The effect of high-altitude exercise on cognitive function

doi:10.3724/SP.J.1042.2024.00800

Abstract

Abstract:

High-altitude (HA) environments are characterized by significant hypobaric hypoxia, and are both physiologically challenging and frequently associated with cognitive impairment. Conversely, aerobic exercise is documented to enhance cognitive function by the promotion of neural plasticity and improvement in brain functioning, thus enhancing overall cognitive performance. However, it is not clear whether the positive effects of exercise on cognition extend to the complex conditions associated with HA environments. Furthermore, the potential modulation of these effects by the type of cognitive task, exercise duration and intensity, and different altitudes and exposure types (real HA environment vs. simulated HA condition; acute exposure vs. long-term exposure) warrants further investigation.

This comprehensive review explores the influence of aerobic exercise on cognitive performance under conditions of both acute and long-term HA exposure. It is proposed that factors, such as hypoxia dose, specific cognitive function, exercise intensity, and type of exposure, modulate the interactive effects of HA hypoxia and exercise on cognitive function. The potential physiological mechanisms are also discussed, suggesting that changes in cerebral oxygenation, levels of neurotrophic factors, oxidative stress, and neuro-immunity may account for the combined effects of HA hypoxia and exercise on cognitive performance.

The findings indicate that HA exercise has a positive influence on psychomotor abilities, attention, working memory, and inhibitory control, and that these effects are modulated by the type of exposure, hypoxia dose, and exercise intensity. Specifically, while exercise may enhance cognitive performance under conditions of acute hypoxia exposure, positive effects during chronic HA exposure require adaptation to the hypoxic conditions of HA environments. While exercise influences cognitive function positively under low levels of hypoxia, it has little effect or even adverse effects on cognitive function when the hypoxia level is high. Furthermore, the intensity of exercise has a variable influence on cognitive function under HA conditions, seen in an inverted U-shaped relationship between exercise intensity and cognitive performance in acute HA exposure conditions, where moderate intensity maximizes cognitive performance. Both moderate and high exercise intensities under conditions of long-term HA exposure positively affect executive control, although the latter can lead to a reduction in aerobic exercise capacity.

Although HA exercise can improve cognitive function by upregulating the expression of neurotrophic factors, it may also reduce brain oxygenation and thus contribute to oxidative stress and neuroimmune responses that could adversely affect cognitive function. Increased expression of BDNF induced by hypoxic exercise can ensure adequate neuronal capacity and improve cognitive function. Nevertheless, exercise undertaken under acute HA exposure could reduce both blood and brain oxygen saturation, potentially impairing cognitive function. Moreover, high intensity exercise can intensify the levels of oxidative stress, disrupting the redox balance, and triggering an inflammatory response affecting the immune activity in the central nervous system and thus influencing cognitive performance.

Although this review provides substantial evidence of the relationship between HA exercise and cognitive performance, several controversial issues, contradictory conclusions, and unexplored topics remain. To formulate a specific "HA exercise prescription" for mitigating cognitive impairment under HA conditions, several directions for future research are proposed. These are 1) further clarification of the modulating effects of exposure type, hypoxia dose and exercise intensity, 2) consideration of demographic factors such as sex and age, 3) the application of advanced scientific techniques to explore the underlying neurological and molecular mechanisms, and 4) investigation of the effects of aerobic exercise on cognitive function in patients with chronic mountain sickness.

In conclusion, this review discusses the effects of HA exercise on different cognitive functions, summarizes the moderating variables and potential physiological mechanisms, and offers future perspectives. As the influx of individuals to HA areas for various purposes rises, addressing the adverse effects of HA on cognitive function has become crucial. This review indicates the significance of understanding the potential effects of HA exercise on cognitive function and provides insights into future research directions for the effective prevention of cognitive impairment.

Key words: high altitudes, high-alitude exercise, cognitive function, moderator, mechanisms

CLC Number:

B842

SU Rui, WANG Chengzhi, LI Hao, MA Hailin, SU Yanjie. The effect of high-altitude exercise on cognitive function[J]. Advances in Psychological Science, 2024, 32(5): 800-812.

