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FACULTY OF SPORT, EDUCATION AND SOCIAL STUDIES
BA (Hons) Adventure Education
2015
I certify that the contents of this dissertation, which are not my own work, have been
identified according to author and source.
The influence of acute simulated high altitude on cognitive abilities and neurobiological
functions
By
Max Burrows

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Acknowledgements
I would like to thank everyone who has helped me in completing this important piece of work.
Firstly, John Kelly, for all his advice and support throughout the dissertation process particularly in
the development of the research idea and testing procedure.
Secondly, to thank all participants who gave up their time to be involved in the research,
and to the people who assisted in the running of the testing procedure.
Finally, I would like to thank my parents for their continuous encouragement and for giving up
their time to proof read my work and assist me in its layout and formatting.
Thank you.

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Abstract
Burrows, M. (2015). The influence of acute simulated altitude on cognitive abilities and
neurobiological functions. University of Chichester – Undergraduate Dissertation.
Keywords: Altitude, High Altitude, Hypoxia, Hypoxaemia, Cognitive Function, Blood Oxygen
Saturation, Heart Rate,Corsi Block Test, Eriksen Flanker Task, Finger Tapping Task, Heart Rate
Objective. To investigate the acute physiological and psychological responses to varying degrees of
hypoxia, created by alterations in the inspired oxygen fraction (FIO2). Method. Eight healthy, male
participants (19.4 ± 1.8 years) completed five exposures to a hypoxic environment: 20.3%, 14.5%,
13.5%, 12.7% and 11.9%. Measurements of heart rate (HR), arterial oxygen saturation (%,SpO2),
Finger tapping test scores,Corsi block test scores and Eriksen Flanker task scores were recorded.
Results. The reduction in FIO2 over the five conditions produced a decline in SpO2 (p<.0005) and a
subsequent increase in HR (p= .032). There was a subtle decrease in Mean Finger Tapping Score
however there was a large individual difference and the decrease was not seen to be significant. Corsi
Block memory span remained uninhibited although, First Tap Latency (FTL) significantly increased
(p= .024) over the five conditions. Mean Total Score oscillated with a decreasing FIO2. Congruent
right and left hand response times were observed to be faster than incongruent responses times across
the five conditions yet, response times decreased with a decrease in FIO2. Conclusion. The
magnitude of the acute physiological response to hypoxia occurred relative to the reduction in FIO2.
Neuromuscular control was witnessed to decrease as arterialSpO2 decreased however; the small
sample size restricted it reaching a significant level. There were confounding results associated with
cognitive function. It was demonstrated to decrease over the five conditions although; due to the
psychological tests applied results may have been diluted compared to real life psychology stressors
that could have been

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Contents
Acknowledgements ...................................................................................................................... 2
Abstract.......................................................................................................................................3
Table and Figures ......................................................................................................................... 6
Chapter 1 - Introduction................................................................................................................ 7
Chapter 2 - Literature Review........................................................................................................9
2.1 The High Altitude Environment............................................................................................ 9
2.2 The Effects of Altitude on Cardio-Pulmonary Physiology...................................................... 11
2.3 Cognitive neuroscience and cerebral blood flow ................................................................. 13
2.4 The Effects of Altitude on Neurobiological Functions........................................................... 16
2.5 Summary of Literature Review........................................................................................... 18
Chapter 3 - Method.................................................................................................................... 19
3.1 Participants....................................................................................................................... 19
3.2 Experimental Design.......................................................................................................... 19
3.3 Experimental Measures..................................................................................................... 20
3.4 Experimental Procedure .................................................................................................... 22
3.5 Statistical Analysis............................................................................................................. 22
Chapter 4 - Results...................................................................................................................... 24
4.1 Overview of Results........................................................................................................... 24
4.2 Variations in SpO2 and Heart Rate with Alterations in Inspired Oxygen Fraction..................... 25
4.3 AlterationsinFingerTappingScores,MeanBlockSpan,Mean Total Score andFTL with
Changes in Inspired Oxygen Fraction........................................................................................ 26
4.4 Changes in Cognitive Function with a Decrease in FIO2......................................................... 29
Chapter 5 – Discussion................................................................................................................ 31
5.1 Overview of Discussion...................................................................................................... 31
5.2 The Hypobaric Environment on Arterial Oxygen Saturation and Heart Rate .......................... 31
5.3 The effects of a decrease in FIO2 on Neuromuscular Control and Cognitive function.............. 32
5.4 Implications of Psychological Tests Stimulating a Stress Response........................................ 34
Chapter 6 – Conclusion ............................................................................................................... 36
6.1 Research Findings.............................................................................................................. 36
6.2 Research Review............................................................................................................... 36
6.3 Future Research................................................................................................................ 37
References................................................................................................................................. 38
Appendices ................................................................................................................................ 44

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Appendix A – Participantsinformed Consent............................................................................ 44
Appendix B- Medical Questionnaire......................................................................................... 45
Appendix C- Ethical Application Form...................................................................................... 47
Appendix D- Information Sheet................................................................................................ 63
Appendix E- Data Recording Sheet........................................................................................... 65
Appendix F- SPSS Outputs ....................................................................................................... 66

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Table and Figures
Figure 1: Effects of changes in Arterial PO2 on CBF in anesthetised rats…………………..…15
Figure 2: Effects of alterations in arterial PCO2 on CBF in anesthetised dogs………………...16
Figure 3: Increase in heart rate with a decrease in arterial SpO2 with a continuing decrease in
FIO2…………….………………………………………………..................................25
Figure 4: A subtle decrease in finger tapping scores with a decrease in FIO2………...……..…26
Figure 5: A decrease in mean total score with a decrease in FIO2, mean block span remaining
constant……………………………………………………………………………....27
Figure 6: Increase in first tap latency with a decrease in FIO2……………………………….....28
Figure 7: Variation in congruent right and left hand response time with a decreasing
FIO2……………………………………………………………………….……….…29
Figure 8: Oscillation in incongruent right and left hand response time with a fall in
FIO2……………………………………………………..……………………………30
Table 1: Disturbance to homeostasis due to hypoxia (modified from Severinghaus et al.
1998)…………………………………………………………………………………10
Table 2: Cognitive capabilities as a percentage of sea-level performance for acclimatised
subjects according to McFarland (1972)…………………………………………..…17
Table 3: Participants anthropometric data…………………………………...………………..19
Table 4: Participants testing sequence ……………………………………….….……………19
Table 5: Conditions within the environmental chamber…………………….………………...20

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Chapter 1 - Introduction
Human beings have a tendency for exploration and challenge, nothing symbolises this more than the
achievements made in mountaineering, possibly the most famous being the first successful ascent of
Everest in 1953 by Edmund Hillary and Tenzing Norgay (Unsworth, 2000). Even more outstanding
Reinhold Messner and Gerlinde Kaltenbrunner’s ascents, without supplementary oxygen, of the
world’s fourteen 8000 meter peaks which had previously been deemed impossible by both
mountaineers and medical scientists (Pines, 1979).
Although, altitude physiology does not only find relevance in the field of record setting achievements
but also in many other domains such as transportation and cultural settlements. With the ease and
accessibility of modern transportation the demographic of people visiting altitude has altered. Areas
that were once only available to all but the fittest and knowledgeable natives can now be accessed by
the most unfit and inexperienced tourists (Pollard & Murdoch, 2008). More than 720 million people
around the world are classed as mountain dwellers and over 63.3 million of those live over 2500
meters (Huddleston, Ataman & Ostiani, 2003).
For the purpose of this study, altitude should be taken as the distance above mean sea level. Any
reference made to high altitude refers to an altitude that is equal to or above 1500 meters (Armstrong,
2000). To maintain clarity all altitudes will be shown in meters. Furthermore, altitudes simulated by
altering the oxygen fraction in this study are referred to by the inspired oxygen fraction percentage
(%FIO2).
With increasing levels of altitude there is in turn, a decrease in barometric pressure, resulting in a
decrease in the partial pressure of oxygen. Consequently there will be a deficit of oxygen within the
blood and body tissue (Sharp & Bernaudin, 2004), which could be responsible for the body’s
responses at high altitude.
The body’s acute and chronic reactions to hypoxia can alter physiological and neurobiological
functions of the body because of the decreased oxygen available. Related to this topic there are
controversies regarding the effects of hypoxia on neurobiological function (Horbein, 2001, Ray,
Dutta, Panjwani, Thakur, Anand & Kumar, 2011).
In order to address the above aims, this study will be presented in the following format. Chapter 2
will introduce relevant literature associated with the high altitude environment including the
significant impact of temperature, hypoxia and hypoxaemia has on human physiology. Furthermore it
will investigate the effects of altitude on cardio-pulmonary physiology outlining two important
changes that occur. It will also review cognitive neuroscience and how the brain adapts to hypoxic

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conditions. Finally, it will summarise all the relevant findings associated with the aim of this
experiment. Chapter 3 summarises the methodology detailing what experimental design was
employed and what statistical treatment was used on the results that were gathered and rationale for
the use of the Corsi Block Test, Eriksen Flanker Task and the Finger Tapping Test. Chapter 4 will
present the results of the study detailing any significant findings that were discovered, followed by
chapter 5 which will propose a discussion of the results and possible explanations for the findings and
finally chapter 6 will conclude the findings and suggest possible directions for further research.

