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.
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METHODS
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.
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RESULTS
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.
Fig.1
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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.
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DISCUSSION
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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