Combined Effects of Moderate Hypoxia and Sleep Restriction on Mental Workload

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The article "Combined effects of moderate hypoxia and sleep restriction on mental workload" is a study that aims to estimate the effects of hypoxia and sleep restriction on cognitive responses to different mental workload levels.

The study design is thorough and well exposed. Despite the small number of subjects included, the results show that the combination of sleep restrinction and hypoxia increases mental workload. Moreover, the authors individuated physiological parameters that can predict increased mental load. These findings could be relevant for the design of further studies that propose to investigate mental workload and stress effect on cognitive functions.

Overall, the article is well written and clear. Citations are adequate. Graphics and tables help to clarify the results. I have no changes to suggest.

Author Response

Reviewer 1

The article "Combined effects of moderate hypoxia and sleep restriction on mental workload" is a study that aims to estimate the effects of hypoxia and sleep restriction on cognitive responses to different mental workload levels.

The study design is thorough and well exposed. Despite the small number of subjects included, the results show that the combination of sleep restrinction and hypoxia increases mental workload. Moreover, the authors individuated physiological parameters that can predict increased mental load. These findings could be relevant for the design of further studies that propose to investigate mental workload and stress effect on cognitive functions.  Overall, the article is well written and clear. Citations are adequate. Graphics and tables help to clarify the results. I have no changes to suggest.

We thank the reviewer for his/her encouragement and the way he looked at our work.

Reviewer 2 Report

Comments and Suggestions for Authors

The authors investigated the combined effect of hypoxia and sleep restriction on the mental workload in healthy subjects. As a result, combining both interventions decreases the performance of MATB-Ⅱ tracking task and increases subjective mental workload. The authors also revealed the change in physiological response to each condition. This study provides changes in psychophysiological performance by practical situations such as those faced by aircraft pilots. I am interested in this study, but there are some concerns points.

 

Major points

The authors conducted an ordinal logistic regression analysis. The reason for this analysis was described as to assess the weight of parameters for the prediction of workload level. Unfortunately, I could not understand the rationale for this analysis. How does the result of this analysis lead to a conclusion and significance for the purpose of this study? The authors should improve the rationale of this analysis and rewrite the manuscript, especially the Introduction. 

 

While the Introduction and Discussion are redundant, the important rationale of this study (described above) has not been written.

 

Why did the MATB-Ⅱ task finish at 11:45 am, but this experiment continued until 2:00 pm? Did the authors perform a different experiment or extract different parameters? 

 

In the sleep restriction condition, participants woke up at 6:00 am, as written in line 586. However, the wake-up time of the habitual sleep condition was not written. Were the participants instructed on the wake-up time? Because the start time of the experiment on the second day and the timing of the task were fixed, the authors should write information about the wake-up time of the habitual sleep condition. 

 

Regarding the result of Pearson correlation analysis, I am concerned about the type Ⅰ error by multiple comparisons. The authors should apply a correction for multiple comparisons.

 

Minor points

Line 18: high altitude?

Line 22: Please write the formal name of TST.

Line 102: Please explain what the sleep efficiency index is. 

 

Author Response

Reviewer 2

The authors investigated the combined effect of hypoxia and sleep restriction on the mental workload in healthy subjects. As a result, combining both interventions decreases the performance of MATB-Ⅱ tracking task and increases subjective mental workload. The authors also revealed the change in physiological response to each condition. This study provides changes in psychophysiological performance by practical situations such as those faced by aircraft pilots. I am interested in this study, but there are some concerns points.

We thank the reviewer for his/her work and help to the improvement of our manuscript.

Major points

The authors conducted an ordinal logistic regression analysis. The reason for this analysis was described as to assess the weight of parameters for the prediction of workload level. Unfortunately, I could not understand the rationale for this analysis. How does the result of this analysis lead to a conclusion and significance for the purpose of this study? The authors should improve the rationale of this analysis and rewrite the manuscript, especially the Introduction. 

We agree with the reviewer for the lack in the Introduction of a rationale for the ordinal logistic regression analysis. We now added this second objective in the Introduction, with a supplementary sentence including the Ayaz et al., 2019 reference (lines 53-55). This secondary objective was to give results that could aid in the design of a predictive model of WM.

In addition, in the Statistics paragraph, one reference (N° 73) has been added relative to the ordinal logistic regression analysis (Wang et al., 2007).

 

While the Introduction and Discussion are redundant, the important rationale of this study (described above) has not been written.

We have tried to reduce the introduction and add the secondary objective of investigating the best physiological parameters for predicting the level of mental workload.