Figures/Tables 1

References 87

[1]	安心, 马海林, 韩布新, 刘冰, 王妍. (2017). 高海拔驻留时间对注意网络的影响. 中国临床心理学杂志 25(3), 502-506. https://doi.org/10.16128/j.cnki.1005-3611.2017.03.023
[2]	毕存箭. (2021). 高海拔地区藏族儿童青少年心肺耐力和执行功能的关系及其运动干预研究 (博士学位论文). 华东师范大学, 上海. https://doi.org/10.27149/d.cnki.ghdsu.2021.002854
[3]	陈爱国, 殷恒婵, 颜军, 杨钰. (2011). 不同强度短时有氧运动对执行功能的影响. 心理学报 43(9), 1055-1062.
[4]	马海林, 党鹏, 苏瑞, 李昊. (2022). 高海拔暴露时间对工作记忆的影响——一项追踪研究. 高原科学研究 6(2), 42-50. https://doi.org/10.16249/j.cnki.2096-4617.2022.02.005
[5]	马强, 侯会生, 李佳鑫. (2020). 高海拔环境中短时有氧运动与大学生执行功能的实验研究. 中央民族大学学报(自然科学版) 29(1), 81-86.
[6]	钱令嘉. (2011). 关于应激与认知的思考. 军事医学 35(9), 658-662. https://doi.org/10.3969/j.issn.1674-9960.2011.09.006
[7]	王成志. (2023). 不同强度有氧运动对高原移居者注意功能的影响 (硕士学位论文). 西藏大学, 拉萨.
[8]	张斌, 刘莹. (2019). 急性有氧运动对认知表现的影响. 心理科学进展 27(6), 1058-1071. https://doi.org/10.3724/SP.J.1042.2019.01058 doi: 10.3724/SP.J.1042.2019.01058 URL
[9]	Aboouf, M. A., Thiersch, M., Soliz, J., Gassmann, M., & Schneider Gasser, E. M. (2023). The brain at high altitude: From molecular signaling to cognitive performance. International Journal of Molecular Sciences, 24(12), 10179. https://doi.org/10.3390/IJMS241210179 doi: 10.3390/ijms241210179 URL
[10]	Ando, S., Hatamoto, Y., Sudo, M., Kiyonaga, A., Tanaka, H., & Higaki, Y. (2013). The effects of exercise under hypoxia on cognitive function. PloS One, 8(5), e63630. https://doi.org/10.1371/journal.pone.0063630
[11]	Ando, S., Komiyama, T., Sudo, M., Higaki, Y., Ishida, K., Costello, J. T., & Katayama, K. (2020). The interactive effects of acute exercise and hypoxia on cognitive performance: A narrative review. Scandinavian Journal of Medicine & Science in Sports, 30(3), 384-398. https://doi.org/10.1111/sms.13573
[12]	Ando, S., Yamada, Y., & Kokubu, M. (2010). Reaction time to peripheral visual stimuli during exercise under hypoxia. Journal of Applied Physiology, 108(5), 1210-1216. https://doi.org/10.1152/japplphysiol.01115.2009 doi: 10.1152/japplphysiol.01115.2009 URL pmid: 20167674
[13]	Attwell, D., Buchan, A. M., Charpak, S., Lauritzen, M., MacVicar, B. A., & Newman, E. A. (2010). Glial and neuronal control of brain blood flow. Nature, 468(7321), 232-243. https://doi.org/10.1038/nature09613 doi: 10.1038/nature09613 URL
[14]	Bayer, U., Likar, R., Pinter, G., Stettner, H., Demschar, S., Trummer, B., ... Burtscher, M. (2017). Intermittent hypoxic-hyperoxic training on cognitive performance in geriatric patients. Alzheimer's & Dementia: Translational Research & Clinical Interventions, 3(1), 114-122. https://doi.org/10.1016/j.trci.2017.01.002 doi: 10.1016/j.trci.2017.01.002 URL
[15]	Becke, A., Müller, P., Dordevic, M., Lessmann, V., Brigadski, T., & Müller, N. G. (2018). Daily intermittent normobaric hypoxia over 2 weeks reduces BDNF plasma levels in young adults - A randomized controlled feasibility study. Frontiers in Physiology, 9, 1337-1337. https://doi.org/10.3389/fphys.2018.01337
[16]	Bigham, A. W., & Lee, F. S. (2014). Human high-altitude adaptation: Forward genetics meets the hif pathway. Genes & Development, 28(20), 2189-2204. http://www.genesdev.org/cgi/doi/10.1101/gad.250167.114 doi: 10.1101/gad.250167.114
[17]	Bliemsrieder, K., Weiss, E. M., Fischer, R., Brugger, H., Sperner-Unterweger, B., & Hüfner, K. (2022). Cognition and neuropsychological changes at altitude—A systematic review of literature. Brain Sciences, 12(12), 1736. https://doi.org/10.3390/brainsci12121736 doi: 10.3390/brainsci12121736 URL
