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1 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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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 arterial SpO2 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 Alterations in Finger Tapping Scores, Mean Block Span, Mean Total Score and FTL with

Changes in Inspired Oxygen Fraction ........................................................................................ 26

4.4 Changes in Cognitive Function with a Decrease in F IO2. ........................................................ 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 – Participants informed 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.

Abbreviations and 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

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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

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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

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(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

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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

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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.

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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.

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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

He

ar R

ate

(b

·min

-1)

Art

eri

al O

xyge

n S

atu

rati

on

(%

)

FIO2 (%)

SpO2

Heart Rate

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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

Fin

ger

Tap

Sco

re

FIO2 (%)

Mean Finger Tap

Score

Page 27: Dissertation 2015.8

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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

Me

an B

lock

Sp

an

Me

an T

ota

l Sc

ore

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.

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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

Re

spo

nse

Tim

e (

ms)

FIO2 (%)

First Tap Latency

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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

Re

spo

nse

Tim

e (

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).

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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

Re

spo

nse

Tim

e (

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).

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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

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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

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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

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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 P aO2. 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).

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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.

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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

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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.

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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 five exposures to a hypoxic (Low Oxygen) environment, whist lying in a supine position for five minutes. Measurements of

heart rate variability, using a three lead electrocardiograph; blood oxygen saturation; blood pressure and respiratory rate. Exposure will

be randomised. Oxygen content in the five conditions will be approximately 20.3%, 17.4%. 14.5%, 12.0% and 9.8%.

By signing this from I confirm that:

The purpose of the test/activity has been explained to me;

I am satisf ied 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

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Appendix C- Ethical Application Form

This form should be used by ALL members of the University including undergraduate students, postgraduate students, staff and those in visiting or emeritus roles who wish to undertake research involving human participants under the name of the University of Chichester. You do not need to complete this form if your research does not involve human participants directly or indirectly (e.g. observation studies) (see section 4.1 of the Research Ethics Policy (REP) for more information), however, you are expected to work within the Research Ethics Policy and Researcher Code of Conduct. The University does not conduct research on animals. If your proposed project involves animals in any way 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 if categorised as Category B it must be 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 must be submitted alongside relevant consent 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 likely to involve participants from vulnerable groups and/or involve sensitive issues or areas/activities that entail a level of risk of distress or harm to participants or researchers. They only need to be approved by your supervisor and do not need to be considered by the Research Ethics Committee. The Research Ethics Policy provides further guidance on categorisation and areas of risk.

Category B projects need to be considered by the Research Ethics Committee. The process of approval can take several weeks or longer depending on the number of applications being considered at any one time and the resolution of any issues that are raised by the Committee. It is fairly common for applications to be returned for further amendments prior to approval. The Committee expects applications from students to be of the same quality as those from staff. A helpful way to consider this position is to consider the research project from the point of 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 project supervisor is responsible for categorising your application as Category A 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 student should not contact the clerk directly.

Postgraduate research students: Your PhD supervisor is responsible for categorising your application as Category A or Category B and for authorising it.

Academic Staff: Your line manager is responsible for categorising your application as Category A or Category B and for authorising it.

Emeritus or Visiting roles: The Head of Department of the area to which you are linked is responsible for categorising your application as Category A or Category B and for authorising it.

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Section A: Basic information

A1: Title of studies:

Max Burrows: Effects of Simulated Altitude on Neurobiological Functions.

A2: Name of Applicant: (in collaborative projects, just name 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 Approval of any other organisation (e.g. NHS, MoD, National Offender Management Service) Recruitment information / advertisement (e.g. draft text for email/ poster/social media/letter) Information sheet for participants

Information sheet for carers/guardians

Information sheet/letter for gatekeepers e.g. Head teacher, teacher, coach Consent form for participants

Assent form for younger children Documentation relating to the permission of third parties other than the participant, guardian, carer or gatekeeper (e.g. external body w hose permission is required) Medical questionnaire / Health screening questionnaire Secondary information sheet for projects involving intentional deceit/w ithholding information

Secondary consent form for projects involving intentional deceit/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 confirm that the relevant documents listed above make use of document references including date and version number I can confirm that I have proof read my application for ethical approval and associated documents to minimise typographical and grammatical errors

YES

YES

Declaration of the applicant:

I confirm my responsibility to deliver the research project in 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 of the research funder.

