Physiology & Behavior 139 (2015) 497–504

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Psychological strain: Examining the effect of hypoxic bedrest and confinement Nektarios A.M. Stavrou c,d,⁎, Adam C. McDonnell a,b, Ola Eiken e, Igor B. Mekjavic a a

Department of Automation, Biocybernetics and Robotics, Jozef Stefan Institute, Ljubljana, Slovenia International Postgraduate School Jozef Stefan, Jozef Stefan Institute, Ljubljana, Slovenia Exercise and Sport Science Department, Aspetar Orthopaedic and Sports Medicine Hospital, Doha, Qatar d Faculty of Physical Education & Sport Science, University of Athens, Athens, Greece e Department of Environmental Physiology, Swedish Aerospace Physiology Centre, Royal Institute of Technology, Stockholm, Sweden b c

H I G H L I G H T S • Hypoxia exerts negative effects on mood. • Ambulation ameliorates hypoxia-induced psychological strain. • Sustained bedrest decreases positive emotions.

a r t i c l e

i n f o

Article history: Received 13 August 2014 Received in revised form 1 December 2014 Accepted 3 December 2014 Available online 5 December 2014 Keywords: Psychological strain Mood Bedrest Inactivity Hypoxia Positive affect Negative affect

a b s t r a c t The aim was to assess the effect of a 10-day exposure to the environmental stressors anticipated in future lunar habitats on indices of psychological strain. In addition to the reduced gravity of the Moon, future habitats on the Moon will likely maintain a hypobaric hypoxic environment. The hypobaric environment will eliminate the need for long decompression profiles prior to each extra-vehicular activity. We investigated the indices of psychological strain during three 10-day conditions, designed to assess the separate and combined effects of inactivity/ unloading and normobaric hypoxia on several physiological systems. Eleven male participants underwent three 10-day campaigns in a randomised manner: 1) normobaric normoxic bed rest (NBR), 2) normobaric hypoxic bed rest (HBR) and 3) normobaric hypoxic ambulatory confinement (HAMB). The most negative psychological profile appeared on day 10 of the HBR and HAMB (hypoxic) conditions. Concomitantly, a decrease in positive emotions was observed from baseline to day 10 of the HBR and NBR conditions. Thus, confinement in a hypoxic environment seems to exert a negative effect on an individual's psychological mood. © 2014 Elsevier Inc. All rights reserved.

1. Introduction Due to the normal ambient gas pressure within the International Space Station, preparation for extravehicular activity (EVA) — during which astronauts are enclosed in a space suit at about one third of an atmosphere [1] — requires several hours of slow decompression and oxygen prebreathing to minimise the risk of decompression sickness. To reduce the preparation time for EVAs the ambient gas within future planetary habitats will be hypobaric and hypoxic. Studies have confirmed that the changes observed in several physiological systems over a given period of time in participants rendered inactive and confined to a horizontal position (bedrest), are similar in ⁎ Corresponding author at: Exercise & Sport Science Department, Aspetar Orthopaedic and Sports Medicine Hospital, P.O. Box 29222, Doha, Qatar. E-mail address: [email protected] (N.A.M. Stavrou).

http://dx.doi.org/10.1016/j.physbeh.2014.12.015 0031-9384/© 2014 Elsevier Inc. All rights reserved.

nature and magnitude to those observed in astronauts during a sojourn in space of equal length [2]. The principal effect of the bedrest model is the unloading of the weight-bearing bones, postural muscles and the withdrawal of the head-to-foot gravity vector with its resultant effect on the pressure gradients in blood vessels. Consequently, the bedrest ground-based analogue for studying microgravity effects on physiological systems has also been used to study countermeasures that would minimise the adaptive changes noted in astronauts during their space missions. In addition to physiological changes, previous research on the psychological effect of bedrest has shown a detrimental effect on mood [3,4] and cognitive function. However, the lack of consistency among these findings [5] supports the need for further research. On the other hand, exercise has a positive effect on participants' mood, affect and mental health [6] increasing the positive emotions (e.g. vigour) while decreasing the negative ones (e.g. tension, anger). The effect of exercise on individuals' mood and affect is highly dependent on exercise

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(type, duration, intensity) and on participants' characteristics (age, physical condition). Recently, the estimated 500-day confinement anticipated during a return mission to Mars has been simulated by confining a group of participants to the living quarters envisaged on the space vehicle to Mars. The main aim of the Mars500 study was to investigate the interaction of the crew, performance of various tasks and also to assess the indices of psychological strain. The present study adds a new dimension to such confinement studies, by introducing deconditioning induced by sustained inactivity and physical unloading in a hypoxic environment. Understanding the psychobiological mechanisms of successful adaptation to adverse environments provides important information regarding human function and needs. Several studies have examined the psychological and affective responses to high altitude exposure [7]. Exposure to high altitude with a consequent reduction of oxygen supply to the central nervous system is associated with a variety of neuropsychological impairments [8] including alterations in a person's psychological mood, behaviour and cognitive function. The symptoms that appear during exposure to hypoxic environments include impairments of coordination, vision, cognitive function, alertness, and vigour. Concomitantly, these symptoms are usually accompanied by increases of apathy, anxiety, negative mood, fatigue, confusion, hostility and generally an increase of a person's negative psychological characteristics [7,9,10]. The effects of hypoxia on mood, behaviour and cognitive function seem to be unclear, presumably due to different characteristics measured, methods of measurement as well as in the duration and degree of the hypoxic exposure. In addition, although significant changes in mood, behaviour and cognition are revealed during exposure to high altitude, to a great extent these changes appear related to the substantial individual variation of adaptation to altitude. Thus, large interindividual differences might reflect differences in the cognitive appraisal of the situation, which is important for one's adaptation to a stressful environment [11]. To better capture participants' psychological changes in the present study the Profile of Mood State (POMS) [12] and the Positive Affect and Negative Affect Schedule (PANAS) [13] were used. The POMS and PANAS are two well-established instruments measuring psychological responses in sport and exercise settings [14]. Far from the wide use of the specific instruments in previous research, the reasons for selecting the POMS and PANAS are based on the fact that the choice can provide the opportunity to compare the current findings with previous ones avoiding methodological issues or contradictory results because of the different instruments used. In addition to the above, the construction of the two instruments has been based on the different theoretical background providing a broad approach and comprehensive assessment, which includes “scales assessing fearful/anxious, sad/depressed, and anger/hostile mood, as well as some type of positive affect” (p. 294) [14]. In order to understand the singular and combined effects of hypoxia and reduced gravity on the indices of psychological strain, the present study took advantage of two experimental paradigms. Thus, the purpose of the present research was to examine the psychological responses of participants rendered inactive in hypoxic and normoxic environments. The responses observed during hypoxic bedrest were compared with responses observed during a condition where the subjects were ambulatory and active, but were confined to the hypoxic living quarters. Based on previous research, we expected hypoxia, as well as, bedrest to have a detrimental effect on the participants' psychological profile (an increase of negative and a decrease of the positive psychological characteristics), while we expected exercise to counteract these effects. 2. Material and methods This study was part of a larger research programme investigating the effects of future lunar and planetary habitats on different physiological

