The Effects of Short-Term and Long-Term Exposure to a High Altitude Hypoxic Environment on Neurobehavioral Function

Abstract

Zhang, Gang, Si-Min Zhou, Chao Yuan, Huai-Jun Tian, Peng Li, and Yu-Qi Gao. The effects of short-term and long-term exposure to a high altitude hypoxic environment on neurobehavioral function. High Alt Med Biol 14:338–341, 2013.— Aims: Examined the change in neurobehavioral function of individuals acclimated to high altitudes and those native to high altitudes. Methods: A neurobehavioral core test battery approved by the WHO (WHO-NCTB) was used to evaluate the effects of high altitude hypoxia on neurobehavioral function. The WHO-NCTB is composed of seven individual tests: a mood state profile, simple reaction time test, digit span test, Santa Ana manual dexterity test, digit symbol test, Benton visual retention test, and pursuit aiming test. Results: The values from the Santa Ana manual dexterity test, digit symbol test, and pursuit aiming test from sea-level subjects acclimated for 5 days at 3700 m were significantly decreased when compared with the same subjects at sea level. The values from the digit span, Santa Ana manual dexterity, digit symbol, Benton visual retention and pursuit aiming tests in subjects native to high altitudes of 3700, 4500, and 5100 m were significantly decreased when compared with subjects at sea level and compared with sea-level subjects acclimated for 5 days at 3700 m. Conclusions: These results demonstrate that high altitude hypoxia induces damage to neurobehavioral functions, and the long-term deficit in neurobehavioral function was more severe than the short-term changes.

Introduction

High altitude environments may have adverse effects on the normal functioning of people accustomed to living at low altitudes; these effects include high altitude cerebral edema, high altitude pulmonary edema, and fatigue (Frisancho, 1975; Peter et al., 2001). The central nervous system (CNS) is very sensitive to hypoxia, and oxygen consumption in the CNS is high (Erecinska and Silver, 2001). Ozaki et al. (1995) reported electroencephalogram (EEG) results showing that the slow wave gradually increased (fast wave decreased) with an increase in altitude and an aggravation of hypoxia. This change is similar to EEG results under anesthesia and indicates that an advanced part of the CNS is inhibited in the hypoxic environment. However, the effects that this hypoxia-induced inhibited state of the CNS has on the neurobehavioral function of individuals are unclear. In addition, Nelson et al. have demonstrated that some neurological behaviors, including decreased language expression and declines in motor conduction and memory, are induced at high altitudes by examining the behavior in climbers of Mount Everest (Nelson et al., 1990; Shukitt-Hale et al., 1994; Wesensten et al., 1993).

As the extension of time to enter the plateau, the various adaptive mechanisms enable both the lowland and highland native to overcome the adverse effects of high altitudes (Frisancho, 1975; Gao et al., 2001). Altitude acclimatization are mainly for stable vital signs (eg., the breathing rate, pulse, and blood pressure), and improvement of work ability (Gao et al., 2001). However, whether the neurobehavioral function will improve with acclimatization to altitude are unclear.

The present study aims to clarify the change of neurobehavioral function and compare the cognitive impairment between individuals acclimated to high altitudes and individuals native to high altitudes. Neurobehavioral test is commonly recognized as a sensitive and valid method for detecting cognitive dysfunction (Zhou et al., 2002). Thus, in the present study, the neurobehavioral test was chosen to evaluate the effects of cognitive function induced by high altitude hypoxia.

Materials and Methods

Subjects

One hundred and ninety-six healthy men were recruited for this study (Table 1). As shown in Table 1, there were five groups in the study. In the group of sea-level subjects, there were 46 healthy men from the plains area (altitude 300 m). After 5 days of acclimating these men to an altitude of 3700 m, they were treated the same as the sea-level subjects at high altitudes of 3700 m. There were 50 healthy men in the groups of individuals native to high altitudes of 3700, 4500 and 5100 m. The characteristics of subjects in the five groups are listed in Table 1.

Table 1.

