PONE-D-22-07057Rapid assessment of hand reaching using virtual reality and application in cerebellar strokePLOS ONE

Dear Dr. Isenstein,

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 find this study to be interesting, however, one reviewer does not feel the issues raised in the introduction have been addressed in the study. Further, some clarification in the methods is needed, and concerns with the statistical analyses are noted. The authors should take into consideration the comments below.

Please submit your revised manuscript by Aug 06 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.

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PLOS ONE

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Additional Editor Comments (if provided):

1) Why was timing information not included? Impaired performance can be shown in more than just accuracy, for example reaction time (time to reach onset, time to reach dot etc..) as well as precision (noted by Reviewer 2).

2) The figures provided are pixelated and hard to read. Please upload ones that adhere to the PLOS ONE policies.

3) How was sample size calculated? Did the authors have enough power with 20 participants? Further, there is no statistical analysis section. Please add a section on power and statistical analyses to the methods.

4) The reviewers had issues with the statistical analyses that need to be addressed.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

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

Reviewer #1: I Don't Know

Reviewer #2: No

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

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

Reviewer #1: Yes

Reviewer #2: Yes

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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

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This is an interesting paper - the introduction raises some important issues but I don't necessarily feel these issues have been addressed in the study. I'm still not exactly sure how the research advances the field - I think this is most that it has not been clearly articulated and in a way that makes sense to lay readers. Some specifics:

1. The introduction is very long and is under referenced. Could it be a little more concise (and references add to support statements where needed)

2. The abstract lacks detail on the design of the studies and number of participants

3. Use of the term 'subjects' is not ideal - should be participants

4. The research question (at the end of the intro is not specific) - how is feasibility defined? this is important given specificity of the research methods

5. Results (number, characteristics of participants) are presented in the 'methods'

6. There are several figures presented which are hard to interpret - perhaps a more selective approach and better explanation would help. I am not able to assess the statistics.

Reviewer #2: Review of PONE-D-22-07057

Summary

The authors aim at testing the feasibility of a Virtual Reality system in assessing reaching performance, both in healthy adults and in pathological populations. The study is designed around a relatively standard paradigm about reaching accuracy, in which participants were to reach to a visual target, either with vision of their virtual hand or not, and either with online visibility of the target or not (memory-guided). In addition, a short version of the first task was applied to two stroke patients. The results show the well-established phenomenon that reach endpoint accuracy is poorer when the moving hand and/or the target is invisible. However, the authors want to emphasize as the main novelty of this work, the feasibility of using such VR systems for easy, portable, and reliable measures of human fine motor skills.

Main comments

The study is well-written, easy to follow, and makes its contributions explicit. It is technically sound, the performed analyses make sense, and the results are plausible. I do not have many comments, nor I feel that any of these require particular attention before recommending to the editor that this manuscript can be part of PLoS One table of contents. I would nevertheless encourage the authors to address the following issues.

1. The assessment of the virtual reality tool is based on the measurement of endpoint constant error (accuracy). This is a common measure in visuomotor research, and captures well the effects of visual information on manual control of action. I would have expected that the authors would assess the tools in a bit more detail though. Accompanying measures of endpoint accuracy is often that of endpoint precision (variable error), which may or may not follow the same pattern of endpoint accuracy (e.g., Monaco et al., 2010, Exp Brain Res). Considering the available data, I believe that reporting about endpoint precision (e.g., area and orientation of 95 CI) in the manuscript would meaningfully enrich the contents of the manuscript.

2. The authors base much of their motivation for this study on the premise that typical experiments impose relatively simple stimuli and restricted scenarios (e.g., lines 64-66), implying that these experiments are far from real-world activities, which is the gap that Virtual Reality can close. Though this is partly true, recently there is a growing number of studies implementing real-world naturalistic experiments. Examples include the recording of body and gaze when walking in the nature (e.g., Matthis et al., 2018, Curr Biol; Valsecchi et al., 2020, ACM in Eye Tracking), or when grasping objects (e.g., Land & Hayhoe, 2001, Vis Res; Voudouris et al., 2019, JoV), just to name a few examples. Without arguing against the importance of assessing Virtual Reality tools on measuring human behavior, the authors should acknowledge that research on the field was not only typically constrained, but that it has also been expanding in real-world settings.

3. Regarding the task itself, I have two main comments:

First, as seen in the supplementary videos, the recorded participant is remarkably accurate, considering that the target sphere ‘explodes’ (hit) in every single trial, even when the moving hand or the target sphere is invisible. Was the target sphere always exploding, no matter whether the participant correctly hit its center? Or is the demonstrated participant a well-trained one? This should be clarified.

Second, the endpoint error is measured as the distance between the center of the sphere and the position of the index finger at the moment when the finger crossed the 60-deg arc. Did the authors consider both remaining directions (lateral error and vertical error) when calculating this error or not?

4. Regarding the analysis, I am not convinced that measuring the p-value as the trials develop is a useful method. First of all, running constantly statistical tests can lead to false positives (even more so when the authors do not even correct for the abundant number of statistical tests). The authors should first explain what is the underlying reason for examining this aspect –is there an underlying hypothesis, which might be addressed in another way? From how I understand the development of the authors’ rationale, their aim is to see at what stage the experimental effect is systematic/robust, so that they can suggest how much the experiment can be reduced with respect to the number of trials and therefore to the time required. If this is the case, running too many statistical tests may also cause the impression that a few trials are necessary to reproduce the effect, but this impression may be false due to a type I error.