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Chapter 2 - Literature Review
This literature review will inspect current research and understanding, relevant to this study, including
the characteristics of a high altitude environment and acute factors that have an impact on an
individual furthermore the effect of the acute factors on the performance of the individual.
2.1 The High Altitude Environment
The high altitude environment presents the body with many physiological challenges; these must be
overcome in order for the human body to maintain homeostasis and perform both mentally and
physically. The same challenges exist within any environment related with an increase in altitude; the
two primary challenges are a decrease in ambient temperature and hypobaric hypoxia (Hainswoth,
Drinkhill & Rivera-Chira, 2007). The decrease in ambient temperature is proportional to the increase
in altitude; temperature is reduced by approximately 1⁰C for every 150 meters ascended (Thomas,
2007). Wind chill, a product of ambient temperature and wind speed, also has a significant impact on
temperature (Thomas, 2007). The possible impact of cold, as well as solar radiation and humidity, on
performance at altitude should not be disregarded; however, the effects of these additional stressors
are outside the aims of this study.
Hypoxia occurs when the rate of oxygen delivery by the body is inadequate to supply all of the body’s
cells with oxygen (Armstrong, 2000). A reduction in the affinity of oxygen at high altitude, known as
hypobaric hypoxia, is, as is often inaccurately expected, not due to a decrease in the percentage of
oxygen available but instead, the reduction in oxygen availability is due to a decrease in the partial
pressure of oxygen (PO2) caused by a decline in pressure produced by high altitude (Armstrong,
2000). Consideration of Boyle’s and Dalton’s laws can be used to grasp the impact high altitude has
on the availability of oxygen. Boyle’s law states that:
For a fixed amount of an ideal gas kept at a fixed temperature, P (pressure) and V (volume)
are inversely proportional (Boyle, 1680).
as atmospheric pressure decreases the weight of air above a given point is reduced. Thus the volume
of air increases allowing oxygen molecules to move further apart reducing PO2. Using Dalton’s law,
which states that:
The pressure of a mixture of gases is equal to the sum of the pressures of all of the constituent
gases alone (Siberberg, 2009).
Using this law, PO2, due to the transition in volume, can be calculated by multiplying the barometric
pressure by the known percentage of a gas:

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Barometric Pressure (mmHg) x Gas (%) = Partial Pressure of an individual gas (Bonnor,
1956, Silberberg, 2009).
Therefore:
Sea level 760 mmHg x 20.93% = PO2 159.07 mmHg
3000m 537 mmHg x 20.93% = PO2 112.39 mmHg
3500m 505 mmHg x 20.93% = PO2 105.70 mmHg
4000m 475 mmHg x 20.93% = PO2 99.41 mmHg
4500m 447 mmHg x 20.93% = PO2 93.56 mmHg
A resulting decrease in PO2 due to an increase in altitude overall means that there is less oxygen
available to the body’s cells, gas exchange depends on a diffusion gradient; a reduction in the
atmospheric PO2 not only means that there is a decrease in the amount of oxygen reaching the lungs,
but also that arterial PO2 decreases and that the decrease in the diffusion gradient occurs down to the
cellular level (Mazzeo, 2008). At lower altitudes there is only a minimal disturbance to homeostasis;
the effects of hypoxia on the body are not normally significant until above 3000 meters (Hainswoth et
al, 2007) (Table 1).
The disturbance to homeostasis is evident (table 1) when an individual is subjected to altitudes greater
than 3000m. However some data was not provided within the data set presented (Severinghaus et al.
1998), this may explain why no significant changes were observed with Hb and Hct. On the other
hand it contained a very small sample size (N= 7) whom all were healthy men implying that these
results may not represent the general population or that of woman.
Abbreviationsand units:Hb; haemoglobin, PaO2 (t (5) =28.514 p=.0005); arterial oxygen tension,
PaCO2 (t (5) =7.948 p=.001); arterial carbon dioxide tension, pHa (t (5) = -4.257 p= .008); arterial
pH, Hct; haematocrit (%),(*
signifies significance (p<0.05) from Sea Level).

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2.2 The Effects of Altitude on Cardio-Pulmonary Physiology
The proportion of atmospheric oxygen remains constant up to the limit of the troposphere (Approx.
15,000m) however oxygen pressure drops rapidly with altitude (Virués-Ortega, Garrido, Javierre &
Kloezeman, 2006). This in turn leads to a reduction in alveolar oxygen pressure; associated with
decreased oxygen concentration within the blood. On exposure to hypoxic environments numerous
vital physiological and metabolic alterations occur, in order to preserve tissue oxygenation (Mazzeo,
2008, Calbet & Lundby, 2009). Chemoreceptors in the carotid bodies and aortic arch are stimulated
by low arterial PO2, known as hypoxaemia (Wilmore, Costill & Kenney, 2008). Compensatory
effects of hypoxaemia include the degree of constriction and systemic resistance of blood vessels,
increasing ventilation and also increasing sympathetic activity, which is responsible for an increase in
heart rate (Bärtsch & Gibbs, 2007).
These acute responses increase oxygen delivery and transportation around the body, in an attempt to
maintain adequate oxygen supply to the tissues due to a reduction in the arterial PO2. This is
demonstrated by numerous studies that used microneurographic recordings of sympathetic discharge
to the skeletal muscle vascular bed (Duplain, Vollenweider, Delabays, Nicod, Bartsch & Scherrer,
1999). The increase in the vasoconstrictive drive is suggested to counteract the hypoxic vasodilator
mechanisms and maintain arterial blood pressure. Furthermore it is possible for the body to react to
reduced PO2 through the use of anaerobic metabolic pathways. However, these are both ineffective
and unsustainable for all but the shortest reactions to hypoxaemia (Calbet & Lundby, 2009). This
next section is going to discuss the most significant acute changes associated with hypoxaemia;
specifically, cardiac output and pulmonary ventilation.
Cardiac output is the product of stroke volume and heart rate. Cardiac output and the volume of
oxygen utilised by the body can be defined using Fick’s principle, which states that the volume of
oxygen (VO2) demand is met be the product of cardiac output (Q) multiplied by the difference
between arterial and venous oxygen:
Fick’s Principle
VO2 = Q x (a – v)
Fick’s principle shows that with a compromised supply of oxygen, due to exposure to high altitude,
there will be a resulting increase in cardiac output to counterbalance the reduction in arterial PO2.
Therefore, due to the increase in cardiac output for a given submaximal workload, VO2 remains stable
from sea level values (Mazzeo, 2008).

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Pulmonary Ventilation. Increased ventilation due to hypoxaemia is mainly associated with an
increase in tidal volume; however respiratory frequency has been shown to increase
(Wilmore et al. 2008). Respiration is primarily controlled by alterations in the partial pressure of
carbon dioxide (PCO2) within the arteries but similarly by arterial partial pressure (PaO2) in hypoxia
(Mazzeo, 2008). An increase in PCO2 and a decrease in blood pH, because of exposure to a hypoxic
environment stimulate the inspiratory centre located within the medulla oblongata (Solomon, 2000) to
increase respiration, in order to remove the build-up of carbon dioxide (CO2). The increase in
ventilation decreases CO2 concentration in the alveoli, causing PCO2 levels to decrease and the blood
pH to increase, known as respiratory alkalosis (Mazzeo, 2008). Respiratory alkalosis causes the
oxyhaemoglobin saturation curve to shift to the left, meaning haemoglobin is more easily saturated
with oxygen (Willmore et al. 2008). Conversely, the alkalosis also restricts the acceleration in
ventilation; although, this is supressed by the hypoxic drive, allowing an increased rate and depth of
respiration to be maintained (Armstrong, 2000). The maximum response occurs within the first five
minutes of exposure (Talbot, Balanos, Dorrington, Robbins, 2005). Breathing 11% O2 for 30 minutes
can increase pulmonary artery pressure from 16 to 25 mmHg (Zhao, Mason, Morrell, 2001).
The Alveolar Gas Equation (Fenn, Rahn & Otis, 1946) which is used to asses if there is a normal
diffusion rate within the alveoli sacs, can demonstrate the importance of this strong response to an
hypoxic environment.
Alveolar Gas Equation:
PAO2 = [FiO2 (Patm – PH2O)] – (
𝑃𝑎𝐶𝑜2
𝑅𝑄
)
Where FiO2= Fraction of inspired air, Patm=Barometric pressure, PH2O=Partial pressure of water
vapour, PaCO2 =Arterial partial pressure of CO2 and RQ=Respiratory Quotient.
A decrease in FIO2 will reduce the total partial pressure of inspired air, therefore the alveolar-arterial
gradient will be reduced causing a decrease in PaO2 (Zhao et al. 2001).
In order calculate the alveolar-arterial gradient (A-a gradient) which states:
A-a gradient = PAO2 –PaO2
You must consider two equations. These are the Alveolar gas equation which assesses alveolar
concentration of oxygen (A) and the Arterial blood gas equation which assess arterial concentration of
oxygen (a) which can be acquired from an ABL90 FLEX blood gas analyser. In cases of high
altitude, there will be a reduction in PAO2 which will adversely reduce PaO2 however the A-a gradient

