Developmental Science 9:4 (2006), pp 400–410

Human behaviour and development under high-altitude

Blackwell Publishing Ltd

conditions
Javier Virués-Ortega,1 Eduardo Garrido,2 Casimiro Javierre3 and
Karen C. Kloezeman4
1. Department of Personality, Assessment and Treatment, Universidad de Granada, Spain
2. Sports Medicine & Exercise Physiology Unit, Hospital General de Catalunya-Capio, St Cugat, Spain
3. Department of Physiological Sciences, University of Barcelona, Spain
4. Department of Psychology, University of Hawai’i at Manoa, USA

Abstract
Although we are far from a universally accepted pattern of impaired function at altitude, there is evidence indicating motor,
perceptual, memory and behavioural deficits in adults. Even relatively low altitudes (2500 m) may delay reaction time, and impair
motor function. Extreme altitude exposure (>5000 m) may result in more pronounced impairment that can persist after returning
to the lowlands. Research into the effects of altitude exposure earlier in development is lacking by comparison. Un-acclimatized
children can suffer from acute mountain sickness, and, in native populations born at altitude, subtle cognitive and behavioural
deficits suggest incomplete adaptation to hypoxia. The study of neurobehavioural functioning at altitude may provide important
information about the effects of clinical hypoxia on the human brain and behavioural development.

Introduction High-altitude mountaineering continues to provide an

Neurobehavioural functioning at altitude has received
relatively little attention within the hypoxia literature,
but against the background of physiological insights over
centuries, research into the cognitive and behavioural
effects of high altitude exposure has shown considerable
recent development. Jose de Acosta, a Spanish Jesuit,
visited the Andean highlands and gave the first account
of mountain sickness in his book, Historia Natural y
Moral de las Indias (Acosta, 1590). However, a descrip-
tion of the neurological presentation of acute mountain
sickness (AMS) is attributed to Thomas Ravenhill (1913),
a British surgeon working in the mines of northern
Chile. Janssen (1890) described how the effort needed to
think was increased by physical exercise while ascending
Mount Blanc. Other anecdotal references have appeared
in the literature, particularly in the descriptions by
alpinists in classic Himalayan expeditions (e.g. Dunlap,
1918; Ruttledge, 1934; Shipton, 1943; Wilmer & Berens,
1918). For instance, alterations in perceptual, memory
and metacognitive processes are described in Herzog’s
Annapurna narration, the first 8000 m summit to be
ascended (Herzog, 1952).
important opportunity for research, but the natural set-
tings of these studies can result in inconsistent method-
ology and care is required in the analysis of the existing
literature (Bahrke & Shukitt-Hale, 1993; Virués-Ortega,
Buela-Casal, Garrido & Alcázar, 2004). Indeed, the
cognitive and behavioural changes described in these early
narratives have been subjected to more rigorous scientific
investigation. Perhaps the first investigator to apply experi-
mental psychology methods in the study of the effects of
altitude and oxygen deprivation was Ross A. McFarland
(1901–76). He observed only minimal impairment at low
altitudes, while more complex processes such as arithmetic
and decision-making were increasingly affected with ascent
to higher altitudes (see Table 1) (McFarland, 1932, 1937,
1972). These seminal papers provided the impetus for
subsequent studies investigating the effects of altitude
exposure on motor, memory and ‘frontal-lobe’ function
in adults (see Virués-Ortega et al., 2004, for review). Our
understanding of the pathophysiological effects of altitude
exposure has also benefited from clinical and experimental
models of short-term hypoxia adaptation such as
obstructive sleep apnoea (OSA), hypoxia induced in
hypobaric chambers, or by hypoxic gas mixtures.

Address for correspondence: Javier Virués-Ortega, Centro Nacional de Epidemiología, Instituto de Salud Carlos III, C/Sinesio Delgado, 6, 28029
Madrid, Spain; e-mail: virues@ugr.es

© 2006 The Authors. Journal compilation © 2006 Blackwell Publishing Ltd, 9600 Garsington Road, Oxford OX4 2DQ, UK and
350 Main Street, Malden, MA 02148, USA.
 Human behaviour and development under high-altitude conditions 401

Table 1 Cognitive capabilities as a fraction of sea-level Nieremyer, Lindgren, Hohigman, Strain & Cairns, 2003).
performance for unacclimatized subjects according to Of greater concern, there is also an increased risk of
McFarland (1972) sudden infant death syndrome (Kohlendorfer, Kiechl &
Altitude Visual Attention Short-term Arithmetic Decision
Sperl, 1998). Taken together, these findings suggest that
(m) sensitivity span memory ability making exposure to altitude is not without risk in the very
young.
2500 83% 100% 97% 100% 100%
3500 67% 83% 91% 95% 98%
In this review, we describe first the physiological
4200 56% 70% 83% 92% 95% processes that occur during human adaptation to high
5000 48% 57% 76% 86% 90% altitude and the effect on motor, perceptual and cogni-
Note: Adapted from McFarland, 1972.
tive function in adults. Secondly, we review the sparse
evidence for the neurobehavioural effects of altitude
exposure in infants and children, describing those studies
investigating AMS alongside studies of native populations
who were born at altitude.

Biological responses to high altitude

The proportion of atmospheric oxygen remains constant

Figure 1 World locations of studies on cognitive and
behavioural impairments due to altitude exposure in children
and adults.
Note: Grey stains portray world areas with extensive regions located ≥ 2500 m
above sea level (modified with permission: Globalis map generator from Global
Virtual University – United Nations University). Green diamonds represent
studies with adults and red circles represent studies with children. Database
search: Medline (1980 – 2005): Mountaineering [MESH] OR Altitude [MESH] OR
Altitude [TI]; PsycInfo (1980–2005): ‘Altitude’ (Keyword or Title) or ‘hypoxia’
(Keyword or Title). Additional references were retrieved from the reviews by
Bahrke and Shukitt-Hale (1993) and Virués et al. (2004). Only empirical studies
testing cognitive and behavioural effects of real altitude in children (age 0–18)
and adults (age above 19) were included. Case reports, retrospective studies,
simulated altitude studies (hypobaric chamber, gas mixture, aircraft travel) and
studies with animals were excluded. Thirty-three studies were found; the location
of two studies was unknown.
While research into the neurobehavioural effects of
altitude exposure in adults has thus progressed, the
impact on the developing brain is relatively unknown, as
very few data have been reported in infants and children
(see Figure 1). It is apparent that lowland children may
display symptoms of AMS (e.g. headache, vomiting,
insomnia and cognitive alteration; Hackett, 1999; Hackett
& Roach, 2001) when exposed to high altitudes (Basnyat,
Sherpa, Basyal & Adhirikari, 1998; Pollard, Murdoch &
Bärtsch, 1998; Yaron, Waldman, Niermeyer, Nicholas &
Honigman, 1998). There is also some evidence showing
increased infant mortality in indigenous populations
(see Saco-Pollitt, 1989, for review), and that young chil-
dren living at altitude have stunted growth (Saco-Pollitt,
1981), and may suffer from sleep disturbance (Vázquez,
Marentes, Aboitiz, Meza & Pérez-Padilla, 2004; Yaron,
up to the limit of the troposphere (approximately
15,000 m), but the oxygen pressure drops exponentially
with altitude. This leads to a reduction of inspired and
alveolar oxygen pressure, associated with a decreased
oxygen concentration in the blood (hypoxaemia). Hyper-
ventilation may then occur, causing a drop in carbon
dioxide levels (hypocapnia). Cerebral blood flow (CBF)
reflects the balance between the levels of oxygen and
carbon dioxide in blood. At high altitude, there is an
increase in CBF, but severe hypocapnia can cause vaso-
constriction to the extent that CBF may be restricted
(Schoene, 1999; Hornbein, 2001). With longer-term
exposure, other adaptive processes may be detected. An
increase of red blood cells (polycythaemia) occurs after
the first week of continuous exposure to high altitude.