Characteristics of the Subjects

	N	Ages (years)	Years of education
Sea-level subjects	46	20.41±1.58	11.69±1.44
#Sea-level subjects acclimated for 5 days at 3700 m^*	(46)	20.41±1.58	11.69±1.44
Subjects native to a high altitude of 3700 m	50	21.05±1.95	11.56±1.83
Subjects native to a high altitude of 4500 m	50	20.32±1.64	11.84±1.79
Subjects native to a high altitude of 5100 m	50	20.38±1.75	11.63±1.94

The sea-level subjects and sea-level subjects acclimated for 5 days at 3700 m are the same men. Subjects native to high altitudes of 3700, 4500, and 5100 m are different men. The values are expressed as the mean±SD.

Neurobehavioral core test battery evaluation

An evaluation of neurobehavioral function was conducted with the neurobehavioral core test battery (NCTB) approved by WHO, as previously described (Wang et al., 2006). The NCTB consists of seven individual tests: a mood state profile, simple reaction time test, digit span test, Santa Ana manual dexterity test, digit symbol test, Benton visual retention test, and pursuit aiming test. Mood state profiles were used to evaluate the recent emotion, and other tests in NCTB were used to evaluate cognitive function, including attention/response, speed, auditory memory, manual dexterity, perceptual motor speed, visual perception/memory, and motor steadiness of the subjects (Wang et al., 2006). In the present study, we evaluated the cognitive function with the NCTB.

Statistical analysis

All of the results are expressed as the mean±SD. The statistical significance of the differences was analyzed using SPSS software (SPSS for Windows 15.0, SPSS Inc., USA). Significant differences between sea-level subjects and sea-level subjects acclimated for 5 days at 3700 m were determined by paired t-test. Significant differences in the means at different altitudes were determined by one-way ANOVA, followed by a LSD t-test for multi-group comparisons. Probability values of p<0.05 were considered significant.

Results

Comparison of the results of the WHO-NCTB between sea-level subjects and sea-level subjects acclimated for 5 days at 3700 m

As shown in Table 2, significant differences were observed between the two groups in the tests for total digit span (p<0.01), dominant hand (p<0.01), nondominant hand (p<0.01), digit symbol (p<0.05), right dotting (p<0.05), and wrong dotting (p<0.01).

Table 2.

WHO-NCTB Results in the Test Groups

	A	B	C	D	E
Simple reaction time	0.69±0.08	0.70±0.07	0.67±0.09	0.67±0.08	0.68±0.09
Digit span
Forward digit span	12.22±1.56	11.61±1.37	11.71±0.61	10.26±2.68^**^††	10.97±1.57^**^†
Back digit span	8.37±2.25	7.93±2.19	6.89±3.08^**^†	6.48±2.54^**^††	6.48±1.90^**^††
Santa Ana manual dexterity test
Dominant hand	25.71±3.72	24.11±3.97^**	17.38±2.04^**^††	17.73±2.39^**^††	18.16±2.31^**^††
Nondominant hand	23.72±3.16	22.87±2.96^**	16.56±2.09^**^††	16.74±2.30^**^††	17.55±1.89^**^††
Digit symbol test	71.30±14.40	68.80±14.25^*	55.71±23.66^**^††	54.48±22.84^**^††	49.62±17.01^**^††
Benton visual retention test	7.98±1.27	7.76±1.18	5.58±1.82^**^††	4.61±1.91^**^††	5.83±1.47^**^††
Pursuit aiming test
Right dotting	145.43±22.01	140.88±20.47^*	106.11±24.57^**^††	109.26±15.53^**^††	107.52±17.37^**^††
Wrong dotting	11.10±4.08	13.94±5.95^*	10.98±4.59	11.53±4.57	9.22±11.39^†

A, sea-level subjects; B, sea-level subjects acclimated for 5 days at 3700 m. C, D, E, subjects native to high altitudes of 3700, 4500, and 5100 m, respectively. The values are expressed as the mean±SD (A,B: n=46; C–E: n=50). ^*p<0.05, ^**p<0.01 vs. A, ^†p<0.05 and ^††p<0.01 vs. B. The significance of the mean difference between A and B was determined by paired t-test. The significance of the mean differences of B–E and the differences of A, C–E was determined by one-way ANOVA, followed by a LSD t-test for multi-group comparisons.

