The effects of verbal and spatial working memory on short- and long-latency sensorimotor circuits in the motor cortex

Markus W. Lenizky; Sean K. Meehan

doi:10.1371/journal.pone.0302989

Peer Review History

Original SubmissionDecember 14, 2023
7 Feb 2024 Decision Letter - Dimitris Voudouris, Editor PONE-D-23-40285The effects of verbal and spatial working memory on short- and long-latency sensorimotor circuits in the motor cortexPLOS ONE Dear Dr. Meehan, 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 expert reviewers evaluated your manuscript. Both reviewers find your paper interesting and worthwhile, but they also raise concerns regarding the data analyses. These relate to possible effects of the different TMS interval on the reported data. Given the specific comments below, I think it should be possible to fully address all of the reviewer concerns, so I look forward to receiving the revised version of your work. Please submit your revised manuscript by Mar 23 2024 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'. 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Please be assured that, once you have provided your new statement, the assessment of your exemption will not hold up the peer review process. [Note: HTML markup is below. Please do not edit.] 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: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 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: Yes ****** 4. 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 ****** 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 authors report short and long -latency afferent inhibition to probe the influence of verbal and spatial working memory load. They describe that specific sensorimotor circuits recruit, with different working memory load and probed short and long -latency afferent inhibition by PA and AP TMS-induced current. However, there are some issues to be addressed. 1. It is not clear how the authors consider TMS stimuli delivery period (i.e 1500, 1750, 2000, 2250 and 2500) during analysis. I see every conditioned was averaged. It is not clear what is the effect on SAI and LAI with different TMS stimuli delivery period. It was also not clear how MEP elicited during these different TMS stimuli delivery period. 2. It is difficult to understand unconditioned or conditioned TMS stimuli, there is no clear statement. 3. It is not clear that why the authors called the task as verbal working memory, it is set of different character (shape). 4. It will be good if authors explain the interstimulus intervals (ISIs) in line 53. 5. Is there any study suggesting that SAI appears to involve a thalamic projection to the motor cortex (line 75)? 6. Please give some reference to support the dissociation between perceptual load and working memory demands suggesting some common elements across the different SAI sensorimotor circuits. 7. The line number 179 is not clear. 8. Does PA in the verbal task reflect subtle differences in SAI and not in AP (SAI as well as LAI)? 9. The authors mentioned every critical question to be asked in this article as limitation of this paper. Reviewer #2: This study examined the response of short (SAI) and long-latency afferent inhibition (LAI) to verbal and spatial working memory loads using posterior-anterior (PA) and anterior-posterior (AP) TMS-induced currents. Participants maintained sets of two or six verbal or spatial stimulus items in two sessions, differing only in current direction. PA SAI decreased with verbal load, while AP SAI remained unchanged. Visuospatial load did not affect PA or AP SAI. Neither PA nor AP LAI responded to memory load. The authors suggest that distinct sensorimotor circuits facilitate context-specific supraspinal control amid increasing verbal working memory load. The authors have described their methodology well and the manuscript is clear and concise. However, I have one minor comment. 1. I think the authors should make some reference to the work using spatial working memory, as it is not clear why they have chosen this task to compare with verbal working memory. 2. The order of the trials with AP and PA-induces current is not clear in the methodology. Can the authors say whether they followed an order or whether it was randomised? 3. Seeing that there are differences in the TRs, I suggest that the authors could carry out the analyses they have done by introducing the TR as a covariate, so as to shed some more light on the results obtained. 4. In both Figure 2 and Figure 3 there is a lot of variability in the effects between participants. Can you address this issue in the discussion? 5. Could you produce a figure showing only the participant averages for both SAI and LAI? ****** 6. 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: Balbir Singh 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. Attachments Attachment Submitted filename: Attachment.docx https://doi.org/10.1371/journal.pone.0302989.r001
Revision 1
22 Mar 2024 Author Response Response to Reviewer Comments We thank the reviewers for their insightful comments on the manuscript. We have addressed each point and made the applicable revisions. Below, we have enumerated their specific comments and replied to each. Changes made to the manuscript text are highlighted in red. In our responses, specific line numbers reference the revised manuscript. Reviewer #1 Point 1. It is not clear how the authors consider TMS stimuli delivery period (i.e 1500, 1750, 2000, 2250 and 2500) during analysis. I see every conditioned was averaged. It is not clear what is the effect on SAI and LAI with different TMS stimuli delivery period. It was also not clear how MEP elicited during these different TMS stimuli delivery period. Response 1. We apologize for any confusion. We have revised the text in the Figure 1 caption (lines 162 to 171) and lines 187 to 192 to clarify the MEP acquisition process. Briefly, a single TMS stimulus was delivered for each trial, either 1500, 1750, 2000 or 2250 after the memory set disappeared but before the probe appeared. We varied the timing of the TMS stimulus to minimize anticipation of the TMS stimulus. The TMS stimulus on a given trial was either TMS delivered without electrical median nerve stimulation (unconditioned) or the same TMS stimulus preceded by electrical stimulation of the median nerve (conditioned). The probability of the TMS stimulus occurring at any given time on a single trial was equiprobable (controlled by a rectangular distribution). To get SAI, we divided the average of all conditioned stimuli delivered across the 1500, 1750, 2000, 2250 and 2500 time points by the average of all unconditioned stimuli delivered across the 1500, 1750, 2000, 2250 and 2500 time points for a given set size and current direction. As acknowledged in the limitations section, we do not have sufficient trials at each specific time point to systematically investigate changes in SAI/LAI across the 1500-2500 ms of the maintenance period. There was not enough time to collect sufficient trials to calculate SAI reliably at each time point. Point 2. It is difficult to understand unconditioned or conditioned TMS stimuli, there is no clear statement. Response 2. We apologize for the ambiguity. We have revised text in the introduction (lines 41 to 47), the methods (lines 241 to 243) and the Figure 1 caption (lines 162 to 163) to make clear that “conditioned” refers to MEPs elicited by TMS stimuli that were preceded by peripheral electrical stimulation and that “unconditioned” refers to TMS stimuli that were not preceded by peripheral electrical stimulation. Point 3. It is not clear that why the authors called the task as verbal working memory, it is set of different character (shape). Response 3. Our terminology is consistent with the cited neuroimaging work using similar verbal and spatial Sternberg tasks to dissociate the neural substrates of verbal and spatial working memory (Thomason et al. J Cog Neurosci 2009; Reuter-Lorenz et al. Neuroscience 2000; Smith et al. Proc Natl Acad Sci 1996). These studies and many others use letters or digits to engage the verbal working memory system, which is responsible for temporarily storing letters, digits, words, and sentences over several seconds. We agree that letters, digits, and even words or sentences may be matched to a probe based on shape in specific circumstances. For example, chronometric studies of stimulus classification often rapidly present a letter or word probe adjacent to or immediately after the memory set to promote recognition based on shape. Given the strong association between letter shape and name, increasing the delay between the memory set and the probe provides time for processing the stimuli at deeper levels to facilitate subvocal rehearsal. Given the success of the cited neuroimaging work in dissociating verbal and spatial neural substrates with similar maintenance periods (~3 seconds) and that we conducted our TMS assessments during the maintenance period (before probe presentation at the central location), we are confident that we are probing the active rehearsal of verbal information even if part of the matching process following probe presentation may be based on recognizing a specific letter shape. Point 4. It will be good if authors explain the interstimulus intervals (ISIs) in line 53. Response 4. We apologize for the oversight in defining the abbreviation ISI on first use in the original manuscript. We have removed the abbreviation from the revised manuscript completely. Further, we have revised lines 44-47 to explain better the inter-stimulus interval in the context of afferent inhibition. Point 5. Is there any study suggesting that SAI appears to involve a thalamic projection to the motor cortex (line 75)? Response 5. We appreciate that there is no definitive evidence to support a direct thalamic projection to the motor cortex in the generation of SAI. However, there is evidence that dissociates the N20 somatosensory evoked potential and SAI in response to thalamic lesions affecting the primary thalamic relay nuclei projecting to S1 and SAI, supporting the involvement of another relatively direct influence given the tight time window. We have revised the text (lines 68 to 79) to illustrate better the evidence for a thalamocortical pathway that traverses the primary somatosensory cortex and at least one other short thalamocortical pathway. Point 6. Please give some reference to support the dissociation between perceptual load and working memory demands suggesting some common elements across the different SAI sensorimotor circuits. Response 