PONE-D-22-11905Reduced Isometric Knee Extensor Force Following Anodal Transcranial Direct Current Stimulation of the Ipsilateral Motor CortexPLOS ONE

Dear Dr. Behm,

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.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

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: Yes

Reviewer #2: No

Reviewer #3: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: I Don't Know

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. 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: The manuscript is a technically sound piece of scientific research with data that supports the conclusions. It appears that all appropriate statistical analyses were utilized to reach the authors' conclusions.

Reviewer #2: The aim of this study was to determine if anodal transcranial direct current stimulation (a-tDCS) to the motor cortex (M1) modulates quadriceps isometric maximal voluntary contraction (MVC) force or fatigue contralateral or ipsilateral to the stimulation site. Authors main conclusions are that a-tDCS may be ineffective at increasing maximal force or endurance and instead may be detrimental to quadriceps force production.

Because of the rise in popularity of a-tDCS as a tool with potential to influence sport performance, the aims of the present study could be considered relevant to the field. However, the manuscript has some limitations that decreased the initial enthusiasm.

First of all, a single blind approach (with only subjects blinded to condition) could not be the best way to perform this research. Double blind is recommended in this kind of study in which investigators can inadvertently influence the experiment’s results due to hypothesis expectations (i.e., for example, with differences in the way subjects are encouraged during the session).

Another question, is the protocol used to induce KE fatigue, which from my point of view does not work well (induced only a 12% decrease in force overall). A time to exhaustion test (TTE) would have been desirable, or at least, a large number of repetitions to increase the perception of effort to a greater extent, since it has previously been argued that modulation of RPE could underpin the tDCS induced beneficial effects on endurance performance.

The other main weaknesses of the study are related to the way it is written. There is a lack of explanations of arguments to support a priori hypothesis and a rather superficial discussion about the results. There are also some inconsistencies between the statistical analysis done and the way results are interpreted and the conclusions raised does not align well with results.

Introduction

Introduction is confusing and the rationale is not clear at all. Overall, introduction needs reorganization of content and a better justification of the aims of the study.

For example, there is no proper explanation of the physiological rationale for the effects of a-tdcs over M1 on muscle force. All the justification is based on the effects of a-tdcs on MEP amplitude. Although elucidating the mechanisms of a-tdcs is not the aim of the present study, a proper justification of the selection of stimulating areas, explaining possible physiological mechanisms by which they might influence motor behavior, should be included. Furthermore, it should be better physiologically justified the interaction between both motor cortices and its reciprocal influences, both in terms of facilitation and inhibition, when altering the “excitability” of one hemisphere. The rationale of cross education does not fit well in the intro, or at least at the main argument.

Lines 137 – 140: This is too speculative Hard to believe that tDCS may exert an effect on the reticulospinal system. My recommendation is to delete this sentence.

There is a need to actualize the citing literature, because there is a lot of missing references regarding the effects of TDCS on maximal force production and endurance performance. See some of them:

The Effect of Anodal Transcranial Direct Current Stimulation on Quadriceps Maximal Voluntary Contraction, Corticospinal Excitability, and Voluntary Activation Levels.

Kristiansen M, Thomsen MJ, Nørgaard J, Aaes J, Knudsen D, Voigt M.

J Strength Cond Res. 2021 Mar 3. doi: 10.1519/JSC.0000000000003710. Online ahead of print.

Anodal transcranial direct current stimulation enhances strength training volume but not the force-velocity profile.

Alix-Fages C, García-Ramos A, Calderón-Nadal G, Colomer-Poveda D, Romero-Arenas S, Fernández-Del-Olmo M, Márquez G.

Eur J Appl Physiol. 2020 Aug;120(8):1881-1891. doi: 10.1007/s00421-020-04417-2.

Transcranial Direct Current Stimulation Does Not Improve Countermovement Jump Performance in Young Healthy Men.

Romero-Arenas S, Calderón-Nadal G, Alix-Fages C, Jerez-Martínez A, Colomer-Poveda D, Márquez G.

J Strength Cond Res. 2019 Jul 31. doi: 10.1519/JSC.0000000000003242. Online ahead of print.

Transcranial direct current stimulation and repeated sprint ability: No effect on sprint performance or ratings of perceived exertion.