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should be normal as it is just low barometric pressure (Sylvester, Cymerman, Gurtner, Hottenstein,
Cote, Wolfe, 1981).
2.3 Cognitive neuroscience and cerebral blood flow
The human brain represents 2% of the total body weight and at normal function consumes 20% of
total body oxygen and 25% of glucose (Sokoloff, 1976). Cognitive function is not a passive process,
in which we retain information via the environment. Alternately, there are many variables that have
an effect. Such as past experiences in which Janowsky, Shimamura & Squire (1989) demonstrated six
patients with damage to their medial temporal lobe (MTL) are still able to form new memories
however; they are unable to state where or when these memories occurred, giving significance to the
MTL in recalling information. Although this raises a question, on whether impaired temporal order
memory reflects a specific deficit in temporal processing or it is a part of a broader cognitive deficit
and also glycaemic state where moderate episodes of hypoglycaemia have proven to cause short term
cognitive deficits, Cox, Gonder-Frederick, Kovatchev, Julian & Clarke (2000) observed individuals
with blood glucose levels between 4.0 and 3.4 mmol/L engaging in some form of less safe driving
during a simulator performance however they did not manage to identify the exact level of which
cognitive performance was impaired signifying that blood glucose levels to be idiosyncratic.
Cognitive function is an umbrella term that is related to all mental abilities, such as, working memory,
judgement, reasoning and perception. The foremost goal of cognitive neuroscience is to comprehend
the specific neural mechanisms that underlie cognitive control (Kerns, Cohen, MacDonald, Cho,
Stenger & Carter, 2002).
There have been two regions of the brain that are associated with cognitive control; these are the
anterior cingulate cortex (ACC) and the prefrontal cortex (PFC). The PFC is more commonly
accepted to be involved in implementing control and the ACC has appeared to be involved with
monitoring the processing of confliction however this region is a small part of a larger structure and
so monitoring processes of conflict may be part of a family of responsibilities (Kerns et al. 2002).
Brain function and tissue integrity are dependent on a continuous and sufficient supply of oxygen
(Ando, Hatamoto, Sudo, Kiyonaga, Tanaka & Higki, 2013, Turner, Byblow & Gant, 2015). In order
to maintain a continuous supply of oxygen the vascular vessels around the brain must be highly
sensitive to acute changes in PaO2. Cerebral Blood flow (CBF) has two major determinants which are
the metabolic activity of the brain (Schmidt, Kety and Pennes, 1945) and arterial gas tension (Kety
and Schmidt, 1948). The next section is going to discuss the two major determinants of CBF.
Neuro-metabolic Activity. Glucose is the obligatory energy substrate for the human brain (McEwen
& Sapolsky, 1995). However under particular circumstances the brain has the ability to use other

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blood-derived energy substrates, such as ketone bodies during development and starvation (Nehlig,
2004). Glucose enters cells through specific glucose transporters (GLUTs) and is phosphorylated by
hexokinase (HK) to produce glucose-6-phosphate. Glucose-6-phosphate can be processed by
different metabolic pathways, the main process being glycolysis. Similarly there is the pentose
pathway and glycogenesis. Overall, glucose is almost entirely oxidized to CO2 and water (H2O)
(Clarke & Sokoloff, 1999). However, as evidenced by the different metabolic routes, neural cells may
not necessarily metabolise glucose to CO2 and H2O. There are a wide range of metabolic
intermediates formed from glucose that can be oxidized for energy production e.g. lactates, pyruvate
or acetate (Zielke, Zielke & Baab, 2009). There is a tight coupling that exists between energy demand
and energy supply within neural energy metabolism. Undeniably, task-dependent increases in
cerebral activity are habitually accompanied be changes in CBF and glucose utilization. Positron
emission tomography (PET) allows determination of the cerebral metabolic rate of glucose
consumption (CMRglc), the cerebral metabolic rate of oxygen consumption (CMRO2) and CBF.
(Raichle & Mintun, 2006, Figley & Stroman, 2011).
As neurons are accountable for most of the energy consumption during brain activity, it was rationally
assumed that CMRglc measurements from F-fluoro-2-deoxyglucose PET signals directly affected the
neuronal use of glucose (Sokoloff, Reivich, Kennedy, Des Rosiers, Patlak, Pettigrew, Sakurada &
Shinohara, 1977). Conversely, during the mid-1980s there were a chain of important PET studies that
challenged this rationale. In conscious adult humans, it was observed that activity dependent
increases in blood flow and glucose utilization were only narrowly matched by parallel increases in
O2 consumption (Fox & Raichle, 1986). Such uncoupling between CBF and CMRO2 led to the
development of blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging
(fMRI) contrast (Raichle & Mintun, 2006). These seminal observations supported the belief that the
metabolic needs of active neural tissues were met partially by non-oxidative glucose metabolism
giving empirical demonstration that both oxidative and non-oxidative processes are involved to match
the increased metabolic requirements (Figley & Stroman, 2011).
Cerebral Arterial Gas Tension. Blood gas tension refers to the partial pressure of gasses within the
blood (Severinghaus, Astrup & Murray, 1998). A decrease of arterial oxygen content due to hypoxia
will mediate cerebral vasodilation and at a normal perfusion pressure a successive increase in CBF.
Figure 1 below, shows usual results found in anesthetised normocapnic rats. CBF was little changed
as arterial PO2 falls to 60mmHg but with a further decrease there is a significant increase in CBF
(Borgstöm, Jóhannsson & Siesjö, 1975).

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The results from figure 1 were recorded from anesthetised animals where the PCO2 was kept constant.
Yet in a conscious human or animal the hyperventilation caused by hypoxaemia will cause a decrease
in PCO2 and an increase in PH which will lead to vasoconstriction. Therefore these results cannot be
applied to an individual at altitude. Although this study holds importance as it separates the effects of
increasing PO2 with a decrease in CO2 by keeping one constant, demonstrating the significant
relationship the two have with one another when both are active (figure 2) furthermore as rats are
warm blooded mammals with similar organs and hormones (Chandra, Sengupta, Goswami & Sarker,
2013) it can give an accurate comparison to a human being.
The vasoconstriction effect mediated from low arterial PCO2 consequently reduces CBF. Figure 2
demonstrates typical results in anesthetised dogs where they were made hypocapnic by increasing
ventilation or hypercapnic by adding carbon dioxide to the inspired gas. Levels of PO2 were kept at a
normoxic state (Harper & Glass, 1965).
Figure 1: Effects of changes in Arterial PO2 on CBF in anesthetised rats
(Borgstöm et al. 1975).

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As shown by figure 1 and figure 2 the two effects of hypoxaemia and hypocapnic will clearly have
opposing effects on CBF within humans at altitude. There have not been systematic studies on CBF
at various levels of altitude partly due to the difficulties with measuring CBF.
2.4 The Effects of Altitude on Neurobiological Functions
Cognitive function at altitude has received reasonably little attention within hypoxia literature
(Virués-Ortega et al. 2006), compared to the background of physiological literature research into this
area, which has seen considerable development (Smith, 2005, Smith, 2006, Kramer, Erickson &
Colcombe, 2006). This could be due to the fact that the natural settings of these studies may result
with an inconsistent methodology affecting reliability (Bahrke & Shukitt-hale, 1993, Virués-Ortega et
al. 2006). McFarland (1932, 1937 & 1972) was possibly the first investigator to apply psychological
methodology in the study of the effects on cognitive function from oxygen deprivation. He observed
only minimal impairment at low altitude (2500m), alternatively more complex processes, such as,
arithmetic and decision making were effected at higher altitudes, <3500m,(table 1). Although
anecdotal evidence that was compiled from several studies by McFarland (1972, Table 2) on cognitive
capabilities is plentiful, Foster (1984) presented findings from nineteen participants signifying there
was little quantitative reduction in cognitive ability at ~4200m, measurements of motor speed and
information recording showed no significance from sea level performance. McFarland’s seminal
work provided the motivation for subsequent studies investigating the effects of cognitive function at
high altitude (Virués-Ortega, Buela-Casal, Garrido & Alcázar, 2004).
Figure 2: Effects of alterations in arterial PCO2 on CBF in anesthetised
dogs (Harper & Glass, 1965).

