健康与遗传心理学研究室知识库

全世界有大量人群生活在高原上。高原具有低氧、低压、寒冷、强紫外线辐射和湿度低等特殊环境。不同高原人群的低氧适应涉及高原环境与人类进化、遗传、生长发育、生理功能和疾病状态等许多问题。已有的研究在呼吸、心血管和血液系统揭示了高原适应的机制。呼吸和心血管系统受中枢神经系统的调控，它们功能的适应性改变必然反馈作用于脑内调节中枢和相关环路。另一方面，大脑皮质对低氧十分敏感，低氧直接影响脑细胞的代谢，导致结构和功能的改变。然而，目前为止，世居高原人类适应的脑调节机制目前尚不清楚。高原环境脑适应后，它的高级功能的改变也有待阐明。另外，中度海拔是高原人口最密集的地区，每年有许多人到这些地区旅行或工作。因此，了解高原环境低氧对人类认知能力有何影响也显得十分重要。

本研究运用活体结构和功能磁共振成像和分析技术，包括基于像素的形态测量CVoxel-based Morphometry, VBM)、弥散张量成像(Diffusion tensor imaging, DTI )结合定量各向异性分数(fractional anisotropy } FA)的分析、基于血氧水平依赖(BOLD)的任务刺激功能磁共振(fMRI )和静息状态fMRI扫描和细胞活动分析，选择世居海拔2616-4200米高原的汉族人群为研究对象，通过与海平而对照人群比较，对世居高原环境人类脑结构、神经细胞活动和功能连接进行了观察。对世居高原和长期慢性中度海拔高原生活人群的认知能力测试包括长时(内隐和外显)和短时记忆、反应时和视觉空间构建。

结果发现，高原环境适应后脑因灰质丢失而导致局部密度降低。这些区域集中在双侧前额叶、双侧岛叶前下端、右侧扣带前回和枕计卜皮质。通过计算FA值发现，右侧扣带后部FA值显著降低，而双侧内囊前支FA值明显升高。高原人群脑神经细胞在没有任务刺激的静息状态下低频活动的同步性在不同脑区表现增加或降低。通过最大吸气任务刺激的功能磁共振研究发现，与平原对照组比较，呼吸相关中枢岛叶前下端的激活在高原人群显著降低。进一步研究揭示，岛叶前下端与中央前后回皮质的功能连接增强。与平原人群比较，世居高原人群在工作记忆，执行能力，反应时和内隐记忆方面能力降低。脑结构和功能的改变是这些认知能力下降的神经基础。长期慢性高原暴露人群仅在视觉构建能力方面轻微减弱。

本研究提示，高原环境适应伴随着局部脑结构和功能的改变。其中，岛叶的结构改变可能参与高原呼吸的适应调节。这种脑的适应性变化以认知能力的损害作为代价。长期慢性中度高原暴露仅轻微影响认知能力。

There were a number of people living at high altitude (HA). At altitude, several environmental challenges are encountered. Physiological stress includes hypobaric hypoxia, cold, UV rays from the sun, and dehydration. Adaptation to high altitude is important for human evolution, heredity, development, and disease. Adaptive changes in respiratory and cardiovascular responses have been well clarified. The brain is the control centre of the body. It controls the cardiovascular system and respiratory system and in turn the functional changes in the cardiovascular system and respiratory system may act on their control centre through afferent feedback. In addition, human brain is very sensitive to hypoxia. At high altitude, it inevitably suffers from hypoxic stress. Regrettably, up to now, how the brain of natives adaptation in structure and function to high altitude and whether there are cognition changes remain unclear.There were many people in the world traveling to mild altitude for short to moderate periods of time every year. Therefore, it is necessary to know the effects of hypoxia at high altitude on human cognitive performance. Using both structural MRI, including Voxel-based Morphometry (VBM) analysis, diffusion tensor imaging with fractional anisotropy (FA) calculation, and fMRI, we investigated Han residents who had been born and raised at HA between 2616 and 4200 m. VBM analyzed showed that the HA natives loss their gray matter (GM) relative to the SL controls in the bilateral anterior insula, bilateral prefrontal cortex, right anterior cingulate gyrus, and right occipital gyrus. There was a lower FA value in the right posterior cingulum and higher FA in bilateral anterior limb of internal capsule in HA subjects compared with SL controls. The HA natives showed significant increased ReHo in pon, left parahippocampus, cerebellum, right hippocampus, bilateral inferior frontal cortex, right posterior insula, left caudate nucleus and medial precentral cortex, and lower in thalamus, middle frontal cortex, left posterior cingulate cortex, right superior frontal cortex,right postcentral cortex, left precuneus, and right precentral cortex, compared with that of SL group. Using fMRI, we found that maximal inspiration in supine position, a task that induces dyspnea, activated the anterior insular cortices and that the bilateral activations in the insula were significantly decreased in the HA subjects compared to the SL controls. Employing fMRI connectivity analysis, we found that, during a resting state when no behavioral task being engaged, there were significant increases in the correlation of the fMRI signals between the insula and both the precentral and postcentral cortices in the HA subjects relative to the SL controls. The cost of those changes is cognition impairments in working memory, executive function, reaction time, and implicit memory. We concluded high-altitude acclimatization at a cost of gray matter loss and white matter change in some areas, with cognitive performance deficits. We suggest that specific changes in the cerebral cortex, especially in the insula, may contribute to ventilatory acclimatization to HA. Long-term hypoxic exposure at mild altitude has minimal effects on human cognition.