Why did the MATB-Ⅱ task finish at 11:45 am, but this experiment continued until 2:00 pm? Did the authors perform a different experiment or extract different parameters? 

The reviewer is right. This study was a part of a global study. We added the following sentence in the Materials and Methods paragraph “It was a part of a global study related to physiological effect of a 5 hours normobaric hypoxic exposure. See the Clinical trial database for the global description of the protocol (NCT055663688).

In the sleep restriction condition, participants woke up at 6:00 am, as written in line 586. However, the wake-up time of the habitual sleep condition was not written. Were the participants instructed on the wake-up time? Because the start time of the experiment on the second day and the timing of the task were fixed, the authors should write information about the wake-up time of the habitual sleep condition. 

 We thank the reviewer for this remark. We changed the sentence as follows “In the habitual sleep condition, the participants have been asked to wake up at 6:00 am and to respect an 8 hours’ time in bed (TIB). In the sleep restriction condition, the participants arrived at the sleep laboratory the previous day (at 8:00 pm) and were then allowed to sleep 3 hours (between 3:00 am and 6:00 am).

Regarding the result of Pearson correlation analysis, I am concerned about the type Ⅰ error by multiple comparisons. The authors should apply a correction for multiple comparisons.

The reviewer is right, and no correction was applied. In order to manage the type 1 error by multiple comparisons, we now added and used the Benjamini and Hichberg (1995) adjustment method. The absolute p value and the corrected p value are now shown in the figure. A sentence has been added to the statistics paragraph.

Benjamini, Yoav, and Yosef Hochberg. "Controlling the false discovery rate: a practical and powerful approach to multiple testing." Journal of the Royal statistical society: series B (Methodological) 57.1 (1995): 289-300.

Minor points

Line 18: high altitude?

We thank the reviewer, we delated the word “low”, the sentence is now “constraints induced by altitude and sometimes sleep restriction (SR).”

Line 22: Please write the formal name of TST.

We apologize and have added the formal name “Total sleep time” for TST.

 

Line 102: Please explain what the sleep efficiency index is. 

We thank the evaluator and add that the sleep efficiency index is an index of sleep quality.

 

 

Reviewer 3 Report

Comments and Suggestions for Authors

Dear Authors,

it was a pleasure for me to review the article concerning the effects of sleep deprivation  and hypoxia on mental workload and cognitive and physiological responses.  The article is an important voice in the discussion concerning the impact of environmental and work-connected conditions experienced by pilots on their cognitive performance. Authors clearly present the idea of the research and the corresponding current knowledge in the introduction. The concept, methods and results are presented very clearly and properly which makes the article easy to read. I recommend to move the material and methods section to the standard place between introduction and results. The methodology of the research is impressive.

The Authors have confirmed that combined exposure to moderate hypoxia and sleep restriction increased subjective mental workload and decreased cognitive performance. Their work has also a great value in future designing of mental workload model. They have observed that breathing rate, pupil size and amplitude of pupil dilatation response to auditory stimuli are associated with increased workload.

The Authors broadly compare their results with other studies in the discussion section.

In my opinion the article is of great value and should be published.

There are some minor things to improve. Below, I present detailed list of suggested improvements:

Line 18: Should it not be „high altitude” instead of “low altitude?

Line 22: Please add explanation “total sleep time) for the TST abbreviation.

Lines 50-57: There two almost the same sentences. Please remove one sentence.

Line 62, 275, 276, 304, 330, 331: I understand that in aviation "feet" is the standard metric measurement, but for the general reader it is better to stick to SI units. I would recommend converting feet to meters or present altitude with both metrics.

Line 82: add space before [16]

Line 107: MV should be changed into MW

Lines 108 and 116 – Should it not be “the highest” instead of “higher”?

Table 2: All abbreviations should be explained in the legend below the table.

Lines 139-153: All abbreviations should be explained before they appear in the text. If the methodology section will be moved, then explanations of abbreviations will come first.

Line 177, 190 and many more: I recommend  the Authors to  decide whether the names will be written in lowercase or uppercase letters and consistently stick to one rule throughout the text. For example line 177 - please write “Pupil” in lower case; line 190: please write “Breathing” in lower case.

Line 431 – The subsection of Material and Methods should be placed between introduction and results. The numbers of figures and tables should be changed accordingly.