Polycythaemia may improve oxygen uptake and delivery
to the brain (Richalet, Souberbielle, Antezana, Dechaux,
Le Trong, Bienvenu, Daniel, Blanchot & Zittoun, 1994),
although this process can result in high blood viscosity,
associated with risk of thrombosis and stroke if the
red cell number is excessive (al Tahan, Buchur, el
Khwsky, Ogunniyi, al-Rajeh, Larbi, Daif & Bamgboye,
1998; Jaillard, Hommel & Mazetti, 1995; Niaz &
Nayyar, 2003). These processes are described further in
Figure 2.
Adaptation to chronic hypoxic conditions has been
shown to differ between indigenous populations, sug-
gesting phenotypic variation in the systemic response
to hypoxia, and a degree of natural selection in the
determination of those adaptations that are associated
with greater survival (e.g. Beall, Song, Elston & Goldstein,
2004). Himalayan highlanders of Tibetan lineage do not
appear to exhibit an exaggerated form of the otherwise
expected signs and symptoms of altitude exposure, such

© 2006 The Authors. Journal compilation © 2006 Blackwell Publishing Ltd.

402 Javier Virués-Ortega et al.
Figure 2 The biological process underlying altitude neurobehavioural impairment.
Note: CBF = cerebral blood flow, PB = barometric pressure, PiO2 = pressure of inspired oxygen in the trachea, PAO2 = alveolar pressure of oxygen, PaO2 = partial
pressure of oxygen in arterial blood, PaCO2 = partial pressure of carbon dioxide in arterial blood, %SaO2 = percent saturation of hemoglobin with oxygen in the
arterial blood.
as periodic sleep apnoeas, polycythaemia and oxyhae-
moglobin desaturation, indicating adaptation to altitude
(Beall & Goldstein, 1987). Similar results have been
reported for Tibetan infants (Niermeyer, Yang, Shan-
mina, Drolkar, Zhuang & Moore, 1995). Polycythaemia
is characteristic of Andean communities, while Tibetans
have been reported to have near-normal haemoglobin
concentration. Amerindian highlanders have developed
a bigger chest size; they also have a rise in pulmonary
pressure causing enlargement of the heart (Beall, 2000a;
Niermeyer, Zamudio & Moore, 2001). However, Amharic
Ethiopian highlanders settled at 3500 m maintain
venous haemoglobin concentrations and arterial oxygen
saturation (SaO2) within the range of those populations
living at sea level, and might therefore have developed
still unknown altitude-adaptation mechanisms (Beall,
Decker, Brittenham, Kushner, Gebremedhin & Strohl,
2002). Adaptive mechanisms may help to maintain
physical and mental performance at altitude. For exam-
ple, Tibetans demonstrate better physical ability at
altitude when compared with lowlanders, Andean com-
munities and European high-altitude residents (Moore,
2000; Moore, Curran-Everett, Droma, Groves, McCullough,
McCullough, Sun, Sutton, Zamudio & Zhuang, 1992).
Acute exposure to hypoxia is associated with severe
neurobehavioural dysfunction and loss of consciousness
after a few minutes at altitudes above 6500 m in non-
acclimatized individuals (see Table 1), and it is assumed
that permanent human life is not possible above 5500 m,
although moderate altitudes can sometimes be tolerated
without supplementary oxygen. Nevertheless, brain vul-
nerability to hypoxia increases from 2500 m above sea
level (Hackett, 1999; Hackett & Roach, 2001). Exercise
(hyperventilation), insomnia and other processes linked
to human activity at high altitudes may contribute to
this effect. Brain vulnerability can manifest as aphasia,
© 2006 The Authors. Journal compilation © 2006 Blackwell Publishing Ltd.
blindness, hemianopia, diplopia and hemiparesis (see
Virués-Ortega et al., 2004, for review).
Neuroimaging studies are sparse and focus on adults
acutely exposed to high altitude. There is only limited
evidence of focal brain damage to hypoxia-sensitive
brain areas (i.e. cortex, medial temporal lobe), suggest-
ing that those symptoms described above may be mostly
transient and associated only with acute perturbations
of brain metabolism. While a single climb below 7000 m
does not seem to cause brain magnetic resonance image
(MRI) changes (Anooshavirani, Dumont, Mardirosoff,
Soto-Debeuf & Delavelle, 1999), ascent to higher alti-
tudes, especially repeatedly and without supplementary
oxygen, has been associated with leuko-araiosis and mild
cortical atrophy in European climbers (Garrido, Castelló,
Ventura, Capdevila & Rodríguez, 1993). Leuko-araiosis,
defined by Hachinski, Potter and Merskey (1987) as neuro-
radiological/MRI signal change in the periventricular
deep white matter, may reflect exposure to critical levels
of environmental hypoxia (Houston, Sutton, Cymerman
& Reeves, 1987). Similarly, high signal intensity in the
splenium of the corpus callosum following rapid ascent
to 5200 m was reported in one 29-year-old man, although
this signal change normalized after four months (Wong,
Turner, Birchall, Walls, English & Schmid, 2004), and
two climbers showed high signal intensity in periven-
tricular brain areas immediately after exposure to 8000 m
(Garrido, Segura, Capdevila, Aldoma, Rodriguez, Javierre
& Ventura, 1995). Usui, Inoue, Kimura, Kirino, Nagaoka,
Abe, Nagata and Arai (2004) described computerized
tomography and MRI findings in two women aged 63
years. Bilateral basal ganglia abnormality was found in
both women, leading the authors to hypothesize that
exposure to high altitudes may be associated with ‘sub-
cortical dementia’. Signal abnormality in the globus
pallidus was also reported in a 49-year-old Korean
 Human behaviour and development under high-altitude conditions
patient after an ascent to 4700 m, and was associated
with changes in personality (Jeong, Kwon, Chin, Yoon
& Na, 2002). There is also evidence for brain abnormality
in a study of EEG activity in eight world-class alpinists
(Regard, Oelz, Brugger & Landis, 1989). In addition,
there is some supportive experimental evidence: for
example, rats exposed to an altitude of 6400 m for four
days suffered neurotoxicity in the hippocampus subfield
CA3 (Shukitt-Hale, Kadar, Marlowe, Stillman, Galli,
Levy, Devine & Lieberman, 1996). Accordingly, develop-
ment under chronic hypoxia (10% O2) decreases the
number of CA1 cells with accompanying memory
impairment in rats (Mikati, Zeinieh, Kurdi, Harb, El
Hokayem, Daderian, Shamseddine, Obeid, Bitar & El
Sabban, 2005).
There is even less brain MRI evidence in indigenous
populations but the available data suggest that there is
only a minor risk of brain damage, despite repeated
ascents to extreme altitudes (Garrido, Segura, Capdevila,
Pujol, Javierre & Ventura, 1996). Specifically, MRI scans
were obtained from seven Sherpa elite climbers who
were born and spent most of their life at an average
altitude of 4000 m. Despite their numerous expeditions
over 8000 m without use of supplementary oxygen,
minor abnormality was found in only one participant
(mild cortical atrophy and a degree of leuko-araiosis).
