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Original Article
Volume 47 - No.1:January 2003 (index)

Indian J Physiol Pharmacol  2003;

Effect of High Altitude (Ha) on Event Related Brain Potentials

Defence Institute of Physiology and Allied Sciences,
Lucknow Road, Timarpur,
Delhi -  110 054


(Received on February 24, 2002)


Abstract : Event Related brain potentials (ERPS) were recorded in 15 subjects using standard auditory odd ball paradigm, in which subjects were presented a sequence of two distinguishable sound stimuli of that occurred frequently (frequently (frequent stimulus-non target) and the other infrequently (rare stimulus - target).  These recordings were made at sea level (SL) and then the subjects were air lifted to 3500 in altitude (HA), where they stayed for 3 weeks.  Their ERPs were recorded during the first and third week of stay at HA and on return to sea level (RSL).  Data indicated impairment in cognitive function as a result of exposure to HA as depicted by increase in the latency of P3 which was significant during the 1st week of stay at HA compared to sea level.  The P3 wave latency during the 3rd week of' stay at HA showed an increase compared to SL but was not statistically significant.  From the results it may be concluded that high altitude hypoxia induced slow processing of stimulus evaluation, may be responsible for increase in P3 latency.  The difference in the latent period of' P3 waves during the first and third week of stay at HA may be due to continuous stay at HA which might lead to the time dependent adaptive processes occurring with increasing duration of' exposure to HA which may induce learning effects.

 Keywords : high altitude, P300, ERP, cognition, hypoxia



High Altitude hypoxic exposures have been  found to diminish cognitive performance (1, 2, 3 , 4). Human performance generally deteriorates abruptly during rapid ascent to HA while some people can successfully perform cognitive tasks even under extremely severe hypobaric hypoxia (5, 6, 7, 8).  The differences in responses may be attributed to different arousal levels, as indicated by electroencephalographic (EEG) activity (9, 10). However, it is not clear how the neuroelectric brain activities are directly related to cognitive deterioration or maintenance. Event related potentials (ERPS) especially P3 component is a good index which objectively quantifies the level of mental impairment as compared to other psychometric tests employed for assessing cognitive functions (11, 12, 13).  ERPs give an idea about the time course of information processing including expectancy, attention, cognition search, decision making and memorization (14).

For the auditory event related potential recording the subject is apprised with the sequence of two distinguishable stimuli, one of which occurs frequently (the frequently Stimulus) and the other which occurs infrequently (the rare stimulus).  The subject is required to count mentally or otherwise respond to one of the two stimuli.  The average response to the target stimulus consists of' two negative peaks designated as N1 and N2 along with two positive peaks P2, P3 or complex P2, P3 (13, 15). 

In the present study, the auditory event related potentials (ERPS) were recorded using odd ball reaction time paradigm.  The target stimuli were presented infrequently among a series of frequently appearing nontarget stimuli.  There is conflicting evidence on how hypoxia influences the latency of N1, P2, N2 waves, since increases have been reported with animal experiments (16, 17) but  not with humans.  The animal study raises the possibility that latency changes of early ERP components influence later components, such as P3 for reasons not directly connected with the slowing of' cognition.  N2 component is sensitive to the cognitive attributes of stimulus (18, 19) and is slowed down by hypoxia in humans (20, 21). Similarly P3 wave too may be getting affected by hypoxia in humans (22, 1).  

The P3 component is an endogenous ERP considered to reflect the time required to evaluate a stimulus, rather than the required to respond to it (23).  Studies carried out by Fowler et al (24) suggested that hypoxia increases the latency of both reaction time (RT) and P3 in a correlated and dose dependent manner.  Fowler and Kelso (22) compared the patterns of changes for N1 and P2 to that of P3 of auditory ERPs and demonstrated that the preprocessing stage of stimulus evaluation is slowed down by hypoxia (induced by inhalation of gas mixture) and both P3 and P2 index this slowing.  They produced acute hypoxia by low oxygen mixtures, which were adjusted to produce SaO2 level of 65%.  Most of the studies reported have been done either in simulated high altitude Hypobaric chamber or hypoxia has been produced by inhalation of gas mixtures where hypoxic exposure was for a limited duration.  There is hardly any study available where ERPs have been recorded in actual high altitude environmental conditions, where subjects are exposed to hypobaric hypoxia continuously.  It is therefore important to understand the effect of chronic HA hypoxia on cognitive functions in the actual field conditions.  The present study was undertaken to investigate the effect of long term stay at 3500 m altitudes in the Western Himalayas on cognitive functions.


