-->PONE-D-26-11054-->-->Objective assessment of cognitive fatigability in elite youth athletes: short protocols detect hypoxia effects for field applications-->-->PLOS One

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"This study was supported by the Ministère de l’Education du Quebec through the “Programme de soutien au développement de l'excellence (PSDE)” and was part of the synergic project “QueFreSkiNO”. We received further financial support from the PRIDI program from the National Institute of Sport of Quebec (PRIDI-76: PRIDI-95) and from the Research Center of the CIUSSS NIM. GV was supported by a Mitacs Accelerate Fellowship (IT42957). GS was supported by the FRQS Research Scholar Program (#297725)."

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Reviewers' comments:

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Reviewer #1: Partly

Reviewer #2: Partly

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: No

Reviewer #2: Yes

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-->5. Review Comments to the Author

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Reviewer #1: General Comments

The manuscript investigates the application of a short cognitive and physical testing protocol to assess cognitive fatigability under normobaric hypoxia in elite youth athletes. While the objective aligns with current needs in sports science for field-deployable monitoring tools, the study design and execution present significant methodological challenges that compromise the integrity of the findings.

Major Weaknesses:

Fixed-Order Crossover Design: The most critical flaw is the lack of randomization in the condition sequence. All participants completed the normoxia session first, followed by the hypoxia session two weeks later. In cognitive assessments involving inhibitory control and psychomotor vigilance, learning, practice, and habituation effects are substantial. Consequently, the effect of hypoxia is inherently confounded by the sequence effect. The baseline differences observed in cMSIT performance strongly indicate a practice effect from session 1 to session 2.

Missing Data and Sample Size: The initial sample size is small ($n=17$), which is typical for elite populations, but subject attrition reduces the analytical power further. Missing physiological data (heart rate and SpO2 during the jump task) due to equipment issues represents a significant loss of objective internal load metrics required to validate the physiological strain of the task.

App Validation: The study relies on a custom-developed iOS application for cMSIT and PVT. Peer-reviewed validation of this specific application against established gold standards (e.g., PC-based E-Prime or standard PVT-192 hardware) is absent from the manuscript.

Minor Weaknesses:

Blinding Efficacy: The authors state participants were naïve to the condition. However, symptoms of hypoxemia (SpO2 ~88%) during physical exertion would likely unblind elite athletes attuned to their physiological states. No manipulation check was reported to confirm if blinding was successful.

Statistical Reporting of Count Data: Table 1 reports count data (lapses) with means and standard deviations, despite the authors explicitly acknowledging a right-skewed Poisson distribution.

Specific Comments

Page 9, Lines 100-101: The title asserts that the protocols "detect hypoxia effects," which is a deterministic claim given the fixed-order design. Reframing the title to reflect the exploratory nature of the study would mitigate definitive claims regarding hypoxia detection.

Page 14, Lines 132-144: A formal a priori power analysis or sample size justification is absent. Providing an a priori statistical justification would determine if the study was adequately powered to detect condition $\times$ time interactions amid high inter-individual variability.

Page 14, Lines 147-148: A testing window spanning three and a half hours introduces potential circadian variation in cognitive fatigability. Controlling for exact time-of-day testing would isolate the hypoxic effect from circadian cognitive fluctuations [Amor SB, Dhahbi W, Bougrine H, Bessifi M, Geantă VA, Ursu VE, Trabelsi K, Souissi N: Differential Time-of-Day Effects of Caffeine Capsule and Mouth Rinse on Cognitive Performance in Adolescent Male Volleyball Athletes: A Randomized Crossover Investigation. Life 2025, 16(1):33].

Page 14, Lines 171-173: The protocol relies on a sham altitude (200m) to maintain blinding. Reporting post-session surveys regarding perceived physical strain would verify the actual efficacy of this blinding strategy.

