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.