[18]	Bolmont, B., Thullier, F., & Abraini, J. H. (2000). Relationships between mood states and performances in reaction time, psychomotor ability, and mental efficiency during a 31-day gradual decompression in a hypobaric chamber from sea level to 8848 m equivalent altitude. Physiology & Behavior, 71(5), 469-476. https://doi.org/10.1016/S0031-9384(00)00362-0 doi: 10.1016/S0031-9384(00)00362-0 URL
[19]	Bouak, F., Vartanian, O., Hofer, K., & Cheung, B. (2018). Acute mild hypoxic hypoxia effects on cognitive and simulated aircraft pilot performance. Aerospace Medicine and Human Performance, 89(6), 526-535. https://doi.org/10.3357/AMHP.5022.2018 doi: 10.3357/AMHP.5022.2018 URL pmid: 29789086
[20]	Castellani, G., Croese, T., Peralta Ramos, J. M., & Schwartz, M. (2023). Transforming the understanding of brain immunity. Science, 380(6640), 7649-7649. https://doi.org/10.1126/science.abo7649
[21]	Chang, Y. K., Labban, J. D., Gapin, J. I., & Etnier, J. L. (2012). The effects of acute exercise on cognitive performance: A meta-analysis. Brain Research, 1453, 87-101. https://doi.org/10.1016/j.brainres.2012.02.068 doi: 10.1016/j.brainres.2012.02.068 URL pmid: 22480735
[22]	de Aquino-Lemos, V., Santos, R. V. T., Antunes, H. K. M., Lira, F. S., Luz Bittar, I. G., Caris, A. V., Tufik, S., & de Mello, M. T. (2016). Acute physical exercise under hypoxia improves sleep, mood and reaction time. Physiology & Behavior, 154, 90-99. https://doi.org/10.1016/j.physbeh.2015.10.028 doi: 10.1016/j.physbeh.2015.10.028 URL
[23]	Dobashi, S., Horiuchi, M., Endo, J., Kiuchi, M., & Koyama, K. (2016). Cognitive function and cerebral oxygenation during prolonged exercise under hypoxia in healthy young males. High Altitude Medicine & Biology, 17(3), 214-221. https://doi.org/10.1089/ham.2016.0036
[24]	Dosek, A., Ohno, H., Acs, Z., Taylor, A. W., & Radak, Z. (2007). High altitude and oxidative stress. Respiratory Physiology & Neurobiology, 158(2-3), 128-131. https://doi.org/10.1016/j.resp.2007.03.013 doi: 10.1016/j.resp.2007.03.013 URL
[25]	Dykiert, D., Hall, D., van Gemeren, N., Benson, R., Der, G., Starr, J. M., & Deary, I. J. (2010). The effects of high altitude on choice reaction time mean and intra-individual variability: Results of the Edinburgh altitude research expedition of 2008. Neuropsychology, 24(3), 391-401. https://doi.org/10.1037/a0018502 doi: 10.1037/a0018502 URL pmid: 20438216
[26]	Enette, L., Vogel, T., Fanon, J. L., & Lang, P. O. (2017). Effect of interval and continuous aerobic training on basal serum and plasma brain-derived neurotrophic factor values in seniors: A systematic review of intervention studies. Rejuvenation Research, 20(6), 473-483. https://doi.org/10.1089/rej.2016.1886 doi: 10.1089/rej.2016.1886 URL
[27]	Hackett, P. H., & Roach, R. C. (2001). High-altitude illness. The New England Journal of Medicine, 345(2), 107-114. https://doi.org/10.1056/NEJM200107123450206 doi: 10.1056/NEJM200107123450206 URL
[28]	Helan, M., Aravamudan, B., Hartman, W. R., Thompson, M. A., Johnson, B. D., Pabelick, C. M., & Prakash, Y. S. (2014). BDNF secretion by human pulmonary artery endothelial cells in response to hypoxia. Journal of Molecular and Cellular Cardiology, 68, 89-97. https://doi.org/10.1016/j.yjmcc.2014.01.006 doi: 10.1016/j.yjmcc.2014.01.006 URL pmid: 24462831