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Table 2. Cognitive capabilities as a percentage of sea-level performance for acclimatised subjects
according to McFarland (1972).
Altitude Visual Sensitivity Attention Span Short-term memory Arithmetic Ability Decision making
2500m 83% 100% 97% 100% 100%
3500m 67% 83% 91% 95% 98%
4200m 56% 70% 83% 92% 95%
5000m 48% 57% 76% 86% 90%
The brain is reliant on a continuous and uninterrupted supply of energy to maintain action potentials
and signalling activities. Impairment of this supply chain such as hypoxia will compromise brain
function and lead to pathogenesis of neurological conditions (Turner et al. 2015). Physical and
psychological stressors, such as hypoxia will provoke the activation of the sympathetic nervous
system. This in turn will cause the secretion of catecholamine epinephrine and norepinephrine and
glucocorticoids by the adrenal gland (Kumar, 2011). The catecholamine-mediated effect on memory
may rise due to enhanced delivery of oxygen to the brain. This is instigated due to the body’s
increased heart rate and ventilation rate.
Pre twenty first century, it was suggested that people could function perfectly well, up to altitudes of
3658m and even higher for short periods of time (Bahrke and Shukitt-Hale, 1993). One study
suggested that an ascent to 3048m produced no symptoms of hypoxia within resting individuals
(Ernsting, 1978).
Post twentieth century, advances in military aviation inevitably meant that individuals could move
quickly from sea level to over 3048m in a few minutes. This is a far shorter time than is necessary for
acclimatization. During a recent study of 53 Australian helicopter aircrew of which 75% reported
experiencing at least one hypoxic symptom during flights between 2437m and 3048m (Smith, 2005).
The most common symptom was ‘difficulty with calculations’ (45% of the air crew reported this).
However the survey also showed that non-pilot aircrew reported a significantly higher number of
symptoms. This may possibly be mediated from the fact that non-pilot crew have increased physical
roles leading them to becoming more susceptible to the effects of hypoxia A follow- up study
revealed that symptoms of hypoxia at 3048m were intensified greatly by physical exertion (Smith,
2006, Ando et al. 2013) a characteristic of non-pilot aircrew. Exercise increases the requirement of
O2, since PO2 is reduced at altitude which leads to a decrease in PAO2 and then ultimately a reduction
in PaO2. The body attempts to compensate this handicap by increasing cardiac output and ventilation
rate however due to acute exposure this initial response is unable to supply the body with sufficient
oxygenated blood resulting in a decrease in performance. Although contemporary studies (Kramer et
al. 2006, Hillman, Erickson & Kramer, 2008, Ando et al. 2013) suggest that regular aerobic exercise
can improve aspects of cognitive function. Improved aerobic capacity, will allow an individual

18. 18
greater efficiency of diffusing O2 out of inspired air of. This in turn reduces the effects of hypobaric
hypoxia.
A study by Li, Wu, Fu, Shen, Wu & Wang (2000) suggested that mood state and fatigue gradually
decreased at altitudes higher than 6,000 m even for acute exposures of less than 1 hour. Conversely,
other studies, cognitive function, tachycardia and insomnia were reported at an altitude of just 3,500
m for 6½ hours (Missoum, Rosnet, & Richalet, 1992). Hence, the interaction between cognitive
function and hypoxia is still a controversial topic.
2.5 Summary of Literature Review
In summary, with an increase in altitude there is a corresponding, relative reduction in atmospheric
pressure. With this alteration there is a decrease in the PO2 in inspired air (hypoxia) thus a decrease in
arterial PO2 (Hypoxaemia). In order to reconcile the effects of hypoxaemia, physiological adaptations
occur, such as hyperventilation and an increase in cardiac output.
The human brain is very sensitive to acute changes in arterial PO2 and PCO2. Previous research has
suggested that with changes in altitude there will be an equivalent change in cognitive function.
However, there is relatively little literature that assesses cognitive function at various levels of
increasing altitude. This study aims to explore trends that may have been overlooked by other
literature.

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Chapter 3 - Method
3.1 Participants
Eight, male, physically fit undergraduate University students participated in this study.
Anthropometric characteristics are shown in Table 3. Participants volunteered for the study and
completed informed consent forms prior to their involvement (Appendix A). Volunteers who smoked
or who had been at altitude within the last four weeks were excluded. Medical health questionnaires
were completed in order to ensure participants were fit and suitable for testing (Appendix B). All
were informed that they were able to withdraw from the experiment at any time. The study was
approved by the University’s ethics committee (Appendix C).
3.2 Experimental Design
The study was a repeated measures design, with each participant required to complete five exposures
to a hypoxic environment. The altitudes simulated were the equivalent of approximately, 0, 3000,
3500, 4000, 4500 m. Participants were required to complete the experiment at the same time each
day to maintain consistency (Table 4). The testing protocol consisted of acute exposures, completed
over a two week period. Resting measures of arterial SpO2 and heart rate (HR) were recorded whilst
exposed to the hypoxic environment, using a pulse oximeter (%, Datex-Ohmeda 3800). Participants
were required to complete a 30 minute acclimation period in which HR and arterial SpO2 were
recorded. Participants then had to complete three psychological tests with a one minute rest in
between each test. HR and arterial SpO2 were recorded during the second test (CBT), finally during
the five minute rest period HR and arterial SpO2 were recorded one last time.
1 8 3500, 4000, 4500, 3000, 0
Value ± SD
Age (Years)
Mass (Kg)
Height (m)
Resting Heart Rate (b·min-1
)
19.4 ± 1.8
83.8 ± 19.2
182.2 ± 6.4
74 ± 7
Table 3: Participants anthropometric data
Test Group Number Simulated Altitude (m) Testing Order
Table 4: Participants testing sequence

20. 20
0
152.1
20.3 ± 0.3
49 ± 0.5
20 ± 0.7
3000
109.5
14.5 ± 0.3
49 ± 0.6
20 ± 0.5
3500
102.6
13.5 ± 0.3
49 ± 0.6
20 ± 0.5
4000
96.5
12.7 ± 0.3
50 ± 0.3
20 ± 0.4
4500
90.4
11.9 ± 0.3
50 ± 0.4
20 ± 0.3
3.3 Experimental Measures
Simulated Altitudes. Adjustments in altitude were replicated in an environmental chamber (TISS
Model 201003-1). The hypoxic conditions were produced by changing the atmospheric O2, through
adjustment of the FIO2 within the chamber, while maintaining temperature and humidity. The
equivalent ambient PO2 and mean FIO2 are shown in table 4 along with the environmental conditions
for each simulated altitude.
Measures Value ± SD
Equiv. Altitude (m)
Equiv. Ambient PO2 (mmHg)
FIO2 (%)
Relative Humidity (%)
Temperature (°
C)
A review of literature by Hainsworth et al. (2007) suggests that the means of creating hypoxic
environments have varied. They included hypobaric hypoxia through increasing altitudes, such as
Chen et al. (2008), or created within a hypobaric chamber, such as Sevre, Bendz, Hanko, Nakstad,
Hauge, Kasin, Lefrandt, Smit et al. (2001), or hypoxic hypoxia through changes in gas composition
used by Liu et al. (2001). Irrespective of the techniques used in previous research used to create the
hypoxic environment, there was very little variation in physiological results obtained.
Moreover, Hainsworth et al. (2007) literature review highlighted several areas within the
experimental protocol which could be developed. Most research only compared a single altitude with
normoxic condition. Therefore, a decision was made to assess participants over five simulated levels
of altitude, from 0m to 4500m in 500m increments, in order to evaluate developments that may have
been overlooked in previous research. Furthermore, this study examined immediate, acute results of
exposure to a hypoxic environment as, with the exemption of Liu et al. (2001), most previous studies
have looked at the initial effects but only after longer periods of exposure (Sevre et al. 2001). Testing
was completed in an environmental chamber in order to maintain control of the testing environment
and increase the reliability of the results.
Arterial Oxygen Saturation. Arterial SpO2 was recorded every minute for five minutes during the
acclimation period, during the Corsi Block Test and throughout the resting period, using a Datex-
Ohmeda 3800 pulse oximeter (%). The pulse oximeter was placed on the little finger on the left hand.
Pulse oximetry allows for a continuous, non-invasive way of monitoring participants arterial SpO2
Table 5: Conditions within the environmental chamber

21. 21
(Varpula, Karlsson, Ruokonen & Pettilӓ, 2006) and has been demonstrated to show good accuracy
between arterial SpO2 levels of 70% and 100% (Grap, 2002). Pulse oximetry results have also been
revealed to be accurate in hypoxic environments, both in hypobaric hypoxia and hypoxic hypoxia
(Kolb, Farran, Norris, Smith & Mester, 2004).
Cognitive Function
The Eriksen Flanker Task. The Eriksen Flanker Task (Eriksen & Eriksen, 1974) is a development of
choice reaction time tasks,using arrows. The arrow flanker paradigm was chosen because it has been
used in clinical literature on cognitive control (Davelaar & Stevens, 2009). Participants respond to a
centrally presented target while simultaneously trying to ignore presented flanker stimuli, responding
to the identity of the central target with a left (left hand) or right (right hand) button press. Reaction
time (RT) is usually smaller when the flankers are pointing the same way as the central target
(congruent) as opposed to facing the opposite way (incongruent). Eighty trials are presented to the
participant for them to complete as fast as possible. The Eriksen Flanker task was selected for this
experiment as it has high construct validity, having been identified as a measurement for the
inhibitory control, planning, and updating components of the central executive. To date there is no
research present which uses the Eriksen Flanker Task to measure cognitive function at varying
increments of altitude.
Finger Tapping Test (FTT). FTT is an essential component of the Halstead-Reitan Battery (Reiten &
Wolfson, 1993). Primarily, it is a test of simple motor speed however a level of coordination is
required. Russell, Neuringer & Goldstein (1970) discovered the motor strip rostral to the central
sulcus functioning to be most important in motor speed control and they demonstrated this by using
the FTT. Participants are required to form a fist with their right hand and place it on the table; they
then use their index finger to tap the spacebar repeatedly within a ten second period. Emphasis is
made on only moving their index finger and not their whole hand when tapping. FTT scores should
reflect central nervous system dysfunction contralateral to the finger with slowed tapping speed
(Finlayson & Reitan, 1980, Reitan & Wolfson, 1993). Similarly, lateralised damage might still be
apparent without being reflected in a lower tapping score (Reitan & Wolfson, 1993). Participants are
required to have three attempts at the FTT to gain a more accurate baseline measure, in consistent
with Wu, Baraldo & Furlant (1999) who exhibited participants FTT results becoming stable after the
third attempt. A computerised version was applied in this study. Computerised FTT have
demonstrated concurrent validity with the more widely used Halstead-Reitan Finger Tapping Test and
Massey University Finger Tapping Test (Muriel, Leathem & Leathem, 2004).
The Corsi Block Task (CBT) assesses non-verbal memory (Milner, 1972). The CBT requires
participants to observe a sequence of blocks that are lit up on a computer screen and then repeat the
sequence back in order. The order starts with a two block sequence; participants must complete the