systems, specifically, the separate and combined effects of hypoxia and inactivity on the function of several physiological systems. The current study focussed on the indices of psychological strain. 2.1. Participants Participants were recreationally active lowland Slovene residents (b500 m). Eleven healthy males successfully completed the study. Their baseline characteristics were (mean ± SD age: 24.09 ± 2.2 years; stature: 1.80 ± 0.07 m; body mass: 72.5 ± 12.1 kg; BMI: 22.4 ± 3.2 kg·m−2; body fat: 21.7 ± 4.9%; VO2max: 42.8 ± 4.4 ml·kg−1 min−1). The participant recruitment process was based on the European Space Agency (ESA) recommendation regarding the standardisation of bedrest study conditions. Potential participants were recruited through local advertisement and the respondents were invited to attend individual interviews by a panel of investigators. Exclusion criteria included a medical history of respiratory, haematological or cardiovascular illness, recent altitude exposures (b 2 months), participation in dietary programmes (b6 months), the use of drugs or medications and a history of mental illness or depression. The participants were given an extensive briefing regarding the study protocol. All participants gave their written informed consent to participate in the study, which was approved by the National Committee for Medical Ethics at the Ministry of Health (Republic of Slovenia) and performed according to the guidelines of the Declaration of Helsinki. 2.2. Experimental design The 10-day bedrest and hypoxia confinements were conducted at the normobaric hypoxic facility of the Olympic Sport Centre, Planica (Rateče, Slovenia), situated at an altitude of 940 m above sea level. One floor and several laboratories in this facility can be maintained hypoxic by regulating and reducing the fraction of oxygen in the ambient air (fraction of inspired oxygen: FiO2) using a Vacuum Pressure Swing Adsorption (VPSA) system (b-Cat, Tiel, The Netherlands). For the purposes of this study, the participants were exposed to a target simulated altitude of 4000 m. The VPSA generated and delivered an oxygen depleted gas mixture to each hypoxic room. A sample volume of the gas in each hypoxic room was withdrawn automatically every 15 min and analysed for O2 and CO2 contents. In the event that the O2 content of the room differed from the pre-set value an immediate adjustment was made to the O2 delivery. If the FiO2 in the room did not increase to the desired level, a large industrial-type fan would be activated ventilating the room with air from the external environment. In addition, for safety reasons, an alarm would be activated, alerting the staff to the problem. Furthermore, each participant was issued a personal clip-on type of oxygen analyser (Rae PGM-1100, California, USA), which provided an indication of the oxygen fraction in its close proximity. In this manner each participant could also monitor the O2 levels within the room. The participants were invited to take part in three 10-day confinements in this balanced crossover design study. The three conditions were: 1) normobaric normoxic bedrest trial (NBR; actual altitude of 940 m above sea level); 2) normobaric hypoxic bedrest trial (HBR; target simulated altitude equivalent to ~4000 m); 3) normobaric hypoxic ambulatory confinement (HAMB; target simulated altitude equivalent to ~4000 m): in this trial, the participants were ambulatory, but were confined to the hypoxic area of the facility. The participants were divided into one of the above groups. The design of the experimental facility at the Olympic Sport Centre, Planica allowed all the three conditions to be conducted simultaneously. Thus, in the first experimental campaign approximately one third of the participants were in the NBR condition, a third in the HBR and a third in the HAMB conditions. In the second and third campaigns the participants underwent the remaining conditions. The ascent to simulated altitude in the HBR and HAMB trials followed the standard mountaineering guidelines and therefore it was achieved over a three-day period. The target simulated altitudes were therefore:

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day 1: 3000 m, day 2: 3400 m and day 3 and thereafter: 4000 m [15]. The participants were confined to a thermoneutral environment where environmental conditions were kept constant throughout the three study campaigns. As aforementioned, the targeted simulated altitude for the hypoxic conditions was 4000 m. As the actual pressure of inspired oxygen is weather dependent the calculated altitude may vary with changes in atmospheric pressure. Please see below the ambient conditions and the calculations for the simulated altitude within the normobaric hypoxic facility. The three experimental campaigns were conducted over a 7month period, from March to September 2011. The temperatures in the confinement area during the first, second and third campaigns were 23.4 ± 0.3 °C, 21.7 ± 0.2 °C and 21.7 ± 0.2 °C, respectively. The relative humidity during the three campaigns was 28.2 ± 1.5% in the first, 49.4 ± 2% in the second and 45.7 ± 1% in the third campaign. The ascent to a simulated altitude during the HBR and HAMB trials was achieved over a three-day period to minimise the risk of altitude sickness, such that FiO2 on day 1 was maintained stable at 0.1629 ± 0.0005 (simulated equivalent altitude of 2990 m), 0.1549 ± 0.0005 on day 2 (simulated equivalent altitude of 3380 m) and 0.144 ± 0.0002 (simulated equivalent altitude of 3881 m) throughout the remaining period of the hypoxic conditions. The equivalent altitudes were derived from the data of Gallagher and Hackett [16]. The partial pressure of inspired oxygen was calculated according to the formula:

During the bedrest conditions, the participants were allocated one pillow for head support and conducted all of their activities (i.e. hygiene, eating) in the horizontal position. Their limbs, particularly lower limbs, had to remain at the level of their heart at all times. They could turn in their bed, but were not permitted to perform any activity, which would require unnecessary contractions of the leg muscles. During meals and transfer to/from a gurney the participants could support themselves on their elbows. They received 5 meals each day, including breakfast, lunch, dinner and morning and afternoon snacks. Regular showering was conducted in a specialised shower bed. The participants in the HAMB condition conducted a step-exercise twice daily for 30-min. The daily physical activity was designed to maintain a heart rate (HR) equivalent to the HR observed at 50% of their hypoxic VO2max, determined during the baseline period. During the physical activity, HR and oxygen saturation (SpO2) were monitored with a pulse oximeter (3100 WristOx, Nonin Medicals, Minnesota, USA). The training impulse (TRIMP) [18] was derived for each step-exercise performed to ensure a constant level of activity throughout the condition. The purpose of the step-exercise was to mimic the level and amount of daily activity that the participants would normally perform outside of the present study. The purpose of the exercise was not to induce a training stimulus.