[29]	Hornbein, T. F., Townes, B. D., Schoene, R. B., Sutton, J. R., & Houston, C. S. (1989). The cost to the central nervous system of climbing to extremely high altitude. The New England Journal of Medicine, 321(25), 1714-1719. https://doi.org/10.1056/NEJM198912213212505 doi: 10.1056/NEJM198912213212505 URL
[30]	Jansen, G. F., Krins, A., Basnyat, B., Odoom, J. A., & Ince, C. (2007). Role of the altitude level on cerebral autoregulation in residents at high altitude. Journal of Applied Physiology, 103(2), 518-523. https://doi.org/10.1152/japplphysiol.01429.2006 doi: 10.1152/japplphysiol.01429.2006 URL pmid: 17463295
[31]	Joanny, P., Steinberg, J., Robach, P., Richalet, J. P., Gortan, C., Gardette, B., & Jammes, Y. (2001). Operation everest III (comex'97): The effect of simulated severe hypobaric hypoxia on lipid peroxidation and antioxidant defence systems in human blood at rest and after maximal exercise. Resuscitation, 49(3), 307-314. https://doi.org/10.1016/S0300-9572(00)00373-7 URL pmid: 11723998
[32]	Jung, M., Zou, L., Yu, J. J., Ryu, S., Kong, Z. W., Yang, L., … Loprinzi, P. D. (2020). Does exercise have a protective effect on cognitive function under hypoxia? A systematic review with meta-analysis. Journal of Sport and Health Science, 9(6), 562-577. https://doi.org/10.1016/j.jshs.2020.04.004 doi: 10.1016/j.jshs.2020.04.004 URL pmid: 32325144
[33]	Kim, C., Ryan, E. J., Seo, Y., Peacock, C., Gunstad, J., Muller, M. D., Ridgel, A. L., & Glickman, E. L. (2015). Low intensity exercise does not impact cognitive function during exposure to normobaric hypoxia. Physiology & Behavior, 151, 24-28. https://doi.org/10.1016/j.physbeh.2015.07.003 doi: 10.1016/j.physbeh.2015.07.003 URL
[34]	Kitaoka, Y., Hoshino, D., & Hatta, H. (2012). Monocarboxylate transporter and lactate metabolism. The Journal of Physical Fitness and Sports Medicine, 1(2), 247-252. https://doi.org/10.7600/jpfsm.1.247 doi: 10.7600/jpfsm.1.247 URL
[35]	Komiyama, T., Katayama, K., Sudo, M., Ishida, K., Higaki, Y., & Ando, S. (2017). Cognitive function during exercise under severe hypoxia. Scientific Reports, 7(1), 10000. https://doi.org/10.1038/s41598-017-10332-y doi: 10.1038/s41598-017-10332-y URL pmid: 28855602
[36]	Komiyama, T., Sudo, M., Higaki, Y., Kiyonaga, A., Tanaka, H., & Ando, S. (2015). Does moderate hypoxia alter working memory and executive function during prolonged exercise? Physiology & Behavior, 139, 290-296. https://doi.org/10.1016/j.physbeh.2014.11.057 doi: 10.1016/j.physbeh.2014.11.057 URL
[37]	Krzeszowiak, J., Zawadzki, M., Markiewicz-Górka, I., Kawalec, A., & Pawlas, K. (2014). The influence of 9-day trekking in the alps on the level of oxidative stress parameters and blood parameters in native lowlanders. Annals of Agricultural and Environmental Medicine, 21(3), 585-589. https://doi.org/10.5604/12321966.1120607 doi: 10.5604/12321966.1120607 URL pmid: 25292134
[38]	Lambourne, K., & Tomporowski, P. (2010). The effect of exercise-induced arousal on cognitive task performance: A meta-regression analysis. Brain Research, 1341, 12-24. https://doi.org/10.1016/j.brainres.2010.03.091 doi: 10.1016/j.brainres.2010.03.091 URL pmid: 20381468
[39]	Lefferts, W. K., Babcock, M. C., Tiss, M. J., Ives, S. J., White, C. N., Brutsaert, T. D., & Heffernan, K. S. (2016). Effect of hypoxia on cerebrovascular and cognitive function during moderate intensity exercise. Physiology & Behavior, 165, 108-118. https://doi.org/10.1016/j.physbeh.2016.07.003 doi: 10.1016/j.physbeh.2016.07.003 URL
