The use of brain-machine interface, motor imagery, and action observation in the rehabilitation of individuals with Parkinson’s disease: A protocol study for a randomized clinical trial

Kátine Marchezan Estivalet; Tatiana Salayaran de Aguiar Pettenuzzo; Natália Lopes Mazzilli; Luis Fernando Ferreira; Fernanda Cechetti

doi:10.1371/journal.pone.0315148

Peer Review History

Original SubmissionNovember 8, 2024
8 Nov 2024 Author Response https://doi.org/10.1371/journal.pone.0315148.r001
5 Jan 2025 Decision Letter - Imre Cikajlo, Editor PONE-D-24-50579The use of brain-machine interface, motor imagery, and action observation in the rehabilitation of individuals with Parkinson's disease: a protocol study for a randomized clinical trialPLOS ONE Dear Dr. Ferreira, 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 Feb 19 2025 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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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 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 If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references.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 If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions? The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses? The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory. Reviewer #1: Yes Reviewer #2: Yes ****** 3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable? Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Have the authors described where all data underlying the findings will be made available when the study is complete? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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 and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics. You may also provide optional suggestions and comments to authors that they might find helpful in planning their study. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: This manuscript presents a study protocol to conduct a single-blinded, randomized clinical trial for comparing 5 experimental groups in rehabilitation with Parkinson's disease. The study was registered in clinicaltrials.gov with a valid NCT number, and approved by the respective Ethics/IRB board. While the objectives and timeliness of this project appear sound and convincing, some comments appear below: (a) Statistical Analysis: For the multiple comparisons, it might be worthwhile to use the false discovery rate (FDR) adjustments over the Tukey's test, since there are a lot of comparisons to be made between the 5 groups. (b) Statistical Analysis: A GEE will be conducted to handle data generated from the longitudinal design (multiple time-points). Any reason, why the usual linear mixed model won't be used? What about assessments of the goodness of fit from the GEE fits, or the linear mixed model fits. (c) Conclusions/Discussion: This section should mention that the expected results and findings from this study is only representative for this sample of patients, and future trials with larger sample sizes and at other geographical locations will be necessary to assess the effectiveness of the interventions. Reviewer #2: The article is really well written, and it doesn’t almost need formal changes. I’ve only a very few formal criticisms: Authors underlined too frequently the fact that their protocol is very detailed, and it is the first one to be presented in a so detailed manner. One time is enough, I think. Table 1: Open medication bottle and the following tasks with medications. Why instructions for AO and MI are different as far as the use of dominant and not dominant hand is concerned? This would make AO and MI not comparable. Moreover, the description seems to me contradictory to the statement at page 26, lines 407-8. Page 27, lines 448-450 “Recruitment based on media outreach and contact with municipal health departments and associations as an enrollment strategy to reach the target sample size.” It seems to me that some words are lacking in this sentence. On the other hand, I’d like to express a few ideas of mine about the protocol content. The Authors are not obliged to change the protocol according to my ideas, but I’d like to give them some suggestions to think of, and maybe better motivate their choices in the text. Selection of participants: “Additionally, those assigned to the BMI groups must not be using deep brain stimulation (DBS) devices.” This should be true for all groups. The presence of a DBS device or not represents a great difference between participants with PD for a lot of reasons. Evaluation of participants: ““How would you rate the severity of your cognitive functions (memory, attention, concentration, organization”. Are the Authors sure that the patients will make a difference between attention and concentration? What’s the difference between attention and concentration according to the Authors? Experimental treatment, motor imagery: “The activities will be narrated by the therapist during the intervention, guiding the participant - eyes closed and seated - to imagine executing the action from a first-person perspective, without the presence of motor symptoms”. How are the Authors sure that the participants affected by PD will be able to imagine the movement without symptoms? Maybe they should at least ask the participant whether they succeeded or not. It's really a great limitation the fact that the follow-up evaluation will be performed only by phone and only using the COPM. Why did the Authors choose not to re-examining the enrolled participants in flesh? ****** 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: Yes: Elisabetta Farina ******** [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: PLOS 1.docx https://doi.org/10.1371/journal.pone.0315148.r002
Revision 1