Working with under 18’s or other vulnerable groups may require a Disclosure and Barring Service Check. Contact [email protected] if you are not sure whether you have an up to date and relevant DBS check or if you require more information. Do note that a DBS check may take several weeks to obtain.

1

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Section C: Ethical Review Questions begin:

C1. Does the study involve human participants?

Participants in research are taken to include all those involved in the research activity either directly or indirectly and either passively, such as when being observed part of an educational context, or actively, such as when taking part in an interview procedure.

NB: the University does not conduct research on animals. If your proposed project involves animals in any way please seek advice from the Research Office before proceeding.

Yes/No

YES

If answer to C1 is ‘No’ then you do not need to complete this form and you do not need to seek formal ethical approval. Nevertheless, you are required to conduct your research in accordance with the Research Ethics Policy (REP) and Researcher Code of Conduct.

C2. Why should this research study be undertaken? Brief description of purpose of study/rationale

A wealth of research suggests that cognitive performance decreases in hypoxic conditions. With increasing altitude, barometric pressure decreases, resulting in the reduced partial pressure of oxygen (PO₂) in body tissues and the blood. Consequently, humans suffer physiological and cognitive impairments.

With the number of people travelling to high altitudes increasing, the effects of hypoxia on physiological and cognitive functioning is a subject of great interest. The safety and well -being of people who work at this level is of major concern, including their ability to make justified decisions and react quickly to inevitable changes in the environment. Risk is often amplified in high-altitude settings, therefore the consequences associated with errors in judgement or cognitive faults can be fatal. This area of research requires thorough exploration to ensure personnel at altitude are capable of completing cognitive tasks efficiently.

Although there is substantial research in this area already, to the author’s knowledge, no research to date has investigated the effects of standardised oxygen desaturation on cognitive functioning. Therefore, this study aims to eradicate some of the variables present in previous investigations, in order to gain a richer insight into the effects that hypoxia has on cognitive functioning.

In addition, cardiovascular responses are also altered as demands for oxygen change as hypoxemia occurs. Integrating this, with cognitive stressors allows us to explore what cardiovascular changes are apparent and to what nature does stress and altitude effect the normative role of the cardiovascular system.

C3a. What are you planning to do?

Provide a description of the methodology for the proposed research, including proposed method and duration of data collection, tasks assigned to participants of the research and the proposed method and duration of data analysis. If the proposed research makes use of pre-established and generally accepted techniques, e.g. established laboratory protocols, validated questionnaires, please refer to this in your answer to this question. (Do not exceed 500 words). If it is helpful for the panel to receive further documentation describing the methodology then please append this to your application and make specific reference to it in box 3a below.

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Measuring participants’ neurobiological responses to a Corsi block test, Eriksen flanker task and Finger tap test at 75% Oxygen Saturation (SaO₂). The Corsi block test assesses non-verbal memory. The Flanker test was selected for use as it has high construct validity, having been identified as a measurement for the inhibitory control, planning, and updating components of the central executive. The finger tapping test is a psychological test given to assess the integrity of the neuromuscular system and examine motor control.

The study consists of a repeated measures design, with each participant required to complete one exposure to a hypoxic environment (Environmental Chamber). The study involves 8 male, physically fit undergraduate University students. Participants volunteered for the study and will complete the consent form prior to involvement. Volunteers who smoke or have been to altitude within the last four weeks are excluded. Medical health questionnaires will be completed, in order to ensure participants are fit and suitable for testing.

Measures: Blood oxygen saturation, Heart rate, Electrocardiogram (ECG), Heart rate variability, Blood pressure. Possibility of participants becoming hypoxic during experiment as a result of a decrease in the partial pressure of oxygen. Low blood oxygen saturation (≥75%) may result from exposure to hypoxic environment.