[40]	Li, Y., & Wang, Y. (2022). Effects of long-term exposure to high altitude hypoxia on cognitive function and its mechanism: A narrative review. Brain Sciences, 12(6), 808. https://doi.org/10.3390/brainsci12060808 doi: 10.3390/brainsci12060808 URL
[41]	Li, Y., Wang, Y., Yu, F., & Chen, A. (2021). Large‐scale reconfiguration of connectivity patterns among attentional networks during context-dependent adjustment of cognitive control. Human Brain Mapping, 42(12), 3821-3832. https://doi.org/10.1002/hbm.25467 doi: 10.1002/hbm.v42.12 URL
[42]	Ludyga, S., Gerber, M., Pühse, U., Looser, V. N., & Kamijo, K. (2020). Systematic review and meta-analysis investigating moderators of long-term effects of exercise on cognition in healthy individuals. Nature Human Behaviour, 4(6), 603-612. https://doi.org/10.1038/s41562-020-0851-8 doi: 10.1038/s41562-020-0851-8 URL pmid: 32231280
[43]	Luks, A. M., & Hackett, P. H. (2022). Medical conditions and high-altitude travel. The New England Journal of Medicine, 386(4), 364-373. https://doi.org/10.1056/NEJMra2104829 doi: 10.1056/NEJMra2104829 URL pmid: 35081281
[44]	Ma, H., Huang, X., Liu, M., Ma, H., & Zhang, D. (2018). 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(1), 17417. https://doi.org/10.1038/s41598-018-34706-y doi: 10.1038/s41598-018-34706-y URL pmid: 30479363
[45]	Mancini, A., Bellingacci, L., Canonichesi, J., & Di Filippo, M. (2023). Immunity and cognition. In N.Rezaei, & N.Yazdanpanah Eds. Translational neuroimmunology, (Vol. 7, pp. 129-149). Academic Press. https://doi.org/10.1016/B978-0-323-85841-0.00017-1
[46]	McMorris, T., Hale, B. J., Barwood, M., Costello, J., & Corbett, J. (2017). Effect of acute hypoxia on cognition: A systematic review and meta-regression analysis. Neuroscience and Biobehavioral Reviews, 74(Pt A),225-232. https://doi.org/10.1016/j.neubiorev.2017.01.019 doi: S0149-7634(16)30707-2 URL pmid: 28111267
[47]	Medawar, P. (1961). Immunological Tolerance. Nature, 189, 14-17. https://doi.org/10.1038/189014a0 doi: 10.1038/189014a0 URL
[48]	Millet, G. P., Faiss, R., & Pialoux, V. (2012). Point: Counterpoint: Hypobaric hypoxia induces/does not induce different responses from normobaric hypoxia. Journal of Applied Physiology (1985), 112(10), 1783-1784. https://doi.org/10.1152/japplphysiol.00067.2012 doi: 10.1152/japplphysiol.00067.2012 URL
[49]	Miller, L. E., McGinnis, G. R., Kliszczewicz, B., Slivka, D., Hailes, W., Cuddy, J., ... Quindry, J. C. (2013). Blood oxidative-stress markers during a high-altitude trek. International Journal of Sport Nutrition and Exercise Metabolism, 23(1), 65-72. https://doi.org/10.1123/ijsnem.23.1.65 URL pmid: 23006582
[50]	Milusheva, E. A., Doda, M., Baranyi, M., & Vizi, E. S. (1996). Effect of hypoxia and glucose deprivation on ATP level, adenylate energy charge and [ca2+] o-dependent and independent release of [3H] dopamine in rat striatal slices. Neurochemistry International, 28(5-6), 501-507. https://doi.org/10.1016/0197-0186(95)00129-8 URL pmid: 8792331
[51]	Moreau, D., & Chou, E. (2019). The acute effect of high-intensity exercise on executive function: A meta- analysis. Perspectives on Psychological Science, 14(5), 734-764. https://doi.org/10.1177/1745691619850568 doi: 10.1177/1745691619850568 URL pmid: 31365839
