TABLE 1.
Brain structures in high altitude (HA) people.
| References | Location (altitude (m), duration) | Group: number (M/F) | Age (years) | MRI (scanning sequence, magnetic field intensity) | Analysis | Changed structures of the brain regions |
| Di Paola et al., 2008 | Everest or K2 (7500), 15 days | HA: 9 (9/0) world-class mountain climbers | 37.9 (31–52) | T2, T1, FLAIR at 1.5 T | Whole brain analysis | Reduced GM volumes in the left angular gyrus (p = 0.003) Reduced WM volumes in the left pyramidal tract near the primary and supplementary motor cortex (p = 0.002). |
| SL:19 | ||||||
| Kottke et al., 2015 | Mount Himlung Himal (7126), 23 days | HA: 38 (20/18) climbers longitudinal | 45.4 (24–69) | FLAIR, SWI, MDEFT at 3.0 T | Whole brain analysis | Increased cerebrospinal fluid (0.34% [95% CI 0.10–0.58], p = 0.006) Reduced WM fraction reduction (−0.18% [95% CI –0.32–−0.04], p = 0.012). GM fraction remained stable (−0.16% [95% CI −0.46–0.13], p = 0.278). |
| Zhang et al., 2012 | 6206, 30 days | HA: 14 (8/6) climbers longitudinal | 21 (19–23) | T1, DTI at 1.5 T | Whole brain analysis | No significant regional changes in GM and WM volumes; Decreased FA in the bilateral corticospinal tract, corpus callosum, reticular formation of dorsal midbrain, left superior longitudinal fasciculus, right posterior cingulum bundles, and left middle cerebellar peduncle (p < 0.05); Increased RD in the left superior longitudinal fasciculus within the inferior parietal lobule (p < 0.05). |
| Foster et al., 2015 | Ev-K2-CNR Pyramid Laboratory (5050), 3 weeks | HA: 7 (5/2) longitudinal | 31.8 | T1, T2, FLAIR, SWI, CVR at 3.0 T | Whole brain analysis | Decreased whole brain volume (+ 0.4 ± 0.3%, P < 0.01); Decreased GM volume (−2.6 ± 1.0%, P < 0.01); No changed in WM; Increased CVR in the brainstem (+ 30 ± 12%), hippocampus (+ 12 ± 3%), and thalamus (+ 10 ± 3%) |
| Verges et al., 2016 | Mont Blanc (4350), 6 days | HA: 11 (11/0) longitudinal | 28 | T1, DWI, ASL at 3.0 T | Whole brain analysis | Not change in GM; Increased WM volume (+ 0.7 ± 0.4%, p = 0.005) and diffusion (+ 1.7 ± 1.4%, p = 0.002); Reduced cerebrospinal fluid volume (–1.4 ± 1.1%, p = 0.009). |
| Chen X. et al., 2017 | Lhasa (3650, Tibet), 0/1/2 years | HA: 69(48/21) longitudinal | 18 (17–20) | T1, rs-fMRI at 3.0 T | Whole brain analysis | Decreased GM volume in the left putamen (p < 0.05). |
| Zhang et al., 2010 | Qinghai-Tibet Plateau (2616–4200), natives | HA: 28(12/16) SL: 28(12/16) |
20.4 (17–22) 20.9 (17–23) |
T1, DTI at 3.0 T |
Whole brain analysis and ROI | Decreased GM in the bilateral anterior insular cortex, right anterior cingulate cortex, bilateral prefrontal cortex, left precentral cortex, and right lingual cortex (p < 0.01); Higher FA in the bilateral anterior limb of internal capsule, bilateral superior and inferior longitudinal fasciculus, corpus callosum, bilateral superior corona radiata, bilateral anterior external capsule, right posterior cingulum, and right corticospinal tract (p < 0.05). |
| Zhang et al., 2013b | Qinghai-Tibet Plateau (2300–4400), 2 years | HA: 16 (16/0)Tibetan SL: 16(16/0) |
20 (20–22) 20 (17–22) |
T1, DTI at 3.0 T |
Whole brain analysis | No changes in total volumes of GM, WM, and cerebrospinal fluid. Decreased GM volumes in the right postcentral gyrus and right superior frontal gyrus, while increased GM in the right middle frontal gyrus, right parahippocampal gyrus, right inferior and middle temporal gyri, bilateral inferior ventral pons, and right cerebellum crus1(p < 0.05); Decreased CT in the right superior frontal gyrus (p < 0.001). |
| Zhang et al., 2013a | Qinghai-Tibetan Plateau (2900–4700), Tibetan | HA: 21(6/15) Control: 21(6/15) |
16.5 (15–18) 16.3 (15–18) |
T1, DTI at 3.0 T |