13 Jan 2025 Author Response Response to Reviewers Dear Academic Editor and Reviewers, In response to your guidance, I address each point raised for corrections to the article. I would like to thank you in advance for your valuable contributions to improving the protocol. For Reviewer #1: a) We have revised the statistical method as suggested, where the False Discovery Rate (FDR) will be used for multiple comparisons among the five groups (lines 462). b) The choice of GEE is to avoid losing potential cases in the event of follow-up loss. The goodness of fit will be assessed using the Quasi-Likelihood under Independence Model Criterion (QIC) (lines 467-468). c) We agree with your comments and have included the suggested information as the last sentence of the article's conclusion (page 32, lines 568-571): “The expected results and findings from this study are representative only of this sample, and future trials with larger sample sizes and conducted in other geographical locations will be necessary to assess the effectiveness of the interventions.” For Reviewer #2: • I have edited the text to avoid repetition regarding the description of the protocol by removing the word "detailed" in the objective section of the abstract (line 34), in the last paragraph of the introduction (line 105), and in the first paragraph of the study design section in the methods (line 112). • Table 1 (pages 17-19): The verbal command directed at the participant during MI is correct according to the images. However, there was an error in the technical description of the movements performed during AO, which has now been corrected in the article. We appreciate the observation. It is worth noting that the technical description is not provided to the participant, as they only observe the videos without any additional stimuli. This description is exclusively for therapists when creating the videos, ensuring proper consideration of the movements for each activity stage. Although the person in the video is right-handed, bimanual activities can be performed with either the dominant or non-dominant hand, while unilateral activities are carried out using the side where motor symptoms are present. Therapists adjust the MI guidance accordingly, instructing participants to use either their right or left hand depending on the side affected by symptoms, using accessible language. • Page 27, lines 448-450: I have revised the sentence to make it complete, including the types of media used for research dissemination (lines 453-455). • Selection of participants: I have corrected the selection criteria (page 7, lines 157-158), specifying that DBS was considered an exclusion criterion for all groups, precisely for the reason mentioned. • Evaluation of participants: The intention is to illustrate cognitive functions (memory, attention, concentration, organization), as participants may not be familiar with the concept of cognition or cognitive functions. However, since the assessment does not focus on any specific function but rather evaluates a general state, we do not believe this presents an issue. Nonetheless, we can incorporate real-life examples, such as: o “If you are watching television and someone asks you for a favor, can you focus only on the television or the request? Can you remember the favor afterward, or do you forget it quickly?” o “Is it easier for you to remember what you need to buy at the market or memorize someone’s phone number?” • Experimental treatment, motor imagery: Since we will use the Kinesthetic and Visual Imagery Questionnaire (KVIQ-10) during screening, we can already evaluate the participant's imagery ability, including image clarity and sensation intensity. However, we agree it is essential to ask participants afterward whether they were able to imagine themselves, and we have added this information to the protocol (page 12, lines 274-277). • We removed the section where we mentioned conducting the COPM by phone as a limitation of the study (lines560-563). The COPM is a semi-structured interview in which individuals assess their own perceptions of changes in occupational performance. This format allows for remote application, making it more convenient for participants by eliminating the need for an additional in-person meeting for data collection. I would like to highlight that I have corrected the formatting of the figures (Fig 1 and Fig 2), placing the captions below the titles (pages 7-8). Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0315148.r003
21 Feb 2025 Decision Letter - Emiliano Cè, Editor The use of brain-machine interface, motor imagery, and action observation in the rehabilitation of individuals with Parkinson's disease: a protocol study for a randomized clinical trial PONE-D-24-50579R1 Dear Dr. Ferreira, 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. 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Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions? The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field. Reviewer #1: Yes ******** 2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses? The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory. Reviewer #1: Yes ****** 3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable? Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible. Reviewer #1: Yes ****** 4. Have the authors described where all data underlying the findings will be made available when the study is complete? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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 ****** 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 ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics. You may also provide optional suggestions and comments to authors that they might find helpful in planning their study. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The authors were able to address my previous round of comments with great satisfation. I have no further comments in this round. ****** 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 ******** https://doi.org/10.1371/journal.pone.0315148.r004
Formally Accepted
Acceptance Letter - Emiliano Cè, Editor PONE-D-24-50579R1 PLOS ONE Dear Dr. Ferreira, 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 Prof. Emiliano Cè Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0315148.r005

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