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Committeri Giorgia, Danilo Bondi, Carlo Sestieri, Ginevra Di Matteo, Claudia Piervincenzi, Christian Doria, Roberto Ruffini, Antonello Baldassarre, Tiziana Pietrangelo, Rosamaria Sepe, Riccardo Navarra, Piero Chiacchiaretta, Antonio Ferretti, and Vittore Verratti. Neuropsychological and neuroimaging correlates of high-altitude hypoxia trekking during the "Gokyo Khumbu/Ama Dablam" expedition. High Alt Med Biol . 23:57-68, 2022. Background: Altitude hypoxia exposure may produce cognitive detrimental adaptations and damage to the brain. We aimed at investigating the effects of trekking and hypoxia on neuropsychological and neuroimaging measures. Methods: We recruited two balanced groups of healthy adults, trekkers ( n  = 12, 6 F and 6 M, trekking in altitude hypoxia) and controls (gender- and age-matched), who were tested before (baseline), during (5,000 m, after 9 days of trekking), and after the expedition for state anxiety, depression, verbal fluency, verbal short-term memory, and working memory. Personality and trait anxiety were also assessed at a baseline level. Neuroimaging measures of cerebral perfusion (arterial spin labeling), white-matter microstructural integrity (diffusion tensor imaging), and resting-state functional connectivity (functional magnetic resonance imaging) were assessed before and after the expedition in the group of trekkers. Results: At baseline, the trekkers showed lower trait anxiety ( p  = 0.003) and conscientiousness ( p  = 0.03) than the control group. State anxiety was lower in the trekkers throughout the study ( p  < 0.001), and state anxiety and depression decreased at the end of the study in both groups ( p  = 0.043 and p  = 0.007, respectively). Verbal fluency increased at the end of the study in both groups ( p  < 0.001), whereas verbal short-term memory and working memory performance did not change. No significant differences between before and after the expedition were found for neuroimaging measures. Conclusions: We argue that the observed differences in the neuropsychological measures mainly reflect aspecific familiarity and learning effects due to the repeated execution of the same questionnaires and task. The present results thus suggest that detrimental effects on neuropsychological and neuroimaging measures do not necessarily occur as a consequence of short-term exposure to altitude hypoxia up to 5,000 m, especially in the absence of altitude sickness.

Bondi, Danilo, Vittore Verratti, Raffaella Nori, Laura Piccardi, Giulia Prete, Tiziana Pietrangelo, and Luca Tommasi. Spatial abilities at high altitude: Exploring the role of cultural strategies and hypoxia. High Alt Med Biol . 22: 157-165, 2021. Background: Over the past couple of decades, the number of people of different cultures traveling to places of high altitude (HA) increased. At HA, a decline in cognitive abilities has been described, including spatial skills. However, it is still unknown whether people accustomed to hypobaric hypoxia are less susceptible to cognitive decline. Method: We aimed to determine if three ethnic groups would show any difference in the performance of spatial abilities. Italian trekkers (46.20 ± 15.83 years), Nepalese porters (30.33 ± 8.55 years), and lowlander and highlander Sherpas (30.33 ± 8.55 and 37.00 ± 16.51 years) were tested with a building photograph recognition, a map orienting, and a mental rotation task during a Himalayan expedition. Accuracy and response times were collected at low altitude (LA) and HA. Results: Nepalese performed the worst (photograph task: p  = 0.015, η 2 p  = 0.36; map task: p  = 0.016, η 2 p  = 0.36), but the difference was mitigated after correcting for length of schooling. Participants took more time to respond at LA than in HA condition (photograph task: 24.0 ± 15.3 seconds vs. 12.7 ± 6.3 seconds, p  = 0.008, η 2 p  = 0.57; map task: 12.5 ± 1.8 seconds vs. 7.8 ± 0.6 seconds, p  = 0.038, η 2 p  = 0.40). In the map task, participants performed with greater accuracy at LA (5.1 ± 0.4 vs. 4.4 ± 0.4 number of correct responses, p  = 0.006, η 2 p  = 0.59). Conclusions: Altitude hypoxia elicited impairments in cognitive spatial tasks. This may be due to the inability to acquire new unfamiliar patterns, and to the difficulty in managing a high cognitive workload. The ethnic differences were ascribed to schooling, even we consider the different system of reference usually exploited in each culture (egocentric: dependent, or allocentric: independent from the personal viewpoint), and that Westerners are more likely to focus on specific details of the scene. Further studies should investigate the diverse strategies to complete spatial tasks.

Depending on the absolute altitude and the duration of exposure, a high altitude environment induces various cellular effects that are strictly related to changes in oxidative balance. In this study, we used in vitro isolated peripheral blood lymphocytes as biosensors to test the effect of hypobaric hypoxia on seven climbers by measuring the functional activity of these cells. Our data revealed that a 21-day exposure to high altitude (5000 m) (1) increased intracellular Ca(2+) concentration, (2) caused a significant decrease in mitochondrial membrane potential, and (3) despite possible transient increases in intracellular levels of reactive oxygen species, did not significantly change the antioxidant and/or oxidative damage-related status in lymphocytes and serum, assessed by measuring Trolox-equivalent antioxidant capacity, glutathione peroxidase activity, vitamin levels, and oxidatively modified proteins and lipids. Overall, these results suggest that high altitude might cause an impairment in adaptive antioxidant responses. This, in turn, could increase the risk of oxidative-stress-induced cellular damage. In addition, this study corroborates the use of peripheral blood lymphocytes as an easily handled model for monitoring adaptive response to environmental challenge.