The brain MRI findings in this individual were similar
to those observed in European extreme-altitude climbers
of similar age, but the incidence of abnormality in the
European climbers was higher (61%). None of a low-
lander control group showed brain MRI alterations.
The lack of brain abnormality in indigenous popula-
tions may be due to a degree of neuro-protection offered
by long-term adaptation to chronic hypoxia. Indeed a
lower resting metabolic rate, particularly in frontal cor-
tical areas, has been described in PET studies of adult
Andean natives (Hochachka, Clark, Brown, Stanley,
Stone, Nickles, Zhu, Allen & Holden, 1994). The authors
interpreted these findings as indicative of hypoxic-
adaptation. However, the subsequent investigation of
adult Himalayan natives did not reveal the same changes
as found in the Andean natives (Hochachka, Clark,
Monge, Stanley, Brown, Stone, Nickles & Holden, 1996).
Other authors suggest that there is greater physiological
adaptation to hypoxia in Himalayan natives resulting
from a longer period for genetic adaptation (Moore,
2001; Wu, Li & Ward, 2005; Niermeyer et al., 2001).
Moreover, chronic mountain sickness like Monge’s dis-
ease, or the adult and infantile type of subacute moun-
tain sickness are rare in Tibetans compared to Andean
natives or altitude newcomers (Sui, Liu, Cheng, Anand,
Harris & Heath, 1988; Monge, Leon-Velarde & Arregui,
2001). Further investigation is required to explore genetic
© 2006 The Authors. Journal compilation © 2006 Blackwell Publishing Ltd.
403
factors underlying cultural differences in systemic oxygen
saturation and transport (Moore, 2001).
In summary, the literature indicates that exposure to
high and extreme altitudes can result in focal ischemic
damage, although the incidence and extent of neuro-
pathology may be determined by the degree to which the
individual is habituated to altitude. However, the evi-
dence is sparse and the clinical significance is not clear
as brain damage has not been reliably associated with
cognitive and behavioural impairment (Hornbein, 1992),
or with other neurological signs and symptoms.
Motor function at altitude
Abnormal motor function has frequently been reported
in the altitude literature, for example, evident in reduced
speed and precision in finger tapping (Berry, McConnell,
Phillips, Carswell, Lamb & Prine, 1989; Hornbein,
Townes, Schoene, Sutton & Houston, 1989). The extent
of environmental oxygen reduction required to demon-
strate this effect is variable: exposure to simulated alti-
tudes through hypobaric chambers and gas mixture
ranging from 2500 to 6000 m (60–95% SaO2) reportedly
has a negative impact.
The finding of motor deterioration may be con-
founded with fatigue, a variable associated with both
motor delay and altitude gain (Bolmont, Thullier &
Abraini, 2000). Thus, it is not clear if motor deficits are
a direct consequence of altitude hypoxia, although the
results of one study suggested that the effect of fatigue
is probably spurious (Sharma, Malhotra & Baskaran,
1975). These authors recorded motor speed using an
eye–hand coordination test in 25 Indian young adults
(21–30-years-old) in a community relocated to 4000 m
from sea level. Importantly, this motor delay did not
decrease over time, and deficits persisted when people
returned to live at lower altitude. Chronic effects on
motor speed may be due to repeated long-term exposure
to high and extreme altitudes, but there are few longitu-
dinal data to support this hypothesis. In 1981, the
American Medical Research Everest Expedition (AMREE)
found significant impairment two years after the termina-
tion of the expedition (West, 1986). In addition, Regard
et al. (1989) noted that finger tapping was significantly
impaired in 25% of world-class alpinists with a long
history of high and extreme altitude exposures.
Perceptual and attentional processing
Delayed reaction time (RT) in complex target-detection
tasks is the most frequently reported effect of altitude.
404 Javier Virués-Ortega et al.
This phenomenon has been observed in a variety of
experimental settings, including high mountaineering
expeditions and hypobaric chambers (Bolmont, Bouquet
& Thullier, 2001; Fowler & Prlic, 1995; Kramer, Coyne
& Strayer, 1993; Mackintosh, Thomas, Olive, Chesner &
Knight, 1988), and significant impairment has been
demonstrated at altitudes as low as 1500 m (Denison,
Ledwith & Poulton, 1966), although more consistent
abnormality is found above 6000 m (e.g. Operation
Everest II; Hornbein et al., 1989). RT delay might reflect
altered sensori-perceptual processing, evident in increased
latency of the P300 component (an event-related poten-
tial associated with basic stimulus identification and
processing) (Fowler & Prlic, 1995; Hayashi, Matsuzawa,
Kubo & Kobayashi, 2005; Kida, 1997; Soltani & Knight,
2000; Wesensten, Crowley & Thomas, 1993). Abnormality
in ERP components reflecting more complex, response-
related, processing have also been described, e.g. the
contingent negative variation (Takagi & Watanabe,
1999).
Auditory discrimination is only slightly affected by
simulated high altitude exposure. For example, a 2.6dB
reduction in auditory sensitivity at a simulated altitude
of 3700 m has been reported (McAnally, Watson, Martin
& Singh, 2003), and longer latency of the auditory
evoked potential was found in a study conducted in the
Himalayas (4300 m), suggesting a delay in sensory
conduction (Singh, Thakur, Anand, Yadav, Banerjee &
Selvamurthy, 2004). Other sensory modalities can become
hypersensitive. An increased luminance threshold for
visual stimuli has been described (Kobrick & Appleton,
1971), while visual contrast sensitivity remains unaffected
or even enhanced due to short-term hypobaric hypoxia
(Benedek, Kéri, Grósz, Tótka, Tóth & Benedek, 2002;
Davis, Kamimori, Kulesh, Mehm, Anderson, Elsayed,
Burge & Balkin, 1995). Colour discrimination can also
be altered, particularly on the yellow-blue and red-blue
axis (Bouquet, Gardette, Gortan, Therme & Abraini,
2000; Leid & Campagne, 2001; Smith, Ernest & Pokorny,
1976; Vingrys & Garner, 1987), suggesting an impair-
ment of retinal ganglion cells. A colour discrimination
test used by Bouquet and colleagues (Everest-Comex ’97
project) consisted of 24 pairs of identical or different
coloured squares. Discrimination errors were altitude-
dependent although the increased error rate only reached
statistical significance at 8000 m and 8848 m simulated
altitudes.
The measurement of perceptual and attentional pro-
cesses may be influenced by hallucinatory experiences
which can occur at altitude. Two reports describe visual
and auditory hallucinatory episodes, with a high inci-
dence of somesthetic illusions, for example described by
climbers as the presence of a ‘companion’. This phenom-
© 2006 The Authors. Journal compilation © 2006 Blackwell Publishing Ltd.
enon occurred above 6000 m, and may result from brain
hypoxia, or from other variables such as emotional
distress, lack of stimulation and physical exhaustion
(Brugger, Regard, Landis & Oelz, 1999; Garrido, Javierre,
Ventura & Segura, 2000).
