, 72, 665–678.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simonson, T. S., Yang, Y., Huff, C. D., Yun, H., Qin, G., Witherspoon, D. J., Bai, Z., Lorenzo, F. R., et al. (2010). Genetic evidence for high-altitude adaptation in Tibet. Science, 329, 72–75.

    Article  CAS  PubMed  Google Scholar 

  • Sokoloff, L. (1973). Metabolism of ketone bodies by the brain. Annual Review Of Medicine, 24, 271–280.

    Article  CAS  PubMed  Google Scholar 

  • Vose, A. K., Welch, J. F., Nair, J., Dale, E. A., Fox, E. J., Muir, G. D., Trumbower, R. D., & Mitchell, G. S. (2022). Therapeutic acute intermittent hypoxia: a translational roadmap for spinal cord injury and neuromuscular disease. Experimental Neurology, 347, 113891.

    Article  CAS  PubMed  Google Scholar 

  • Wang, J., Zheng, L., Wang, Z., Wu, X., Ma, N., Zhang, T., Chen, K., Biswal, B. B., et al. (2021). Alteration of behavioral Inhibitory Control in High-Altitude Immigrants. Frontiers In Behavioral Neuroscience, 15, 712278.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang, X., Wei, W., Yuan, F., Li, S., Lin, J., & Zhang, J. (2018). Regional cerebral blood flow in natives at high altitude: an arterial spin labeled MRI study. J Magn Reson Imaging.

  • Wang, Z. X., Zhang, D. L., & Ma, H. L. (2019). The effect of high altitude on human color perception. Sheng Li Xue Bao: [Acta Physiologica Sinica], 71, 833–838.

    PubMed  Google Scholar 

  • Wei, W., Wang, X., Gong, Q., Fan, M., & Zhang, J. (2017). Cortical thickness of native Tibetans in the Qinghai-Tibetan Plateau. Ajnr. American Journal Of Neuroradiology, 38, 553–560.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xin, J., Zhang, H., He, Y., Duren, Z., Bai, C., Chen, L., Luo, X., Yan, D. S., et al. (2020a). Chromatin accessibility landscape and regulatory network of high-altitude hypoxia adaptation. Nature Communications, 11, 4928.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xin, Z., Chen, X., Zhang, Q., Wang, J., Xi, Y., Liu, J., Li, B., Dong, X., et al. (2020b). Alteration in topological properties of brain functional network after 2-year high altitude exposure: a panel study. Brain Behav, 10, e01656.

    Article  PubMed  PubMed Central  Google Scholar 

  • Yan, C. G., Wang, X. D., & Lu, B. (2021). DPABISurf: data processing & analysis for brain imaging on surface. Sci Bull, 66, 2453–2455.

    Article  Google Scholar 

  • Yan, X., Zhang, J., Gong, Q., & Weng, X. (2011). Cerebrovascular reactivity among native-raised high altitude residents: an fMRI study. Bmc Neuroscience, 12, 94.

    Article  PubMed  PubMed Central  Google Scholar 

  • Yeo, B. T., Krienen, F. M., Sepulcre, J., Sabuncu, M. R., Lashkari, D., Hollinshead, M., Roffman, J. L., Smoller, J. W., et al. (2011). The organization of the human cerebral cortex estimated by intrinsic functional connectivity. Journal Of Neurophysiology, 106, 1125–1165.

    Article  PubMed  Google Scholar 

  • Yu, J. J., Non, A. L., Heinrich, E. C., Gu, W., Alcock, J., Moya, E. A., Lawrence, E. S., Tift, M. S., et al. (2022). Time domains of hypoxia responses and -Omics Insights. Frontiers In Physiology, 13, 885295.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang, D., Zhang, X., Ma, H., Wang, Y., Ma, H., & Liu, M. (2018). Competition among the attentional networks due to resource reduction in tibetan indigenous residents: evidence from event-related potentials. Scientific Reports, 8, 610.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, H., Lin, J., Sun, Y., Huang, Y., Ye, H., Wang, X., Yang, T., Jiang, X., et al. (2012). Compromised white matter microstructural integrity after mountain climbing: evidence from diffusion tensor imaging. High Altitude Medicine & Biology, 13, 118–125.