Page 15, Lines 175-179: The justification for the non-randomized design relies purely on logistical convenience (chamber stabilization time). Providing secondary statistical analyses comparing session 1 vs. session 2 learning trajectories in a control group would clarify the sequence effect.

Page 16, Lines 198-212: The custom iOS application lacks formal validation against standard hardware, and touchscreen latencies vary significantly by device. Detailing the internal latency of the iPad model would demonstrate that touchscreen polling rates do not artificially skew the PVT response times. Furthermore, establishing a framework for technological validity would clarify the reliability of the derived response times [Dhahbi W, Chamari K: The Algorithmic Athlete: A Call to Standardize Assessment of Sensor Technologies and Artificial Intelligence. International Journal of Sports Physiology and Performance 2026, 1(aop):1-2].

Page 16, Lines 223-228: Utilizing repeated tuck jumps exclusively as the physical fatiguing mechanism neglects the complex multi-joint strength profiling necessary to fully assess lower-body endurance under hypoxia. Acknowledging the multi-dimensional nature of vertical jump performance would provide a more precise biomechanical context for the observed decrement in the third series [Sever O, Ceylan Hİ, Dhahbi W, Yilmaz HH, Özdemir K, Yazici AG, Jalalov F, Günay AR, Bayrakdaroğlu S, Stefanica V: Multi-joint isokinetic strength profiling as a predictor of vertical jump performance in elite freestyle wrestlers: A cross-sectional principal component analysis. Medicine 2026, 105(2):e47084].

Page 17, Lines 238-241: The failure to capture HR and SpO2 data during the jump task removes the primary objective markers of internal physiological load. Clarifying the absence of alternative sensor placements (e.g., chest strap HR monitors) would elucidate how the missing physiological data impacts the interpretation of the physical task's fatiguing effect.

Page 18, Lines 287-289: Baseline cMSIT response time was significantly worse in normoxia compared to hypoxia. The divergence in baseline performance across sessions suggests a temporal artifact or learning effect rather than mere "daily variations." Integrating temporal control designs would identify whether such baseline shifts are biological anomalies or systematic measurement artifacts [Dhahbi W, Dergaa I: Machine learning with temporal control designs for testing rhythmic specificity in chronobiology: A multivariate framework proposal for distinguishing genuine biological rhythms from temporal artifacts. Chronobiology International 2026:1-8].

Page 19, Lines 314-324 & Table 1: Reporting mean $\pm$ SD for PVT lapses ($1.5 \pm 4.25$) is statistically inappropriate for highly skewed count data. Presenting median and interquartile ranges (IQR) for all lapse data in Table 1 would accurately reflect the non-normal distribution.

Page 20, Lines 330-332: The condition $\times$ set interaction for the jump task is marginal ($p=0.048$) with $n=14$. Reporting the confidence intervals for the post-hoc comparisons would demonstrate the precision of the finding at the third series.

Page 21, Lines 354-361: The discussion of SpO2 differences between simulated normobaric hypoxia and real-world hypobaric hypoxia is superficial. Contextualizing how the physiological responses to normobaric hypoxia specifically mimic or diverge from the hypobaric conditions these winter athletes actually face on the mountain would strengthen the external validity.

Reviewer #2: Abstract

The abstract presents a clear and relevant objective, addressing the assessment of cognitive fatigability in field-applied contexts, which represents a strength with practical relevance for athlete training and monitoring. However, the designation “elite youth athletes” warrants some caution, given that the sample has a mean age of 18±2 years; in this regard, the use of the term “late-adolescent elite athletes” would be more precise and scientifically rigorous.

Introduction

The introduction presents a globally solid and well-structured conceptual foundation, guiding the reader from the general context of altitude exposure to the specific issue of cognitive fatigability. The relevance of the topic is clearly established, particularly in the context of winter sports and the increasing intermittent exposure to hypoxia. The distinction between fatigue and fatigability is a strength, demonstrating conceptual rigor and alignment with contemporary literature.