Alix-Fages C, Romero-Arenas S, Calderón-Nadal G, Jerez-Martínez A, Pareja-Blanco F, Colomer-Poveda D, Márquez G, Garcia-Ramos A.

Eur J Sport Sci. 2021 Feb 25:1-10. doi: 10.1080/17461391.2021.1883124. Online ahead of print.

Acute effects of transcranial direct current stimulation on cycling and running performance. A systematic review and meta-analysis.

Shyamali Kaushalya F, Romero-Arenas S, García-Ramos A, Colomer-Poveda D, Marquez G.

Eur J Sport Sci. 2021 Jan 7:1-13. doi: 10.1080/17461391.2020.1856933. Online ahead of print.

Effects of Anodal Transcranial Direct Current Stimulation on Training Volume and Pleasure Responses in the Back Squat Exercise Following a Bench Press.

Rodrigues GM, Machado S, Faria Vieira LA, Ramalho de Oliveira BR, Jesus Abreu MA, Marquez G, Maranhão Neto GA, Lattari E.

J Strength Cond Res. 2021 May 5. doi: 10.1519/JSC.0000000000004054. Online ahead of print.

Transcranial Direct Current Stimulation Does Not Affect Sprint Performance or the Horizontal Force-Velocity Profile.

Alix-Fages C, Garcia-Ramos A, Romero-Arenas S, Nadal GC, Jerez-Martínez A, Colomer-Poveda D, Márquez G.

Res Q Exerc Sport. 2021 Nov 4:1-9. doi: 10.1080/02701367.2021.1893260. Online ahead of print.

Methods

There are some concerns regarding some questions of the methods and design:

Why authors have chosen a single blind approach (only subjects blinded to condition)? Double blind is needed in this type of research because the authors´ a priory expectation could influence the results of the study (e.g.: via changes in the feedback provided, etc).

For sample size estimation authors have chosen the effect size based on previous literature (Hazime et al. (2017) and Lattari et al. (2020a)) who found very large effect sizes. However, all the meta-analysis that studied the effects of a-TDCS on motor performance (strength and endurance) found much lower effect sizes (SMD: 0.20 to 0.40). Please justify this decision, and how it would influence the selection of lower ES.

Regarding the stimulation site, it has been located at the C3/C4 according to the 10-20 electrode placement system. However, leg representation is located in Cz (just in the sulcus), so it is rather difficult to argue that it is possible to focally stimulate left leg M1 using a 5 x 5 cm anode placed over C3. If we take this into account, the “a priory hypothesis” of this study could not be tested.

Line 207 -211: Why authors use different protocols before and after the application of tDCS (anodal/sham)? Subjects warmed-up in the PRE but not after 10 minutes of rest (while applying tDCS). Furthermore, they performed 2 to 3 MVCs in the PRE, but only one in the POST. This could influence the results obtained.

Line 222: please revise the Fatigue Index equation (and the obtained results), it is wrong. It should be as follow:

FI= ((a-b)/a)*100, where “a” is the initial performance and “b” the final performance.

Discussion

Discussion needs substantial improvement. Overall arguments and explanations exposed by the authors are rather superficial and imprecise. As with the rest of the manuscript, writing needs a thoughtful revision. See some specific comments below:

Line 303: fatigability

Line 308-3318: I do not understand why it is hypothesized an increase in the MVC while most of the papers who tested 1RM or MVC failed to demonstrate an effect of tDCS on maximal force production, regardless of the muscle tested (please see Alix-Fages et al., 2019). Kristiansen et al., 2021 previously found a lack of increase in MEP amplitude and MVC in a KE MVC after a-tDCS. It should be better addressed and discussed.

Line 334-337: This is mere speculation. First, M1 excitability has not been measured. Second, it is not well stablished a causal link between M1 increased excitability and force enhancement. Furthermore, this is not aligned with the main interpretation and conclusion of the paper, which is completely opposed to this result.

Line 352-354: This is important, because the task could influence results. See Kaushalya et al., who showed that only TTE test are affected by TDCS during running and cycling endurance activities. Furthermore, recent papers found that aTDCS does not influence performance during repeated “all out” efforts (4-6 sec) interpesed with 30 sec rests (i.e.: RSA test: Alix-Fages et al., 2021). Moreover, as previously commented, the task used in this study only produced a 12% reduction in force overall. This should be discussed further.

