Introduction

The human brain, especially the cerebral cortex, is extremely sensitive and vulnerable to hypoxia . Oxygen supply is essential to maintaining the normal function of brain’s cognitive processes, which can be conceived as a hierarchy of several serial phases, from early sensory-perceptual stages, to higher-order cognitive processes (Mayevsky et al., 1986). Hypoxia, whether environmental or pathological, such as exposure to a hypobaric chamber or living at high altitude (HA), chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), has been found to broadly impact cognitive functions . Among them, HA is an important residential region for human beings. Despite thousands of years of struggle, hypoxia remains a significant public health problem. Extant studies have documented neurologic deficits, cognitive dysfunctions, and brain abnormalities, such as hallucinations under HA conditions , which directly impair people’s living quality and work efficiency and thus cannot be ignored. Exposure to HA provides a natural, convenient to observe, low-cost and reproducible model for studying hypoxia in healthy individuals, which not only has guiding significance on plateau activity, but also might provide new insights for understanding hypoxia in clinical settings.
A number of studies have shown that HA exposure exerts a range of deleterious effects on cognitive processes, verbal fluency, cognitive flexibility, executive function, metacognition, etc. (Taylor et al., 2016; Yan, 2014), while others indicating the presence of compensation mechanisms to help maintaining cognitive performances . The inconsistence across studies may be attributed to the cognitive domain being interrogated . Since the human brain is inherently plastic, its functional structure can be reorganized in response to environmental and physiological alterations , those cognitive processes, e.g. higher-order cognitive functions which involve the prefrontal lobe, may employ an adaptive process to compensate for the neurocognitive impairment and thus be less affected by hypoxia . Nonprefrontal lobe functions, such as visual perception processing, reaction time (RT) , perceptive discrimination, and color perception, demonstrated to be more sensitive to hypoxia and are critical for the brain in adaptation to HA (Chen et al., 2016), making it particularly suitable for monitoring hypoxia adaptation of cognitive processes, which may help us understand how the brain acclimates to harsh environments.
Previous studies indicated that brain electrophysiological activity in the visual cortex may explain the alterations in visual cognition . Among all visual inputs, face perception is one of the most developed visual perceptual skills of human beings, and it plays a major role in social interaction, which constitute the perceptual basis for interpersonal communication. Nevertheless, few studies have directly examined the neural processing of face information under HA hypoxia conditions. Perceptual organization refers to the process of integrating fragments of stimuli into a coherent pattern . ERPs are widely used in perceptual organization studies. P1 and N170 are universally recognized as two main face-sensitive brain potentials. The P1 component reflects the low-level processing of face perception . The N170 component is considered to index the perceptual categorization of faces , which reflects high-level face perception and the configural encoding of facial features as well as their integration into a holistic perception . As a crucial cognitive function, perceptual alteration under HA can help advance our understanding of the impact of HA hypoxia on nonprefrontal tasks.
After prolonged HA exposure, the individual experiences a series of physiological and biochemical adaptive responses, e.g., increases in oxygen-carrying hemoglobin levels and ventilation, vasodilatation, and so on, to compensate for hypoxia . Generally, the human beings could acclimatize to a new altitude in one to three months . This gradual acclimatization may counteract impaired cognitive performance during prolonged exposure to HA . However, the results have been remarkably mixed, with other studies reporting that the cognitive deficit under long-term hypoxia is more severe than the short-term hypoxia (Sharma et al., 2014; G. Zhang et al., 2013). Therefore, more empirical research is needed to provide convincing evidence on how prolonged exposure to high altitude environment affects cognitive processes.
Instead of settling in the plateau, many people return to sea level after short periods of hypoxic exposure at HA. HA deadaptation refers to the process of readaptation to a low-altitude environment involving a series of changes in neural function, metabolism or even structure in acclimatized HA residents. Physiological studies have shown that returning to sea level requires approximately one week for the arterial partial pressure of carbon dioxide (PCO2) to normalize . Biochemical parameters such as Hypersensitive C-reaction protein (hsCRP) and homocysteine returned to baseline level following return to sea level one month compared to baseline . Other evidences suggests deficits in neuropsychological functions may also last when sojourners return to sea level . A study investigated visual spatial and visual non-spatial discrimination abilities, found that the behavioral performances and ERP measurements returned to baseline three months after sojourners returned to the lowlands . Whether cognitive processes will recover accompanied by physiological alterations during HA adaptation and deadaptation has rarely been discussed. Investigating how cognitive processes change in the HA environment and the possibility of long-lasting deficits after returning to sea level could promote the understanding of our brain’s protective mechanism for survival and neuroplasticity, and ultimately pave the way for neuroprotection.
Summing up, high altitude hypoxia/reoxygenation changes the neuronal activity and physiological activities. Nevertheless, there are several limitations in existing literatures. Firstly, most studies adopt a cross-sectional design to compare HA residents or sojourners with matched sea-level residents, lacking the comprehensive depiction regarding alterations of cognitive processing under both HA adaptation and deadaptation conditions. Secondly, there are abundant studies concerning higher-order cognitive processes, while perceptual process is often ignored. Thirdly, there are limited studies using ERP methods, with high temporal resolution to index cognitive processing and provide insight into the dynamic neural mechanisms of cognitive processes, which are particularly suitable to monitor hypoxia adaptation.
To fill this knowledge gap, the present study adopted a S1-S2 paradigm to evaluate the underlying perceptual processes electrophysiological mechanisms of lowlanders who sojourned at an altitude and then returned to the lowlands. Based on previous research , we anticipated that after approximately four weeks of acclimatization to HA, compared with baseline in the lowlands, the heart rate (HR) and diastolic pressure (DBP) would be higher, while the peripheral capillary oxygen saturation (SpO2) would be lower; the N170 amplitude would be significantly increased, and the P1 and N170 latency would be significantly shortened in the HA environment. For the deadaptation process, we speculated that physiological and perceptual organization patterns persist as in the HA environment upon return to sea level after one week, but after one month, we expected them to return to baseline.