However, I believe it could benefit from some improvements:

1) Although the literature review is comprehensive, the narrative becomes somewhat lengthy and, at times, overly descriptive, particularly in the section addressing the analogy with neuromuscular fatigability. While relevant, this part could be more concise and more directly linked to the cognitive domain, avoiding some dispersion of the main focus.

2) The justification of the scientific gap could be more incisive. The manuscript correctly highlights the scarcity of studies on cognitive fatigability under hypoxia and the limited transferability of laboratory protocols, but the link between these limitations and the specific need for short, field-applicable protocols could be articulated more directly and critically. In other words, a clearer transition between “what exists” and “why it is insufficient” is needed.

3) The target population is only introduced in the final part of the introduction, without sufficiently strong prior framing. The reference to “elite youth athletes” appears somewhat late and without critical discussion. As noted in the abstract, considering that the sample has a mean age of 18±2 years, it would be more accurate to use the term “late-adolescent elite athletes,” which would also better align the sample characterization with the literature on development and sports performance.

4) Another point to consider concerns the coherence between the introduction and the study objective. Although the rationale for using short, portable tasks is present, it could be more clearly emphasized as a central element of the study’s innovation, rather than appearing diluted throughout the text.

5) Finally, the hypothesis is clearly stated but could benefit from stronger direct grounding in the previously cited studies, thereby reinforcing its predictive rationale.

Methods

The methods section is, overall, detailed, transparent, and well structured, allowing for a clear understanding of the experimental procedures and supporting the reproducibility of the study. Nevertheless, I identified several aspects that warrant reflection and potential improvement:

1) The attempt to blind participants is interesting and well justified (simulation of altitude in both conditions), but it raises some concerns regarding its actual effectiveness, particularly in athletes who may be familiar with sensations associated with hypoxia. It would be useful to clarify whether participants’ perception of the experimental condition was assessed.

2) Regarding the cognitive tasks, the choice of the cMSIT and PVT is well grounded and aligned with the literature. However, the operational definition of “cognitive fatigability” as the change in PVT performance pre–post cMSIT could be better conceptually justified, reinforcing the distinction between the inducing task and the outcome measure. Furthermore, the relatively short duration of the cMSIT (10 min) raises the question of whether it is sufficient to consistently induce fatigability, especially considering that previous studies cited by the authors used longer tasks.

3) The within-subject design is appropriate, and the selected tasks (cMSIT and PVT) are consistent with the literature for assessing inhibitory control and vigilance. However, some methodological limitations should be considered. In particular, the use of a fixed order of conditions (normoxia followed by hypoxia) may introduce learning, fatigue, or expectation effects, thereby compromising the internal validity of the findings.

Results

The results section is overall detailed and technically robust, with a careful description of the statistical analyses and a clear effort to ensure the adequacy of the models used. Nevertheless, several aspects could be improved to enhance clarity, coherence, and interpretation of the findings:

1. The section is, at times, overly technical and dense, with a level of statistical detail that may compromise readability. The inclusion of extensive information on model adjustments, distributions, and assumption checks (e.g., Q-Q plots, robust models) is relevant, but could be partially moved to supplementary material, allowing for a smoother presentation of the main results.

2. The presentation of the cMSIT results raises some issues of interpretative coherence. Initially, performance is reported as better in hypoxia (~8%), but after baseline adjustment it appears worse (~6%). While this inversion is methodologically explainable, it is not sufficiently clarified in the text and may confuse the reader. It would be important to more explicitly explain the role of baseline in this shift in interpretation.

3. The absence of a time effect in the cMSIT (i.e., no decline over the 10 minutes) raises questions about the effectiveness of the task as an inducer of cognitive fatigability. Although the authors refer to supplementary material, this point is central to the interpretation of the results and should be more explicitly addressed in this section or, at least, acknowledged as a potential limitation.