Higher cognitive functions
Memory
The brain areas associated with learning and memory
(e.g. structures of the medial temporal lobe) are particu-
larly sensitive to hypoxia (e.g. see Raman, Tkac, Ennis,
Georgieff, Gruetter & Rao, 2005), but a direct relation-
ship between altitude exposure, hippocampal dysfunc-
tion and learning and memory impairment in humans is
not established. Nevertheless, Litch and Bishop (1999)
described two cases of transitory global amnesia associ-
ated with AMS and cerebral oedema at 4400 m and 3750 m;
Garrido and colleagues (1995) reported a similar case
in a mountaineer climbing to 8000 m. A recent study in
humans by Pelamatti, Pascotto and Semenza (2003)
showed that 15 adults (29–37 years old), tested under
high altitude (4500 and 5050 m) conditions, displayed
difficulties on the recall of supraspan word lists, specifi-
cally those words that came early in the list (primacy
effect). A number of other studies have shown that ver-
bal and visual short-term memory capacity and recall is
impaired from altitudes starting at 2500 m (Cavaletti,
Moroni, Garavaglia & Tredici, 1987; Hopkins, Kessner
& Goldstein, 1995; Hornbein et al., 1989; Phillips &
Pace, 1966; Regard et al., 1989; Townes, Hornbein,
Schoene, Sarnquist & Grant, 1984; West, 1984, 1986). In the
study by Pelamatti and colleagues (2003) memory recall
remained impaired 45 days after descent. There is fur-
ther evidence that memory impairment may last several
months after returning to the lowlands. One retrospec-
tive study administered the Wechsler short stories and
the Rey Auditory-Verbal Learning Test to eight world-
class (26–44-year-old) alpinists and a control group of
low-altitude climbers, all but two of whom had never
been beyond 4800 m (Regard et al., 1989). Verbal memory
deficit (≥1 SD below the mean of controls) was found in
five out of the eight participants. However, the results of
other longitudinal studies (>1 year) by West (1984, 1986)
suggest that memory impairment is reversible.
Language
Case reports of transient aphasia associated with high
altitude have been published (e.g. Botella, Garrido &
Catalá, 1993). Significantly diminished performance on
 Human behaviour and development under high-altitude conditions
verbal fluency tests with altitude exposure beyond 6000 m
has been reported during actual ascent and in retro-
spective studies (Cavaletti et al., 1987; Kennedy, Dunlap,
Banderet, Smith & Houston, 1989; Regard et al., 1989),
although others have found that impairment at high altitude
may not persist after descent to sea level (West, 1986).
Articulation and language processing speed (time required
to comprehend a sentence) was found to be altitude-
dependent in alpinists climbing Mount Everest (Lieber-
man, Protopapas, Reed, Youngs & Kanki, 1994). The
authors described this pattern of deficit as similar to that
seen in Parkinson’s disease, suggesting that the function
of frontal-striatal circuits may be adversely affected (Lie-
berman, Protopapas & Kanki, 1995); this is consistent
with the basal ganglia involvement in those MRI studies
described above (Usui et al., 2004; Jeong et al., 2002).
Indeed, articulation impairment has been used as a sim-
plified assessment strategy of AMS severity (Cymerman,
Lieberman, Hochstadt, Rock, Butterfield & Moore, 2002).
Executive function
To our knowledge, there is little evidence in expedition
studies concerning cognitive flexibility and inhibition:
executive functions associated with the frontal lobes that
can be assessed by measures such as the Stroop Test and
the Wisconsin Card Sorting Test. However, neuro-
psychological data from world-class alpinists by Regard
and colleagues (1989), alongside research into clinical
hypoxia syndromes, suggest that these aspects of cognitive
functioning may be affected (Crews, Jefferson, Bolduc,
Elliott, Ferro, Broshek, Barth & Robbins, 2001). A few
studies have investigated metacognitive function at high
altitude: individuals have been found to underreport
their own problems with performance on motor tasks,
long-term memory capacity and their duration of sleep
(Clark, Heaton & Weins, 1983; Nelson, Dunlowsky,
White, Steinberg, Townes & Anderson, 1990; Reite,
Jackson, Cahoon & Weil, 1975).
Developmental perspectives of
neurobehavioural functioning at high altitude
We have previously suggested that one of the obvious
flaws in altitude research concerns the limited popula-
tions with which these studies have been carried out
(Virués-Ortega et al., 2004). Of necessity, most research
has involved middle-to-upper social class male alpinists
aged between 25 and 45 years, who are of Western Euro-
pean/North American nationality. With this in mind,
extrapolation or use of adult altitude research as a
model for cognitive effects of hypoxia in other popula-
© 2006 The Authors. Journal compilation © 2006 Blackwell Publishing Ltd.
405
tions is likely to be contentious. The potential effects of
acute, intermittent and/or chronic altitude exposure on
neurobehavioural development is no exception, as there
are few data available in infants and children visiting or
living at high altitude.
Altitude may have a differential effect on indigenous
populations of children and adults. Some studies have
shown that infants in communities settled beyond 3000 m
have a level of arterial oxyhaemoglobin saturation
(SpO2) that is 13–15% less than lowlanders (∼97%). The
magnitude of this difference decreases steadily through
the first decade of life so that children eventually have a
more normal level of SpO2 (∼90%); this level will be
maintained with small changes throughout adulthood
(Beall, 2000b; Gamponia, Babaali, Yugar & Gilman,
1998). Another study of infants born at 1610 m reported
oxyhaemoglobin saturations of 92–93% during the first
few days of life, increasing only slightly to 93–94%
(awake) by 3 months of age; but the lowest recorded
values were ∼85% (Thilo, Park-Moore, Berman & Carson,
1991). While close to normative values (∼95%), this level
of oxyhaemoglobin saturation is nevertheless lower
than normal and suggests potential hazards for young
children: high altitude pulmonary and cerebral oedema,
and sudden infant death syndrome have been reported
(Samuels, 2004). Infants living at high altitude may also
have an immaturity of the respiratory control mecha-
nism (Ward, Milledge & West, 2000).
Young children experiencing acute exposure to altitude
may show symptoms of cerebral hypoxia (Yaron et al.,
2003). Sleep is described as abnormal and children can
be affected by AMS within 1 or 2 days after ascent,
especially in those below 5 years of age, usually mani-
festing as excessive crying and irritability, food refusal,
playfulness or lethargy. Clinical evaluation of preverbal
infants by means of AMS diagnostic criteria showed the
same incidence found for adults up to an altitude of
3500 m (22%) (Yaron et al., 1998). There is also a risk
of high-altitude pulmonary oedema if the child is recov-
ering from a respiratory tract infection (Durmowicz,
Noordeweir, Nicholas & Reeves, 1997). In general, AMS
should be assumed when a child becomes unwell above
2500 m. Preverbal infants are advised not to sleep above
2000 m, and children aged between 2 and 10 years
should not sleep above 3000 m (Pollard et al., 1998).
Likewise, prolonged exposure to high altitude should be
avoided under the age of 1 year because of the risk of
‘infantile subacute mountain sickness’, a congestive type
of heart failure. This syndrome can be fatal, presenting
as sleeplessness and irritability, and is not uncommon in
those infants of lowlander parents who are born above
3000 m or have migrated from lower altitude shortly
after birth (Sui et al., 1988).
406 Javier Virués-Ortega et al.
Infant cognitive development at altitude is a neglected
area of research with little evidence in paediatric or psy-
chology journals. Saco-Pollitt (1981) administered the
Brazelton Neonatal Behavioural Assessment Scale to 40
Peruvian infants born at Cerro de Pasco (4300 m; PiO2
∼82 mmHg) and to 40 sex- and age-matched controls
born in Lima (150 m; PiO2 ∼150 mmHg). High-altitude
newborns showed diminished stature and signs of behavi-
oural immaturity compared to controls. Moreover, the
infants at Cerro de Pasco were significantly less attentive
to environmental stimuli, less likely to orient to visual
and auditory stimuli and to maintain their heads up, less
active and more hypotonic. However, Haas (1976) also
studied Peruvian infants aged between 2 months and
2 years using the Bayleys Scales of Infant Development,
but did not find any deficit in early motor development.