Participants will have their height and mass recorded prior to testing. They will be briefed during their 30 minute acclimatization period inside the environmental chamber before the test begins. Participants will then begin to complete each of the three tests once. After all tests are comple ted, they will be debriefed and be allowed to leave the environmental chamber.

Monitor participants at all time. If participants shows sign/symptoms of hypoxia during the experiment they will be immediately removed from the environment chamber. If blood oxygen saturation falls below 75% they will be immediately removed from the environment chamber. Total laboratory time = 10 hours for all participants to complete all tests in each altitude.

C3b. When are you planning to do it?

Please enter the anticipated s tart and end dates of your study (Consider at which point you will be involving human participants, this would typically be in the data collection/information gathering phase of the project but may be earlier):

01/10/2014 - 26/04/2015

I will be involving human participants between w/c 09/02/2014 – w/c 23/02/2015

C4. Where will the research be undertaken?

Briefly describe the location of the study, provide details of any special facilities to be used and any factors relating to the study site/location that might give rise to additional risk of harm or distress to participants or members of the research team together with measures taken to minimise and manage such risks:

The University of Chichester, Bishop Otter Campus. Environmental Chamber/Lab.

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C5. Who are the participants?

Please indicate the number of participants in each of the groups in the table below. If the precise number of participants is not known then please make an estimate. Please enter ‘0’ in the ‘Numbers in study’ column for those groups that are not included in your study. Please note that the examples provided of different sorts of vulnerability are not an exhaustive list.

Participant

Adults with no known2 health or social problems i.e. not in a vulnerable group:

Children aged 16-173 with no known3 health or social problems:

Children under 16 years of age with no known3 health or social problems:

Adults who would be considered as vulnerable e.g. those in care, with learning difficulties, a disability, homeless, English as a second language, service users of mental health services, with reduced mental capacity4

Identify reason for being classed as vulnerable group and indicate ‘numbers in study’ in next column adjacent to each reason (expand the form as necessary):

………………………………………………..

………………………………………………..

Children (aged <18) who would be considered as particularly vulnerable e.g. those in care, with learning difficulties, disability, English as a second language

Identify reason for being classed as vulnerable group and indicate ‘numbers in study’ in next column adjacent to each reason (expand the form as necessary):

………………………………………………..

………………………………………………..

Other participants not covered by the categories listed above (please list):

List other categories here: ……………………………………………..

0

0

Numbers in study

8

0

0

0

C6a. Is there something about the context and/or setting which means that the potential risk of harm/distress to participants or research is lower than might be expected?

Answer: Yes

Consider if the study is part of routine activity which involves persons with whom you normally work in a typical work context e.g. Teachers working with children in a classroom setting, researchers in the performing arts working with performers, sports coaches working with athletes/players or research involving students in an academic setting.

Optional: Further information to justify answer to 6a

2

3

Known to the researcher

A summary of UK definition of ‘Child’ : http://www.nspcc.org.uk/Inform/research/briefings/definition_of_a_child_wda59396.html

ity_Act_code_of_practice.pdf

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4https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/224660/Mental_Capac

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Participants will be in a controlled laboratory environment. Participants will be required to wear a pulse oximeter, if blood oxygen saturation falls below 75% they will be immediately removed from the environmental chamber.

Participants will be monitored at all times for signs/symptoms of hypoxia. Signs and symptoms that will be observed to give indication of hypoxia will be light-headedness, tingling of extremities, dizziness , nausea, fatigue, confusion and behavioural changes. Oxygen bottles will be available to participants if they require them.

All participants have the right to stop the experiment at any point.

C6b. Are there any conflicts of interests which need to be considered and addressed? (For example, does the research involve students whom you teach, colleagues, fellow students, family members? Do any of the researchers or participants have any vested interest in achieving a particular outcome? See section 9 of the Research Ethics Policy (REP))

Answer: NO

If conflicts of interest are envisaged, indicate how they have been addressed:

C7. How will potential participants in the study be identified, approached and recruited?