22. 22
one out of the two sequences correct before it increases. The maximum length is a nine block
sequence. One study that used the CBT, suggested that during exposure to altitude (4500m) for 24
hours, there was a significant difference in non-verbal memory between sea-level and altitude
(Lemos, Antunes, Santos, Lira, Tufik & Mello, 2012). Nelson, Dickson & Baǹos (2000) compared
the use of a manual CBT to an automated CBT, 30 participants took part (15 Male and 15 Females) in
a repeated crossover design. The results proposed that manual and automated forms of CBT showed
similar results. Therefore, an automated CBT was used in this study. To date, no widely applicable
model for cognitive impairment is available (Lemos et al. 2012).
3.4 Experimental Procedure
Prior to all experiments, participants’ height and mass were recorded (Table 3). Participants were
then required to complete five exposures, on five separate occasions. A hypoxic gas mixture was
used to simulate the changes in ambient PO2 by varying FIO2 (Table 4). Each participant received
approximately one hour of exposure to the hypoxic environment during each session. Recordings
were taken during the acclimation period, during the Corsi Block test and the resting phase.
After collecting anthropometric data, participants were required to attach a pulse oximeter to the little
finger of their left hand. Once equipped, participants were instructed to sit on a chair and rest for 30
minutes. This period, allowed participants to acclimatise to the environmental chamber.
10 minutes into the 30 minute acclimation period, resting levels of HR and arterial SpO2 were
recorded. Once the 30 minute acclimation period finished, participants were instructed to begin the
Eriksen Flanker Task. On completion, participants were required to rest for one minute before
beginning the Finger Tapping Task. After resting for one minute participants began the Corsi Block
Test. Measurements of HR and arterial SpO2 were recorded again during the Corsi Block Test. After
completion of the final test participants were required to rest for one minute before a final recording
of HR and arterial SpO2 was achieved. All recordings of HR and arterial SpO2 were taken every
minute for five minutes (Appendix E). To gain a five minute average value, unless participants
withdrew voluntarily or participants showed sign/symptoms of hypoxia.
3.5 Statistical Analysis
Data was analysed using IBM SPSS (Version 22). Descriptive statistics were first calculated for all
variables. All values are reported as Mean ± SD. Standard deviation has been removed from certain
graphs to maintain clarity. One-way repeated measure analysis of variance’s (ANOVA) were
conducted on all dependent variables in order to assess differences between the five simulated

23. 23
altitudes. Paired sample t-tests were applied to further investigate differences shown. A value of
p<0.05 was considered significant for all analysis conducted.

24. 24
Chapter 4 - Results
From the results gathered there are three important areas that require exploration; the variations in
SpO2 and heart rate with alterations in inspired oxygen fraction, secondly, the alterations in finger
tapping scores, mean block span and mean total score with changes in inspired oxygen fraction.
Finally, changes on cognitive function with a drop in FIO2.
4.1 Overview of Results
Overall, the results exhibit acute psychophysiological and physiological responses that occur in
response to a decrease in FIO2. They also demonstrate a great amount of individual variation, as
shown by the large standard deviation in all measures obtained. The decrease in FIO2,across all five
conditions, stimulated a significant fall in arterial SpO2 in all participants. With this there is a
significant antagonist response in HR. FTT showed a small non-significant reduction with a fall in
FIO2. Block span remained unchanged whereas total score showed a larger variation with a decrease
in FIO2. However, a one-way repeated measure ANOVA did not find it to be significant. Both
congruent and incongruent right hand response times revealed there to be a significant difference with
a drop in FIO2 and that there was a significant difference between 20.3% and 14.5% FIO2 with both
congruent and incongruent right hand response times. Equally congruent and incongruent left hand
response times did not present a significant difference however incongruent left hand response time
showed a significant difference between 20.3% and 11.9% FIO2.

25. 25
4.2 Variations in SpO2 and Heart Rate with Alterations in Inspired Oxygen
Fraction
Arterial Oxygen Saturation. A decrease in SpO2 was observed, with a 21.7% difference in mean
arterial oxygen saturation from 20.3% to 11.9% FIO2 (97 ± 2.0% to 78 ± 3.9% SpO2; Figure 3). After
14.5% FIO2 standard deviation of the mean is shown to progressively increase with a further decrease
in SpO2. A one-way repeated measure ANOVA was conducted and showed a significant difference
(F 4, 28 =59.113 p<.0005) in SpO2 over the five conditions. SpO2 decreased sharply from 20.3% to
14.5% FIO2 and then appeared to be linear from 14.5% to 11.9% FIO2. Also t tests signified
significance was reached at 14.5%, 13.5%, 12.7% and 11.9% FIO2 (t (7) =11.960 p<.0005, t (7) =8.979
p<.0005, t (7) = 9.949 p<.0005 and t (7) =10.563 p<.0005).
Heart Rate. With a decrease in FIO2 and drop in SpO2 there is a resulting 11% rise in HR (77 ± 7.3 to
86 ± 8.4 b·min-1
; Figure 3) from 20.3% to 11.9% SpO2. A one-way repeated measure ANOVA was
conducted and presented a significant difference (F4, 28=3.093 p=.032) in HR over the five conditions.
HR remained unchanged at 14.5% to 13.5% FIO2 however increased discernibly between 13.5% and
12.7% FIO2 but then decreases at 12.7% to 11.9% FIO2. Additionally t tests indicated significance was
achieved at 12.7% FIO2 (t (7) =-2.876 p=.024).
Figure 3: Increase in heart rate with a decrease in arterial SpO2 with a continuing decrease
in FIO2 (*signifies significance (p<0.05) from 20.3% FIO2).
70
72
74
76
78
80
82
84
86
88
90
60
65
70
75
80
85
90
95
100
20.3 14.5 13.5 12.7 11.9
HearRate(b·min-1)
ArterialOxygenSaturation(%)
FIO2 (%)
SpO2
Heart Rate

26. 26
4.3 Alterations in Finger Tapping Scores, Mean Block Span, Mean Total
Score and FTL with Changes in Inspired Oxygen Fraction
Finger Tapping Test. A decrease in FIO2 presented a 1.6% difference in finger tapping scores (62 ± 8
to 61 ± 7; Figure 4) from a decrease of 20.3% to 11.9% FIO2. A subtle disproportionate drop was
observed from 20.3% to 14.5% FIO2. Finger tapping scores plateaued from 14.5% to 12.7% FIO2 with
a slight increase from 12.7% to 11.9% FIO2 then finally plateauing again from 12.7% to 11.9% FIO2.
A one-way repeated measure ANOVA did not find this small change to be significant.
Figure 4: A subtle decrease in finger tapping scores with a decrease in FIO2
45
49
53
57
61
65
69
73
77
20.3 14.5 13.5 12.7 11.9
FingerTapScore
FIO2 (%)
Mean Finger Tap
Score

27. 27
Corsi Block Test. Block span remained unaffected with a subsequent decrease of 20.3% to 11.9%
FIO2 (6 ± 0.74 to 6 ± 0.76; Figure 5) with the greatest deviation from the mean noticed at 14.5% FIO2.
A one-way repeated measure ANOVA showed no significant difference in block span, however a
decrease from 20.3% to 11.9% FIO2 exhibited a 13.5% difference in mean total score (63 ± 16.5 to 55
± 13.9; Figure 5). Mean total score decreased from 20.3% to 14.5% FIO2 then plateaued until 13.5%
FIO2. A visible increase which does not fit with the overall trend can be observed from 13.5% to
12.7% FIO2 in which after mean total score resumed back to a more linear trend at its end point of
11.9% FIO2. A one-way repeated measure ANOVA showed there to be no significant difference.
0
1
2
3
4
5
6
7
8
50
52
54
56
58
60
62
64
66
68
20.3 14.5 13.5 12.7 11.9
MeanBlockSpan
MeanTotalScore
FIO2 (%)
Mean Total Score
Mean Block Span
Figure 5: A decrease in mean total score and with mean block span remaining constant with
a decrease in FIO2.