  Pi O2 ¼ Pb −PH2 O  Fi O2

2.3.1. Profile of mood states The participants' mood state was measured using the Profile of Mood States (POMS) — Short Form [12]. The POMS is a 37-item selfevaluation questionnaire of six subscales: tension–anxiety, depression–dejection, anger–hostility, vigour–activity, fatigue–inertia, and confusion–bewilderment. The participants' description of their feelings were provided based on a 5-point scale with anchors of 0 representing “not at all” and 4 referring to “extremely”. Several validation studies [19] have supported the internal consistency for the POMS subscales, as well as, for the test–retest reliability of the instrument [12].

where, Pb = ambient pressure and PH2O is the saturation partial pressure of water vapour at body temperature. During the hypoxic conditions (HBR and HAMB), PiO2 was 13.7 ± 0.01 .01 kPa on day 1, 13.1 ± 0.01 kPa on day 2 and 12.2 ± 0.17 kPa for the remaining days of the condition. During the normoxic condition at the altitude of 940 m, PiO2 was 17.9 ± 0.1 kPa. Each 10-day confinement period commenced at 09:00 on day 1 and the participants exited the confinement area at 09:00 on day 11, so that the cumulative exposure for each individual was exactly 240 h. Each confinement period was preceded by a 4-day normoxic period of baseline measurements and proceeded by a 4-day normoxic period of postcondition measurements (also termed recovery period). The interval between the confinement periods was a minimum of twenty-five days or 2.5 times the length of the confinement. This ensured that the physiological status of the participants returned to baseline values. This was confirmed by comparing the baseline values for all three of the confinement periods. The participants were accommodated two per room. The floor of the Olympic Sport Centre, Planica that can be rendered hypoxic is separated into two areas by a glass partition. In the present study, one half of the floor was maintained hypoxic, whereas the ambient air of the other half of the floor remained normoxic. Each part of the floor had a living area and a dining area. The living areas had large couches, on which the bedrest participants could socialise, watch television together and play board games, while retaining the required horizontal posture. The participants started the first day of each 10-day confinement in the same manner. They woke up at 07:00, had a blood sample withdrawn for analysis, voided, completed their morning hygiene, ate a light breakfast and commenced the condition, either NBR, HBR, or HAMB, at 09:00. During each 10-day confinement, the participants followed a daily programme of hygiene, nutrition and experimental trials. The participants were placed on a prescribed diet, ensuring appropriate energy intake based on their in/activity, the results of which are published in a separate paper [17]. The participants conducting the bedrest protocol were under continuous surveillance. Each room had a closed circuit camera, which allowed the duty nurse to monitor their activities.

2.3. Measurements

2.3.2. Positive and Negative Affect Schedule The Positive and Negative Affect Schedule (PANAS) [13] is a selfreport instrument comprising two 10-item moods and was developed to provide measures of positive affect (PA; 10 items) and negative affect (NA; 10 items). Respondents are asked to rate the extent to which they experience each of the emotions that are described in the PANAS items. The participants answer each item based on a 5-point scale with anchors of “very slightly or not at all” (1) to “very much” (5), with intermediate points of 2 repressing “a little”, 3 “moderately” and 4 “quite a bit”. Each affect factor's (PA and NA) total score, ranging from 10 to 50, was produced by adding the 10-items' score in each factor together. The POMS and PANAS questionnaires were presented to the participants in a hardcopy format and they were asked to complete the questionnaires promptly on completion of their other tasks or activities. The participants completed the POMS and the PANAS during the baseline measurement days, specifically two days before the onset of each experimental condition (PRE). Thereafter, they completed the questionnaires on the 5th (D5) and 10th (D10) day of each condition and on the third day of recovery (POST) following each condition. The participants completed the questionnaires based on how they felt at the exact time of answering. The instruments indicated acceptable reliability in the current study (POMS Cronbach's a range = .65–.90 and PANAS Cronbach's a range = .66–.75). 2.3.3. Lake Louis mountain sickness Due to the possibility that acute mountain sickness (AMS) might occur on the ascent to altitude, its presence was assessed with the Lake Louis Mountain Sickness (LLMS) questionnaire [20], which was administered and completed daily at 21:00 during the three campaigns. The LLMS questionnaire is self-reported and involves the participants

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PANAS Score

rating their own perception of five symptoms. The participants were asked to rate each of the following on a scale from 0 to 3: headache, gastrointestinal symptoms, fatigue and/or weakness, dizziness or lightheadedness and difficulty sleeping.

40

*

**

^

35

Positive Affect

30

2.3.4. Cardiovascular variables In order to monitor the participants' well-being daily measurements of pertinent cardiovascular variables were carried out at 16:00. The staff nurse on duty measured arterial pressure (AP) with a manual sphygmomanometer. Heart rate (HR) and capillary oxyhemoglobin saturation (SpO2) responses were monitored using a personal finger oximetry device (3100 WristOx, Nonin Medicals, Minnesota, USA) throughout all experimental conditions.