The cohort in Haas’s studies (1976; Haas, Baker & Hunt,
1977) were at slightly lower altitude (3780 m vs. 4300 m),
and had greater birth weight (3260 g vs. 2824 g), but
these factors are unlikely to fully account for the con-
flicting findings. More likely, socioeconomic (but see
Saco-Pollitt, 1989) and as yet unknown adaptive (genetic)
mechanisms may be important in determining the quality
of early development.
More recent studies with Andean populations settled
up to 3500 m above sea level have shown that altitude
accelerates development of lung function but has
negligible effects on a child’s final stature or weight
(Freyre & Ortíz, 1988; Villena, Spielvogel, Vargas,
Obert, Alarcon, Gonzales, Falgairette & Kemper, 1994).
However, as these studies focused on anthropometric
variables, the extent to which the behavioural changes
identified by Saco-Pollitt (1981) are associated with
long-term cognitive and social development is unknown.
Accelerated lung development in the Peruvian infants
described by Villena and colleagues (1994) suggests that
some indigenous young children may be able to com-
pensate for lowered levels of oxygen, at least initially,
although chronic hypoxia may still have a deleterious
effect on the brain and cognitive function in the long
term. Longitudinal studies extending into adolescence
and adulthood are required to address this possibility,
although it is of interest that the higher prevalence of
chronic neurological diseases (e.g. Parkinson disease) in
populations settled at 3500 m (Gonzáles, 1998) might
also be related to long-term failure to adapt to hypoxic
exposure.
The lack of research on the effects of altitude on neuro-
behavioural development may reflect the methodologi-
cal complexity of this area. These studies, if they are to
be developed in the future, should compare culturally
and ethnically matched groups living at low and high
altitude, and must be of longitudinal as well as cross-
© 2006 The Authors. Journal compilation © 2006 Blackwell Publishing Ltd.
sectional design to take into account possible long-term
adaptation effects. An understanding of epidemiological,
genetic and socio-cultural issues may be of particular
importance. Intrauterine growth restriction, low birth
weight and/or foetus mortality is particularly common
in Bolivian women living above 2500 m (Keyes, Armaza,
Niermeyer, Vargas, Young & Moore, 2003), suggesting a
restriction of oxygen delivery during critical stages of
prenatal development. However, Tibetan women with
genotypes for high oxygen saturation of haemoglobin
(reduced hypoxia) have more surviving children than
those with the low oxygen saturation genotype (Beall
et al., 2004). Indeed, it has been suggested that high
altitude offers an ‘experiment of nature’ for investigating
genetic factors associated with foetal susceptibility to
hypoxia (Moore, Shriver, Bemis, Hickler, Wilson, Brut-
saert, Parra & Vargas, 2004). Malnutrition may be a
confounding factor in those children who do survive,
being a frequent finding in highlanders (Greene, 1973;
Harris, Crawford, Yangzom, Pinzo, Gyaltsen & Hudes,
2001). In particular, iron deficiency anaemia, associated
with poor cognitive performance, is common in children
living at high altitude (Sherriff, Emond, Bell & Golding,
2001).
There are other cultural considerations which may
affect the rate of neurodevelopment (see Saco-Pollitt,
1989, for review). For example, Tronick, Thomas and
Daltabuit (1994) described how the Manta pouch, a
traditional garment used by the Quechua to protect
newborns against the extreme environment, can lower
the partial pressure of oxygen compared to the ambient
environment, but may also dramatically limit the social-
ization and stimulation opportunities available to the
child. As a result, exploration and language repertoires
may be limited, reflecting a culturally shaped behaviour
and not necessarily an effect solely due to altitude hypoxia.
In summary, the influence on neurobehavioural develop-
ment of the hypoxia to which children are exposed
acutely or chronically at altitude remains undetermined.
Notwithstanding the methodological and cultural con-
siderations that must be taken into account, this is an
important area for research. Adaptation to altitude has
implications for our understanding of the neurobehavi-
oural deficits exhibited by lowland children clinically
exposed to acute, intermittent and chronic forms of
hypoxia.
Acknowledgement
The authors would like to express their gratitude to
Alexandra Hogan, Guest Editor of this Special Issue, for
her valuable comments.
 Human behaviour and development under high-altitude conditions
References
Acosta, J. de (1590). Historia Natural y Moral de las Indias
[Natural and moral history of America] (V. III, pp. 140–
146). Seville: Juan de León.
al Tahan, A., Buchur, J., el Khwsky, F., Ogunniyi, A., al-
Rajeh, S., Larbi, E., Daif, A., & Bamgboye, E. (1998). Risk
factors of stroke at high and low altitude areas in Saudi
Arabia. Archives of Medical Research, 29, 173 –177.
Anooshiravani, M., Dumont, L., Mardirosoff, C., Soto-Debeuf,
G., & Delavelle, J. (1999). Brain magnetic resonance imaging
(MRI) and neuronal changes after single high altitude
climb. Medicine & Science in Sports & Exercise, 31, 969–
972.
Bahrke, M.S., & Shukitt-Hale, B. (1993). Effect of altitude on
mood, behavior and cognitive functioning. Sports Medicine,
16, 97–125.
Basnyat, B., Sherpa, N., Basyal, G., & Adhirikari, P. (1998).
Children in the mountains: advice given was too conserva-
tive. British Medical Journal, 317, 540.
Beall, C.M. (2000a). Tibetan and Andean patterns of adapta-
tion to high-altitude hypoxia. Human Biology, 72, 201–228.
Beall, C.M. (2000b). Oxygen saturation increases during child-
hood and decreases during adulthood among high altitude
native Tibetans residing at 3800 – 4200 m. High Altitude
Medicine and Biology, 1, 25 –32.
Beall, C.M., Decker, M.J., Brittenham, G.M., Kushner, I.,
Gebremedhin, A., & Strohl, K.P. (2002). Ethiopian pattern
of human adaptation to high-altitude hypoxia. Proceedings
of the National Academy of Sciences of the United States of
America, 99, 17215 –17218.
Beall, C.M., & Goldstein, M.C. (1987). Hemoglobin con-
centration of pastoral nomads permanently resident at
4850 –5450 meters in Tibet. American Journal of Physical
Anthropology, 73, 433 – 438.
Beall, C.M., Song, K., Elston, R.C., & Goldstein, M.C. (2004).
Higher offspring survival among Tibetan women with high
oxygen saturation genotypes residing at 4000 m. Proceedings
of the National Academy of Sciences of the United States of
America, 101, 14300 –14304.
Benedek K., Kéri, S., Grósz, A., Tótka, Z., Tóth E., &
Benedek, G. (2002). Short-term hypobaric hypoxia enhances
visual contrast sensitivity. NeuroReport, 13, 1063 –1066.
Berry, D., McConnell, J.W., Phillips, B.A., Carswell, C.M.,
Lamb, D.G., & Prine, B.C. (1989). Isocapnic hypoxemia and
neurobehavioural functioning. Journal of Clinical and Experi-
mental Neuropsychology, 11, 241–251.
Bolmont, B., Bouquet, C., & Thullier, F. (2001). Relationship
of personality traits with performance in RT, psychomotor
ability, and mental efficiency during a 31-day simulated
climb of Mount Everest in a hypobaric chamber. Perceptual
and Motor Skills, 92, 1022–1030.
Bolmont, B., Thullier, F., & Abraini, J.H. (2000). Relationship
between mood states and performances in RT, psychomotor
ability, and mental efficiency during 31-day gradual decom-
pression in a hypobaric chamber from sea level to 8848 m
equivalent altitude. Physiology and Behaviour, 71, 469–
476.