An alternative idea would be to split each block of trials performed by each subject in smaller subblocks of, say, 25 trials each, and then run a one-way ANOVA with four levels (epochs) to test whether these change over time. In any case, I recommend removing the analysis about the temporal evolution of the p-value from all sections of the manuscript.

5. More specific comments

Line 133: muscle contraction and visual perception in the same sentence, next to each other, read somewhat odd. It feels there should be a connection between the two, but I do not see any apparent one. Perhaps some revision would help here.

Line 138: How ‘small’ is ‘small’? Writing this sample size in a more explicit way will make the sentence more straightforward.

Line 195: “…they approached the periphery”. When periphery was approached with their hands or with some other part of their body?

Lines 220-221: At what distance was the target presented? From later information, it appears that this was at arm length, but I think it should be made more explicit here already.

Methods: Please mention what statistical tests are being used and whether there were normality checks supporting the use of parametric testing.

Results: Reporting the p-values in a more conventional way would probably facilitate readability.

Discussion: I think some parts can be shortened or merged. For instance, the contents of paragraph starting in line 470 made me think in what way VR can be used effectively to measure endpoint accuracy. Is it based on feasibility (e.g., portability, comfort, battery…) or on the fact that endpoint accuracy values reproduce previous experimental work? Reading the paragraph, it becomes apparent that the former is the correct answer, but this aspect is then back into discussion a couple of paragraphs later (e.g., starting at line 501). I feel that this paragraph is too detailed and does not contribute much, rather distracting from the main messages. One idea would be to merge such instances in more concise piece.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-22-07057R1Rapid assessment of hand reaching using virtual reality and application in cerebellar strokePLOS ONE

Dear Dr. Isenstein,

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. Specifically, the reviewer is requesting more of a discussion on action in the Introduction, and clarification for some of the Methods and Results regarding the direction of the error that is recorded and the reaching time. Other minor suggestions are provided.

Please submit your revised manuscript by Oct 02 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

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

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

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

We look forward to receiving your revised manuscript.

Kind regards,

Krista Kelly, Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

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

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

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

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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

Reviewer #1: I Don't Know

Reviewer #2: Yes

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

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

Reviewer #1: Yes

Reviewer #2: Yes

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

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

Reviewer #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: I have no additional feedback for the authors. They have addressed my previous feedback satisfactorily.

Reviewer #2: The authors have addressed all my comments and I believe that the manuscript now reads more focused and clearer. I still have some remaining comments, some of which arise due to the revisions whereas a few others concern issues that I could have spotted in the first round. Apologies for not bringing these up earlier. All lines mentioned below concern the track-changes document.

Abstract: the first lines of the abstract greatly focus on the ‘perception’ side and the limitations of the traditional experiments on perception. Though this true, this study here focuses more on action/behavior. I would encourage the authors to either bring the ‘action’ part more explicitly, or even discuss the perception-action part altogether (than only talking about ‘perception’).

Introduction, paragraph 1 (lines 55-68): Similarly here, the focus appears to be on ‘perception’. Yes, perception research started with rather passive, highly controlled designs, but this has now evolved to more naturalistic experiments. In the same line, ‘action’ research started with constrained paradigms, such as the studies of Jeannerod on grasping, but has evolved to whole-body tracking in the nature, as the authors also cite the work of Matthis and colleagues. Therefore, as in the abstract, I recommend also here to focus also on action, not only on perception.

Methods, lines 149-154: Please introduce the participants of experiment 3 somewhere here. This is important otherwise the term ‘healthy’ in line 152 reads odd, while doing so will facilitate reading of the subsequent section (e.g., lines 161-162).

Line 207: It remains unclear whether the error is measured only on the lateral direction or the vertical direction is also accounted. Please make this more explicit.

Line 209: did the reaching time indeed consider the moment when the participant ‘touched the target’? In other instances (e.g., lines 199-201), it is mentioned that the trial ended when the participant crossed the arc, implying that this would be used as the reaching time. If reaching time is indeed measured based on when the participant touched the target, what happened in trials in which the participant did not touch the target? If the reaching time is measured based on the time when the participant crossed the arc, this line needs to be revised (as also other instances throughout the manuscript, for instance line 232, 262, and possibly elsewhere).

Lines 226-227: Could you please clarify whether the 100 trials of one of the conditions were presented before/after the 100 trials of the other condition, or whether the two conditions were randomly presented randomly interleaved across the 200 trials?

Line 276: “…of their accuracy”. I think the authors here should state “…of their endpoints”. Also, is precision calculated as the SD along the lateral direction only? Please clarify in the manuscript.

Lines 309-312: These here read as ‘methods’ but are presented in the ‘results’. My recommendation is to define the three measures (accuracy, precision, reaching time) in the Methods, one after the other, so that it easier for the reader to follow the analysis.

Line 326: “of this measure”. Which measure? The previous part refers to two different variables, accuracy and precision. Why not calculate precision and reaching time also on the basis of the first 25 trials? Then the authors, for each experiment, would have a first paragraph with results about the three measures (accuracy, precision, time) considering all trials, and a second paragraph with the respective results when considering only the first 25 trials. Then the results would be easier to follow and interpret.

If the authors would like to focus mainly on accuracy, this should become more explicit, ideally with a reason why.

Lines 333-335: Does this refer to reaching time considering all trials or only the first 25 trials of each condition?

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Reviewer #1: No

Reviewer #2: No

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Rapid assessment of hand reaching using virtual reality and application in cerebellar stroke

PONE-D-22-07057R2

Dear Dr. Isenstein,

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.

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Kind regards,

Krista Kelly, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

No further comments.

Reviewers' comments: