Dear Mister Mereles Menesse,

Thank you very much for submitting your manuscript "Information dynamics efficiently discriminates high γ-rhythms in EEG brain waves" for consideration at PLOS Computational Biology.

As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. In light of the reviews (below this email), we would like to invite the resubmission of a significantly-revised version that takes into account the reviewers' comments.

We cannot make any decision about publication until we have seen the revised manuscript and your response to the reviewers' comments. Your revised manuscript is also likely to be sent to reviewers for further evaluation.

When you are ready to resubmit, please upload the following:

[1] A letter containing a detailed list of your responses to the review comments and a description of the changes you have made in the manuscript. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

[2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file).

Important additional instructions are given below your reviewer comments.

Please prepare and submit your revised manuscript within 60 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email. Please note that revised manuscripts received after the 60-day due date may require evaluation and peer review similar to newly submitted manuscripts.

Thank you again for your submission. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments.

Sincerely,

Daniele Marinazzo

Section Editor

PLOS Computational Biology

Daniele Marinazzo

Section Editor

PLOS Computational Biology

***********************

Reviewer's Responses to Questions

Comments to the Authors:

Please note here if the review is uploaded as an attachment.

Reviewer #1: The review file is attached as a pdf file

Reviewer #2: This is potentially an interesting work on the intersection of EEG network modelling, the role of oscillatory activity in information processing and application of current method of analysis to shed light on information dynamic in multivariate system. In this paper the authors present the phase diagram of the simulated EEG model to characterize different regimes related to the network activity. Subsequently, the authors show how different rhythms emerge in the phase diagram and provide an information dynamic analysis. High-gamma rhythms emerge in different neuronal populations (excitatory or inhibitory) with different information processing characteristics.

The underlying concept of the manuscript, as presented in the abstract and introduction, specifically pertains to using a model to gain insights into the information processing characteristics of low/high gamma oscillations. This aims to enhance our understanding and ability to distinguish between pathological oscillatory activity and that related to cognitive functions. However, the manuscript devotes only a final part to the role of high-frequency oscillatory activity. Furthermore, the analyses are predominantly descriptive and may be overly influenced by the modelling choices. Thus, the differentiation of functional vs pathological stats seems mostly speculative and not supported by additional experimental data, where new insights from the model analysis can, at least in part, be found in EEG data recordings of patients.

In my view, there are two possible directions for improvement:

1) Re-evaluate the paper's main focus. It seems more that the authors want to provide a comprehensive understanding the role of the modeling parameters in the emergence of different oscillatory dynamic and their information processing capabilities. The role of high-frequency oscillations and their role on functional vs pathological brain states distinction can be only discussed at the end in a 'Future direction' section, but it' s not the highly introduced as the main focus of the paper.

2) Alternatively, streamline the initial sections to focus more narrowly on high-frequency oscillations and think of a possible application to EEG data (with open epilepsy datasets, maybe) where the findings on high-frequency oscillation apply or provide new insights on EEG data. Although the modeling approach offers a level of detail that EEG data alone cannot provide, the authors might consider analyses that establish correspondences between the two. This could involve examining the IID differences (such as redundancy, differentiation, etc.), for example in epilepsy versus control groups, as well as mutual information in both the time and frequency domains. The goal would be to determine if similar conclusions can be drawn from EEG data as those inferred from the model.

I can not recommend the paper for publication without this and the following substantial revisions.

Major comments:

The paper requires significant enhancement in terms of writing quality, grammar, and the clear exposition of concepts. The minor comments I provided address only a few issues, but a comprehensive review is needed for improvements.

1. Did the authors assess the robustness of their results by altering the E-I and I-E connections in the networks? For example, by replacing an I-E connection within a circle with a randomly positioned neuron outside of that circle.

2. In Figure 6, do the white areas on the phase diagram represent regions driven solely by noise, without a distinct PSD maximum? A brief explanation in the figure caption would be helpful.

3. Is the coexistence of low-frequency (delta-theta) and high-frequency (gamma) oscillations in the phase diagram related to the low-high frequency coupling often observed in EEG data? Could the model provide new insights in terms of information dynamics?

4. Do the authors have an explanation for the high differentiation information observed in region III of the phase diagram, which appears prominent only at specific ranges of u noise levels? (Refer to Figure 7 and mainly S7).

5. The estimation of Φ-ID in continuous data, without relying on kNN methods, is possible (as shown in Luppi, Mediano et al., 2022, Nature Neuroscience, and Mediano et al., 2021, ArXiv:2109.13186). Why didn’t the authors apply these measures to analyse average membrane potential (LFP-like) in continuous data? This could be discussed in the 'Limitations of our analysis' section."