Acute effects of transcranial direct current stimulation on cycling and running performance. A systematic review and meta-analysis.

Shyamali Kaushalya F, Romero-Arenas S, García-Ramos A, Colomer-Poveda D, Marquez G.

Eur J Sport Sci. 2021 Jan 7:1-13. doi: 10.1080/17461391.2020.1856933. Online ahead of print

Transcranial direct current stimulation and repeated sprint ability: No effect on sprint performance or ratings of perceived exertion.

Alix-Fages C, Romero-Arenas S, Calderón-Nadal G, Jerez-Martínez A, Pareja-Blanco F, Colomer-Poveda D, Márquez G, Garcia-Ramos A.

Eur J Sport Sci. 2021 Feb 25:1-10. doi: 10.1080/17461391.2021.1883124

Conclusions

“This study found that 10 minutes of 2 mA of a-tDCS is not an effective or consistent method for increasing maximal force production or reducing fatigue in the KE either contralateral or ipsilateral to the stimulated M1.”

This conclusion contrast with those mentioned in lines 334-337.

Reviewer #3: This reviewer is thankful for the opportunity to review this submission by Savoury et al. The aim of the study was to measure the effect of anodal transcranial direct current stimulation (a-tDCS) of the left motor cortex (M1) on both ipsilateral and contralateral knee extension strength and fatigue using a sham-controlled crossover study design. The authors concluded that, contrary to their initial hypothesis, the use of a-tDCS did not significantly increase strength of muscle contraction with contralateral knee extension and significantly decreased muscle contraction with ipsilateral knee extension. They additionally found no significant effect of a-tDCS on muscle fatigue. This work contributes to a growing collection of publications on a-tDCS, all with inconsistent findings regarding its efficacy on muscle contraction augmentation. While the topic is interesting and has promise to translate into clinical space, its findings add to overall ambiguity within the current science. The work is generally well-written, although there is opportunity to provide more clear and consistent use of right/left and contralateral/ipsilateral as shifting between the two sets of terms leads to an unnecessary cognitive burden for the reader. This work provides findings contrary to many published studies, which may be noteworthy, but the authors do not sufficiently reconcile issues they raise in their introduction regarding inconsistency in published tDCS protocol. Consequently, it is difficult to conclude if their contrary findings are a true finding or a result of poorly controlled method with small sample size. With some modifications this work may be fit for publication.

ABSTRACT

Minor Comments

1. Break into sections: Background, Methods, Results, and Conclusion (See Plos One criteria)

INTRODUCTION

Major Comments

1. The authors spend a paragraph describing variables that contribute to the efficacy of tDCS. Even when they describe previously used methods in muscle force production and fatigue, they highlight heterogeneity (i.e., contralateral M1 vs temporal cortex vs prefrontal cortex). It is not well resolved what approach might be the most efficacious. Based on what is written, there seems to be insufficient knowledge to support methodological choices.

2. Moreover, the introduction is hard to follow, unfocused, and too lengthy. The previous research is presented without flow and how it relates to the current study as well as muscular force specifically. Additionally, much of the details should be reserved for the Discussion Section.

3. Lines 148-150: Sex differences did not seem to be an active area for investigation. Authors may add background for this or exclude this hypothesis, as no meaningful investigation was conducted to actually observe differences and as of now seems out of place.

Minor Comments

1. Line 148: Due TO the lack…

2. Throughout the paper, this reviewer suggests using the wording “targeting the left M1” instead of “of the” as it is more reflective of the administration of tDCS

3. Line 79-81: If this sentence remains in the article, make wording clearer with more detailed outcomes.

4. Issues with sentence structure and clearly presenting the previous literature to introduce the topic to the reader.

METHODS

Major Comments

1. Although the authors refer to Thair et al., 2017 paper for screening, it is important to spell out for the reader in the methods the specific Inclusion/exclusion criteria used to enroll participant.

2. Works cited in the methods session regarding intervention design are not addressed in the introduction. Why were particular protocols chosen as opposed to others?

3. The introduction states that this work builds upon the work of Vargas et al. (2018), but this study chose to stimulate and then test versus test at 13 minutes in a 20-mintue stimulation. It is unclear why the authors strayed from this established protocol.

