Clinical factors affecting evoked magnetic fields in patients with Parkinson's disease

Ryoji Naganuma; Ichiro Yabe; Megumi Takeuchi; Kirari Morishita; Shingo Nakane; Ryoken Takase; Ikuko Takahashi-Iwata; Masaaki Matsushima; Mika Otsuki; Hideaki Shiraishi; Hidenao Sasaki

doi:10.1371/journal.pone.0232808

Peer Review History

Original SubmissionApril 19, 2020
8 Jun 2020 Decision Letter - Jiaojian Wang, Editor PONE-D-20-11314 Clinical factors affecting evoked magnetic fields in patients with Parkinson's disease PLOS ONE Dear Dr. Yabe, 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 Jul 23 2020 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Jiaojian Wang 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 https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf Additional Editor Comments (if provided): We have recieved two reviewers' comments. One suggests major revision, and the other recommends acceptance. Thus, a minor revision is needed for this submission. [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: Partly Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No 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: No 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: No 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 paper compared multiple cognitive functions between PD patients and controls using various cognitive tests and explored the relationship between cognitive performances and evoked magnetic fields. Although sever significant results were described, there are several problems about sample, statistical analysis and results interpretation. Specific concerns are described below: 1. There is too small sample size, especially the HC group. I strongly suggest to recruit more healthy participants and re-analyzed again. 2. In Introduction section, more special description about the different evoked potential, what specific evoked potential reflect physiological feature? It is wonderful if hypothesis was present based on physiological feature. 3. In Clinical characteristics and measures, cognitive function should be provided for all tasks and its sub-domains. 4. There are patients in the off-state and on-state, what difference between two kinds of patients. 5. Multiple corrections should also be conducted for group comparison. 6. In Conclusion section, authors stated that evoked fields reflect basal ganglia function, what cognitive function or evoked fields are linked with ganglia function based on your results or previous studies? Reviewer #2: In this manuscript, the authors investigated the characteristics of the visual (VEF), auditory (AEF), and somatosensory (SEF) evoked magnetic fields in patients with Parkinson’s disease (PD), as well as the correlations between evoked fields and the patient’s clinical characteristics, motor symptoms, and cognitive functions. The authors found that the latencies of the VEF N75m, P100m, N145m, AEF P50m, P100m, and SEF P60m components increased significantly in patients with PD. Besides, the latencies were found to be correlated with medication and motor symptoms. The reported results are novel and provide new insights into the understanding of the pathophysiology of PD. The manuscript is well organized,technically sound and well-written. ****** 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: 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.0232808.r001
Revision 1
30 Jun 2020 Author Response PONE-D-20-11314 Clinical factors affecting evoked magnetic fields in patients with Parkinson's disease Dear Editor and Reviewers: Thank you for your e-mail on June 8, 2020 informing us that you would be willing to consider a revised version of our manuscript entitled “Clinical factors affecting evoked magnetic fields in patients with Parkinson's disease”. We found the points raised by the reviewers to be most helpful, and we have revised our manuscript accordingly. Please find attached the revised manuscript and our detailed point-by-point responses to the comments of the reviewers. We hope that our paper is now acceptable for publication in PLOS ONE, and we thank you for your consideration. Sincerely yours, Ryoji Naganuma, Ichiro Yabe Address: Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan Telephone: 81-11-706-6028 Fax; 81-11-700-5356 E-mail: yabe@med.hokudai.ac.jp >Reviewer #1 > 1. There is too small sample size, especially the HC group. I strongly suggest to recruit more healthy participants and re-analyzed again. As you indicated, the sample size of the HC group was small. It would have been ideal if the number of HCs would be the same as the patients, but it was difficult to recruit more controls because we could not find more new controls until the study’s approval had expired. However, the results were reliable for the number because the population of the controls was homogeneous in terms of the SDs and interquartile range despite the controls being recruited randomly. We believe that the results of this study are significant even with 10 people in the HC group. Of course, the confirmation study should be conducted in another study protocol. We added “Third, the number of HCs was small. It would have been ideal if the number of HCs was the same as the number of patients, but it was difficult since we could not recruit more controls. This was due to our inability to find new HC’s as the study’s approval had also expired. However, the results were reliable for the number chosen owing to the homogeneity of the control group in terms of the SD’s and interquartile range despite the controls being recruited randomly. A confirmation study to verify the same could be conducted at a later point in time. Line 542 > 2. In Introduction section, more special description about the different evoked potential, what specific evoked potential reflect physiological feature? It is wonderful if hypothesis was present based on physiological feature. As you indicated, the Introduction section was insufficient to describe the associations between evoked potential and physiological feature. Based on previous studies, we added associations between VEP P100 latency and polysynaptic visual pathway, SEP N30 amplitude and a cortico-subcortico-cortical