6. – We apologize for any ambiguity surrounding the accidental use of “perceptual load”. It should have read “perceptual attention load.” We have also revised parts of this paragraph (lines 105 to 108) to clarify the point about common elements across the sensorimotor circuits. Point 7. The line number 179 is not clear. Response 7. We have revised the text (lines 197 to 202 in the revised manuscript) to better describe electrode placement and the triggered recording of data epochs around the TMS stimulus. Point 8. Does PA in the verbal task reflect subtle differences in SAI and not in AP (SAI as well as LAI)? Response 8. We apologize if we have misinterpreted the reviewer’s comment. We believe the reviewer is asking whether the specific effect of verbal working memory reflects a specific influence over the afferent pathways probed by PA-induced current. Yes, we believe that something about the working memory task is specifically changing the strength of the afferent projections to the population of interneurons preferentially recruited by PA-induced current. The effect on the afferent projection is much more robust for verbal memory than spatial memory. Finally, we believe that the dissociation between SAI and LAI to verbal working memory demands likely reflects the increasing complexity of the processing pathways across the longer interstimulus interval (200 ms) to elicit LAI. We hope revisions to lines 452 to 467 and lines 393 to 399 better illustrate these points. Point 9. The authors mentioned every critical question to be asked in this article as a limitation of this paper. Response 9. We thank the reviewer for their comment. Our goal in the discussion was to provide a rigorous placement of our results within the current literature. Part of this process reflects the trade-off between internal and external experimental validity. While we believe our results to be valid for the dominant hand and during the window of the maintenance period under study, we felt it prudent to address the generalizability to the non-dominant hand and early memory maintenance. To make this explicit, we have revised the text spanning lines 441 to 467. The limitation of the MagStim 2002 stimulator also attempts to provide guidance for future work that can leverage new knowledge generated by recent technological advances. Reviewer #2 Point 1. I think the authors should make some reference to the work using spatial working memory, as it is not clear why they have chosen this task to compare with verbal working memory. Response 1. We thank the reviewer for their comment and recognize this oversight. We have expanded the last paragraph of the introduction (lines 124-133) to address their comment. Briefly, both verbal and spatial memory play important roles in sensorimotor control. We sought to determine if the effect of working memory on the PA and AP sensorimotor circuits was a general effect or dependent on the particular domain. Point 2. The order of the trials with AP and PA-induces current is not clear in the methodology. Can the authors say whether they followed an order or whether it was randomized? Response 2. We apologize for the lack of clarity. We revised lines 246 to 262 to enhance the description of how the order of trials was determined. Point 3. Seeing that there are differences in the TRs, I suggest that the authors could carry out the analyses they have done by introducing the TR as a covariate, so as to shed some more light on the results obtained. Response 3. We thank the reviewer for their comment. We are unsure what adding threshold (TR) as a covariate would do to the results. The experimental design does not have between-subject factors, so the within-subjects error term captures the covariate. Further, TMS threshold standardizes the effect of the TMS stimulus across participants, with the magnitude of SAI shown to be relatively consistent across stimulus intensities that elicit MEPs ranging from 0.5 to 2 microvolts (Ni et al. J Neurophysiology 2011). That said, we did investigate the potential effect of threshold on the SAI response to Set Size and Task using multi-level modelling to account for our experiment's repeated measures design. The model was set to predict six-item SAI. The model included the stimulator output required to elicit a 1 mV motor-evoked potential and two-item SAI as continuous predictors. Task (Spatial vs. Verbal) was included as a categorical factor. For PA SAI, the 1 mV TMS threshold was not a significant term in the model [F(1,20)=0.06, p=0.80]. Only the terms consistent with the Task x Set Size interaction reported in the manuscript were significant. An F-test comparing a model with the predictor 1 mV threshold against a model with all other factors excluding threshold confirmed that the factor Threshold did not significantly improve the variance explained (p=0.81). The same was also true for the effect of the TMS threshold for AP SAI, PA LAI, and AP LAI. Point 4. In both Figure 2 and Figure 3 there is a lot of variability in the effects between participants. Can you address this issue in the discussion? Response 4. We thank the reviewer for their comment. For AP current, part of the variability across individuals may reflect heterogeneity in the sensorimotor circuits recruited by the fixed pulse width of the Magstim 