The study was carried out on 15 healthy male volunteers in the age group of 21-25yrs.  The participants had no previous exposure to high altitude.  Clearance from the Ethics committee of Institute was obtained.  All the subjects had thorough ENT check-up including audiometry to find out any ear pathology affecting hearing.  The procedure was explained to the subjects in detail and their written consent was obtained.  The event related potentials were recorded at sea level (SL), high altitude (HA) and on return to sea level (RSL).  The ERPs were recorded in the morning from 0900 hrs to 1300 hrs at SL, HA and RSL.  The sea level recordings were carried out at Delhi. The subjects were airlifted to an altitude of 3500 m (HA) in the Western Himalayas where they stayed for a month and were transported back to sea level (RSL).  At HA the ERPs were recorded in the 1st and 3rd week.

Recording of ERPs

The recordings were carried out in an air-conditioned laboratory with background noise attenuation.  The ERPs were recorded using the prefixed program of Nicolet Compact-4 System.  P3 was measured from the vertex (CZ and PZ) in response to random stimuli presented mono-aurally through headphones applied to the subject's ear.  The ground electrode was placed at FPZ. The input impedance was kept below 5 k Ohms.  Standard auditory odd ball paradigm was used.  In this paradigm design, the subject was presented a sequence of two distinguishable sound stimuli, one of which occurred frequently (frequent stimulus non-target) and the other infrequently (rare stimulus-target).  The subjects were instructed to count whenever a target, infrequent stimulus was presented.  Alternating tone bursts with 100 µsec duration (plateau time), intensity 70 dB were used.  Eighty percent of total stimuli were frequent and 20% were rare.  The stimulus sequence was random.  The Nicolet-4 settings were properly selected and evoked responses to the rare stimuli were filtered with a band pass 1-30 Hz and averaged.  The latency of N1, P2, N2, P3 and amplitude of waves P2 and P3 for target stimuli (rare) were calculated.  In case any trial contained more than 10% artifacts, the entire trial was rejected.  In this manner only artifact free data was used in the final analysis.  The responses to the frequent and rare stimuli were averaged.  The wave form pattern was replicated.  The different wave form latencies and amplitudes were calculated.  The latency of the largest positive potential occurring between 300 m sec and 500 m sec was designated as P3 component and for N1, P2 and N2 components latency windows were 75-175, 150-260 and 190-360 msec respectively.  Amplitude (µv) was measured relative to the pre stimulus baseline.  During recording session, subject was instructed to fix his eyes on a particular spot on the roof or wall to avoid electro-oculographic artifacts due to eye movements and improve his concentration and attention to the stimuli presented.  Data were tabulated and computed by using epistat software package for various statistical measures.  Two-way ANOVA was applied to find out the level of significance.


Figure 1 shows the representative wave form of ERPs recorded at SL and on induction to HA during 1st and 3rd week of the stay from a subject.  Table I shows the changes in the latencies of waves N1, P2, N2 and P3 and amplitude of P2 and P3 waves at sea level, during the 1st and 3rd week of stay at HA (3500 m) and on return to sea level.


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Fig. 1: Tracing of P300 waveform recorded from a subject at sea level (SL). 1st week and 3rd week at high altitude. Please note the increase in the P3 latency at high altitude.