© 2006 The Authors. Journal compilation © 2006 Blackwell Publishing Ltd.
407
Botella, J., Garrido, E., & Catalá, J. (1993). Transient motor
aphasia at high altitude. Revista Clínica Española, 193, 296–
298.
Bouquet, C., Gardette, B., Gortan, C., Therme, P., & Abraini,
J.H. (2000). Color discrimination under chronic hypoxia
conditions (simulated climb ‘Everest-Comex 97’). Perceptual
and Motor Skills, 90, 169–179.
Brugger, P., Regard, M., Landis, T., & Oelz, O. (1999).
Hallucinatory experiences in extreme-altitude climbers.
Neuropsychiatry, Neuropsychology and Behavioural Neurology,
12, 67–71.
Cavaletti, G., Moroni, R., Garavaglia, P., & Tredici, G. (1987).
Brain damage after high-altitude climbs without oxygen.
The Lancet, 10, 101.
Clark, C.F., Heaton, R.K., & Weins, A.N. (1983). Neurobehavi-
oural functioning after prolonged high altitude exposure in
mountaineering. Aviation, Space and Environmental Medicine,
54, 202–207.
Crews, W.D., Jefferson, A.L., Bolduc, T., Elliott, J.B., Ferro,
N.M., Broshek, D.K., Barth, J.T., & Robbins, M.K. (2001).
Neurobehavioural dysfunction in patients suffering from
end-stage chronic obstructive pulmonary disease. Archives of
Clinical Neuropsychology, 16, 643–652.
Cymerman, A., Lieberman, P., Hochstadt, J., Rock, P.B.,
Butterfield, G.E., & Moore, L.G. (2002). Speech motor control
and acute mountain sickness. Aviation, Space and Environ-
mental Medicine, 73, 766–772.
Davis, H.Q., Kamimori, G.H., Kulesh, D.A., Mehm, W.J.,
Anderson, L.H., Elsayed, A.M., Burge, J.R., & Balkin, T.J.
(1995). Visual performance with the Aviator Night Vision
Imaging System (ANVIS) at a simulated altitude of 4300
meters. Aviation, Space and Environmental Medicine, 66,
430–434.
Denison, D.M., Ledwith, F., & Poulton, E.C. (1966). Complex
reaction times at simulated cabin altitudes at 5000 feet and
8000 feet. Aerospace Medicine, 37, 1010–1013.
Dunlap, K. (1918). Medical studies in aviation: IV. Psychologic
observations and methods. Journal of the American Medical
Association, 71, 1392–1393.
Durmowicz, A.G., Noordeweir, E., Nicholas, R., & Reeves, J.T.
(1997). Inflammatory processes may predispose children to
high altitude pulmonary edema. Journal of Pediatrics, 130,
838–840.
Fowler, B., & Prlic, H. (1995). A comparison of visual and
auditory reaction time and P300 latency thresholds to acute
hypoxia. Aviation, Space and Environmental Medicine, 66,
645–650.
Freyre, E.A., & Ortiz, M.V. (1988). The effect of altitude on
adolescent growth and development. Journal of Adolescent
Health Care, 9, 144–149.
Gamponia, M.J., Babaali, H., Yugar, F., & Gilman, R.H.
(1998). Reference values for pulse oximetry at high altitude.
Archives of Disease in Childhood, 78, 461–465.
Garrido, E., Castelló, A., Ventura, J.L., Capdevila, A., &
Rodriguez, F.A. (1993). Cortical atrophy and other brain
magnetic resonance imaging (MRI) changes after extremely
high altitude climbs without oxygen. International Journal of
Sport Medicine, 14, 232–234.
408 Javier Virués-Ortega et al.
Garrido, E., Javierre, C., Ventura, J.L., & Segura, R. (2000).
Hallucinatory experiences at high altitude. Neuropsychiatry,
Neuropsychology and Behavioural Neurology, 13, 148.
Garrido, E., Segura, R., Capdevila, A., Aldomá, J., Rodríguez,
F.A., Javierre, C., & Ventura, J.L. (1995). New evidence from
magnetic resonance imaging of brain changes after climbs at
extreme altitude. European Journal of Applied Physiology,
70, 477– 481.
Garrido, E., Segura, R., Capdevila, A., Pujol, J., Javierre, C.,
& Ventura, J.L. (1996). Are Himalayan Sherpas better pro-
tected against brain damage associated with extreme altitude
climbs? Clinical Science, 90, 81–85.
Gonzáles, G.F. (1998). Patrones demográficos, reproductivos y
de morbi-mortalidad en las poblaciones de altura del Perú
[Demographic, reproductive, morbidity and mortality patterns
in high altitude populations in Peru]. Acta Andina, 7, 85–93.
Retrieved 1 June 2005 from http://sisbib.unmsm.edu.pe/
BVRevistas/Acta_Andina/vol7_n2_1998/patrones.htm
Greene, L.S. (1973). Physical growth and development, neuro-
logical maturation and behavioural functioning in two
Ecuadorian Andean communities in which goiter is endemic.
American Journal of Physical Anthropology, 38, 119 –134.
Haas, J.D. (1976). Prenatal and infant growth and develop-
ment. In P.T. Baker & M.A. Little (Eds.), Man in the Andes.
A multidisciplinary study of high-altitude Quechua (pp. 161–
179). Stroudsburg, PA: Dowden, Hutchinson & Ross.
Haas, J.D., Baker, P.T., & Hunt, E.E. (1977). The effects of
high altitude on body size and composition of the infant in
Southern Peru. Human Biology, 49, 611– 628.
Hachinski, V.C., Potter, P., & Merskey, H. (1987). Leuko-
araiosis. Archives of Neurology, 44, 21–23.
Hackett, P.H. (1999). The cerebral etiology of high-altitude
cerebral edema and acute mountain sickness. Wilderness and
Environmental Medicine, 10, 97–109.
Hackett, P.H., & Roach, R.C. (2001). High-altitude illness. The
New England Journal of Medicine, 345, 107–114.
Harris, N.S., Crawford, P.B., Yangzom, Y., Pinzo, L., Gyaltsen, P.,
& Hudes, M. (2001). Nutritional and health status of
Tibetan children living at high altitudes. New England Jour-
nal of Medicine, 344, 341–347.
Hayashi, R., Matsuzawa, Y., Kubo, K., & Kobayashi, T.
(2005). Effects of simulated high altitude on event-related
potential (P300) and auditory brain-stem responses. Clinical
Neurophysiology, 116, 1471–1476.
Herzog, M. (1952). Annapurna, Premier 8000 [Annapurna, first
8000]. Paris: Arthaud.
Hochachka, P.W., Clark, C.M., Brown, W.D., Stanley, C.,
Stone, C.K., Nickles, R.J., Zhu, G.G., Allen, P.S., & Holden,
J.E. (1994). The brain at high altitude: hipometabolism as a
defense against chronic hypoxia? Journal of Cerebral Blood
Flow and Metabolism, 14, 671– 679.
Hochachka, P.W., Clark, C.M., Monge, C., Stanley, C., Brown,
W.D., Stone, C.K., Nickles, R.J., & Holden, J.E. (1996). Sherpa
brain glucose metabolism as defence adaptation against
chronic hypoxia. Journal of Applied Physiology, 81, 1355 –1361.
Hopkins, R.O., Kesner, R.P., & Goldstein, M. (1995). Item
and order recognition memory in subjects with hypoxic
brain injury. Brain and Cognition, 27, 180 –201.
© 2006 The Authors. Journal compilation © 2006 Blackwell Publishing Ltd.