25 20 15 10 5 HBR

0

NBR

2.4. Statistical analysis

3. Results 3.1. Psychological responses The participants' responses to the PANAS (PA: positive affect, NA: negative affect) and POMS subscales (tension, vigour, anger, fatigue, confusion and depression) in the three experimental conditions (HBR, NBR and HAMB) were examined for significant difference at the baseline measure before the experimental protocol. The results indicated no significant differences among the three experimental conditions on either the PANAS (Pillai's trace V = .494, ns, η2p = .032) or the POMS (Pillai's trace V = .690, ns, η2p = .137) subscales. 3.2. Positive–negative affect (Positive and Negative Affect Schedule, PANAS) A significant Condition (3) × Time (4) interaction was detected (F = 2.592, p b 0.01, η2p = .374) for both of the PANAS subscales (PA and NA). The means and standard deviations of the PANAS subscales are presented in Fig. 1. The results indicated a significant Condition × Time interaction for PA (F = 2.470, p b 0.05, η2p = .141). There was a significant change in the HBR condition (F = 13.961, p b 0.001, η2p = .583), specifically, a reduction of PA from PRE to D5 (p b 0.001) and from PRE to D10 (p b 0.01). While PA was increased on POST it was compared with D5 (p b 0.001) and D10 (p b 0.01). Differences were also noted in the NBR condition (F = 5.557, p b 0.01, η2p = .357), which indicated a decrease of PA

HAMB

35 Negative Affect (NA)

Two 3 (Conditions: NBR, HBR, HAMB) × 4 (Time: PRE, D5, D10, POST) multivariate analysis of variance, with repeated measure on the second factor (RMANOVA) were computed. One RMANOVA was conducted for PANAS subscales and one for POMS subscales. Although, the assumption of equality of covariance matrices was satisfactory at the univariate level (Levene's test), it was violated in some cases at the multivariate level (Box's M test). Therefore, Pillia's trace was chosen as the appropriate multivariate test statistic due to its robustness over test violations [21,22]. Based on the results of the RMANOVA, separate mixed analysis of variance were performed, 3 (Conditions: NBR, HBR, HAMB) × 4 (Time: PRE, D5, D10, POST), on each of the affect (PANAS) and mood (POMS) factors to examine the between-subject condition differences and the within-subject repeated measures of the experimental conditions. In cases where the assumptions of sphericity were not met in the within-subjects repeated measure analyses, based on the results of Mauchly's test of sphericity, the Green-House Geisser correction and the corresponding degrees of freedom, were applied for subsequent F statistic estimation [21,22]. Bonferroni corrected t-tests followed any significant between and within effects in the ANOVA models testing pairwise comparisons [21,22]. The significance level was set at p b 0.05. The Statistical Package for Social Sciences (SPSS 19.0 Win) was used for the statistical analyses.

40

#

30 25 20 15 10 5 0 PRE

D5

D 10

POST

Fig. 1. The participants' subjective ratings of the Positive Affect and Negative Affect Schedule (PANAS) are presented for each intervention; Hypoxic bedrest (HBR: solid black line), normoxic bedrest (NBR: solid grey line) and hypoxic ambulatory (HAMB: broken black line). Positive Affect (PA) is presented in the upper panel, while Negative Affect (NA) is presented in the lower panel for each time point (PRE, D5, D10 and POST) throughout each condition. Data are means (SD). * denotes a significant difference on D5 compared with PRE in HBR. ** denotes a significant difference on D10 compared with PRE in both HBR and NBR. ^ denotes a significant difference from D5 and D10 to POST in both HBR and NBR. § denotes a significant difference on D10 compared with D5 and PRE in HBR. # denotes a significant difference between HAMB and both HBR and NBR on POST.

from PRE to D10 (p b 0.05). However, PA was increased at POST compared to D5 (p b 0.05) and on D10 (p b 0.01). Finally, no significant changes appeared over time in the HAMB condition (F = 0.759, ns, η2p = .071). Furthermore, no significant differences were revealed between the three experimental conditions in the four time measures. With regard to the analysis of the PANAS NA subscale, the results indicated that there was a significant Condition × Time interaction (F = 5.082, p b 0.01, η2p = .253). A significant change for NA appeared in the HBR condition (F = 5.396, p b 0.05, η2p = .350), indicating an increase of NA from PRE to D10 (p b 0.05) and from D5 to D10 (p b 0.05). NA subsequently decreased from D10 to POST (p b 0.05). Finally, no significant changes over Time appeared in the NBR (F = 3.519, p = 0.052, η2p = .260) or the HAMB conditions (F = .567, p = 0.61, η2p = .054). On D10, the participants in the HBR condition indicated higher NA compared with those in the NBR (p b 0.05) and HAMB (p b 0.05), while during the POST measure the HAMB condition indicated higher NA compared with the HBR (p b 0.05) and NBR (p b 0.05). 3.3. Mood (Profile of Mood States, POMS) The Condition (3) × Time (4) interaction for the POMS subscales was significant (F = 2.196, p b 0.05, η2p = .767), suggesting that mood-state changes over time differed depending on the condition. The means and standard deviations of the POMS subscales are presented in Table 1. The analysis of tension showed a significant Condition × Time interaction (F = 5.383, p b 0.001, η2p = .277). The tension values in the HBR trial (F = 9.089, p b 0.05, η2p = .502) changed significantly over time.

N.A.M. Stavrou et al. / Physiology & Behavior 139 (2015) 497–504 Table 1 Subjective ratings (means, M; standard deviations, SD) of tension, vigour, confusion, depression, anger and fatigue derived from the Profile of Mood State (POMS) questionnaire during the second day of baseline measurements (PRE), during days 5 (D5) and 10 (D10) of the intervention and on the third day of recovery (POST) during the normoxic bedrest (NBR), hypoxic bedrest (HBR) and hypoxic ambulatory (HAMB) experimental conditions. Variable

Condition

PRE M ± SD

D5 M ± SD

D10 M ± SD

POST M ± SD

Tension

HBR NBR HAMB HBR NBR HAMB HBR NBR HAMB HBR NBR HAMB HBR NBR HAMB HBR NBR HAMB

2.00 ± 1.27 1.64 ± 1.75 1.09 ± 1.22 10.09 ± 6.58 10.73 ± 5.64 8.09 ± 5.38 0.91 ± 2.39 1.73 ± 3.64 1.00 ± 1.48 2.55 ± 2.58 1.91 ± 2.55 1.73 ± 1.49 1.55 ± 2.02 1.55 ± 1.21 1.09 ± 0.83 0.73 ± 1.42 0.27 ± 0.90 0.45 ± 1.04