28. 28
With a decrease from 20.3% to 11.9% FIO2 there was a 57.4% increase in FTL (807 ± 262.4 to
1456.13 ± 745 ms; Figure 6), with the largest deviation from the mean observed at 11.9% FIO2. A
one-way repeated measure ANOVA revealed a significant difference (F4, 28 =3.309 p=.024) over the
five conditions. There was a linear increase from 20.3% to 13.5% FIO2, followed by a shallow
decrease to 12.7% FIO2. FTL increased subtly at 11.9% FIO2. Furthermore t tests indicate
significance was reached at 13.5% FIO2 (t (7) =-4.114 p=.004) and 11.9% FIO2 (t (7) =-2.655 p=.033).
Figure 6: Increase in first tap latency with a decrease in FIO2 (*signifies significance (p<0.05)
from 20.3% FIO2).
0
500
1000
1500
2000
2500
20.3 14.5 13.5 12.7 11.9
ResponseTime(ms)
FIO2 (%)
First Tap Latency

29. 29
4.4 Changes in Cognitive Function with a Decrease in FIO2.
Eriksen Flanker Task. With a decreasing FIO2 (20.3% to 11.9% FIO2) there was a resulting 3.2%
decrease in congruent right hand response time (462.88 ± 56.7 to 448.25 ± 45.6 ms; Figure 6) a one-
way repeated measure ANOVA found this change to be significant (F4,28=3.592 p=.017). Response
time decreased from 20.3% to 14.5% FIO2 which was not expected. From14.5% to 12.7% FIO2
response time increased following a more linear pattern which was anticipated however fell again at
12.7% to 11.9% FIO2. Furthermore, t-tests indicated that significance was reached at 14.5% FIO2 (t(7)
=2.818 p=.026).
Congruent left hand specified a 2.1% decrease in response time (458.70 ± 46 to 449.17 ± 55.6 ms;
Figure 6) with a falling FIO2 of 20.3% to 11.9% FIO2. A one-way repeated measure ANOVA did not
find this to be a significant difference. There is a slight increase in response time from 20.3% to
14.5% FIO2 although there is a shallower increase to 13.5% FIO2. There is a notable drop which does
not fit the fashion of the graph from 13.5% to 11.9%.
410.00
420.00
430.00
440.00
450.00
460.00
470.00
480.00
490.00
500.00
510.00
20.3 14.5 13.5 12.7 11.9
ResponseTime(ms)
FIO2 (%)
Congruent Right
Correct
Congruent Left
Correct
Figure 7: Variation in congruent right and left hand response time with a decreasing FIO2
(*
signifies significance (p<0.05) from 20.3% FIO2).

30. 30
Figure 8: Oscillation in incongruent right and left hand response time with a fall in FIO2 (*
signifies
significance (p<0.05) from 20.3% FIO2).
460.00
470.00
480.00
490.00
500.00
510.00
520.00
530.00
540.00
20.3 14.5 13.5 12.7 11.9
ResponseTime(ms)
FIO2 (%)
Incongruent Right
Correct
Incongruent Left
Correct
A decrease in FIO2 (20.3% to 11.9% FIO2) showed a 4.2% decrease in right hand incongruent
response time (521.24 ± 43.5 to 500.04 ± 47 ms; Figure 7). A one-way repeated measure ANOVA
presented this change to be significant (F4, 28=3.055 p=.033). There is a sharp decrease in response
time from 20.3% to 14.5% FIO2 followed by an equally sharp increase in response time from 14.5% to
13.5% FIO2 it continued to increase less sharply with a decrease in FIO2 to 12.7% FIO2. There is a
steep decrease in response time from 12.7% to 11.9% FIO2. Moreover t-test presented that
significance was reached at 14.5% FIO2 (t(7) =5.328 p=.001).
Incongruent left hand response time exhibited a 7.7% decrease (510.98 ± 49 to 473.17 ± 46.3 ms;
Figure 7) with a decrease from 20.3% to 11.9% FIO2. Although there is a subtle percentage difference
a one-way repeated measure ANOVA did not find it to be significant (F4, 28=2.651 p=.054). There is
a large reduction in response time from 20.3% to 14.5% FIO2 followed by an equally large escalation
in response time from 14.5% to 13.5% FIO2. It continued to increase less sharply with a decrease in
FIO2 to 12.7% FIO2. The largest reduction in response time can be observed at 11.9% FIO2. A t-test
showed that significance was achieved at 11.9% FIO2 (t(7) =3.304 p=.013).

31. 31
Chapter 5 – Discussion
5.1 Overview of Discussion
The observations shown in this study support findings and conclusions made by other studies. Results
displayed that, with an increase in hypoxia these is a decrease in arterial SpO2. With the reduction in
arterial SpO2 there was a rise in HR, possibly produced by an increase in sympathetic tone and vagal
withdrawal. A very slight decrease in FTT was observed however there was a large amount of
individual variation shown, indicating that the effects of altitude will have a more significant effect on
neuromuscular control within some individuals than others. FTL specify evidence that participants
response to sequence presented, is not planned during the sequence but during the time of the end of
one sequence and the beginning of the next response. Contrary to previous studies memory span
remained unaffected, it can be speculated that this was mediated by the increase in HR allowing for an
increase in CBF preventing deterioration of cognitive function, this is supported by the Eriksen
Flanker Task results indicating that the ACC and PFC areas of the brain were able to maintain an
adequate level of cognitive function. Finally, the use of a more pronounced stressor should be applied
to participants inciting a stronger stress response.
5.2 The Hypobaric Environment on Arterial Oxygen Saturation and Heart
Rate
On exposure to a high altitude environment, there will be a reduction in PO2 this in turn will lead to a
further reduction to alveolar PO2 and thus a decrease in arterial PO2 known as hypoxaemia (Bärtsch &
Gibbs, 2007). With a decrease in arterial PO2 there will be a relative reduction in tissue oxygenation
(Armstrong, 2000). In the circumstance of this study hypoxia was not induced through a reduction in
ambient PO2; instead hypoxia was created through reducing FIO2. Comparable techniques were used
by previous studies which produced results similar to those conducted at high altitude (Sevre et al.
2001, Liu et al. 2001).
Arterial Oxygen Saturation. Chemoreceptors within the aortic arch and carotid bodies detect the
subtle differences in PaO2 (Wilmore, Costill & Kenney, 2008). Previous research is undivided on the
findings of arterial SaO2 with increasing levels of altitude; increasing levels of altitude produce a
corresponding decrease in arterial SaO2 (Sylvester et al.1981, Sevre et al. 2001, Liu et al. 2001,
Virués-Ortega et al. 2006). The significant (P<.0005) 21.7% (97 ± 2.0% to 78 ± 3.9% SpO2; Figure
3) decrease in participants arterial SpO2 with a decreasing FIO2 presented in this study is strongly
supported by former observations. The greatest de-saturation was observed at 11.9% FIO2, reducing

32. 32
linearly from 14.5% FIO2. There was also a constant increase in standard deviation from 20.3% to
11.9% FIO2.
Heart Rate. Numerous physiological reactions occur when exposure to hypoxic environments occur in
order to preserve tissue oxygenation (Wilmore, Costill & Kenney, 2008, Bärtsch & Gibbs, 2007,
Mazzeo, 2008). Prior research indicates that with a decrease in FIO2 there is a subsequent rise in HR
partly due to vagal withdrawal and an increase in sympathetic activity (Duplain et al. 1999). It has
been suggested that catecholamine secretion and vagal withdrawal synergistically account for the R-R
shortening and elevation of the P wave (Koller, Drechsel, Hess, Macherel & Boutellier, 1998),
although this was observed at 6000 m it can be assumed that a less prominent response would occur at
lower altitudes. There is significant (p<.032) 11% increase (77 ± 7.3 to 86 ± 8.4 b·min-1
; Figure 3) in
HR with a decrease from 20.3% to 11.9% FIO2.
5.3 The effects of a decrease in FIO2 on Neuromuscular Control and
Cognitive function
Assessment of FTT, CBT and Eriksen Flanker Tasks results, provide an understanding to the acute
changes when an individual is exposed to a hypoxic environment. As previously discussed in the
literature review, the effects of hypoxia can possibly have contradicting effects on neuromuscular
control and cognitive function (Li et al. 2000, Missoum et al. 1992, McFarland 1972, Foster 1984)
regardless of this, numerous interesting trends were observed. This study has provided evidence to
support both arguments concerned with altitude and cognitive function and neuromuscular control.
FTT, CBT and Eriksen Flanker Task scores will now be discussed in relation to a decrease in FIO2.
Finger Tapping Task. A decrease in FIO2 presented a 1.6% alteration in finger tapping scores (62 ± 8
to 61 ± 7; Figure 4) after a decrease of 20.3% to 11.9% FIO2 a one-way ANOVA did not find this
change to be significant. The observed slight decrease in FTT scores can be accredited to the reduced
FIO2 (Sokoloff, 1976, Ando et al. 2014, Turner et al. 2015), since there is a reduction in PaO2 oxygen
for cell metabolism, muscles will become more inhibited with a further decrease in FIO2 (figure 4). An
acute physiological change can be observed within all participants in order to attempt to compensate
for the decrease in PaO2 (Ando et al. 2013) which was an increase in HR (Figure 3). This 11% rise (77
± 7.3 to 86 ± 8.4 b·min-1
; Figure 3) in HR can be a primary reason why there was not a more
significant change in FTT scores with a decreasing FIO2. Participant’s responses were strong enough
to the decreasing FIO2 so that there neuromuscular system was not significantly impaired.
However, Smith (2005) observed helicopter crews and reported that non-pilot crewmen stated they
experienced one or more hypoxic symptom compared to pilots who reported that they did not feel any
or fewer hypoxic symptoms. It was later discovered (Smith 2006) that non-pilot crewmen exerted