4. Regarding the assessment of fatigability through the PVT, the results are more consistent and aligned with the hypothesis, showing an effect of hypoxia. However, the magnitude of the effects (e.g., relatively small η²p values) is not discussed, which makes it difficult to assess their practical relevance. Additionally, the need to use robust models due to the presence of extreme values suggests some variability in the data that could be better contextualized.

5. Another important aspect concerns the loss of participants at different stages (missed sessions, exclusion from the jump task), which further reduces the sample size in some analyses. This issue is not addressed in the section and may have implications for the robustness of the findings.

Discussion

The discussion section shows good alignment with the study objectives and demonstrates a consistent effort to interpret the findings in light of the existing literature. Nevertheless, several aspects could be improved to strengthen the clarity, consistency, and scientific rigor of the discussion:

1. The interpretation of the cMSIT results remains somewhat ambiguous and, at times, speculative. The authors correctly acknowledge the absence of a time×condition interaction, but propose multiple possible explanations (insufficient task duration, differences in effort, inter-session variability) without clearly prioritizing the most plausible one. This multiplicity of interpretations, without a more assertive position, may weaken the main message. Moreover, the explanation based on baseline differences is relevant but could be presented more clearly and better integrated with the results.

2. Although the authors acknowledge that the 10-minute task may not have been sufficient to induce fatigability in normoxia, this limitation is central and should be more strongly emphasized. Indeed, it raises a fundamental question about the validity of the protocol for assessing cognitive fatigability, particularly considering that the operational definition of the construct depends on inducing performance decline over time.

3. Another critical point concerns the interpretative complexity introduced by including a physical task prior to cognitive assessment. While well justified from an ecological perspective, this choice makes it more difficult to disentangle the effects of hypoxia from those of physical fatigue. This limitation is only partially acknowledged and should be discussed more explicitly.

4. Regarding the comparison with the literature, it is adequate but could be more critical. For example, differences in oxygen saturation levels are mentioned as an explanation for inconsistent findings, but other relevant variables (e.g., task duration, sample characteristics) could be more systematically integrated.

5. The limitations section is relevant and appropriately acknowledges the lack of randomization. However, the potential impact of this limitation on the internal validity of the findings could be discussed in greater depth, particularly in relation to the order effects already evidenced in the results (baseline differences).

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Reviewer #1: Yes:  Wissem Dhahbi

Reviewer #2: No

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-->PONE-D-26-11054R1-->-->Objective assessment of cognitive fatigability in elite youth athletes: short portable protocols for field monitoring under hypoxia-->-->PLOS One

Dear Dr. Varesco,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jun 10 2026 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Julio Alejandro Henriques Castro da Costa

Academic Editor

PLOS One

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Reviewers' comments:

Reviewer's Responses to Questions

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1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.-->

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

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The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. -->

Reviewer #1: Partly

Reviewer #2: Partly

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #2: Yes

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-->6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)-->

Reviewer #1: General Comments

Major Weaknesses:

Physiological Validation: The failure to collect usable heart rate and blood oxygen saturation data during the jump task due to sensor displacement limits the physiological validation of the hypoxic stimulus during the actual physical effort. Relying solely on resting data is a limitation that must be addressed more prominently.

Statistical Covariates: The rationale for replacing sex with body mass in the linear mixed-effects models requires stronger physiological justification within the main text. Sex differences in neuromuscular and cognitive fatigability are well-documented and extend beyond simple anthropometric differences.

Minor Weaknesses:

Terminology: The manuscript occasionally interchanges "hypoxia" (environmental condition) and "hypoxemia" (physiological state). Strict differentiation is required.

Formatting and Typography: There are several typographical errors, missing punctuations in statistical reporting, and inconsistent formatting in Table 1 that require correction.

Specific Comments

Page 2, Line 64: Specify the number of male athletes. You list "$n=17$, 7 women," but the male count should be explicit for immediate clarity.

Page 2, Line 82: Insert "a" before "condition set interaction" and use the standard notation "condition $\times$ set".