1.1 ± 1.66 2.00 ± 2.53 1.45 ± 1.92 4.80 ± 3.55 8.27 ± 6.68 7.00 ± 6.00 2.40 ± 3.24 2.27 ± 2 .57 1.18 ± 2.14 2.80 ± 2.97 1.91 ± 2.81 2.64 ± 2.84 2.00 ± 2.79 0.73 ± 1.27 1.63 ± 1.96 1.90 ± 2.81 0.91 ± 1.30 0.55 ± 1.51

7.00 ± 5.72 1.10 ± 1.37 2.00 ± 1.79 4.70 ± 4.30 7.10 ± 5.22 7.27 ± 7.14 8.70 ± 7.93 0.50 ± 0.85 2.45 ± 3.91 7.40 ± 6.36 3.90 ± 3.03 4.73 ± 4.00 3.20 ± 2.57 1.00 ± 1.76 1.45 ± 2.25 5.3 ± 8.77 0.90 ± 1.52 2.09 ± 3.39

1.09 ± 1.58 1.18 ± 1.25 4.27 ± 6.17 13.00 ± 5.23 14.73 ± 3.41 9.00 ± 7.16 0.36 ± 0.92 0.09 ± 0.30 5.27 ± 6.44 4.00 ± 2.90 3.36 ± 3.53 4.09 ± 3.81 0.45 ± 0.69 0.82 ± 1.25 1.82 ± 3.06 0.55 ± 0.82 0.09 ± 0.30 1.63 ± 4.15

Vigour

Anger

Fatigue

Confusion

Depression

Tension on D10 was higher than PRE (p b 0.05), D5 p b 0.01) and POST (p b 0.05) measures, as well as in POST compared with the PRE (p b 0.05) measure. Finally, no significant tension-level changes appeared over time in NBR (F = .741, p = 0.45, η2p = .076) or HAMB (F = 1.961, p = 0.18, η2p = .164). Examining the differences between the three experimental conditions, significant differences were only revealed on D10, where HBR indicated higher tension compared with the NBR (p b 0.01) and HAMB (p b 0.01) conditions. There was a significant Condition × Time interaction for vigour (F = 2.470, p b 0.05, η2p = .150). The results indicated that vigour significantly decreased in the HBR condition (F = 18.455, p b 0.001, η2p = .672) from PRE to D5 (p b 0.01) and from PRE to D10 (p b 0.01). On the other hand, an increase of vigour was detected on D10 (p b 0.001) and at POST (p b 0.001) compared with D5. Differences were also revealed during the NBR (F = 6.606, p b 0.01, η2p = .423), showing an increase of vigour in the POST measure compared with the PRE measure (p b 0.05). Additionally, vigour was significantly lower on D5 (p b 0.01) and D10 (p b 0.01) compared with the POST measure. Finally, no significant changes over time appeared in the HAMB experimental condition (F = .496, p = 0.62, η2p = .047), or between the experimental conditions across the three time measures. The results for the anger subscale indicated a significant Condition × Time interaction (F = 6.643, p b 0.001, η2p = .322). A significant change in the HBR condition appeared across time (F = 8.110, p b 0.01, η2p = .474). Specifically, anger was increased on D5 (p b 0.05) and on D10 (p b 0.01) compared with PRE and that anger then decreased from D10 to POST (p b 0.05). Additionally, on D10 of the HBR condition anger was higher when compared with the NBR (p b 0.01) and HAMB (p b 0.05). The participants' anger in the HAMB condition was higher in the POST measure compared with the HBR (p b 0.05) and the NBR (p b 0.01) conditions. No significant differences were found across the four time measures for anger in the NBR (F = 2.508, p = 0.11, η2p = .218) or HAMB (F = 3.056, p = 0.09, η2p = .234). In confusion, a significant Condition × Time interaction was detected (F = 2.623, p b 0.05, η2p = .158). The results indicated a significant change in the HBR condition (F = 4.841, p b 0.01, η2p = .350). Post hoc analysis indicated that confusion decreased from D10 to POST (p b 0.05) during HBR. No significant main effect was found for the NBR (F = 2.591, p = 0.07, η2p = .224) or HAMB (F = .360, p = 0.68, η2p = .035). No significant Condition × Time interaction for depression (F = 1.394, p = 0.28, η2p = .091) or fatigue (F = .679, p = 0.62, η2p = .046) was detected.

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Finally the total mood disturbance score (TMD1) [23] based on all POMS subscales was examined across the four time measures among the experimental conditions, signifying a significant Condition × Time interaction (F = 4.438, p b 0.01, η2p = .241) (Fig. 2). A significant change in the HBR condition was detected (F = 8.909, p b 0.01, η2p = .497). The TMD was significantly increased on D10 when compared with PRE (p b 0.01) and D5 (p b 0.05), while there was a tendency for TMD to increase from PRE to D5 (p = 0.059). On the other hand, a decrease of TMD appeared from D5 to POST (p b 0.01) and from D10 to POST (p b 0.01). Regarding the NBR condition a significant change of the TMD was revealed across time (F = 2.966, p b 0.05, η2p = .248). A significant decrease of TMD was detected in the POST measure compared with the D5 (p b 0.05) and D10 (p b 0.01). Finally, no significant differences were revealed across time in the HAMB condition (F = 1.421, p = 0.266, η2p = .124). Examining the differences among the experimental conditions the results indicated that on D10 (F = 4.755, p b 0.05) significant differences were revealed between the HBR and NBR conditions (p b 0.05), while the differences between the HBR and HAMB (p = 0.06) conditions approached statistical significance. There were no significant differences that were also revealed in the POST measure (F = 4.882, p b 0.05) between the HAMB and HBR (p b 0.05), as well as, between the HAMB and NBR conditions (p b 0.05).

3.4. Mountain sickness (Lake Louise Mountain Sickness Score, LLMS) The LLMS scores recorded on D1, D5 and D10 are presented in Fig. 3. There were no statistically significant differences noted between the HAMB, HBR or NBR conditions on D1, D5 or D10. However, taking an average of the LLMS scores over the first four days revealed a significant difference between the hypoxic conditions (HAMB (0.9 ± 1.4) and HBR (1.2 ± 1.2)) and the NBR conditions (0.2 ± 0.2), p b 0.05. The average LLMS scores were less than 3, indicating an absence of AMS. Thus, an analysis of individual results over the first four days was carried out and revealed that one participant presented with mild AMS symptoms in both the HAMB and HBR conditions. Five participants presented with mild AMS symptoms during the HBR campaign. Of the 11 participants, 5 also complained of a headache during the NBR condition.