Lines 422-430 are the same as Lines 634-643 – Please remove one paragraph

Author Response

 

Reviewer 3

 

Comments and Suggestions for Authors

Dear Authors,

it was a pleasure for me to review the article concerning the effects of sleep deprivation and hypoxia on mental workload and cognitive and physiological responses.  The article is an important voice in the discussion concerning the impact of environmental and work-connected conditions experienced by pilots on their cognitive performance. Authors clearly present the idea of the research and the corresponding current knowledge in the introduction. The concept, methods and results are presented very clearly and properly which makes the article easy to read. I recommend to move the material and methods section to the standard place between introduction and results. The methodology of the research is impressive.

The Authors have confirmed that combined exposure to moderate hypoxia and sleep restriction increased subjective mental workload and decreased cognitive performance. Their work has also a great value in future designing of mental workload model. They have observed that breathing rate, pupil size and amplitude of pupil dilatation response to auditory stimuli are associated with increased workload.

The Authors broadly compare their results with other studies in the discussion section.

In my opinion the article is of great value and should be published.

 

We sincerely thank the reviewer for his opinion on our experimental work.

 

There are some minor things to improve. Below, I present detailed list of suggested improvements:

Line 18: Should it not be „high altitude” instead of “low altitude?

We apologize for this error and have now modified the text accordingly.

 

Line 22: Please add explanation “total sleep time) for the TST abbreviation.

This has been done.

 

Lines 50-57: There two almost the same sentences. Please remove one sentence.

This has been done, we thank the reviewer.

 

Line 62, 275, 276, 304, 330, 331: I understand that in aviation "feet" is the standard metric measurement, but for the general reader it is better to stick to SI units. I would recommend converting feet to meters or present altitude with both metrics.

We now changed accordingly with the two metrics.

 

Line 82: add space before [16]

This has been done.

 

Line 107: MV should be changed into MW

We thank the reviewer and we changed.

 

Lines 108 and 116 – Should it not be “the highest” instead of “higher”?

Yes it is, and we now changed accordingly.

 

Table 2: All abbreviations should be explained in the legend below the table.

We added the information below the table as follows “all other abbreviations can be found in the Appendix A1 and A2 tables”.

 

Lines 139-153: All abbreviations should be explained before they appear in the text. If the methodology section will be moved, then explanations of abbreviations will come first.

We apologize and to keep the text simple we now added « See the Appendix A1 table for abbreviations details. » at the end of the paragraph 2.3.

 

Line 177, 190 and many more: I recommend  the Authors to  decide whether the names will be written in lowercase or uppercase letters and consistently stick to one rule throughout the text. For example line 177 - please write “Pupil” in lower case; line 190: please write “Breathing” in lower case.

We apologize and we now changed accordingly.

 

Line 431 – The subsection of Material and Methods should be placed between introduction and results. The numbers of figures and tables should be changed accordingly.

We apologize, but we have followed the instructions for authors of the journal.

 

Lines 422-430 are the same as Lines 634-643 – Please remove one paragraph

We thank the reviewer, and we now removed lines 422-430.

 

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for your comments and for updating the manuscript. I have checked the updated points and think it is almost OK. There are still some minor points and please confirm and update them. 

 

1. In line 54, the authors refer to Ayaz et al. and state that "brain activity captured during a cognitive task can be used as a predictor of future performance". However, the authors only measured and used physiological parameters to predict a change in performance with mental workload, and this sentence seems to deviate slightly from the focus of this manuscript. The authors should mention the usefulness of physiological parameters in predicting performance. Or, if the authors refer to Ayaz et al, the authors should add the significance of predicting performance using physiological parameters rather than brain activity.

 

2. The authors described that the sentence in line 18 was changed to “constraints induced by altitude and sometimes sleep restriction (SR)”. However, in the updated manuscript, this sentence is stated "high altitude". I think both patterns are OK, but please make sure which is what the authors want to express.

 

Author Response

1. In line 54, the authors refer to Ayaz et al. and state that "brain activity captured during a cognitive task can be used as a predictor of future performance". However, the authors only measured and used physiological parameters to predict a change in performance with mental workload, and this sentence seems to deviate slightly from the focus of this manuscript. The authors should mention the usefulness of physiological parameters in predicting performance. Or, if the authors refer to Ayaz et al, the authors should add the significance of predicting performance using physiological parameters rather than brain activity.

We agree with the reviewer that we didn't measure brain activity, so we're deleting the sentence and adding the Charles and Nixon 2019 reference for the previous sentence.

 

2. The authors described that the sentence in line 18 was changed to “constraints induced by altitude and sometimes sleep restriction (SR)”. However, in the updated manuscript, this sentence is stated "high altitude". I think both patterns are OK, but please make sure which is what the authors want to express.

We thank the reviewer, and we apologize because it is indeed “high altitude”, following the request of reviewer 3.