Please include details of:

Basis for selection of participants in the study: e.g. participants must be clinically obese adults; participants must be social workers over the age of 50; participants must have achieved Grade 5 in an appropriate musical instrument Any criteria for exclusions (e.g. participants declaring a heart problem will be excluded) How the selection criteria will be applied e.g. Health questionnaire completed prior to joining the study

The means by which the participants will be recruited (e.g. through an advert, through a school, through a sports club), please be specific about the medium of the advertisement/recruitment information (e.g. poster, email, website, social media, word of mouth) and mention any third parties who may be involved in supporting the recruitment.

8 male, right handed volunteers were recruited via word of mouth. Exclusion criteria: Overt Diseases, Medication, Smokers and anyone to have travelled to altitude recently (≥2 months).

C8. Will any payment, gifts, rewards or inducements be offered to participants to take part in the study? See section 11 of the REP.

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Answer: NO

Please provide brief details and a justification:

C9a. Is the process of the study and/or its results likely to produce distress, anxiety or harm in the participants even if this would be what they would normally experience in your work with them? See section 5 of the REP.

Answer: YES

If you answered Yes to 9a, please answer 9b below:

C9b. Is the process of the study and/or its results likely to produce distress or anxiety in the participants beyond what they would normally experience in your work with them?

Answer: NO

If yes this Application must be categorised as ‘B’

Please provide details:

C9c. What steps will you take to deal with any distress or anxiety produced?

E.g. have a relevant professional on-hand to support distressed/anxious participants. Careful signposting to counselling or other relevant professional services. Other follow-up support.

Participants will be briefed before the experiment and debriefed after the experiment. They will be allowed to withdraw at any time.

C9d. What is the potential for benefit to research participants, if any? E.g. Participants may gain an increased awareness of hypoxia issues or acquire new knowledge of themselves.

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Participants may gain an insight into how their body reacts at altitude. Plus, how the cardiovascular system changes as the body undergoes stress in different levels of oxygen.

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C10. Will the study involve withholding information or misleading participants as part of its methodology? (Please refer to sections 6.11 and 10 of the REP for further guidance)

Answer: NO

If ‘yes’ this Application must be categorised as ‘B’

Please provide details:

C11a. Does your proposal raise other ethical issues apart from the potential for distress, anxiety, or harm?

Answer: NO

C11b. If your answer to C11a. was ‘yes’, please briefly describe those ethical issues and how you intend to mitigate them and/or manage them in the proposed study.

C11c Does your proposed study give rise to any potential risk of harm or distress to yourself or other members of the research team? OR is there any risk that you could find yourself in a vulnerable position as you carry out your study.

Answer: YES

If you answer ‘yes’ to either of these points please explain briefly what the risks are and what steps you are taking in order to minimise and manage those risks.

For example does your study involve you in 1-1 interviews in a private setting that might suggest precautions need to be taken relating to lone-working (See section 9 of the REP), Have you considered the likelihood of a participant(s) disclosing sensitive information to you about illegal or harmful behaviour and what actions you would take in such circumstances?

I will be exposed to the hypoxic conditions for long periods of time. I will have frequent breaks and I will be rotating with two other members in order to minimise the risks of exposure to the hypoxic environment.

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C12. Will informed consent of the participants be obtained and if so, how?

Answer: YES

See section 6 of the REP to help you answer this question. Section 6.2 covers research that involves observing behaviour in a public place where gaining informed consent may not be practical or feasib le.

When and how will informed consent be obtained? Will it be written or oral consent bearing mind that oral consent will not be considered adequate other than in exceptional circumstances and must be appropriately justified in your application?

NB: Ethical approval should, as a principle, be sought before research participants are approached.

Participants will complete a consent form which will provide an outline of the experiment includin g the potential risks that are involved. It will inform participants how long they will be required for and that they have the right to stop the experiment at any point.

C13. Is there anyone whose permission should be sought in order to conduct your study? E.g. Headteacher of a school, parents/guardians of child participants.

Answer: NO

When and how will informed consent be obtained and from whom? Will it be written or oral consent bearing mind that oral consent will not be considered adequate other than in exceptional circumstances and must be appropriately justified in your application? If you are seeking to gain ‘loco parentis’ consent from a school rather than seeking individual parental consent please describe your reasoning.