3.5. Heart rate (HR, min−1), oxygen saturation (SpO2, %) and arterial pressure (AP, mm Hg) The HR, SpO2 and AP values recorded on D1, D5 and D10 are presented in Table 2. There was a main effect for Condition (p b 0.01), Time (p b 0.01) and a Condition × Time interaction (p b 0.01) for HR. Tukey's post hoc analysis indicates that HR increased from D1 to D5 (p b 0.01) and from D1 to D10 (p b 0.01) in the HAMB condition. Additionally, HR on D5 (p b 0.01) and D10 (p b 0.01) were significantly reduced in the HAMB condition compared with that of the NBR. There were no changes in the HBR or NBR conditions. SpO2 showed significant main effects for Condition (p b 0.01) and Time (p b 0.01), however there was no significant Condition × Time interaction. SpO2 significantly decreased from D1 to D5 in the HAMB condition (p b 0.01). Furthermore, SpO2 in the HAMB condition was significantly lower on D1 (p b 0.05), D5 (p b 0.01) and D10 (p b 0.01) than during the NBR condition. There was a main effect for Time on systolic AP (p b 0.05), however Tukey's post hoc analysis revealed no significant difference between the time points D1, D5 and D10. Suggesting that systolic AP is increasing during the 10 day interventions, but there was no difference between the conditions (HAMB, HBR, NBR). Finally, there were no significant effects for diastolic AP.

1

TMD = tension + depression + anger + confusion + fatigue + (24 — vigor).

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Total Mood Disturbance (POMS) *

Table 2 Heart rate (HR), capillary oxyhemoglobin saturation (SpO2) and arterial pressure (AP) recorded at 16:00 on D1, D5 and D10.

** HBR

80

Condition

70

HAMB

60

HAMB

50 HBR

40 30

NBR

20 10 0

PRE

D5

D 10

POST

Fig. 2. The participants' Total Mood Disturbance (TMD) scores are presented for each intervention; hypoxic bedrest (HBR: solid black line), normoxic bedrest (NBR: solid grey line) and hypoxic ambulatory (HAMB: broken black line). The TMD score is calculated from the POMS subscales and are presented for each time point (PRE, D5, D10 and POST) throughout each condition. Data are means (SD). * HBR significantly different to NBR. ** HAMB significantly to HBR and NBR.

3.6. Daily physical activity There was no difference in any of the variables measured during the stepping exercise performed in the morning and afternoon during the HAMB condition. The HR during the morning and afternoon activities were 116 ± 3 and 113 ± 3 min−1, respectively. The SpO2 values were 88.3 ± 0.4 and 88.2 ± 0.4% during the morning and afternoon activities, respectively. The TRIMP values did not vary significantly between the morning (2.2 ± 0.1) and afternoon (2.1 ± 0.1) activities.

4. Discussion The principle finding of the present study is that the changes in positive and negative emotions associated with bedrest are exacerbated by hypoxia. During the ambulatory condition participants did not suffer the same psychological changes, suggesting that ambulation counteracts the effects of hypoxia. The factors that may have contributed to these psychological changes are discussed below.

LLS Mountain Sickness Score

HBR NBR

4

HAMB

AMS threshold Line Lake Louise Score

Day

HR (min−1)

SpO2 (%)

AP (mm Hg) Systolic

Diastolic

D1 D5 D10 D1 D5 D10 D1 D5 D10

68 ± 13⁎

93.5 ± 1.9⁎ 89.9 ± 2.3 90.5 ± 2.7 93.6 ± 2.5 92.1 ± 2.6 90.6 ± 2.7 96.9 ± 1.4^ 96.4 ± 1.9§ 96.5 ± 1.7#

117 ± 9 114 ± 10 127 ± 16 112 ± 12 120 ± 9 124 ± 13 114 ± 9 113 ± 13 118 ± 11

67 ± 6 71 ± 7 76 ± 7 66 ± 7 71 ± 6 73 ± 8 66 ± 6 66 ± 9 66 ± 8

NBR

3 2 1 0 -1 D1

D5

D 10

Fig. 3. The participants' self perceived rating of Lake Louise Mountain Sickness Score (LLMS) is presented for day 1 (D1), day 5 (D5) and after the tenth day (D10) of each intervention: Hypoxic bedrest (HBR: solid black line), normoxic bedrest (NBR: solid grey line) and hypoxic ambulatory (HAMB: broken black line. No difference was noted between conditions at these time points. Data are means (SD).

82 ± 9 89 ± 10⁎⁎ 68 ± 8 77 ± 10 79 ± 8 67 ± 8 67 ± 9§ 74 ± 13#

⁎ Denotes a significant difference between D1 and D5. ⁎⁎ Denotes a significant difference between D1 and D10. ^ Denotes a significant difference on D1 compared with NBR. § Denotes a significant difference on D5 compared with NBR. # Denotes a significant difference on D10 compared with NBR. Data are presented as mean (SD).

4.1. Acute mountain sickness (AMS) Mountain sickness normally occurs upon arrival at altitude, particularly if and when, the ascent rate is fast. At higher altitudes, AMS may develop into high altitude pulmonary oedema or high altitude cerebral oedema. This is unlikely to occur at an altitude of 3881 m as simulated in the present study. More likely, mountain sickness may develop within the first days of ascent, but it will subside with continued exposure to this altitude. The first measures of POMS and PANAS after baseline were derived on day 5, at which point any occurrence of AMS was resolved according to our LLMS score (Fig. 3). Mountain sickness will undoubtedly have an effect on the traits rated by the POMS and PANAS scales, but this correlation was not the aim of the present study. Instead, we wished to examine the effect of hypoxia, in the absence of mountain sickness on the indices of psychological strain. Signs and symptoms of mountain sickness were observed in some participants upon arrival at altitude, but the symptoms were not so severe that a descent to a lower altitude was required. During the second half of the condition, some participants in the NBR condition reported slight headaches, as did the participants in the HBR condition. While such transient occurrences of headaches can influence the LLMS score, they are not consistent with AMS and were therefore attributed to bedrest rather than hypoxia per se.