Page 4, Line 124: Change "refers as" to "is defined as" or "refers to".

Page 6, Line 227: There is a typographical error and a missing closing parenthesis in the Brugmann scale reporting: "physical item 3 2)". Correct the value and add the parenthesis.

Page 8, Line 282: The use of a sham condition (200 m) involves participant deception. Specify in the ethical procedures section if a debriefing occurred post-study.

Page 11, Line 396: The loss of oximetry data during the jump task is briefly mentioned. Add a sentence in the Limitations section acknowledging that the exact degree of hypoxemia during the physical task remains unquantified.

Page 11, Line 427: Adjusting for body mass instead of sex is a specific analytical choice. Add a brief sentence in this section justifying why body mass is a superior predictor for this specific youth mogul skier cohort, rather than referring solely to the supplement.

Page 12, Line 447: The phrase "influenza, different individuals" is grammatically awkward. Revise to "due to influenza (different individuals)."

Page 13, Line 475: Missing a semicolon or comma before the p-value in the accuracy data: "$(97\pm2\% \eta^{2}p=0.11 p=0.18)$".

Page 13, Line 489: Missing the subscript "$p$" for partial eta squared: "$\eta^{2}<0.001$ $p=0.98$".

Page 14, Line 521 (Table 1): The formatting is inconsistent. The response time cells for Hypoxia and Normoxia lack the standard deviation symbol (e.g., "363 74" should be "363 $\pm$ 74").

Page 16, Line 604: Change "different effort put in the task" to "differences in effort exerted during the task".

Page 18, Line 676: Specify the exact statistical threshold or method used to determine the curvilinear association mentioned.

Page 19, Line 712: Change the comma to a period or semicolon before "while this reflects ecologically valid conditions" to correct the run-on sentence.

Reviewer #2: I would like to thank the authors for their thorough and thoughtful revision of the manuscript. The responses provided demonstrate a clear effort to address the reviewers’ comments, and several aspects of the manuscript have been improved, particularly in terms of clarity, structure, and justification of methodological choices.

That said, I would like to highlight a few remaining concerns that, in my view, would benefit from further clarification and strengthening.

First, regarding the blinding procedure, although the authors provide a rationale for not including a manipulation check, the absence of any assessment of participants’ perception of the experimental condition remains a relevant limitation. Given the nature of hypoxia and the population studied, this issue should be more explicitly acknowledged in the manuscript as a potential source of bias affecting internal validity.

Second, the operationalization of cognitive fatigability, particularly the use of pre–post changes in PVT performance following the cMSIT, is better justified in the revised version. However, the conceptual distinction between the inducing task and the outcome measure could still be more clearly articulated, especially considering the broader theoretical debate around fatigability assessment.

Third, the duration of the cMSIT (10 minutes) remains a critical point. The absence of a time effect within the task raises important questions about its effectiveness as an inducer of cognitive fatigability. While this is acknowledged, I believe this limitation should be more strongly emphasized and more directly discussed in relation to the validity of the fatigability construct used in the study.

Finally, I would also encourage the authors to further reinforce the discussion around the interpretative complexity introduced by the inclusion of a physical task prior to cognitive assessment. Although this choice enhances ecological validity, it also limits the ability to disentangle the independent effects of hypoxia and physical fatigue, and this should be clearly and critically reflected in the discussion.

Addressing these points would, in my opinion, further strengthen the manuscript and improve its conceptual clarity and methodological transparency.