reentry loop, and ABR wave V latency and brainstem dysfunction. Therefore, we added “Till date, it is considered that dopamine deficiency affects polysynaptic visual pathway, and an increase in the latency of the P100 component of the visual/visually evoked potential (VEP) is reported in PD [2]. In addition, a decrease in the amplitude of the N30 component of the somatosensory evoked potential (SEP) is reported in PD [3]. This could be since the frontal P20-N30-P40 complex (responsible for SEP) is generated with a cortico-subcortico-cortical reentry loop indicating cortical dysfunction in PD. An increase in the latency of wave V (seen as AEP) of the auditory brainstem response has also been reported in PD [4], and it is known that brainstem dysfunction is present in PD patients with dementia. Line 63 > 3. In Clinical characteristics and measures, cognitive function should be provided for all tasks and its sub-domains. As we adopted as much as 10 cognitive tests, the clinical characteristics and measures section has become very complicated. In addition, some of them are not familiar to people other than Japanese. To provide cognitive function for all tasks and its sub-domains, we added: These are accordingly listed in Table 1. Note that, each task for attention is designed to evaluate a specific attention, but it is also affected by other attention such as working memory, sustained attention and divided attention. Line 103. > 4. There are patients in the off-state and on-state, what difference between two kinds of patients. We are sorry for lacking the description about the patients in the off- state and on-state. We tested UPDRS part 3 in the on-state on all 20 patients, and 8 of the 20 patients were also tested UPDRS part 3 in the off-state: The 8 patients were inpatients to assess DBS adaptation. We added “eight patients out of the total 20 patients were administered UPDRS part 3 in the off-state since their antiparkinsonian drugs were withdrawn for the purpose of assessing deep brain stimulation (DBS) indications. Line 184 > 5. Multiple corrections should also be conducted for group comparison. As you pointed out, we did not perform Bonferroni correction in group comparisons, and statistical analysis methods were not unified. For cognitive tests, VCT time of simple symbol, complex symbol and number and ADT hit rate of the CAT remained significant after Bonferroni correction. From this result, sustained attention deficits are likely to be in PD because VCT and ADT remained significant. We added “Especially, VCT time of simple symbol, complex symbol and number and ADT hit rate of the CAT remained significant after Bonferroni correction.” on line 188 as a result, and “ “Sustained attention deficits are likely to be present in PD since among all the cognitive tests performed in our study, VCT and ADT remained significant after Bonferroni correction. Line 285. For evoked fields, SEF P60m (R, M), P60m – N20m (R, M) and P60m - P35m (R, M) remained significant after Bonferroni correction. As SEF P60m (R, M) (and SEF P60m – P35m (R, M) and SEF P60m – N20m (R, M)) remained significant after Bonferroni correction among all the evoked fields, it is strongly suspected that P60m is affected by PD pathology. We added “Especially, SEF P60m (R, M), P60m – N20m (R, M) and P60m - P35m (R, M) remained significant after Bonferroni correction.” on line 223 as a result, and “However, as SEF P60m (R, M), SEF P60m – P35m (R, M) and SEF P60m – N20m (R, M) values remained significant after Bonferroni correction among all the evoked fields, it is strongly suspected that P60m is affected by underlying PD pathology.” Line 471 In addition, for site location, there were no significant differences between patients with PD and HCs after Bonferroni correction. We added “Further, after applying Bonferroni correction the values for these three components became insignificant. Line 234. > 6. In Conclusion section, authors stated that evoked fields reflect basal ganglia function, what cognitive function or evoked fields are linked with ganglia function based on your results or previous studies? As you pointed out, Conclusions section was just a list of Results section. We added “We investigated the characteristics of cognitive functioning and evoked fields in patients with PD. PD patients presented with cognitive impairment on assessment tests such as MoCA-J, S-PA, FAB, TMT-A, B, CAT, ADT and VPTA. Especially, sustained attention deficits are likely to be present in PD. The latencies of the VEF N75m, P100m, N145m, AEF P50m, P100m, and SEF P60m components were greater in PD patients than in HCs. The increased latencies of VEF, AEF, and SEF were correlated mainly with medication and motor symptoms and less with cognitive tasks. Interestingly, AEF P100m and SEF P60m latency could strongly reflect basal ganglia functioning as per our findings. These specific responses are candidates for assessing motor symptoms or drug treatment effects in PD patients.” Lines 553-561. https://doi.org/10.1371/journal.pone.0232808.r002
1 Sep 2020 Decision Letter - Wing-ho Yung, Editor Clinical factors affecting evoked magnetic fields in patients with Parkinson's disease PONE-D-20-11314R1 Dear Dr. Yabe, 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, Wing-ho Yung, PhD 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 #2: All comments have been addressed ******** 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 #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? 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 #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 #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 #2: (No Response) ****** 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 #2: Yes:** Yuanchao Zhang https://doi.org/10.1371/journal.pone.0232808.r003
Formally Accepted
8 Sep 2020 Acceptance Letter - Wing-ho Yung, Editor PONE-D-20-11314R1 Clinical factors affecting evoked magnetic fields in patients with Parkinson's disease Dear Dr. Yabe: 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. Wing-ho Yung Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0232808.r004

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .