Peer Review History
Original SubmissionJanuary 31, 2022 |
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PONE-D-22-03125Cerebellar transcranial direct current stimulation disrupts neuroplasticity of intracortical motor circuits.PLOS ONE Dear Dr. Opie, 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. ============================== Two experts reviewed your manuscript. As you will see below, both reviewers have questions regarding the methodological approach. However, since your paper was based on a previously registered protocol in PLoS one, I suggest you examine these questions to see if you can provide some justification for the reviewers. Otherwise, you can focus your attention on the reviewers' suggestions about the interpretation of the results and their significance for the field. ============================== Please submit your revised manuscript by Apr 23 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:
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, François Tremblay, PhD Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and 2. 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. 3. Thank you for submitting the above manuscript to PLOS ONE. During our internal evaluation of the manuscript, we found significant text overlap between your submission and the following previously published work: - https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0236005 We would like to make you aware that copying extracts from previous publications, especially outside the methods section, word-for-word is unacceptable. In addition, the reproduction of text from published reports has implications for the copyright that may apply to the publications. Please revise the manuscript to rephrase the duplicated text, cite your sources, and provide details as to how the current manuscript advances on previous work. Please note that further consideration is dependent on the submission of a manuscript that addresses these concerns about the overlap in text with published work. We will carefully review your manuscript upon resubmission, so please ensure that your revision is thorough. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Does the manuscript adhere to the experimental procedures and analyses described in the Registered Report Protocol? If the manuscript reports any deviations from the planned experimental procedures and analyses, those must be reasonable and adequately justified. Reviewer #1: Yes Reviewer #2: No ********** 2. If the manuscript reports exploratory analyses or experimental procedures not outlined in the original Registered Report Protocol, are these reasonable, justified and methodologically sound? A Registered Report may include valid exploratory analyses not previously outlined in the Registered Report Protocol, as long as they are described as such. Reviewer #1: Yes Reviewer #2: Partly ********** 3. Are the conclusions supported by the data and do they address the research question presented in the Registered Report Protocol? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. The conclusions must be drawn appropriately based on the research question(s) outlined in the Registered Report Protocol and on the data presented. Reviewer #1: Yes Reviewer #2: Partly ********** 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 #1: Yes Reviewer #2: Yes ********** 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 #1: Yes Reviewer #2: Yes ********** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: In this article written by Liao et al., the authors present the results of registered result that investigated whether applying cathodal tDCS over the cerebellum influences the activity of intracortical neurons within the primary motor cortex. To do this, the authors made use of a technique, termed iTMS, that produces neuromodulatory affects over M1 when applied at specific intervals that represent early and late indirect inputs on to corticospinal neurons, and assessed whether the changes in M1 excitability following iTMS is disrupted with cathodal tDCS. The article is easy to follow as it is very well-written, and from a technical stand-point, it appears the authors did a good job of reliably conducting some quite complex physiological measures. I have some issues with some of the selected produces conducted in their experiments that require justification and with some of the result interpretations that could be revised, but the overall quality of this manuscript is quite high. Considering this is a registered study, I think the results carry a lot of weight, especially when considering that these types of reports are not easy to find in the literature of brain stimulation. Below are my concerns: For the iTMS protocol, can the authors justify why they selected to target the I3 wave (at 4.5 ms) as opposed to (or in addition to) selecting an interval that would predominately target the I2 wave? Since both the I2 and I3 wave get lumped together as “late I-waves”, should we expect a similar finding if one were to target the I2 wave? “The absence of additional control conditions in which real iTMS was applied over M1 in conjunction with sham tDCSCB is a limitation of the current study.” The problem with not conducting this additional control condition is that we don’t really know the reliability and reproducibility of iTMS. For instance, what do the authors believe is the error of margin of using the ISI of 4.5 ms for targeting the I3 wave? For instance, Long et al., 2017 ( 10.1093/brain/awx102) used an ISI of 4.3 ms for their late I-wave protocol, and the authors of this manuscript previously show that an ISI of 4 ms and 5ms yielded greater facilitation on M1 excitability when compared to 4.5ms. Thus, it seems that another potential interpretation of the results could be that the lack of changes on intracortical excitability and corticospinal excitability might be due to the variability of the “late” iTMS protocol and not influences from the cerebellum. Why did the authors select cathodal cerebellar Tdcs as their cerebellar neuromodulatory technique as opposed to cerebellar theta burst protocol? Cerebellar tDCS does appear to exclusively produces changes in cerebellar excitability and not corticospinal activity (Galea et al., 2009; 10.1523/JNEUROSCI.2184-09.2009), which has been suggested to produce tonic changes at the Purkinje cell level without activating cerebellar-thal-M1 pathways. However, cerebellar theta burst does yield changes in M1 excitability (10.1016/j.clinph.2008.08.008 ; 10.1038/srep36191), which might reflect this protocol depolarizing cerebellar Purkinje cells and engaging cerebellar-thal-M1 pathways (that produce changes in M1).Thus, one could presume that cerebellar theta burst would have yielded a more disruptive affect on the iTMS protocol. “Second, this pattern of response – simultaneously suggesting that late I-waves were (MEPPA) and were not (MEPAP) responsive to iTMS – can only be consistent with the more contemporary interpretation that different current directions recruit from different intracortical populations (for review, see; [54]). As previous work has shown that AP MEPs are potentiated by iTMS in isolation [44], our results therefore suggest that tDCSCB influenced (reduced) the neuroplastic response of intracortical circuits activated by AP stimulation.” While I agree with that different currents are likely recruiting different population of neurons, the previous results by the authors demonstrating changes in AP MEPs following iTMS performed with PA currents (ref 44) does not seem to exactly fit with this notion. One would rather expect that iTMS with PA currents produces greater facilitation of PA MEPs than AP MEPs if distinct populations are being targeted with directional TMS. Thus, if the authors are suggesting that cerebellar tDCS targets AP circuits, would it not be more reasonable to perform iTMS with AP currents? “SICF utilised a conditioning stimulus set at 90% RMT, a test stimulus set at MEP1mV and two ISIs of 1.5 (SICF1.5) and 4.5 (SICF4.5) ms, which correspond to the early and late MEP peaks apparent in a complete SICF curve [22, 26, 27]. Measurements of SICF included 12 trials for each condition, at each time point” Why did the authors select only 12 trials for each SICF measure, as opposed to 15 trials for each CBI measure and 20 trials for 1 mV assessment? Is SICF considered more reliable than these other measures to justify the much smaller sample? “The intensity of CB stimulation was set at 70%MSO, but was at times reduced for participant comfort (no lower than 60%MSO [33]), whereas M1 stimulation was set at MEP1mV” ; “Because antidromic activation of corticospinal neurons may confound measures of CBI [34], we ensured that the CB conditioning stimulus was at least 5% MSO below the active motor threshold for the corticospinal tract [35]” I think it would be useful for the authors to mention how many individuals could not withstand the cerebellar stimulation at 70% MSO, and if any individuals displayed evidence of antidromic activation. Moreover I suggest the authors to also add this reference for cerebellar stimulation comfort and reliability: https://doi.org/10.1016/j.brs.2019.09.005 Reviewer #2: General comment This study aims to elucidate the potential influences of the cerebellum (CB) on neuroplasticity in the primary motor cortex (M1), specifically the role of different indirect wave inputs in M1. To this end, they assessed the magnitude of neuroplasticity of early and late indirect-wave circuits before, during, and after the application of cerebellar tDCS which has been suggested to have modulatory effects on the cerebellar excitability (e.g., reduction of excitability). Based on multiple, complicated though, sets of neurophysiological assessments, the authors concluded that the disruptive effects of CB modulation on M1 plasticity may be selectively mediated by a certain circuit (i.e., late indirect wave circuit). Although the results are in general complicated, it looks that the authors carefully interpreted each data and explained underlying mechanisms. However, as discussed at the end of the Discussion part, the major issue of this study would be that the sham-controlled design was not adopted for the cerebellar tDCS, leading to the study being less conclusive. In particular, the fact that the cathodal cerebellar tDCS failed to modulate CBI, likely a prerequisite for this study, would have a strong impact enough to ruin all the present findings. Nevertheless, I believe that the study could provide preliminary but suggestive findings in this field to guide future studies in the right direction. Therefore, I think that this study is reasonable to be published in this journal after the authors address the following concerns: Major comments 1. Although the limitation and the conclusion look carefully reported in the Discussion part, the conclusion in the Abstract reads too strong. The conclusion should be weakened not to mislead the readers' interpretation. 