4.2. The effect of bedrest Positive affect was decreased during NBR on D5 and D10 compared with the PRE measure, while a “rebound” in the positive affect appeared in the POST measure. The same pattern of changes was found in the vigour subscale, whereas the TMD improved in the POST measure compared with during the condition. These results indicate that positive emotions decreased during bedrest and then returned to the initial levels following the conclusion of the condition. On the other hand, it seems that bedrest does not elicit negative emotions (e.g., anger, tension), as indicated by non-significant alterations in these variables. The present findings are in accordance with previous results [3,24]. Presumably, the bedrest-induced reductions in positive emotions can be ascribed to the strict confinement and restriction of body movements, as well as to the isolation away from familiar environments, such as a reduction of or a lack of social interaction [4]. The results reported in the literature regarding the effects of bedrest on cognitive functions and psychological aspects lack consistency and further studies are needed to address the reasons behind these findings [5]. Some studies support a detrimental effect of bedrest [25,26], while others found an improvement during bedrest [3,27] or no change [28].

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Such contradictory findings might be due to the different instruments used, research methodologies applied, participants' characteristics (age, gender) and duration of bedrest exposure. It seems that having a baseline measure in order to examine the potential impact of sustained bedrest compared with the upright position, as the current study did, will resolve some of the methodological problems inherent in previous studies [5]. Understanding the effects of reducing physical activity below that of a sedentary lifestyle has implications for individuals with severely restricted physical activity [29–31]. 4.3. The effect of hypoxia The differences in the emotional state on D10 between the NBR and HBR conditions indicated that the HBR participants had higher negative affect, confusion, tension, anger and total mood disturbance compared with the NBR condition. It thus seems that the HBR elicits negative emotions compared with the NBR, whereas no significant effect seems to be exerted on positive emotions such as positive affect and vigour. This further supports the notion that positive and negative emotions do not follow an opposite pattern and are not reciprocally affected by hypoxia, since alterations appeared only on the negative emotions. Although research findings in bedrest conditions are lacking, the results of the present study are in accordance with previous research findings indicating that exposure to high altitude with a consequently reduced oxygen supply to the central nervous system causes a variety of neuropsychological impairments [7–9]. A possible physiological explanation of the deterioration of psychological responses may be the effect of the hypoxia on the prefrontal cortex and amygdala. Based on previous findings [32], it seems that the prefrontal cortex does not exert a direct mediation of emotional responses, but mainly seems to have a moderating pattern of activity on other parts of the neural circuit that controls emotional responses, such the modulation of the amygdala [33]. According to Davidson and colleagues [4,34,35] the prefrontal cortex exerts an inhibitory control of the amygdala during exposure to aversive stimuli, helping to regulate and shorten the duration of the negative affective responses, while the time course of the positive emotions is accentuated. Davidson et al. [35] conclude that “in the absence of this normal inhibitory input, the amygdala remains unchecked and continues to remain activated” (p. 898). Furthermore, as regards the effect of altitude exposure on psychological indices, additional research is needed to assess whether the observed changes are linked to alterations in an individual's behaviour and cognitive function, factors crucial for performance in adverse environments (e.g., high altitude). 4.4. The effect of activity Examining the differences in the emotional state between the HBR and HAMB indicated that the participants in the HBR condition revealed their most negative psychological profile on D10. Specifically, the participants in the HBR condition indicated more pronounced negative affect, tension, anger and total mood disturbance than those in the HAMB condition. In the HAMB condition, the participants were not confined to the horizontal position as they were in the HBR condition, meaning that activities such as personal hygiene and eating could be completed in the upright position. It seems that the regular daily 30 min of low to moderate physical activity or indeed other activities performed in the HAMB condition reduced the psychological strain noted in the HBR condition. However, no significant differences were found for positive emotions between these two experimental conditions, supporting the notion that the positive and negative emotions did not follow an opposite and inverse pattern during exposure to the experimental conditions. It is also noteworthy that the participants' emotional state continuously deteriorated during the HBR condition, as indicated by significant differences between the baseline measure (PRE) and the measures

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observed during the hypoxic exposure (D5, D10). On the other hand, the emotional status in HAMB remained stable with no differences during the hypoxic exposure, since no differences emerged for positive or negative emotions from PRE or POST measures to D5 or/and D10. The factors associated with the HAMB condition, particularly the daily physical activity, were sufficient to ameliorate the psychological strain of the participants observed during HBR. The purpose of the activity during the HAMB condition was to simulate the cumulative daily activity of the subjects during their normal lifestyle. The activity was not meant to provide a training stimulus. However, future research should focus on the effects of various exercise training programmes on psychological status during hypoxic confinement. The current result is in accordance with previous research findings confirming the positive effects exercise has on mood, emotion, cognitive performance, well-being and brain function [36]. Yeung's [6] review of eighty-one studies regarding the influence of exercise on mood and mental health, noted that the majority (85%) of the studies supported an improvement on mood and this benefit seems dependent on the duration and intensity of the exercise [37,38]. Data from the Mars105 [39] study show that mood was highly correlated with the overall brain cortical activity and that even short exercise programmes were able to restore mood and brain cortical function to pre-isolation values. Presumably, this could be attributed to the increased blood flow and oxygenation in the prefrontal cortex during exercise, as measured with near-infrared spectroscopy [40], causing an inhibition of the amygdala. Ekkekakis and Acevedo [41], based on neuroanatomical and neurophysiological findings, indicated that the amygdala appears to be a key component in the coordination and regulation of the affective responses during exercise. However, other studies showed no effect of exercise on mood and emotion. DeRoshia and Greenleaf [27] indicated that exercise training during 30-day bedrest experiments did not counter the deterioration of psychological mood; similar results were found by Ishizaki and colleagues [3]. The contradictory results suggest that further research is needed to clarify the effect of exercise during bedrest and confinement. Presumably, these inconsistencies could be attributed to the participants' characteristics (age and/or physical condition), types of exercise (duration, frequency, intensity), and the instruments' used to examine participants' emotional state (mood, affect, emotion). Ultimately, further work is also required to examine the effect of exhaustive exercise, as would be performed by athletes during training on psychological strain. 4.5. Implications for patients with chronic illnesses rendering them hypoxic The patients with a chronic disease rendering them hypoxic, such as chronic obstructive pulmonary oedema, may not only have hypoxiainduced elevated levels of psychological strain, but a substantially reduced exercise capacity. Whether the ability of these patients to become more active would also reduce their psychological strain remains unresolved. 4.6. Implications for planetary habitats During exposures to microgravity on the International Space Station (ISS) and moderately reduced gravity in future habitats on the Moon and Mars, astronauts will conduct regular exercise to prevent muscle atrophy, loss of bone mass and cardiovascular deconditioning. It is also anticipated that the atmosphere in the Moon and Mars habitats will be moderately hypoxic [42]. Whether the levels of hypoxia and unloading/ reduced physical activity will be severe enough to increase psychological strain remains to be settled. The level of unloading/inactivity is much more pronounced in the present study than is anticipated in future Lunar and Mars habitats, as is the level of hypoxia. Lower levels of hypoxia and higher levels of exercise in future space missions will potentially diminish the hypoxia-induced negative psychological profile observed in the HBR condition.