Whole brain analysis | Increased GM volume in the left insula, left inferior parietal gyrus, and right superior parietal gyrus (p < 0.001); decreased GM in the left precentral cortex and multiple sites in cerebellar cortex (p < 0.001); decreased WM volume was found in the right superior frontal gyrus (p < 0.001). Higher FA in a broad range of brain areas (p < 0.05). Decreases MD in most WM tracts (p < 0.05). |
| Fan et al., 2016 | Dangxiong city (4300, Tibet), 30 days | HA: 31 (16/15) Control: 21 |
19.7 | T1,T2, DTI at 3.0T | Whole brain analysis | Decreased cortical thickness in the bilateral superior frontal gyrus, rostral anterior cingulate gyrus, superior parietal gyrus, supramarginal gyrus, and insula, left fusiform gyrus, and right inferiorparietal gyrus and increased in the bilateral pericalcarine gyrus and precentral gyrus (p < 0.05). Increased curvature was significantly in the bilateral precentral gyrus, superior frontal, supramarginal gyrus, inferior frontal gyrus, paracentral lobule, precuneus, superior parietal cortex, temporal gyrus, parahippocampal gyrus, insula, and fusiform gyrus and decreased in the postcentral gyrus and right cingulate gyrus (p < 0.05). Increased NBV (p < 0.001), GMV (p = 0.003), and WMV (p < 0.001). |
| Wei et al., 2017 | Qinghai- Tibet Plateau (2300–5300), Tibetan | HA: 77(34/43) Control: 80(34/46) |
14–18 14–18 |
T1,T2 at 3.0 T |
Whole brain analysis | Decreased CT in the left posterior cingulate cortex, lingual gyrus, superior parietal cortex, precuneus, rostral middle frontal cortex, right medial orbitofrontal cortex, lateral occipital cortex, precuneus, and paracentral lobule (p < 0.05); Decreased curvature in the left superior parietal cortex and right superior marginal gyrus; Increased depth of sulcus in the left inferior temporal gyrus, while decreased depth of sulcus in the right superior marginal gyrus, superior temporal gyrus, and insular cortex (p < 0.05). |
| Chan et al., 2012 | 3600, a few hours | A men | - | T1, magnetic field intensity unknown | Directly observe | He was confirmed ischaemic infarcts in the medial left occipital lobe and left thalamus. |
| Fayed et al., 2006 | Mt. Everest (8848), Mt. Aconcagua (6959), Mont Blanc (4810), Mt. Kilimanjaro (5895) | HA: 35 climbers SL: 20 |
33.8 (22–46) | T1,T2, FLAIR at 1.5 T | Directly observe | Only 1 in 13 of the Everest climbers had a normal MRI; the amateur showed frontal subcortical lesions, and the remainder had cortical atrophy and enlargement of Virchow-Robin spaces but no lesions. |
| Garrido et al., 1993 | 7000 | HA: 26 SL: 21 |
35 (25–42) | T2 at 1.5 T | Directly observe | Almost half of the climbers showed MRI abnormalities (46%), 5 subjects had cortical atrophy. |
| Garrido et al., 1995 | Over 7500 | HA:9(7/2) | 34 | T1,T2, magnetic field intensity unknown | Directly observe | Five climbers MRI abnormalities (high signal areas, cortical atrophy). |
| Garrido et al., 1996 | Over 8000 | HA: 7 natives 21 lowland elite climbers SL:21 |
33 31 |
T1,T2 at 1.5 T |
Directly observe | Thirteen of lowland climber (61%) and 1 Sherpa (14%) showed MRI abnormalities (mild cortical atrophy, high signal areas in the white matter) |
| Anooshiravani et al., 1999 | Over 6000 | HA:8(8/0) climbers | 31–48 | T1,T2 at 0.5 T |
Directly observe | Did not observe the changes in brain imaging. |
| D’Arrigo et al., 2019 | 4000, 36 h | A women | 50 | FLAIR, DWI, magnetic field intensity unknown | Directly observe | Showed abnormal hyperintense signaling in the right insular lobe and smaller similar lesions in the right temporal lobe and in the contralateral insular lobe. |
| Miyamura et al., 2007 | 3700 | A women | 71 | T1, magnetic field intensity unknown | Directly observe | Revealed localized lesions at the globus pallidus, bilaterally. |
| Chen et al., 2019a | Lhasa (3650, Tibet), 2 years | HA: 49(32/17) longitudinal SL:49(32/17) |
17–20 17–20 |
T1,DWI at 3.0 T | Whole brain analysis | FA increased in the regions of right posterior corona radiate, anterior corona radiate, splenium of corpus callosum, decreased in the regions of superior longitudinal fasciculus, right anterior limb of internal capsule, body of corpus callosum (p < 0.05). |
| Chen et al., 2019b | Lhasa (3650, Tibet), 2 years | 69 | 17–20 | Rs-fMRI at 3.0 T |
Whole brain analysis | The regions with highest contributions to the predictions of psychomotor function were bilateral putamen and bilateral pallidum (p < 0.05). |
| McGuire et al., 2016 | U.S. Air Force U-2 pilots(8534–914) | HA:102 (100/2) SL:114 (109/5) |
37.9 (28–50) 34.9 (26–50) |
T1, FLAIR DTI at 3.0T | Whole brain analysis | Pilots had higher FA values in the fronto-occipital tract where FA values positively correlated with visual-spatial performance scores (p < 0.05). |
| Chen et al., 2016 | Qinghai-Tibet Plateau (2300–4400),2 years | HA: 16 SL: 16 |
20.5 (19–22) 19.9 (19–22) |
Whole brain analysis at 3.0 T |
DTI | Increased the path length of the commissural fibers connecting homotopic visual areas (p < 0.05). |
| McGuire et al., 2013 | high-altitude U-2 pilots | HA:102 SL:91 |
37 (28–50) 36 (28–50) |
T1,T2 at 3.0 T |
Whole brain analysis |
U-2 pilots demonstrated an increase in volume (394%; p = 0.004) and number (295%; p < 0.001) of WM hyperintensities. |
| Guo et al., 2020 | Lhasa (3650, Tibet),Tibetan | HA:135(62/73) | 19.9 (17–23) | T1, DTI at 3.0 T |
Whole brain analysis and ROI | No significant effects were observed for any SNP on any global or intermediate metric from any type of structural and functional network in Tibetan participants (p > 0.05). Positive correlation for the GAS over all 45 HA adaptive SNPs with inter-module communication scores between the right frontal and parietal module and the left occipital module (r = 0.283, p < 0.05). |
| Kühn et al., 2019 | 4554, 12 h and 7 days | HA:10(5/5) longitudinal | 41 | T1, magnetic field intensity unknown | Whole brain analysis | 12 h after descent HA had increased GM and WM (p < 0.05). 7 days after descent HA increased cerebral tissue volume changes in the paracentral gyrus region, postcentral gyrus, thalamic area of the left brain; and putamen (p < 0.05). |
| Chen X. et al., 2017 | Qinghai-Tibet Plateau (4200), 4 weeks | 29 longitudinal | 20 (19–21) | QSM, DTI at 3.0 T |
ROI | Increased iron concentration in basal ganglia, including caudate nucleus, putamen, globus pallidus and substantia nigra; FA increased and the MD decreased after HA exposure in caudate nuclei, putamen, globus pallidus, substantia nigra, red nucleus, dentate nucleus, with linear dependence on iron concentration only in putamen. |
| Yan et al., 2010 | Qinghai-Tibet Plateau (2616–4200), 20 years | HA: 28(12/16) SL:28(12/16) |
20 (17–24) 20 (18–24) |
T1,DTI at 3.0 T |
Whole brain analysis and ROI | Decreased GM volume at bilateral anterior insula, bilateral prefrontal cortex, the left precentral, the left cingulate and the right lingual cortex (p < 0.01). Decrease of the FA value in the right posterior cingulum and the right precentral cortex (p < 0.01). |
M, male; F, female; CT, cortical thickness; DWI, diffusion-weighted imaging; DTI, diffusion tensor imaging; FA, fractional anisotropy; FDR, false discovery rate; FLAIR, fluid attenuated inversion recovery; FWE, family wise error; GM, gray matter; MD, mean diffusion; MRI, magnetic resonance imaging; QSM, quantitative susceptibility mapping; RD, radial diffusivity; TBSS, tract-based spatial statistics; VBM, voxel-based morphometry; WM, white matter; T, tesla.