2. The reason why the authors selected downregulating cerebellar stimulation (i.e., cathodal tDCS) is unclear. The authors would better carefully explain the rationale why cathodal but not anodal was selected. 3. How many trials (MEP samples) were finally excluded from the analysis due to voluntary contraction prior to TMS application? The exact number or percentage should be reported in the manuscript. 4. The information of Fig. 2B and C seems redundant, basically the same as Fig. 2A. The authors should better explain why they needed to perform these additional analyzes and prepare these figures. Otherwise, they may better be removed for the sake of simplicity. ********** 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 #1: Yes: Danny Spampinato Reviewer #2: No [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. |
Revision 1 |
PONE-D-22-03125R1Cerebellar transcranial direct current stimulation disrupts neuroplasticity of intracortical motor circuits.PLOS ONE Dear Dr. Opie, 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. The Reviewers were mostly satisfied with the revised version. Your manuscript is basically accepted. Reviewer #2 has only two minor issues for you to address. I am sure you can proceed quickly and resubmit a revised version. Please submit your revised manuscript by Aug 05 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:
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, François Tremblay, PhD 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. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Does the manuscript adhere to the experimental procedures and analyses described in the Registered Report Protocol? If the manuscript reports any deviations from the planned experimental procedures and analyses, those must be reasonable and adequately justified. Reviewer #1: Yes Reviewer #2: Yes ********** 2. If the manuscript reports exploratory analyses or experimental procedures not outlined in the original Registered Report Protocol, are these reasonable, justified and methodologically sound? A Registered Report may include valid exploratory analyses not previously outlined in the Registered Report Protocol, as long as they are described as such. Reviewer #1: Yes Reviewer #2: Yes ********** 3. Are the conclusions supported by the data and do they address the research question presented in the Registered Report Protocol? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. The conclusions must be drawn appropriately based on the research question(s) outlined in the Registered Report Protocol and on the data presented. Reviewer #1: Yes Reviewer #2: Yes ********** 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 #1: Yes Reviewer #2: Yes ********** 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 #1: Yes Reviewer #2: Yes ********** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The authors have addressed my concerns. My final suggestion would be for the authors to include two recent papers in the introduction paragraph #3, which have shown the interaction of cerebellar projections to specific excitatory (DOI: 10.1523/JNEUROSCI.2397-19.2020) and inhibitory (DOI: 10.1016/j.brs.2021.08.022) interneurons. Reviewer #2: General comment Although the authors addressed my previous comments and fairly modified the manuscript, there remain some points that need to be further or properly clarified before getting accepted. I hope that the authors address the following comments accordingly. Specific comments #1. The rationale for selecting cathodal but not anodal remains unclear. The authors explained in the revised manuscript that “previous work has reported that tDCS to CB modulates concurrent plasticity induction of M1 [15: Hamada et al., 2014]” followed by “therefore, we investigated whether enhancement of M1 plasticity could be achieved by downregulating CB excitability using cathodal tDCS~”. Hamada et al. (2014) demonstrated that concurrent anodal cerebellar tDCS abolishes M1 plasticity, without testing with cathodal one. Hamada et al. (Journal of Physiology, 2012), on which Hamada et al. (2014) rely, also found that both anodal and cathodal cerebellar tDCS block M1 plasticity. These previous findings do not look directly support the authors’ decision to select cathodal but not anodal. A more careful and logical explanation should be achieved. #2. Is 1.9% the average of excluded MEPs among participants? Or, is it the percentage of pooled MEPs among all participants and conditions, etc.? Please specify in more detail. ********** 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 #1: Yes: Danny Spampinato Reviewer #2: No ********** [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. |
Revision 2 |
Cerebellar transcranial direct current stimulation disrupts neuroplasticity of intracortical motor circuits. PONE-D-22-03125R2 Dear Dr. Opie, 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, François Tremblay, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: |
Formally Accepted |
PONE-D-22-03125R2 Cerebellar transcranial direct current stimulation disrupts neuroplasticity of intracortical motor circuits. Dear Dr. Opie: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. François Tremblay Academic Editor PLOS ONE |
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