[52]	Northey, J. M., Cherbuin, N., Pumpa, K. L., Smee, D. J., & Rattray, B. (2018). Exercise interventions for cognitive function in adults older than 50: A systematic review with meta-analysis. British Journal of Sports Medicine, 52(3), 154-160. https://doi.org/10.1136/bjsports-2016-096587 doi: 10.1136/bjsports-2016-096587 URL pmid: 28438770
[53]	Nybo, L., & Rasmussen, P. (2007). Inadequate cerebral oxygen delivery and central fatigue during strenuous exercise. Exercise and Sport Sciences Reviews, 35(3), 110-118. https://doi.org/10.1097/jes.0b013e3180a031ec URL pmid: 17620929
[54]	Ochi, G., Yamada, Y., Hyodo, K., Suwabe, K., Fukuie, T., Byun, K., Dan, I., & Soya, H. (2018). Neural basis for reduced executive performance with hypoxic exercise. NeuroImage, 171, 75-83. https://doi.org/10.1016/j.neuroimage.2017.12.091 doi: S1053-8119(17)31115-1 URL pmid: 29305162
[55]	Peltonen, J. E., Paterson, D. H., Shoemaker, J. K., DeLorey, D. S., duManoir, G. R., Petrella, R. J., & Kowalchuk, J. M. (2009). Cerebral and muscle deoxygenation, hypoxic ventilatory chemosensitivity and cerebrovascular responsiveness during incremental exercise. Respiratory Physiology & Neurobiology, 169(1), 24-35. https://doi.org/10.1016/j.resp.2009.08.013 doi: 10.1016/j.resp.2009.08.013 URL
[56]	Quindry, J., Dumke, C., Slivka, D., & Ruby, B. (2016). Impact of extreme exercise at high altitude on oxidative stress in humans. The Journal of Physiology, 594(18), 5093-5104. https://doi.org/10.1113/JP270651 doi: 10.1113/JP270651 URL pmid: 26453842
[57]	Raichle, M. E. (2010). Two views of brain function. Trends in Cognitive Sciences, 14(4), 180-190. https://doi.org/10.1016/j.tics.2010.01.008 doi: 10.1016/j.tics.2010.01.008 URL pmid: 20206576
[58]	Regard, M., Oelz, O., Brugger, P., & Landis, T. (1989). Persistent cognitive impairment in climbers after repeated exposure to extreme altitude. Neurology, 39(2), 210. https://doi.org/10.1212/WNL.39.2.210 doi: 10.1212/WNL.39.2.210 URL
[59]	Robinet, C., & Pellerin, L. (2010). Brain-derived neurotrophic factor enhances the expression of the monocarboxylate transporter 2 through translational activation in mouse cultured cortical neurons. Journal of Cerebral Blood Flow and Metabolism, 30(2), 286-298. https://doi.org/10.1038/jcbfm.2009.208 doi: 10.1038/jcbfm.2009.208 URL pmid: 19794395
[60]	Schega, L., Peter, B., Brigadski, T., Leßmann, V., Isermann, B., Hamacher, D., & Törpel, A. (2016). Effect of intermittent normobaric hypoxia on aerobic capacity and cognitive function in older people. Journal of Science and Medicine in Sport, 19(11), 941-945. https://doi.org/10.1016/j.jsams.2016.02.012 doi: S1440-2440(16)00063-3 URL pmid: 27134133
[61]	Shannon, O. M., Duckworth, L., Barlow, M. J., Deighton, K., Matu, J., Williams, E. L., ... O'Hara, J. P. (2017). Effects of dietary nitrate supplementation on physiological responses, cognitive function, and exercise performance at moderate and very-high simulated altitude. Frontiers in Physiology, 8, 401-401. https://doi.org/10.3389/fphys.2017.00401 doi: 10.3389/fphys.2017.00401 URL pmid: 28649204
[62]	Simonson, T. S., Yang, Y., Huff, C. D., Yun, H., Qin, G., Witherspoon, D. J., ... Ge, R. (2010). Genetic evidence for high-altitude adaptation in Tibet. Science, 329(5987), 72-75. https://doi.org/10.1126/science.1189406 doi: 10.1126/science.1189406 URL pmid: 20466884