The results indicate no statistical significant changes in N1, P2 and N2 wave latencies and in the amplitude of P2 wave during 1st and 3rd week of their stay at  HA as compared to the SL values.  The latency of P3 wave recorded an increase during 1st and 3rd week of stay at HA as compared to SL values.  The P3 wave latency increased from SL value of 321.92 ± 23.67 ms to 337.28 ± 22.62 ms during the 1st week of recording and this increase was statistically significant (Table I).  Similarly P3 wave latency during the 3rd week was 330.55 ± 25.97 ms, which was higher than the SL value of 321.92 ± 23.67 ms but this increase was not significant statistically (Table I).  On return to SL all the mean values of latencies of wave N1, P2, N2 and P3 came back to values recorded at SL before induction to HA.. There was no significant difference between SL and RSL values of the ERPs. 

There was variation in the amplitude of P2 and P3 waves at 1st and 3rd week of recordings at HA as compared to the SL values which were not significant statistically (Table I).  The amplitude of' P3 wave at SL was 13.73 ± 5.35 mv and during 1st and 3rd week was 15.58 ± 6.17 mv and 13.50 ± 4.69 mv respectively.  The amplitude of P2 and P3 wave came back to near SL values on return from HA.

Table I

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Table I: Event related potentials on induction to high altitude.



The results indicate deterioration in the cognitive processes involved in stimulus evaluation, when the subjects were inducted to high altitude (hypobaric hypoxia) of 3500 m as evident from increase in P3 wave latency at HA as compared to the sea level (Table I).  It is well known that hypoxia impairs cognitive function in a linear fashion with increasing altitude (25).  In the present studies we have recorded ERPs during the first and third week of stay at HA. Among other physical variables, high altitude is characterized by hypobaric hypoxia though we did not measure oxygen saturation but data suggest that at heights more than 3000 m, there is a decrease in arterial oxyhaemoglobin saturation (SaO2) and physiological disorders known as acute mountain sickness (AMS) appear.  AMS symptoms include breathlessness, headache, insomnia, dizziness and abnormal tiredness (26, 27).  Exposure to HA also induces behavioural and mood disturbances and alteration in cognitive functions like mental and reasoning processes and psychosensorimotor skill (28, 29, 30).

The results of the present study indicate an increase in the latency of P3 wave during the 1st and 3rd week of stay at HA as compared to SL.  The P3 component of ERPs reflects the processes of stimulus evaluation or categorization (8, 31, 32).  The N2 preceding P3 may directly affect the absolute timing of decision processes in sensory discrimination (18, 19).  Moreover changes in an earlier component of the N1 and P2 vertex complex, reflecting an initial selection or selective attention of a stimulus (33), may be related to impaired reaction times.

On induction to HA, all HA induced symptoms are generally more severe during the 1st or 2nd day and recede rapidly thereafter but reappear if up hill climbing continues at rapid pace thereafter (34).  The symptoms, their severity, rapidity of onset and duration vary between individuals and are related to both the altitude and the rate of ascent (35).  The difference in the latency of P3 wave when recorded during the first and third week of stay at HA in the present study may be due to the time dependent adaptive processes occurring with increasing duration of exposure to high altitude which may induce learning effects and thus improve performance (34,36). The decrements in mental functions may be greater than those in psychomotor functions and complex decision processes are affected more than simple decision processes (36).

We did not find any change in the latency of N2 wave at HA as compared to SL while another study (22) has reported an increase in latency of N2 waves.  The differences in findings may be due to difference in severity of hypoxia to which subjects were exposed (Takagi and Watanabe, 37), who recorded contingent negative variation (CNV) and examined its relationship with changes in reaction time under hypobaric conditions.  The study showed that recognition of stimulus is affected by acute hypoxia.  In these studies subjects were exposed to simulated hypobaric hypoxia varying between 0 – 6000 m.  The findings of the present study are in line with the other researchers who have reported an increase in the latency of P300 wave (20, 21, 1).  Moreover changes in the latency of P300 cannot be explained by a generalized slowing of the ERP wave form, since N1 and N2 did not slow down by hypoxia. 

It may be concluded that HA exposure brings about impairment in cognitive function as indicated by increase in the latency of P3 wave.  The increase in latency of P3 wave may be due to the slower processing of the stimulus evaluation because of high altitude hypoxia.


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