33. 33
more physical effort than pilots did. This suggests that if participants HR in this study increased
higher the acute physiological response may not be sufficient enough to compensate (Ando et al.
2013), causing a more dramatic decrease in FTT scores.
Corsi Block Test. The main results demonstrated that with a decrease from 20.3% to 11.9% FIO2,
block span remained unaffected (6 ± 0.74 to 6 ± 0.76; Figure 5) however mean total score decreased
(63 ± 16.5 to 55 ± 13.9; Figure 5) and FTL increased (807 ± 262.4 to 1456.13 ± 745 ms; Figure 6).
Concerning block span, previous studies have identified that an individual is able to hold up to 7 ± 2
numbers or objects within the working memory (Miller 1956, Baddeley, 1992). The results from this
study are consistent with these previous studies. It is demonstrated that with a reduction in FIO2,
individuals are still able to maintain a consistent memory span. This may be explained by the fact that
participants were in a state of rest and the physiological response e.g. increased HR, to a reduced FIO2
(Ando et al. 2013, Smith 2006, Kety and Schmidt, 1948) was able to prevent deterioration of
participants memory span.
Regarding mean total score, which is the product of block span and the number of correctly recalled
sequences until the individual completes the trial correctly, it is therefore considered to be a more
sensitive measure (Kessels, Zandvoort, Postma, Kappelle & Haan, 2000). As individuals recalled
longer sequences the brains ability to store the stimulus within the short-term memory store becomes
increasingly more stressed (Miller 1956). Previous studies (De Renzi, Faglioni & Previdi, 1977,
Milner, 1971) support the notion that the right hemisphere has a higher role in processing visuospatial
short-term memory. It is therefore suggested from the results obtained on total score that certain sub
structures within the right hemisphere have been inhibited by the low cerebral PaO2. One drawback of
Corsi Block scores is the large individual variation, this makes it hard to standardise the scores
(Kessels et al. 2000).
The increase in FTL can give evidence that participants response to sequence presented, is not
planned during the sequence but during the time of the end of one sequence and the beginning of the
next response (Brunetti, Gatto and Delogu, 2014). Furthermore if participants recognised that they
were at altitude they may have taken longer to encode the sequence they observed to guarantee that is
was the correct response (Sackett, 1979, McFarland, 1972). This would subsequently increase the
time participants would take to respond to the stimulus. One way that this study tried to mitigate this
response bias was to randomly order the sequences of simulated altitudes participants were exposed to
(Podsakoff, MacKenzie, Lee and Podsakoff, 2003).
Eriksen Flanker Task. A reduction in FIO2 presented confounding Eriksen Flanker Task results.
Although congruent right hand response time (462.88 ± 56.7 to 448.25 ± 45.6 ms; Figure 6) and
congruent left hand response times (458.70 ± 46 to 449.17 ± 55.6 ms; Figure 6) were always faster

34. 34
than right hand incongruent response time (521.24 ± 43.5 to 500.04 ± 47 ms; Figure 7) and left hand
incongruent response time (510.98 ± 49 to 473.17 ± 46.3 ms; Figure 7) which is consistent to previous
studies (Eriksen &Eriksen, 1974, Davranche, Hall & McMorris, 2009).
This indicates that the ACC and PFC were not significantly impacted by the reduced cerebral PaO2. It
can be inferred that cerebral vasodilation that was mediated from this reduction of cerebral PaO2
caused a successive increase in CBF, (Borgstöm et al. 1975, Harper & Glass, 1965) that was effective
enough to prevent weakening of participant’s cognitive function. This is in agreement with
McFarland’s (1972) meta-analysis of cognitive function, implying that an individual’s cognitive
function may not become significantly weaker until < ~5000m; results obtained from the meta-
analysis were all from unacclimatised individuals and therefore they may be applicable to participants
used in this study.
It can be further derived from the Eriksen Flanker Task results that participants response times in all
conditions to the central target got quicker with a decrease in FIO2. One explanation for this
phenomenon could rely on the experimental design that was applied. A repeated measures condition
was utilised in this study as it requires less participants which was needed due to time constraints.
However, the order of conditions (table 4) may have had an important effect upon participants. Since
participants were exposed to the 4500m before the sea level condition, they would have had more
practice, allowing for improved response times. This order effect (Cozby, 2009) is known as practice
effect. Since sea level was the last condition participants were exposed to they may have become
tired or bored causing response times to become slower (fatigue effect). It has been well documented
that studies lasting over a prolonged period of time can produce two major influences to performance.
Süss and Schmiedek (2000) conducted two studies (N=128 and N=133) in which participants were
tested on batteries of computerised working memory tests. Results demonstrated that although it was
not significant there was a loss of performance due to the cognitive strain.
5.4 Implications of Psychological Tests Stimulating a Stress Response
It should be noted that the Eriksen Flanker Task and CBT tests used in this present study were
designed to elicit a significant stress response within participants. Results from Eriksen Flanker Task
response times show very little increase and memory span during the CBT remained unchanged with
a decrease in FIO2. This is different to the findings of many studies (McFarland, 1972, Foster, 1984,
Smith, 2005, Smith, 2006, Li et al. 2000, Missoum et al. 1992) who demonstrated that there was a
decrease in cognitive function with a following increase in altitude.
Frequently studies have used single, brief exposures to tasks dissimilar to daily stressors, such as
mental arithmetic and reaction time tasks (Smith, 2005, Smith 2006, Virués-Ortega, 2006).

35. 35
Responses produced by these studies and this study are likely to be small as compared to responses in
daily life (Ewart & Kolodner, 1993, Dimsdale, Stern & Dillon, 1988).
Investigators should employ a more socially salient task, such as a public presentation (Saab,
Matthews, Stoney & McDonald, 1989) or a group problem-solving interaction (Brown & Smith,
1992). Such tasks involve stimulating components, including fear of evaluation and implicit or
explicit demands to maintain control in front of a real or simulated audience. All these components
resemble stresses of daily life which will provoke a stronger stress response rather than purely
cognitive stressors. Their use will enhance the ecological validity of the study in the laboratory.

36. 36
Chapter 6 – Conclusion
The aim of this study was to assess the effects of alterations of hypoxia, on acute physiological
responses and neurobiological functions, through the application of psychological tests. The effects
of hypoxia were induced through the reduction of FIO2. This reduction was used to simulate the
decrease in PO2 related to an increase in altitude.
6.1 Research Findings
The findings of this study support the general assumption that, exposure to a hypoxic environment
will facilitate immediate physiological responses. The responses occur due to the decrease in arterial
SpO2. The more significant level of hypoxia the greater physiological response is produced. The
results of this study are in general agreement with previous research, although not all findings
represent the majority of results from former research.
Arterial SpO2 decreased uniformly with a decrease in FIO2. With an ensuing fall in SpO2 there was an
observed increase in HR; it was proposed that the rise in HR delivered an increase in cardiac output.
It can be assumed that the increase in HR is related to increased sympathetic activity and vagal
withdrawal. No change was displayed in CBT memory span, although there were subtle individual
variations. FTL, mean total score and FTT followed former research trends; they became impaired
when participants were exposed to the hypoxic environment. However only FTL was significantly
impaired, this suggests that different areas of the brain may be more susceptible to the reduction in
arterial SpO2. Congruent right and left hand response times were shown to be faster than right and
left incongruent response times in all conditions; however response times were seen to improve with a
fall in FIO2, this contradicts previous research displaying that not only did an increase in altitude have
not effect,it improved the mean response time to the central target. It can be argued that order effects
may have been the reason for this anomaly.
6.2 Research Review
This study has positively contributed to the understanding of the effects of hypoxia on acute
physiological and neurobiological changes. As stated previously this study explored these changes
over a range of simulated altitudes which previous studies have lacked. Although the use of pure
psychological tests to produce a significant stress weakens results as participants may not have
perceived them to be stressful, thus the confounding results gathered. Individual variation was
emphasized by the small sample size; this inevitably meant that responses did not achieve the same

37. 37
level of significance shown in previous studies, leading to obscured trends that would otherwise have
been displayed.
Furthermore, the use of an environmental chamber to simulate a hypoxic environment although,
allowed for a close control of temperature, pressure and FIO2 meant that realistic environmental
stressor as previously discussed such as, cold, solar radiation and wind that would have had an effect
on individuals were not taken into consideration. Therefore this limits the applicability of this study
to real world, high altitude, situations. Finally, participants of this study do not represent the entire
demographic of people who visit high altitude environments moreover comparisons to this study
should be limited to populations likewise to this study.
6.3 Future Research
Future research is needed to address the limitations that were experienced in this study. The effects of
purely psychological tests have been suggested to produce relatively small stress responses as
compared to stressors that resemble real life situations. Therefore research should be conducted using
stressors stated earlier as they produce more ecologically valid results. However such stressors can
elicit a very strong stress response causing psychological harm to participants, thus closer
observations of participants will be required. Conducting future research at a high altitude
environment will allow for all factors that effect and individual to be measured this will further raise
the ecological validity although, the logistics of these experiments may prove to inhibit reliable data
collection. The effects of large individual differences can be mediated by the recruitment of more
participants this will reinforce trends that have been observed.
The results of this study clearly suggest that there is a value for future research to be conducted in this
area. It is anticipated that future results gathered will enable the development of understanding on the
effects altitude has on acute physiological and neurobiological responses. This will inevitably lead to
implements that will improve an individual’s safety and performance at high altitude.