C14. Do you need to seek the permission of any other organisations, individuals or groups other than outlined in section 13? E.g. the Research Ethics Committee of partner or participating organisations. Organisations like the NHS and the Prison Service have specific systems for granting ethical approval for research.

Answer: NO

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Please note that all applications must go through the University of Chichester Application for Ethical Approval process and that they must meet the Research Ethics Policy (REP) requirements. Other prior approval will be taken into account but will not in itself be sufficient to gain University Research Ethics Approval. Each application must normally be accompanied by evidence (e.g. formal statement from the appropriate Ethics Committee) confirming approval by the external body (and any concerns/issues identified). In cases where an external body requires prior approval from the University Research Ethics Policy (such as some NHS work) the Research Ethics Committee (REC) may grant in principle approval pending written confirmation of ethical approval by the external body.

Please describe the permission that is required and how you will be seeking that permission: Please attach any relevant documentation e.g. letter, that relates to the seeking of the relevant permissions.

C15. It is normally required that a participant’s data is treated confidentiality at the outset of, during and after the research study. Will this be the case?

Answer: YES

If the answer is ‘yes’ please describe how you will be maintaining the confidentiality of participants’ data. If the answer is ‘no’ please justify the exceptional circumstances that mean that confidentiality will not be guaranteed. See section 7 of the REP.

Please make reference to measures you are taking to ensure security of data from the point of data collection, transfer from notebooks/voice recorders etc., onto secure devices, to the point of analysis, sharing and final storage. Actions should be in accordance with the University’s Data Systems and Security Policy and Data Protection Policy (in particular see Appendix 4 of the Data Protection Policy for guidance for University staff).

Please provide details:

All participants will be kept anonymous. All data will be stored on an encrypted USB data stick. All data will be destroyed after the results have been gathered and sorted.

C16. It is normally required that the anonymity of participants is maintained and/or that an individual’s responses are not linked with their identity. Will this be the case?

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Answer: YES

If the answer is ‘yes’ please describe how you will be maintaining the anonymity of participants. If the answer is ‘no’ please justify the circumstances that mean that anonymity will not be guaranteed. See section 7 of the REP. NB: in group studies it is likely that each individual in the group will be aware that others in the group are participating in the study – they are therefore not anonymous to each other. However, their identity should not normally be associated with their individual responses. In some studies individual participants may not want their identify known to other participants and the study must be designed and undertaken accordingly.

Please provide details:

Participants will be placed into groups and numbered. Participants will not interact with one another. Discussion of participants will be strictly prohibited.

C17. Will participants have a right to comment or veto material you produce about them?

Answer: YES

Please give details and if your answer is ‘no’ then please provide a justification.

Participants will be provided an opportunity to give feedback about the experiment after they have completed it.

C18. Does the project involve the use of or generation/creation of audio, audio visual or electronic material (e.g. Dictaphone recording, video recording) directly relating to the participants?

Answer: YES

If yes, please describe how the collection and storage of this will be managed bearing in mind data protection and anonymity issues (see section 7 of the REP).

ECG, Heart rate variability. Data will be collected via an ECG and stored on an encrypted USB data stick.

C19. How will the participants be debriefed?

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It is expected that wherever possible all participants will receive some form of debriefing. This might be a verbal debriefing or a written debriefing depending on the context of the study. Debriefing provides an opportunity to remind participants of the procedures and outcomes of the research, and to provide further assurances on areas such as confidentiality, anonymity, and retention of data. Projects that intentionally withhold information or deceive as part of their methodology must include a written debrief sheet. (Please refer to sections 6.1 and 6.2 of the REP for further guidance)

Participants will be verbally debriefed after the experiment. Information will be given about where to go if they feel unwell and what will happen to the information that was collected about them.

C20a. Might the research entail a higher than normal risk of damage to the reputation of the University, since it will be undertaken under its auspices? (e.g. research with a country with questionable human rights, research with a tobacco company. See section 9.3 of the REP).

Answer: NO

C20b. If your answer to 20a was yes, please describe the potential risk to the University’s reputation and how this risk will be mitigated.

C21. Will your results be available in the public arena? (e.g. publication in journals, books, shown or performed in a public space, presented at a conference, internet publication and placing a dissertation in the library. See section 8 of the REP.

