PONE-D-21-04261

Temporal dynamics of animacy categorization in the brain of patients with mild cognitive impairment

PLOS ONE

Dear Dr. Karimi,

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.

I have received the comments from two reviewers. One of the two reviewers raised an issue with the small sample size of patients group.

In my opinion, you can estimate the power of your analysis and also you can add Cohen's d statistic while

you can avoid strong use of significance.

A paragraph with limitation should be added in the discussion part.

If you decided to revise according to reviewers' comments, you should update the manuscript and prepare

a response letter to every comment.

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Stavros I. Dimitriadis

Academic Editor

PLOS ONE

Additional Editor Comments:

Dear authors,

I have received the comments from two reviewers. One of the two reviewers raised an issue with the small sample

size of patients group.

In my opinion, you can estimate the power of your analysis and also you can add Cohen's d statistic while

you can avoid strong use of significance.

A paragraph with limitation should be added in the discussion part.

If you decided to revise according to reviewers' comments, you should revise the manuscript and prepare

a response letter to every comment.

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2. Thank you for stating the following in the Competing Interests section:

"SKR and CK serve as the CSO and CMO at Cognetivity ltd., and MM as the lead data scientist. Other authors declared no competing interests."

We note that one or more of the authors are employed by a commercial company: Cognetivity ltd.

2.1. Please provide an amended Funding Statement declaring this commercial affiliation, as well as a statement regarding the Role of Funders in your study. If the funding organization did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support in the form of authors' salaries and/or research materials, please review your statements relating to the author contributions, and ensure you have specifically and accurately indicated the role(s) that these authors had in your study. You can update author roles in the Author Contributions section of the online submission form.

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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: Yes

Reviewer #2: I Don't Know

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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: No

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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: Overall:

The manuscript analyzes the ERP response during the integrated cognitive assessment to find differences between healthy controls and patients with mild cognitive impairment.

Results suggest a slower response in the MCI population.

Recommend:

Major comments:

* In Section 1, relevant works on the use of EEG for AD and MCI assessment are missing, e.g.:

- Regarding resting state EEG: "Systematic Review on Resting-State EEG for Alzheimer’s Disease Diagnosis and Progression Assessment Resting-state EEG" (Cassani, 2018), and

- Regarding ERPs: "P300 Amplitude in Alzheimer’s Disease: A Meta-Analysis and Meta-Regression" (Hedges, 2016)

- Regarding slower EEG signals: "Slowing and Loss of Complexity in Alzheimer's EEG: Two Sides of the Same Coin?" (Dauwels, 2011)

* The MoCA and ACE-R tests are described in Sections 2.2 and 2.3 respectively. In Section 2.4, it is stated the participants completed these tests, however the scores are not presented nor used.

* In Section 2.5, describe the electrode layout that was used, as well as the location of the reference electrode.

* In Section 2.7, describe the kernel used in the SVM classifier, as well as the hyperparameters.

* Provide a Conclusion section at the end of the manuscript

* Discuss in how the findings about the ERP amplitude are in line with the results provided in (Hedges, 2016)

Minor comments:

* Pay attention to the capitalization of words, e.g., "Congestive Cardiac Failure" and "Diabetes Mellitus" should not be capitalized.

* Remove extra space in "80 ±20" and all the instances in the manuscript.

* Use always space between quantity and units (e.g., "66 ms" instead of "66ms")

Reviewer #2: The manuscript presents a novel study investigating animacy categorization in MCI patients vs healthy older adults using univariate and multivariate pattern analysis. Results demonstrated decreased speed of processing in MCI patients and differences in activation patterns across a range of electrodes. While the study is well presented, I have a number of concerns around reliability and generalizability of the results, which prevent me from recommending the manuscript from publication.

The statistical analyses appear to have been performed in a technically sound way. However, the small sample size significantly limits the reliability and generalizability of the classification findings. Several studies have highlighted the dangers of small sample sizes when using brain data for classification (e.g. Hosseini et al., 2020). Based on this limitation, it is difficult to interpret the findings (or their significance).

MOCA and ACE-R results should be presented in the manuscript.

The authors should include information on the number of EEG trials rejected at each stage of processing across each condition and for each group. Without this information, it is difficult to interpret the reliability of findings.

The manuscript is presented in an intelligible fashion. However, the Introduction would benefit from more detailed description of previous literature on visual processing in MCI and why this is important to explore (beyond the fact that differences between MCI and HCs have yet to be investigated). Typically, the final paragraph of the Introduction would state the study hypotheses – not the main findings. I suggest the authors revise this accordingly.

Similarly, the Discussion requires a more detailed interpretation of the study findings, especially with regard to the overall pattern of differences found, e.g. why were there group differences in midline frontal, left frontal, left parietal and right centro-parietal electrodes? How does this relate to previous findings?

In my opinion, the authors’ conclusion that the results “suggest the IPS as a potential biomarker for the early detection of AD” is overstated. As mentioned in the Introduction, not all cases of MCI will progress to AD. This fact, coupled with the small patient sample (n=18), significantly limit generalizability to AD.

The authors state that the ICA task is “more challenging than the typical memory tasks, making it more sensitive to less severe brain deteriorations”. This is also at odds with the suggestion of IPS as a potential biomarker for AD, as the task may not be suitable for AD patients. The authors should comment on this in their Discussion.

As far as I can tell, the data underlying the findings have not been made available.

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Reviewer #1: No

Reviewer #2: No

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Temporal dynamics of animacy categorization in the brain of patients with mild cognitive impairment

PONE-D-21-04261R1

Dear Dr. Karimi,

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,

Stavros I. Dimitriadis

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The authors responded properly to the reviewers' comments.

I have reviewed personally the draft and I have no further comments to add.

I recommend the acceptance of the manuscript.

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

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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 #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

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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 #2: Yes

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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: All comments have been addressed. I have no further suggestions for revisions.

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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: No