38. 38
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Appendices
Appendix A – Participants informed Consent
Tel: +44 (0)1243 816000
Fax: +44 (0)1243 816080
Bishop Otter Campus,
College Lane,
The University of Chichester Chichester,
West Sussex.
PO19 6PE UK
Consent Form www.chiuni.ac.uk
I, …………………………………………………………. (PRINT NAME)
Herby give my consent to participate in the follow ing test/activity [please delete as appropriate].
[Insert details]
To complete fiveexposuresto a hypoxic (Low Oxygen) environment, whist lyingin a supineposition for five minutes. Measurementsof
heart rate variability, using a three leadelectrocardiograph; bloodoxygensaturation; blood pressure and respiratory rate. Exposure will
be randomised. Oxygencontent inthe fiveconditionswill be approximately 20.3%, 17.4%. 14.5%, 12.0% and9.8%.
By signing this from I confirm that:

The purpose of the test/activity has been explained to me;
I am satisfied that I understand the procedures involved;
The possible benefits and risks of the test/activity have been explained to me;
Any questions w hich I have asked about the test/activity have been answ ered to my satisfaction;
I understand that, during the course of the test/activity, I have the right to ask further questions about it;
The information w hich I have supplied to The University of Chichester prior to taking part in the test/ activity is true and
accurate to the best of my know ledge and belief and I understand that I must notify promptly of any changes to the
information;
I understand that my personal information w ill not be released to any third parties w ithout my permission;
I understand that my participation in the test/activity is voluntary and I am therefore at liberty to w ithdraw my
involvement at any stage;
I understand that, if there is any concern about the appropriateness of continuing in the test/activity, I may be asked to
w ithdraw my involvement at any stage;
I understand that once the test/activity has been completed, the information gained as a result of it w ill be used for the
follow ing purposes only:
[insert details]
Dissertation
NAME OF THE SUBJECT…………………………………
SIGNATURE OF THE SUBJECT…………………………
DATE…………………………………………………………

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Appendix B- Medical Questionnaire

46. 46

47. 47
Appendix C- Ethical Application Form
This form should be used by ALL members ofthe University including undergraduate students,
postgraduate students,staffand those in visiting or emeritus roles who wish to undertake research
involving human participants under the name ofthe University of Chichester.You do not need to
complete this form if your research does notinvolve human participants directlyor indirectly(e.g.
observation studies) (see section 4.1 ofthe Research Ethics Policy(REP) for more information),
however, you are expected to work within the Research Ethics Policyand Researcher Code of
Conduct.The University does not conductresearch on animals.If your proposed projectinvolves
animals in anyway please seek advice from the Research Office before proceeding.
Application for Ethical Approval: For all
applications for ethical approval
Max Burrows
(Staff/PGR/Masters/UG)
THIS FORM MUST BE COMPLETED AND APPROVED by the relevant person(s) and ifcategorised
as Category B it mustbe approved by the Research Ethics Committee (REC) prior to commencement
of research.Full guidance on the Application process can be found in the body and appendices of
the Research Ethics Policy.
REQUIRED DOCUMENTATION Each Application mustbe submitted alongside relevantconsent
forms,information letters/sheets,and debriefing sheets.This documentation should be version
numbered and dated.
Categorisation of applications for ethical approval
Category A projects are less likelyto involve participants from vulnerable groups and/or involve
sensitive issues or areas/activities thatentail a level of risk of distress or harm to participants or
researchers.They only need to be approved by your supervisor and do notneed to be considered by
the Research Ethics Committee.The Research Ethics Policyprovides further guidance on
categorisation and areas ofrisk.
Category B projects need to be considered bythe Research Ethics Committee.The process of
approval can take several weeks or longer depending on the number ofapplications being considered
at any one time and the resolution ofany issues thatare raised by the Committee.Itis fairly common
for applications to be returned for further amendments prior to approval. The Committee expects
applications from students to be of the same qualityas those from staff. A helpful way to consider this
position is to consider the research projectfrom the pointof view of the research participant.
Undergraduate or taught postgraduate student applicants: Your tutors and programme team will
be able to advise you on how and when to complete this form.Your projectsupervisor is responsible
for categorising your application as CategoryA or Category B and for authorising it.Communications
relating to Category B applications should be between the supervisor and the clerk to the Research
Ethics Committee.The studentshould not contactthe clerk directly.
Postgraduate researchstudents: Your PhD supervisor is responsible for categorising your
application as CategoryA or Category B and for authorising it.
Academic Staff: Your line manager is responsible for categorising your application as CategoryA or
Category B and for authorising it.
Emeritus or Visiting roles: The Head of Departmentof the area to which you are linked is
responsible for categorising your application as CategoryA or Category B and for authorising it.
Research Ethics Policy approved at Academic Board 18/6/14. Pro-forma approved at Research Ethics Committee 01/07/2014
Page 1 of 16

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Max Burrows
Section A: Basic information
A1: Title of studies:
Max Burrows: Effects of Simulated Altitude on Neurobiological Functions.
A2: Name of Applicant: (in
collaborative projects,justname the
lead applicant)
A3: Position of Applicants (e.g.
UG/Masters/PGR student,academic)
A4: Programme of study: (for UG or
taught Masters students only)
A5: Department of Applicant:
Max Burrows
Undergraduate Student
Adventure Education BA (Hons)
Adventure Education
A6: Checklist to ensure application is complete. Have you prepared the following documents to accompany
your application for ethical approval, please tick the appropriate column for each of the following:
Document
Confirmation of Ethical Approvalof any other organisation
(e.g. NHS, MoD, National Offender Management Service)
Recruitment information / advertisement (e.g. draft text for email/ poster/socialmedia/letter)
Information sheet for participants
Information sheet for carers/guardians
Information sheet/letter for gatekeepers e.g. Head teacher, teacher, coach
Consent formfor participants
Assent formfor younger children
Documentation relating to the permission of third parties other than the participant, guardian,
carer or gatekeeper (e.g. externalbody w hose permission is required)
Medical questionnaire / Health screening questionnaire
Secondary information sheet for projects involving intentional deceit/w ithholding information
Secondary consent formfor projectsinvolving intentionaldeceit/w ithholding information
Debrief sheet to give to participants after they have participated
Yes No
NO
N/A
YES
YES
N/A
N/A
YES
N/A
N/A
YES
N/A
N/A
Yes
NO
No N/A
N/A
Statements about completeness of the application
For research involving under 18s or vulnerable groups, w here necessary, a statement has
been included on all information sheets that the investigators have passed appropriate
Disclosure and Barring Service1 checks
I can confirmthat the relevant documents listed above make use of document references
including date and version number
I can confirmthat I have proof read my application for ethical approvaland associated
documents to minimise typographicaland grammatical errors
YES
YES
Declaration of the applicant:
I confirm my responsibilityto deliver the research projectin accordance with the University of
Chichester’s policies and procedures,which include the University’s ‘Financial Regulations’, ‘Research
Ethics Policy’, ‘Data Systems and Security Policy’ and ‘Data Protection Policy’ and, where externally
funded,with the terms and conditions ofthe research funder.
Working with under 18’s or other vulnerable groups may require a Disclosure and Barring Service
Check.Contact HR@chi.ac.uk if you are not sure whether you have an up to date and relevantDBS
check or if you require more information.Do note that a DBS check may take several weeks to obtain.
1
Research Ethics Policy approved at Academic Board 18/6/14. Pro-forma approved at Research Ethics Committee 01/07/2014
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49. 49
Max Burrows
Research Ethics Policy approved at Academic Board 18/6/14. Pro-forma approved at Research Ethics Committee 01/07/2014
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50. 50
Max Burrows
Research Ethics Policy approved at Academic Board 18/6/14. Pro-forma approved at Research Ethics Committee 01/07/2014
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