Answer: NO

If yes, please provide brief details:

NB: Have you considered the date by which it would be impractical for participants to withdraw their data from your study? Once you have begun to analyse the data or prepare it for publication it is reasonable for you to state that it will not be possib le for a participant to request that their data is removed from the study. You need to make this clear on the information sheet.

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C22. Are there any additional comments or information you consider relevant, or any additional information that you require from the Committee?

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Appendix D- Information Sheet

Information Sheet

[Adventure Education] Academic Department

PLEASE READ THE FOLLOWING CAREFULLY

Study titles:

The influence of acute simulated high altitude on cognitive abilities and neurobiological functions

We would like to invite you to take part in a research study. Before you decide you need to

understand why the research is being done and what it would involve for you. Please take time to

read the following information carefully.

What is the purpose of the research and how will the research be carried out?

This study is important as it can be related to many aspects in the adventure environment. The ability

for humans to adapt physically and mentally to their surrounding environments is essent ial for them

to succeed. The effects of hypoxia, on human physiology are complex, involving the respiratory,

cardiovascular and cerebrovascular systems and their associated autonomic control. This study will

help to uncover key changes that take place within the human body due to hypoxia.

What will you be asked to do?

- You will need to be in an altitude chamber for up to 1 hour 15 minutes, four times.

- You will be required to complete three short cognitive tasks up to 6 times.

The level of detail will be study specific and will depend on the complexity of each research

project.

- You will be given a time slot that you will be required to turn up to.

- There will be no follow up experiments, videoing or interviews.

- Please be aware that if you are a smoker or have recently (1 month) returned from

altitude (3000m <) then you are unable to participate in this study.

- You must not suffer from any cardiac or respiratory diseases

- This is a male only experiment.

- You must be right-handed.

What are the anticipated benefits of participating in the research?

There will be no physical or mental benefits; however you will be contributing to the further

understanding of hypoxia at simulated altitudes and may learn something about your own responses

to hypoxic conditions. The research gathered will be used to further study the effect of altitude.

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Are there any risks associated with participating in the research?

Hypobaric Hypoxia is defined as a reduction in the partial pressure of oxygen, therefore participants

may experience light headedness and/or dizziness. These effects are normally experienced at more

extreme altitudes than this study involves. All participants have the right to leave the chamber if they

begin to experience these effects. Furthermore all participants will be monitored during the entire

time the experiment is taking place.

Do you have to take part?

You are voluntarily agreeing to participate in this study therefore you have the right to leave the

study at any time without reason.

Who can you contact if you have any questions about the project?

Name: Max Burrows

Mobile: 07909094002

Email: [email protected]

What happens if you change your mind and want to withdraw?

If you wish to withdraw your application from the experiment you can send a text, email or give

verbal confirmation that you wish to leave the experiment at anytime.

What will happen to the information collected as part of the study?

The information that is collected during this experiment will be entered into a database for statistical

analysis. The data will be stored on a secure laptop until 15/04/15 and all participants will remain

anonymous throughout the research. You have the right to withdraw from the experiment at any

time without giving a reason, you can choose if you want any data collected about you or the

experiment to be destroyed.

Who can you contact if you have a complaint about the project?

This should be the supervisor for UG, MSc or PhD students, or Head of Department for academic

staff. In other circumstances this could be the Director of Research – Email [email protected]: Phone

01243 812125

This project was approved in accordance with the University of Chichester Research Ethics Policy

on 3rd February 2015.

Thank you for your time

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Appendix E- Data Recording Sheet Resting/Briefing

Time SaO2 Heart Rate

1 Minute

2 Minute

3 Minute

4 Minute

5 Minute

Mean Systolic Pressure Diastolic Pressure

During Corsi Block Test

1 Minute

2 Minute

3 Minute

4 Minute

5 Minute

Mean Systolic Pressure Diastolic Pressure

Resting

1 Minute

2 Minute

3 Minute

4 Minute

5 Minute

Mean Systolic Pressure Diastolic Pressure

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Appendix F- SPSS Outputs

T-Tests

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One-Way ANOVA

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