Hornbein, T.F. (1992). Long term effects of high altitude on
brain function. International Journal of Sports and Medicine,
13, S43–S45.
Hornbein, T.F. (2001). The high altitude brain. The Journal of
Experimental Biology, 204, 3129–3132.
Hornbein, T.F., Townes, B.D., Shoene, R.B., Sutton, J.R., &
Houston C.S. (1989). The cost to the central nervous system
of climbing to high extremely altitude. The New England
Journal of Medicine, 321, 1714–1719.
Houston, C.S., Sutton, J.R., Cymerman, A., & Reeves, J.T.
(1987). Operation Everest II: man at extreme altitude. Journal
of Applied Physiology, 63, 877–882.
Jaillard, A.S., Hommel, M., & Mazetti, P. (1995). Prevalence
of stroke at high altitude (3380 m) in Cuzco, a town of Peru:
a population-based study. Stroke, 26, 562–568.
Janssen, J. (1890). Club Alpin Francais. Annuaire 1882–1887.
Jeong, J.H., Kwon, J.C., Chin, J., Yoon, S.J., & Na, D.L.
(2002). Globus pallidus lesions associated with high moun-
tain climbing. Journal of Korean Medical Science, 17, 861–
863.
Kennedy, R.S., Dunlap, W.P., Banderet, L.E., Smith, M.G., &
Houston, C.S. (1989). Cognitive performance deficits in a
simulated ascent climb of Mount Everest: Operation Everest
II. Aviation, Space and Environmental Medicine, 60, 99–104.
Keyes, L.E., Armaza, F., Niermeyer, S., Vargas, E., Young,
D.A., & Moore, L.G. (2003). Intrauterine growth restriction,
preeclampsia, and intrauterine mortality at high altitude in
Bolivia. Pediatric Research, 54, 20–25.
Kida, M. (1997). Psychophysiological studies under simulated
high altitude. Japanese Journal of Psychonomic Science, 16,
37–44.
Kobrick, J.L., & Appleton, B. (1971). Effects of extended
hypoxia on visual performance and retinal vascular state.
Journal of Applied Physiology, 31, 357–362.
Kohlendorfer, U., Kiechl, S., & Sperl, W. (1998). Living at high
altitude and risk of sudden infant death syndrome. Archives
of Diseases in Childhood, 79, 506–509.
Kramer, A.F., Coyne, J.T., & Strayer, D.L. (1993). Cognitive
function at high altitude. Human Factors, 35, 329–344.
Leid, J., & Campagne, J. (2001). Colour vision at very high
altitude. Color Research and Application, 26 (Suppl), S281–
S283.
Lieberman, P., Protopapas, A., & Kanki, B.G. (1995). Speech
production and cognitive deficits on Mt. Everest. Aviation,
Space and Environmental Medicine, 66, 857–864.
Lieberman, P., Protopapas, A., Reed, E., Youngs, W., &
Kanki, B.G. (1994). Cognitive defects at altitude. Nature,
372, 325.
Litch, J.A., & Bishop, R.A. (1999). Transient global amnesia
at high altitude. The New England Journal of Medicine, 318,
1444.
McAnally, K.I., Watson, D.B., Martin, R.L., & Singh, B.
(2003). Effect of hypobaric hypoxia on auditory sensitivity.
Aviation, Space and Environmental Medicine, 74, 1251–
1255.
McFarland, R.A. (1932). The psychological effects of oxygen
deprivation (anoxemia) on human behaviour. Archives of
Psychology, 145, 1–135.
 Human behaviour and development under high-altitude conditions
McFarland, R.A. (1937). Psychophysiological studies at high
altitude in the Andes. Journal of Comparative Physiology, 23,
191–225.
McFarland, R.A. (1972). Psychophysiological implications of
life at altitude and including the role of oxygen in the process
of aging. In M.K. Yousef, S.M. Horvath, & R.W. Bullard
(Eds.), Physiological adaptations: Desert and mountain
(pp. 157–182). New York: Academic Press.
Mackintosh, J.H., Thomas, D.J., Olive, J.E., Chesner, I.M., &
Knight, R.J.E. (1988). The effect of altitude on tests of reac-
tion time and alertness. Aviation, Space and Environmental
Medicine, 59, 246–248.
Mikati, M.A., Zeinieh, M.P., Kurdi, R.M., Harb, S.A., El
Hokayem, J.A., Daderian, R.H., Shamseddine, A., Obeid, M.,
Bitar, F.F., & El Sabban, M. (2005). Long term effects of
acute and of chronic hypoxia on behavior and hippocampal
histology in the developing brain. Developmental Brain
Research, 157, 98 –102.
Monge, C.C., León-Velarde, F., & Arregui, A. (2001). Chronic
mountain sickness in Andeans. In T.F. Hornbein & R.B.
Schoene (Eds.), High altitude: An exploration of human adap-
tation (pp. 815 – 838). New York: Marcel Dekker.
Moore, L.G. (2000). Comparative human ventilatory adapta-
tion to high altitude. Respiration Physiology, 121, 257–276.
Moore, L.G. (2001). Human genetic adaptation to high alti-
tude. High Altitude Medicine and Biology, 2, 257–279.
Moore, L.G., Curran-Everett, L., Droma, T.S., Groves, B.M.,
McCullough, R.E., McCullough, R.G., Sun, S.F., Sutton, J.R.,
Zamudio, S., & Zhuang, J.G. (1992). Are Tibetans better
adapted? International Journal of Sports Medicine, 13
(Suppl. 1), 86 – 88.
Moore, L.G., Shriver, M., Bemis, L., Hickler, B., Wilson, M.,
Brutsaert, T., Parra, E., & Vargas, E. (2004). Maternal adap-
tation to high altitude pregnancy: an experiment of nature –
a review. Placenta, 25, S60–S71.
Nelson, T.O., Dunlowsky, J., White, D.M., Steinberg, J.,
Townes, B.D., & Anderson, D. (1990). Cognition and meta-
cognition at extreme altitudes on Mount Everest. Journal of
Experimental Psychology: General, 119, 367–374.
Niaz, A., & Nayyar, S. (2003). Cerebrovascular stroke at high
altitude. Journal of the College of Physicians and Surgeons –
Pakistan, 13, 446 – 448.
Niermeyer, S., Zamudio, S., & Moore, L.G. (2001). The people.
In T.F. Hornbein & R.B. Schoene (Eds.), High altitude: An
exploration of human adaptation (pp. 43 –100). New York:
Marcel Dekker.
Niermeyer, S., Yang, P., Shanmina, M., Drolkar, R.,
Zhuang, J., & Moore L.G. (1995). Arterial oxygen saturation
in Tibetan and Han infants born in Lhasa, Tibet. New Eng-
land Journal of Medicine, 333, 1248 –1252.
Pelamatti, G., Pascotto, M., & Semenza, C. (2003). Verbal free
recall in high altitude: proper names vs. common names.
Cortex, 39, 97–103.
Phillips, L.W., & Pace, N. (1966). Performance changes at
moderately high altitude: short-term memory measured by
free recall. Psychological Reports, 19, 655 – 665.
Pollard, A.J., Murdoch, D.R., & Bärtsch, P. (1998). Children
in the mountains. British Medical Journal, 316, 874–875.
© 2006 The Authors. Journal compilation © 2006 Blackwell Publishing Ltd.
409
Raman, L., Tkac, I., Ennis, K., Georgieff, M.K., Gruetter, R.,
& Rao, R. (2005). In vivo effect of chronic hypoxia on the
neurochemical profile of the developing rat hippocampus.
Developmental Brain Research, 156, 202–209.