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Reviewer #1: Yes:  Wissem Dhahbi

Reviewer #2: Yes:  Ana Filipa Silva

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Assessment of cognitive performance and fatigability in elite athletes: short and portable protocols for field monitoring under hypoxia

PONE-D-26-11054R2

Dear Dr. Varesco,

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Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

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Reviewer #1: Yes

Reviewer #2: Partly

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #2: Yes

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-->6. Review Comments to the Author

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Reviewer #1: The revised manuscript (PONED-26-11054R2) evaluates the utility of short, field-deployable cognitive protocols to detect fatigability under normobaric hypoxia in elite youth mogul skiers. The authors have uniquely strengthened their original design by conducting a subsequent randomized crossover study (Study II) to isolate the environmental effects of hypoxia from pre-fatiguing physical exercise. This replication drastically improves the internal validity of the research framework. The methodological adjustment regarding touchscreen-specific PVT lapse thresholds (>500) provides essential clarity for applied sports science settings. The text is precise, the statistical treatment is sound, and the manuscript is ready for publication.

Reviewer #2: Dear Author,

please see below my comments and suggestions:

1. Construct validity of the cognitive fatigability outcome

One of my main concerns relates to the construct validity of the primary outcome, namely "cognitive fatigability". Throughout the manuscript, the authors state that the proposed protocol is able to detect cognitive fatigability under hypoxic conditions. However, I am not entirely convinced that the current experimental design fully supports this conclusion.

Cognitive fatigability is generally understood as a progressive decline in cognitive performance during sustained mental effort. In the present study, however, cognitive fatigability is inferred indirectly from changes in Psychomotor Vigilance Task (PVT) performance before and after completion of the cMSIT, rather than from a progressive deterioration in performance during the cognitive task itself. Interestingly, performance during the cMSIT itself showed little or no evidence of temporal decline, particularly in Study I.

Although the authors provide a rationale for using the pre-post PVT comparison, I believe the manuscript would benefit from a more cautious interpretation of what this protocol actually measures. At present, the evidence appears to support that the protocol detects changes in cognitive performance following a cognitively demanding task under hypoxia, rather than directly demonstrating cognitive fatigability itself. I therefore encourage the authors to better acknowledge this conceptual distinction and moderate the wording throughout the manuscript, particularly in the Discussion and Conclusions.

2. Ecological validity

The manuscript repeatedly emphasizes the ecological validity and field applicability of the proposed protocol. While I agree that the protocol is portable and considerably more feasible than laboratory-based cognitive assessments, I believe the concept of ecological validity is occasionally overstated. Portability alone does not necessarily imply ecological validity. The cMSIT and PVT remain standardized laboratory cognitive tasks that do not directly reproduce the perceptual, decision-making, or motor-cognitive demands experienced during alpine skiing or other sporting activities. Consequently, I suggest that the authors distinguish more clearly between “field feasibility” and “ecological validity”. Describing the protocol as a portable field-based assessment is fully justified, whereas claiming ecological validity may require a more nuanced discussion and acknowledgement of its limitations.

3. External validity and generalizability

The conclusions occasionally appear broader than the study population allows. The study was conducted exclusively in a relatively small sample of elite youth mogul skiers, yet several statements throughout the Discussion refer more generally to "athletes" or "sport performance." Although the proposed mechanisms may plausibly extend to other athletic populations, the current data do not directly support such broad generalizations. I recommend that the authors explicitly acknowledge that the findings are currently limited to this specific cohort and moderate statements implying wider applicability until further evidence becomes available.

4. Interpretation of practical implications

Finally, I encourage the authors to moderate several statements regarding the practical implications of their findings. For example, the Discussion suggests that "ignoring hypoxia during altitude training could increase injury risk." While this is an interesting and plausible hypothesis, it extends beyond the evidence generated in the present study. The current investigation did not assess injury incidence, technical errors, sport-specific decision-making, or other performance outcomes directly related to injury risk. Therefore, statements of this nature should be presented as potential hypotheses or speculative implications rather than direct conclusions supported by the data. More cautious wording (e.g., "may contribute to..." or "may have implications for...") would more accurately reflect the evidence presented.

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Reviewer #1: Yes:  WIssem Dhahbi

Reviewer #2: Yes:  Ana Filipa Braga Barroso Campos Silva

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