2002 stimulator as acknowledged in the limitations section of the manuscript. In addition, we have revised the text (lines 393 to 399 and lines 452 to 467) to discuss additional sources of variability explicitly. We do not believe that the inter-individual variability compromises the group-level effects. We presented individual data in our figures to demonstrate the consistency (or inconsistency) of the effect across individuals within a task and current configuration to provide confidence in the group-level changes, with the dashed bars representing a difference from zero that would be considered meaningful (a moderate effect at the group level). For PA SAI, it is quite clear that the group effect reflects a relatively predictable decrease of meaningful magnitude across individuals not seen in other conditions. Point 5. Could you produce a figure showing only the participant averages for both SAI and LAI? Response 5. We have revised figures 2 (SAI) and 3 (LAI), and their captions, to include separate figures for the group averages. As part of the revision process, we rearranged the placement of the specific figures. The task (verbal or spatial) is now arranged by row, and the current direction (PA or AP) is now arranged by column. Attachments Attachment Submitted filename: Lenizky and Meehan - Response to Reviewer Comments.docx https://doi.org/10.1371/journal.pone.0302989.r002
8 Apr 2024 Decision Letter - Dimitris Voudouris, Editor PONE-D-23-40285R1The effects of verbal and spatial working memory on short- and long-latency sensorimotor circuits in the motor cortexPLOS ONE Dear Dr. Meehan, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit and meets PLOS ONE’s publication criteria. Yet, Reviewer 2 has a final minor point that I would like to invite you to address before making a final decision on the manuscript. Please submit your revised manuscript by May 23 2024 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, Dimitris Voudouris 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. 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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: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: N/A 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. 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 authors revised the manuscript "the effect of verbal and spatial working memory on short- and long-latency sensorimotor cicuits in motor cortex". And the authors incorporated my comments. Reviewer #2: Thank you very much to the authors for all of your explanations and corrections. I would like to make one final suggestion. Please rewrite the two sentences contained between lines 39-42. Afferent inhibition is not a stimulation technique. Afferent inhibition is the phenomena by which a sensory afferent volley inhibits the motor response in a given muscle and is typically studied by combining non-invasive electrical nerve stimulation with TMS over M1 (Claudia V. Turco, Jenin El-Sayes, Mitchell J. Savoie, Hunter J. Fassett, Mitchell B. Locke, Aimee J. Nelson, Short- and long-latency afferent inhibition; uses, mechanisms and influencing factors, Brain Stimulation,Volume 11, Issue 1, 2018,Pages 59-74) ****** 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: No 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. https://doi.org/10.1371/journal.pone.0302989.r003
Revision 2
15 Apr 2024 Author Response Response to Reviewer Comments We thank the reviewer for their additional comment. We have made the applicable revisions. Changes made to the manuscript text are highlighted in red. In our responses, specific line numbers reference the revised manuscript. Reviewer #2 Point 1. Please rewrite the two sentences contained between lines 39-42. Afferent inhibition is not a stimulation technique. Afferent inhibition is the phenomena by which a sensory afferent volley inhibits the motor response in a given muscle and is typically studied by combining non-invasive electrical nerve stimulation with TMS over M1 (Claudia V. Turco, Jenin El-Sayes, Mitchell J. Savoie, Hunter J. Fassett, Mitchell B. Locke, Aimee J. Nelson, Short- and long-latency afferent inhibition; uses, mechanisms and influencing factors, Brain Stimulation,Volume 11, Issue 1, 2018,Pages 59-74) Response 1. We have the sentences in question (lines 39 to 43). Attachments Attachment Submitted filename: Lenizky and Meehan - Response to Reviewer Comments.docx https://doi.org/10.1371/journal.pone.0302989.r004
17 Apr 2024 Decision Letter - Dimitris Voudouris, Editor The effects of verbal and spatial working memory on short- and long-latency sensorimotor circuits in the motor cortex PONE-D-23-40285R2 Dear Dr. Meehan, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, 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, Dimitris Voudouris Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0302989.r005
Formally Accepted
3 May 2024 Acceptance Letter - Dimitris Voudouris, Editor PONE-D-23-40285R2 PLOS ONE Dear Dr. Meehan, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, 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 customercare@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. Dimitris Voudouris Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0302989.r006

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