Ravenhill, T.H. (1913). Some experiences of mountain sickness
in the Andes. Journal of Tropical Medicine and Hygiene, 16,
313–320.
Regard, M., Oelz, O., Brugger, P., & Landis, T. (1989). Persistent
cognitive impairment in climbers after repeated exposure to
extreme altitude. Neurology, 39, 210–213.
Reite, M., Jackson, D., Cahoon, R.L., & Weil, J.W. (1975).
Sleep physiology at high altitude. Electroencephalography
and Clinical Neurophysiology, 38, 463–471.
Richalet, J.P., Souberbielle, J.C., Antezana, A.M., Dechaux, M.,
Le Trong, J.L., Bienvenu, A., Daniel, F., Blanchot, C., &
Zittoun, J. (1994). Control of erythropoiesis in humans dur-
ing prolonged exposure to the altitude of 6542 m. American
Journal of Physiology, 266, 756–764.
Ruttledge, H. (1934). Everest: The unfinished adventure, 1933.
London: Hodder and Stoughton.
Saco-Pollitt, C. (1981). Birth in the Peruvian Andes: physical
and behavioural consequences in the neonate. Child Devel-
opment, 52, 839–846.
Saco-Pollitt, C. (1989). Ecocultural context and developmental
risk: birth in the high altitudes (Peru). In K.J. Nugent, B.M.
Lester & T. Brazelton (Eds.), The cultural context of infancy:
Biology, culture, and infant development (pp. 3–25). Westport,
CT: Ablex Publishing.
Samuels, M.P. (2004). The effects of flight and altitude.
Archives of Diseases in Childhood, 89, 448–455.
Schoene, R.B. (1999). The brain at high altitude. Wilderness
and Environmental Medicine, 10, 93–96.
Sharma, V., Malhotra, M.S., & Baskaran, A. (1975). Varia-
tions in psychomotor efficiency during prolonged stay at
high altitude. Ergonomics, 18, 511–516.
Sherriff, A., Emond, A., Bell, J.C., & Golding, J. (2001).
Should infants be screened for anaemia? A prospective study
investigating the relation between haemoglobin at 8, 12, and
18 months and development at 18 months. Archives of Disease
in Childhood, 84, 480–485.
Shipton, E. (1943). Upon that mountain. London: Hodder and
Stoughton.
Shukitt-Hale, B., Kadar, T., Marlowe, B.E., Stillman, M.J.,
Galli, R.L., Levy, A., Devine, J.A., & Lieberman, H.R. (1996).
Morphological alterations in hippocampus following hypobaric
hypoxia. Human and Experimental Toxicology, 15, 312–319.
Singh, S.B., Thakur, L., Anand, J.P., Yadav, D., Amitabh,
Banerjee P.K., & Selvamurthy, W. (2004). Effect of high alti-
tude on human auditory brainstem responses. Indian Journal
of Physiology and Pharmacology, 48, 230–234.
Smith, V.C., Ernest, J.T., & Pokorny, J. (1976). Effect of
hypoxia on FM 100-hue test performance. Modern Problems
in Ophthalmology, 17, 248–256.
Soltani, M., & Knight, R.T. (2000). Neural origins of the P300.
Critical Reviews in Neurobiology, 14, 199–224.
Sui, G.J., Liu, Y.H., Cheng, X.S., Anand, I.S., Harris, E.,
Harris, P., & Heath, D. (1988). Subacute infantile mountain
sickness. Journal of Pathology, 155, 161–170.
410 Javier Virués-Ortega et al.
Takagi, M., & Watanabe, S. (1999). Two different components
of contingent negative variation (CNV) and their relation to
changes in reaction time under hypobaric hypoxic conditions.
Aviation, Space and Environmental Medicine, 70, 30 –34.
Thilo, E.H., Park-Moore, B., Berman, E.R., & Carson, B.S.
(1991). Oxygen saturation in healthy infants at an altitude of
1610 m (5280 ft). What is normal? American Journal of Diseases
in Childhood, 145, 1137–1140.
Townes, B., Hornbein, T., Schoene, R., Sarnquist, F., & Grant, I.
(1984). Human cerebral function at extreme altitude. In
J.B. West & S. Lahiri (Eds.), High altitude and man (pp. 31–
36). Bethesda, DC: American Physiological Society.
Tronick, E.Z., Thomas, R.B., & Daltabuit, M. (1994). The
Quechua manta pouch: a caretaking practice for buffering
the Peruvian infant against the multiple stressors of high
altitude. Child Development, 65, 1005 –1013.
Usui, C., Inoue, Y., Kimura, M., Kirino, E., Nagaoka, S., Abe,
M., Nagata, T., & Arai, H. (2004). Irreversible subcortical
dementia following high altitude illness. High Altitude
Medicine and Biology, 5, 77– 81.
Vázquez, J.C., Marentes, F., Aboitiz, C., Meza, S., & Pérez-
Padilla, R. (2004). Clinical predictors of sleep disordered
breathing in children at moderate altitude. Archives of Medical
Research, 35, 525 –531.
Villena M., Spielvogel, H., Vargas, E., Obert, P., Alarcon,
A.M., Gonzales, C., Falgairette, G., & Kemper, H.C. (1994).
Anthropometry and lung function of 10- to 12-year-old
Bolivian boys. International Journal of Sports Medicine, 15
(Suppl. 2), 75 –78.
Vingrys, A.J., & Garner, L.F. (1987). The effect of a moderate
level of hypoxia on human color vision. Documenta Ophthal-
mologica, 66, 171–185.
© 2006 The Authors. Journal compilation © 2006 Blackwell Publishing Ltd.
Virués-Ortega, J., Buela-Casal, G., Garrido, E., & Alcázar B.
(2004). Neurobehavioural functioning associated with
high-altitude exposure. Neuropsychology Review, 14, 197–
224.
Ward, M.P., Milledge, J.S., & West, J.B (2000). Women, children
and elderly people at altitude. In M.P. Ward, J.S. Milledge,
& J.B. West (Eds.), High altitude medicine and physiology
(pp. 329–335). London: Arnold.
Wesensten, N.J., Crowley, J.B., & Thomas, K.G. (1993). Effects
of simulated high altitude exposure on long latency event-
related brain potentials and performance. Aviation, Space
and Environmental Medicine, 64, 30–36.
West, J.B. (1984). Human physiology at extreme high altitudes
on Mount Everest. Science, 323, 784–788.
West, J.B. (1986). Do climbs to extreme altitude cause brain
damage? The Lancet, 16, 387–388.
Wilmer, W.H., & Berens, C. (1918). Medical studies in avia-
tion: V. The effect of altitude on ocular functions. Journal of
the American Medical Association, 71, 1394–1398.
Wong, S.H., Turner, N., Birchall, D., Walls, T.J., English, P., &
Schmid, M.L. (2004). Reversible abnormalities of DWI in
high-altitude cerebral edema. Neurology, 62, 335–336.
Wu, T., Li, S., & Ward, M.P. (2005). Tibetans at extreme altitude.
Wilderness and Environmental Medicine, 16, 47–54.
Yaron, M., Waldman, N., Niermeyer, S., Nicholas, R., &
Honigman, B. (1998). The diagnosis of acute mountain
sickness in preverbal children. Archives of Pediatrics and
Adolescent Medicine, 152, 683–687.
Yaron, M., Nieremyer, S., Lindgren, K.N., Hohigman, B.,
Strain, J.D., & Cairns, C.B. (2003). Physiologic response to
moderate altitude exposure among infants and young children.
High Altitude Medicine and Biology, 4, 53–59.