[63]	Sinha, S., Ray, U. S., Saha, M., Singh, S. N., & Tomar, O. S. (2009). Antioxidant and redox status after maximal aerobic exercise at high altitude in acclimatized lowlanders and native highlanders. European Journal of Applied Physiology, 106, 807-814. https://doi.org/10.1007/s00421-009-1082-x doi: 10.1007/s00421-009-1082-x URL pmid: 19466447
[64]	Sorond, F. A., Hurwitz, S., Salat, D. H., Greve, D. N., & Fisher, N. D. L. (2013). Neurovascular coupling, cerebral white matter integrity, and response to cocoa in older people. Neurology, 81(10), 904-909. https://doi.org/10.1212/WNL.0b013e3182a351aa doi: 10.1212/WNL.0b013e3182a351aa URL pmid: 23925758
[65]	Steele, A. R., Tymko, M. M., Meah, V. L., Simpson, L. L., Gasho, C., Dawkins, T. G., ... Steinback, C. D. (2021). Global REACH 2018: Volume regulation in high-altitude andeans with and without chronic mountain sickness. American Journal of Physiology- Regulatory, Integrative and Comparative Physiology, 321(3), 504-512. https://doi.org/10.1152/ajpregu.00102.2021
[66]	Stillman, C. M., Esteban-Cornejo, I., Brown, B., Bender, C. M., & Erickson, K. I. (2020). Effects of exercise on brain and cognition across age groups and health states. Trends in Neurosciences, 43(7), 533-543. https://doi.org/10.1016/j.tins.2020.04.010 doi: S0166-2236(20)30101-6 URL pmid: 32409017
[67]	Su, R., Wang, C., Liu, W., Han, C., Fan, J., Ma, H., ... Zhang, D. (2022). Intensity-dependent acute aerobic exercise: Effect on reactive control of attentional functions in acclimatized lowlanders at high altitude. Physiology & Behavior, 250, 113785. https://doi.org/10.1016/j.physbeh.2022.113785 doi: 10.1016/j.physbeh.2022.113785 URL
[68]	Subudhi, A. W., Dimmen, A. C., & Roach, R. C. (2007). Effects of acute hypoxia on cerebral and muscle oxygenation during incremental exercise. Journal of Applied Physiology, 103(1), 177-183. https://doi.org/10.1152/japplphysiol.01460.2006 doi: 10.1152/japplphysiol.01460.2006 URL pmid: 17431082
[69]	Sun, S., Loprinzi, P. D., Guan, H., Zou, L., Kong, Z., Hu, Y., Shi, Q., & Nie, J. (2019). The effects of high-intensity interval exercise and hypoxia on cognition in sedentary young adults. Medicina (Kaunas, Lithuania), 55(2), 43. https://doi.org/10.3390/medicina55020043
[70]	Sweller, J. (2016). Working memory, long-term memory, and instructional design. Journal of Applied Research in Memory and Cognition, 5(4), 360-367. https://doi.org/10.1016/j.jarmac.2015.12.002 doi: 10.1016/j.jarmac.2015.12.002 URL
[71]	Taylor, L., Watkins, S. L., Marshall, H., Dascombe, B. J., & Foster, J. (2016). The impact of different environmental conditions on cognitive function: A focused review. Frontiers in Physiology, 6, 372-372. https://doi.org/10.3389/fphys.2015.00372
[72]	Vermehren-Schmaedick, A., Jenkins, V. K., Knopp, S. J., Balkowiec, A., & Bissonnette, J. M. (2012). Acute intermittent hypoxia-induced expression of brain-derived neurotrophic factor is disrupted in the brainstem of methyl-CpG-binding protein 2 null mice. Neuroscience, 206, 1-6. https://doi.org/10.1016/j.neuroscience.2012.01.017 doi: 10.1016/j.neuroscience.2012.01.017 URL pmid: 22297041
[73]	Vij, A. G., Dutta, R., & Satija, N. K. (2005). Acclimatization to oxidative stress at high altitude. High Altitude Medicine & Biology, 6(4), 301-310. https://doi.org/10.1089/ham.2005.6.301
[74]	Villafuerte, F. C., & Corante, N. (2016). Chronic mountain sickness: Clinical aspects, etiology, management, and treatment. High Altitude Medicine & Biology, 17(2), 61-69. https://doi.org/10.1089/ham.2016.0031
[75]	Villafuerte, F. C., Cardenas, R., & Monge-C, C. (2004). Optimal hemoglobin concentration and high altitude: A theoretical approach for andean men at rest. Journal of Applied Physiology, 96(5), 1581-1588. https://doi.org/10.1152/japplphysiol.00328.2003 URL pmid: 14672972
[76]	Virués-Ortega, J., Garrido, E., Javierre, C., & Kloezeman, K. C. (2006). Human behaviour and development under high-altitude conditions. Developmental Science, 9(4), 400-410. https://doi.org/10.1111/j.1467-7687.2006.00505.x URL pmid: 16764613
[77]	Walsh, J. J., Drouin, P. J., King, T. J., D'Urzo, K. A., Tschakovsky, M. E., Cheung, S. S., & Day, T. A. (2020). Acute aerobic exercise impairs aspects of cognitive function at high altitude. Physiology & Behavior, 223, 112979-112979. https://doi.org/10.1016/j.physbeh.2020.112979 doi: 10.1016/j.physbeh.2020.112979 URL
[78]	Wang, N. N., Yu, S. F., Dang, P., Hu, Q. L., Su, R., Li, H., ... Zhang, D. L. (2023). Association between the acceleration of access to visual awareness of grating orientation with higher heart rate at high-altitude. Physiology & Behavior, 268, 114235. https://doi.org/10.1016/j.physbeh.2023.114235 doi: 10.1016/j.physbeh.2023.114235 URL
[79]	Welford, A. T. (1984). Psychomotor performance. Annual Review of Gerontology and Geriatrics, 4(1), 237-273.
[80]	West, J. B. (1984). Human physiology at extreme altitudes on mount everest. Science, 223(4638), 784-788. https://doi.org/10.1126/science.6364351 URL pmid: 6364351
[81]	Wu, T., & Kayser, B. (2006). High altitude adaptation in Tibetans. High Altitude Medicine & Biology, 7(3), 193-208. https://doi.org/10.1089/ham.2006.7.193
[82]	Xue, X. J., Su, R., Li, Z. F., Bu, X. O., Dang, P., Yu, S. F., ... Zhang, D. L. (2022). Oxygen metabolism-induced stress response underlies heart-brain interaction governing human consciousness-breaking and attention. Neuroscience Bulletin, 38(2), 166-180. https://10.1007/s12264-021-00761-1 doi: 10.1007/s12264-021-00761-1 URL
[83]	Yu, S., Wang, N., Hu, Q., Dang, P., Chang, S., Huang, X., … Zhang, D. (2023). Neurodynamics of awareness detection in Tibetan immigrants: Evidence from electroencephalography analysis. Neuroscience, 522, 69-80. https://doi.org/10.1016/j.neuroscience.2023.04.025 doi: 10.1016/j.neuroscience.2023.04.025 URL
[84]	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(1), 610. https://doi.org/10.1038/s41598-017-18886-7 doi: 10.1038/s41598-017-18886-7 URL pmid: 29330442
[85]	Zhang, X., Xie, W., Du, W., Liu, Y., Lin, J., Yin, W., ... Zhang, J. (2023). Consistent differences in brain structure and functional connectivity in high-altitude native Tibetans and immigrants. Brain Imaging and Behavior, 17, 271-281. https://doi.org/10.1007/s11682-023-00759-5 doi: 10.1007/s11682-023-00759-5 URL
[86]	Zhang, X., & Zhang, J. (2022). The human brain in a high altitude natural environment: A review. Frontiers in Human Neuroscience, 16, 915995. https://doi.org/10.3389/fnhum.2022.915995 doi: 10.3389/fnhum.2022.915995 URL
[87]	Zubieta-Calleja, G. R., Paulev, P., Zubieta-Calleja, L., & Zubieta-Castillo, G. (2007). Altitude adaptation through hematocrit changes. Journal of Physiology and Pharmacology, 58(5), 811-818.