    Article  CAS  Google Scholar 

  • Zhang, J., Yan, X., Shi, J., Gong, Q., Weng, X., & Liu, Y. (2010). Structural modifications of the brain in acclimatization to high-altitude. PLoS One, 5, e11449.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang, J., Zhang, H., Chen, J., Fan, M., & Gong, Q. (2013). Structural modulation of brain development by oxygen: evidence on adolescents migrating from high altitude to sea level environment. PLoS One, 8, e67803.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, X., Kang, T., Liu, Y., Yuan, F., Li, M., Lin, J., & Zhang, J. (2022). Resting-State Neuronal Activity and Functional Connectivity Changes in the Visual Cortex after High Altitude Exposure: A Longitudinal Study. Brain Sci 12.

  • Zhang, X., & Zhang, J. (2022). The human brain in a high altitude natural environment: a review. Frontiers In Human Neuroscience, 16, 915995.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhao, M., Jiang, X. F., Zhang, H. Q., Sun, J. H., Pei, H., Ma, L. N., Cao, Y., & Li, H. (2021). Interactions between glial cells and the blood-brain barrier and their role in Alzheimer’s disease. Ageing Research Reviews, 72, 101483.

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank Jani Sonnleitner for proofreading and Nina Dongni Li, PhD (the Head of Science at OSIN Light, Ltd, Auckland, New Zealand) for her comments that greatly improved the manuscript.

Funding

This work was supported by the National Natural Science Foundation of China (81871519, 82171864, and 32260212), the Reformation and Development Funds for Local Region from the Chinese Government in 2022 (XZ202201YD0018C), the Science and Technology Major Project of Tibetan Autonomous Region of China (XZ202201ZD0001G).

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Authors and Affiliations

  1. Institute of Brain Diseases and Cognition, School of Medicine, Xiamen University, Xiamen, 361102, China

    Xinjuan Zhang, Yanqiu Liu, Fengjuan Yuan, Ran Zhang & Jiaxing Zhang

  2. Plateau Brain Science Research Centre, Tibet University, Lhasa, 850012, China

    Weiwei Xie & Hailin Ma

  3. Department of Clinical Medicine, School of Medicine, Xiamen University, Xiamen, 361102, China

    Wenrui Du

  4. Department of Radiology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361102, China

    Jianzhong Lin

  5. Department of Radiology, Tibet Autonomous Region People’s Hospital, Lhasa, Tibet Autonomous Region, 850000, China

    Wu Yin

  6. Department of Endocrinology, Tibet Autonomous Region People’s Hospital, Tibet Autonomous Region, Lhasa, 850000, China

    Lihui Yang

  7. Department of Radiology, Tibet Autonomous Region Women’s and Children’s Hospital, Tibet Autonomous Region, Lhasa, 850000, China

    Haipeng Liu

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  1. Xinjuan Zhang
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Contributions

All authors made substantial contributions to this manuscript and take responsibility for its content. Hailin Ma and Jiaxing Zhang was responsible for the study design. Weiwei Xie, Yanqiu Liu, Jianzhong Lin, Wu Yin, Lihui Yang, Fengjuan Yuan, Haipeng Liu, and Ran Zhang contributed to the acquisition of fMRI and demographical data. Xinjuan Zhang and Weiwei Xie performed the MRI data analysis. Wenrui Du and Yanqiu Liu performed the behavior data collect and analysis. Hailin Ma and Jiaxing Zhang assisted with data analysis and interpretation of funding. Xinjuan Zhang drafted the manuscript and prepared all figures. All authors critically reviewed content and approved the final version for publication.

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Correspondence to Hailin Ma or Jiaxing Zhang.

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The study was conducted in accordance with the Declaration of Helsinki, and the experimental protocol was approved by the Ethical Committee of Xiamen University.

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Zhang, X., Xie, W., Du, W. et al. Consistent differences in brain structure and functional connectivity in high-altitude native Tibetans and immigrants. Brain Imaging and Behavior 17, 271–281 (2023). https://doi.org/10.1007/s11682-023-00759-5

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