The effects of a high altitude hypoxic environment on the WHO-NCTB results

To determine the effects of a high altitude hypoxic environment on the neurobehavioral function in the subjects, the NCTB tests were conducted to evaluate the differences between the test groups and control group (sea-level subjects) and the differences between subjects native to high altitudes of 3700, 4500, 5100 m, and sea-level subjects acclimated for 5 days at 3700 m. The differences as shown in Table 2, compared to group A, there were significantly declined on some aspects of neurobehavioral function in groups B, C, D, and E. Compared to group B, there were significant declines on some aspects of neurobehavioral function in groups C, D, and E.

Discussion

The objective of the present work was to determine the effects of short-term and long-term exposure to a high altitude hypoxic environment on neurobehavioral function. Therefore, the WHO-NCTB was administered to evaluate the attention/response, speed, auditory memory, manual dexterity, perception, motor speed, visual perception/memory, and motor steadiness in subjects (Wang et al., 2006; Yuan et al., 2006). The values of the Santa Ana manual dexterity test (dominant and nondominant hand), digit symbol test, and pursuit aiming test (right and wrong dotting) in the group of sea-level subjects acclimatized for 5 days at 3700 m were significantly decreased when compared with the group of sea-level subjects (p<0.05), which indicate that there are observable impaired in the neurobehavioral function of people who are introduced to a high altitude hypoxic environment for a short term.

As some researchers previously considered, with the entry of the plateau time prolonging, the body could gradually acclimate. However, in the present study, the values for the digit span (forward and back digit span), Santa Ana manual dexterity (dominant and nondominant hand), digit symbol, Benton visual retention, and pursuit aiming tests in the subjects native to high altitudes of 3700, 4500, and 5100 m were significantly decreased compared with the sea-level subjects acclimated for 5 days at 3700 m, respectively. These results suggested that the long-term deficit in neurobehavioral function was more severe than the short-term changes observed in the WHO-NCTB test. Recently, we conducted a questionnaire survey of 288 native residents at altitude of 3800–4700 m, and the results indicated that 63.3% subjects cannot concentrate and 70.21% subjects experience memory decline. This is similar to the results of the present study and indicated that long-term exposure to hypoxia environment contributed to the damage of neurobehavioral function. The results clearly demonstrated that exposure to hypoxia environment had damaged some aspects of neurobehavioral function, which suggests that the damage effects may decrease the efficiency of study and work by declined ability of learning, memory, and others. These results also suggested that neurobehavioral function might not be recovered by prolong residence time in high altitude, whereas it may be recovered through nutrition (Zhang et al., 2008), medicine (Liu et al., 1999), training (Zhao et al., 2005), and some other methods.

Many researchers have previously reported that brain disorders can be induced by high altitude hypoxic environments (Hackett and Roach, 2001; Michael, 1978; Ostadal and Kolar, 2007). The balance between the excitatory and inhibitory processes in the brain can be damaged by a hypoxic environment. Nerve conduction velocity is decreased and conduction in the visual and auditory systems and the functions of the central nervous system are affected (Chen et al., 1994; Zhang et al., 2004). These effects demonstrate that the structure of hippocampal neural synapses in rats in hypobaric and hypoxia conditions can lead to changes in the advanced functioning of the brain (eg, learning, memory, and thinking). In addition, many studies have shown that the ability to work, learn, think, react, and coordinate motor skills is decreased in long-term hypobaric and hypoxic environments (Shukit et al., 1996; Wu et al., 1998). Thus, the effect of a hypoxic environment on the morphosis, energy metabolism, and cognitive function of the brain may be the reason for the changes in neurobehavioral function observed in the subjects in the present study. In addition, researchers found that reactive oxygen species (ROS) can be generated in brain during exposure to hypoxia (Erecinska and Silver, 2001; Halliwell and Gutteridge, 1999). ROS is capable of inducing oxidative damage (Liu et al., 2007; Riley and Showker, 1991), which may be also one of the mechanisms for damage to neurobehavioral function. However, further studies to clarify the detailed mechanisms involved in the effects of short-term and long-term exposure to a high altitude hypoxic environment on neurobehavioral function are necessary.

Conclusion

The results obtained from this work are noteworthy, and our results demonstrate that a high altitude hypoxic environment can induce obvious damage to individuals' neurobehavioral function. The long-term deficit in neurobehavioral function was more severe than the short-term changes.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

This study was supported by the National Key Technology Research and Development Program of the Ministry of Science and Technology of China (No. 2009BAI85B06).

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