4. Cogiamanian et al. (2007), Kan et al. (2013), Abdelmoula et al. (2016), and Lampropoulou & Nowicky (2013) all use tDCS to measure changes in elbow flexion. The knee and elbow are distinct areas of the motor strip with leg and knee sitting more midline/parasagittal. Montenegro et al. (2015) measured knee flexor, but this was a negative study. Explanation for why this protocol is applicable for your knee flexion study would be helpful.

5. It was noted that measurements of the knee joint were acquired as knee angle can affect the isometric MVC, however the angles were not documented.

6. It is understandable that post-tDCS, participants performed only one MVC to minimize the effect on fatigue protocol, but this leads to a comparison of pre-tDCS measurements after 2 -3 attempts that took participant related effort (change of +5%) into account.

7. Tables mentioned EMG MVC data but were not explicitly stated in the paper; only a strain gauge.

8. Typically blinding of tDCS conditions are implemented in protocols. It does not appear the testing was double-blinded. If so, authors will need to comment on this limitation.

Minor Comments

1. Experimental design noted to be crossover in abstract. Similar verbiage not used in the body of the manuscript. The authors do say, “repeated measures design, with all participants completing four protocols,” which is the equivalent, but there may be some value to maintain consistency.

2. Line 183: 10–20 electroencephalography (EEG) electrode placement system.

3. While testing order was randomized, given the sample size was small, did randomization protocol actually result in equal variances?

4. The Supplementary questionnaire could be improved by asking the participants if they believe they just received the a-tDCS or s-tDCS, but again blinding should be made clearer.

5. Authors should consider reviewing sentence structure, as run-on and missing words make the narrative hard to follow.

RESULTS

Major Comments

1. It would be helpful to report the specific main effects that were not significant

2. Line 282: The title should be more specific. Also, the two paragraphs should be more concise. Moreover, this reviewer does not think this section adds much to the overall aim of the study.

3. Tables 1-3: Discrepancy with Tables and reporting. Table 3 is referenced in-text (Line 290), but as Table 1 in Line 300. Tables 1 and 2 (at the end of the manuscript) are not referenced in-text at all and does not have a Table legend.

4. Figures 2-4: Authors should add more details of the figures to captions

Minor Comments

5. Define a very good and excellent reliability score outside of parentheses.

6. Line 262: the results are presented as ipsilateral with a-tDCS then s-tDCS followed by contralateral with s-tDCS then a-tDCS. Would recommend reversing the order of s-tDCS and a-tDCS in the contralateral group so that the ipsilateral and contralateral are presented using a similar convention.

DISCUSSION

Major Comments

1. First paragraph, it is not commonplace to re-report statistics (i.e., the p-values) in the discussion section. This reviewer suggests removing.

2. First paragraph should include specific details of the results. For example, it appears the authors are including both results of maximal force production and muscle fatiguability in “force impairment.” Please rectify.

3. Lines 320-321: “a-tDCS is not a consistently effective ergogenic aid when the goal is to increase maximal KE force for a discrete contraction”. Is the variation in outcomes (specifically an increase in maximal KE force) a product of the technology or a product of experimental designs with small sample sizes and numerable uncontrolled, confounding variables? (as stated in the next sentence).

4. This reviewer is not sold on the importance of Lines 365-380. These statements can be concise enough to mention in the limitations section (which needs more exploration) due to the fact the participants were not directly asked if they believe they received a-tDCS or s-tDCS.

5. Limitation section needs to be developed. Potentially the comments provided in this review will trigger additional limitations of the study besides the small sample size (e.g., blinding efficacy/expectancy beliefs, other regions of the brain that the authors mention). Other considerations would be the 10-min stimulation, could it be that the length of stimulation inadequate to produce a change?

6. In the conclusion section, the authors mention athletes and performance enhancements, but this was not previously mentioned as a potential impetus of this study. This should be rectified.

7. Lines 392-392 offers a limitation to only studying quadriceps/KE. This should be moved up to the limitations section. Again, same comments for Lines 392-397 are recommendations to limitations and should be discussed in the Limitations section.

Minor Comments

1. Restatement of hypothesis on line 308 is hard to follow. Consider rewording to say, “the hypothesis that …” or adding another hyphen in “a-tDCS-induced..”