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5. Conclusion The participants did not demonstrate significant differences between the pre- and post-intervention measurements, since the emotions (positive and negative) returned to the initial levels on recovery following the BR and/or hypoxia. The results indicate that bed rest has a detrimental effect on positive emotions and hypoxia augments the negative affect in the inactive, bedrest participants. This augmented negative psychological mood is not evident in the hypoxic ambulatory participants. The activity level in the current study was specifically designed to mimic a low level of daily physical activity and not as a training stimulus. While there may be other factors involved, i.e. simply not being confined to a horizontal position, the introduction of a normal level of daily activity while under a hypoxic stimulus appeared to reduce the negative psychological strain of the participants. While bedrest may be a useful model of microgravity in certain situations, it does not provide a good representation of an astronauts' workload or the volume of exercise training that they complete as a countermeasure to muscle atrophy and cardiovascular deconditioning. Given that a small volume of physical activity in the upright position can negate the hypoxia-induced increase in negative emotional status, it is germane to both astronauts and athletes to further investigate the potential for exercise to improve the psychological state within a hypoxic environment. In conclusion, the study suggests that inactivity and unloading induced by sustained bedrest have a detrimental effect on positive emotions and that hypoxia provokes negative emotions in bedridden, but not ambulatory participants. References [1] W.T. Norfleet, B.D. Butler, Decompression sickness in extravehicular activities, in: G.K. Prisk, M. Paiva, J. West (Eds.), Gravity and the Lung: Lessons from Microgravity, Informa Health Care, 2001, pp. 289–333, http://dx.doi.org/10.1201/b15295-14. [2] A. Pavy-Le Traon, M. Heer, M.V. Narici, J. Rittweger, J. Vernikos, From space to Earth: advances in human physiology from 20 years of bed rest studies (1986–2006), Eur. J. Appl. Physiol. 101 (2007) 143–194, http://dx.doi.org/10.1007/s00421-007-0474-z. [3] Y. Ishizaki, T. Ishizaki, H. Fukuoka, C.-S. Kim, M. Fujita, Y. Maegawa, et al., Changes in mood status and neurotic levels during a 20-day bed rest, Acta Astronautica 50 (7) (2002) 453–459, http://dx.doi.org/10.1016/S0094-5765(01)00189-8. [4] C.M. Winget, C.W. DeRoshia, Psychosocial and chronophysiological effects of inactivity and immobilization, in: H. Sandler, J. Vernikos (Eds.), Inactivity: Physiological Effects, Academic Press, New York, CA, 1986, pp. 123–147, http://dx.doi.org/10. 1016/B978-0-12-618510-2.50010-5. [5] D.M. Lipnicki, H.-C. Gunga, Physical inactivity and cognitive functioning: results from bed-rest studies, Eur. J. Appl. Physiol. 105 (2009) 27–35, http://dx.doi.org/10. 1007/s00421-008-0869-5. [6] R.R. Yeung, The acute effects of exercise on mood state, J. Psychosom. Res. 40 (2) (1996) 123–141, http://dx.doi.org/10.1016/0022-3999(95)00554-4. [7] M.S. Bahrke, B. Shukitt-Hale, Effects of altitude on mood, behaviour and cognitive functioning: a review, Sports Med. 16 (1993) 97–115, http://dx.doi.org/10.2165/ 00007256-199316020-00003. [8] R.J. Davidson, The neural circuitry of emotion and affective style: prefrontal cortex and amygdala contributions, Soc. Sci. Inf. 40 (1) (2001) 11–37, http://dx.doi.org/ 10.1177/053901801040001002. [9] L.E. Banderet, R.L. Burse, Effects of high terrestrial altitude on military performance, in: R. Gal, A.D. Mangelsdorff (Eds.), Handbook of Military Psychology, John Wiley & Sons, New York, CA, 1991, pp. 233–254. [10] G. Missoum, E. Rosnet, J.P. Richalet, Control of anxiety and acute mountain sickness in Himalayan mountaineers, Int. J. Sports Med. 13 (Suppl. 1) (1992) S37–S39, http:// dx.doi.org/10.1055/s-2007-1024587. [11] E.O. Acevedo, P. Ekkekakis, The transactional psychobiological nature of cognitive appraisal during exercise in environmentally stressful conditions, Psychol. Sport Exerc. 2 (2001) 47–67, http://dx.doi.org/10.1016/S1469-0292(00)00013-3. [12] D. McNair, M. Lorr, L. Droppleman, Profile of Mood States, Educational and Industrial Testing Service, San Diego, CA, 1971. [13] D. Watson, L.A. Clark, A. Tellegen, Development and validation of brief measures of positive and negative affect: the PANAS Scales, J. Pers. Soc. Psychol. 47 (1988) 1063–1070, http://dx.doi.org/10.1037/0022-3514.54.6.1063. [14] D. Watson, L.A. Clark, Measurement and mismeasurement of mood: recurrent and emergent issues, J. Pers. Assess. 68 (2) (1997) 267–296. [15] P. Bartsch, B. Saltin, General introduction to altitude adaptation and mountain sickness, Scand. J. Med. Sci. Sports 18 (Suppl. 1) (2008) 1–10, http://dx.doi.org/10.1111/ j.1600-0838.2008.00827.x SMS827.

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