2. Would consider changing work reported on line 317 – MVC is measured not reported.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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PONE-D-22-11905R1Reduced isometric knee extensor force following anodal transcranial direct current stimulation of the ipsilateral motor cortexPLOS ONE

Dear Dr. Behm,

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 Nov 18 2022 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.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Xin Ye, Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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 #3: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

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 #3: Partly

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #3: I Don't Know

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #3: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #3: 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 #3: Summary of feedback:

This reviewer appreciates the consideration of previous feedback and revision of the manuscript. The manuscript has improved, however, this reviewer found it difficult and time-consuming to identify what changes the authors made. On any subsequent revisions, the authors should include a “tracked changes” version, so that reviewers can easily follow the revisions. This reviewer still found sentence structure, clarity issues, and punctuation errors. Attention to detail is imperative. Lastly, more detail should be included in the methods section as to the measures used to assess MVC.

ABSTRACT:

Minor Comments

1. As mentioned in this Reviewer’s previous comments, there is inconsistent use of right/left and contralateral/ipsilateral as shifting between the two sets of terms leads to an unnecessary cognitive burden for the reader. (Lines 42-47 and throughout the manuscript)

2. Line 37, was MVC force tested <immediately> following the a-tDCS and s-tDCS? If so, please specify.

3. Line 40 – remove “The main finding of this study..” and simply say “There was a ….”

4. Line 48 – remove the comma after “Although”

5. Line 50 – remove “Hence”

INTRODUCTION:

Major Comments

1. Third paragraph and fourth paragraph describe positive results and negative results of tDCS, respectively. The third paragraph speaks generally about studies that showed increased muscle force and endurance. The fourth paragraph speaks specifically about tDCS applied to the dorsolateral prefrontal cortex/M1. While the conclusion the authors draw starting on line 77 is likely sound, comparing a general pool of studies to those in a particular area may not be comparing the same phenomenon. The authors discuss this in the final line of paragraph four. If the point to be communicated with the reader is that there is likely heterogeneity in results likely as a result of variation in protocols, this point could likely be made more succinctly.

2. Appreciate the addition of discussion around mechanism and selection of tDCS target added from last version

3. Clear stated aim in final paragraph is helpful - would consider adding ‘left’ prior to M1 in this sentence.

4. The inclusion of sex differences, while appreciated, seems to emerge suddenly. Consider providing some additional context.

5. SICI was not introduced previously to line 112.

6. The differences in sex was outlined without including why this should be studied, despite the lack of research.

Minor comments

1. Errors in punctuation: Lines 64, 70, 72

2. Line 74: prefrontal is generally not hyphenated

3. In line 81, the word “reviews” should be removed and state “meta-analyses” instead.

4. Line 99, a-tDCS was already introduced, and should be used.

5. Line 102: It is unclear to this reader what you mean by “acute studies”. Perhaps, “No studies to date have tested the acute effects of a-tDCS on fatigue/endurance…”?

6. Line 124: Neurones -> neurons (twice)

METHODS:

Minor Comments

1. Appreciate the inclusion of the tDCS Questionnaire in methods. While the results may be in supplementary data, using ‘supplementary’ in the title is confusing. Would consider retitling to “tDCS Blinding Questionnaire”

2. Punctuation Errors: Lines 146, 235

3. Either session or protocol should be used in line 162.

4. Line 182: Consider a different word than “deceptive” – “blinding protocol” would be more appropriate

5. Line 193: use of semi-colon between two and four is unclear. Consider using comma “two, four-second…”

RESULTS:

Minor Comments:

1. Line 243-244 for clarity, consider leading the sentence with “Coefficient of variations …”

2. Line 285: Similar concern about removing supplementary from title, and if truly supplemental, direct readers to the supplemental material within the body of the paragraph

3. Define a very good and excellent reliability score outside of parenthesis.

DISCUSSION:

Major Comments:

1. There is opportunity to discuss more about the gender differences and recommendations for future tests based on why gender was included as exploratory in this study. The introduction referred to a lack of literature, however the discussion noted a previous study. Additionally, in the conclusion that there is no difference between males and females is perhaps overstated. Was the experiment actually powered to observe this? Agree that it is worth noting, but that a recommendation for further research with a specific aim on sex differences is warranted.

2. Line 312: you reiterate the point, “this lack of reliability and high variability in the literature may be also related to the great diversity of implemented protocols (e.g., differences in electrode location, size, number, current density, polarity, and stimulation duration) [42].” after reading the introduction and discussion I am still left wondering how your study attempts to address this. Ideally stronger commentary should be provided as to why your method is optimal and why others should continue to apply this method in future studies.

3. Addition of expanded limitations section is appreciated

4. Lines 350-353 should be included in the introduction as well.

5. Final sentence of your last paragraph again noted heterogeneity in protocol - what is your recommendation?</immediately>

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Reviewer #3: No

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PONE-D-22-11905R2Reduced isometric knee extensor force following anodal transcranial direct current stimulation of the ipsilateral motor cortexPLOS ONE

Dear Dr. Behm,

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 Jan 06 2023 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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If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

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We look forward to receiving your revised manuscript.

Kind regards,

Xin Ye, Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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 #3: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

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 #3: Partly

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #3: I Don't Know

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #3: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #3: No

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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 #3: Summary of feedback:

This reviewer thanks the author for addressing most of the previous comments. This reviewer, however, still identified issues in organization, sentence structure, clarity, and references, especially in the Introduction. This reviewer suggest that the authors recruit a few other researchers, outside of the authors, to review and provide feedback. I offer the additional suggestions, although not exhaustive, below.

ABSTRACT:

Minor Comments

1. Methods: Label the fatigue protocol.

2. Line 44: Replace “impairments” with “reduction” to specify direction of the change.

INTRODUCTION:

Major Comments

1. The Introduction is too long for the information provided. This reviewer suggests being more succinct in reporting information. For example, Lines 82-98 has unnecessary and repetitive details in which the information can be reduced to about 2 sentences. The authors can reserve some of the details for the discussion.

2. Lines 58-62 should be better linked. For example, use of “however” or some other revision to which it would tell the reader, this is what is known clinically without much discrepancy in the literature, however, when investigating the effects of tDCS on exercise and sport performance there appears to be mixed results. This would be a better transition in

3. There are over 60 references in the Introduction alone, which leads to an indication that the information in the introduction is unfocused. The authors should focus in on only articles specific to their research study. For example, are the effects of tDCS on elbow flexion necessary when the current study focuses on lower limb force and endurance? Are studies that target the dlPFC necessary to compare to a study targeting M1?

Minor Comments

1. Lines 139-143: use active voice or make line 139-140 its stand-alone sentence after the stated aim.

METHODS:

Minor Comments

1. Lines 185-187: It is unclear why the authors are using 5 study references just say that M1 is located at C3/C4 on EEG placement. Are the authors trying to say something else? If not, this reviewer thinks 1 major reference of an EEG placement paper is sufficient.

2. Line 194: Remove double word.

RESULTS:

Minor Comments:

1. It would be helpful to restate the statistical models for each analysis in the results since the variables of the ANOVA vary.

DISCUSSION:

Minor Comments:

1. Line 336-338: Make the sentence more detailed based on the references provided (i.e., #10 and #19). For example, the target of tDCS and MVC, etc in these articles.

2. Line 364: Make the effects on sex more specific to the current studies protocol, parameters and variables and not so general.

3. Lines 365-369: Authors should highlight the a-tDCS results first, since it relevant to the current study and then introduce that cathode tDCS generated different results.

4. Line 382: The authors introduced TMS without defining it or providing insight into how TMS may determine potential changes in M1 excitability.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #3: No

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Reduced isometric knee extensor force following anodal transcranial direct current stimulation of the ipsilateral motor cortex

PONE-D-22-11905R3

Dear Dr. Behm,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Xin Ye, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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 #3: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

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 #3: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #3: I Don't Know

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #3: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #3: 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 #3: This Reviewer thinks that the manuscript has improved greatly since initial review. This Reviewer does not have any other MAJOR comments, and just a few MINOR comments. Once those are fixed, this Reviewer believes it has reached a point for acceptance.

1. Page 5 Line 105 AND Page 15 Line 363: The Page 5 can be used to define TMS and Page 15 can be moved to abbreviation.

2. Page 7 Line 161: Revise for clarity. This sentence is missing a word or two.

3. Page 9 Line 201-101 Revise for clarity.

4. Page 13 Line 35: Revise to "....may also be related to greater diversity..."

5. Page 15 Line 346: Authors can use the abbreviation tDCS here.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #3: No

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