6. In the 'Limitations of our analysis' section, the authors should include references related to pathological HFOs and the less rich information dynamics and mutual information.

7. All elements depicted in the figures should be explained in their captions. For example, the significance of the black arrows in Figure 6.

8. The supplementary material contains subsection 2.1, 'Excitatory and inhibitory activity', and Figure S5, which appear to be exact duplicates of content from the main text.

Minor comments:

In the following I reported some of the issues with the writing. Please revise the all manuscript since it was impossible to track all grammar and syntax problems.

The title point to EEG brain waves, the paper use only a model maybe change to -EEG neural network model

Abstract

- NN ? Does it mean Neural network ?

- integrate-and-fire

- “However, in regions where high gamma … we observe generally lower ..”

Author summary:

-“i.e. the recording of ..”

-“where EEG-like signals emerge within a neural population”

-“Through this approach , we explore ...”

Improve writing of the Abstract and Author summary

Line 9: is loosely

Line 10: relaxation

Line 82- PID framework is not restricted to only 3 sources. Also PID is multivariate the difference with IID is that PID the does not allow to decompose multiple targets.

Be consistent with the verb tense in the rest of the Introduction

Line 98: “which has not been explored ..”

Line 145: “which provides a”

Line 154 “it can be applied to decompose”

In general I find “give us” too formal.

Line 223: “expressed”

Line 251-254 split sentence

Line 258 “in inducing” ?

Line 261 “Using a simplified approach”

Line 266: “This model aims to capture the essentials of the cerebral cortex

where it is reported that excitatory neurons occur almost four times more than inhibitory ones.”

Line 268: “To couple”

Line 368: “.., making the observation of active information dynamics between distant neurons less probable;”

Line 335: Wrong Figure 3a, maybe Figure 4a ??

Line 384: “attention on Γ waves”. Is Γ symbol introduced already?

Line 388: Finally, we focus (remove and)

Line 689 write always High or H

Figure 6. colored stars ? not starts

Wrong figure reference in Supplementary material. Many figures show Figure ??

**********

Have the authors made all data and (if applicable) computational code underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data and code 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 and code 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 or code —e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No: I did not find in the manuscript the Data and Code availabiltiy section.

Reviewer #2: No: The authors did not provide the code for the modeling and the analysis.

**********

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

Figure 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. 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 us at figures@plos.org.

Data Requirements:

Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example in PLOS Biology see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5.

Reproducibility:

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Attachments

Attachment

Submitted filename: Review_PLoSCB.pdf

Dear Mister Mereles Menesse,

Thank you very much for submitting your manuscript "Information dynamics of in silico EEG Brain Waves: Insights on oscillations and functions" for consideration at PLOS Computational Biology. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. The reviewers appreciated the attention to an important topic. Based on the reviews, we are likely to accept this manuscript for publication, providing that you modify the manuscript according to the review recommendations.

Please prepare and submit your revised manuscript within 30 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email.

When you are ready to resubmit, please upload the following:

[1] A letter containing a detailed list of your responses to all review comments, and a description of the changes you have made in the manuscript. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out

[2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file).

Important additional instructions are given below your reviewer comments.

Thank you again for your submission to our journal. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments.

Sincerely,

Daniele Marinazzo

Section Editor

PLOS Computational Biology

Daniele Marinazzo

Section Editor

PLOS Computational Biology

***********************

A link appears below if there are any accompanying review attachments. If you believe any reviews to be missing, please contact ploscompbiol@plos.org immediately:

Reviewer's Responses to Questions

Comments to the Authors:

Please note here if the review is uploaded as an attachment.

Reviewer #1: The reviewed manuscript has significantly clarified several open issues that I raised during the first review. However, there are a few minor points which are not clear. I think the final manuscript should try to clarify the following points.

INTRODUCTION

There is an imprecision about the definition of HFOs. There is no such thing as “HFOs in the γ band (30-150 Hz)”. Normally HFO are defined above approximately 80 Hz. To avoid confusion, I would stick to the definitions HFOs given by this paper:

https://www.nature.com/articles/s41467-020-18975-8

See refs 3 and 4 in the above paper for example

The definition of gamma band activity is also not precise. Studies investigating gamma-band neural activity are often considering two types of neural modulations. A narrow-band low-gamma oscillations in the 30–80 Hz range during sensory stimulation (Ray and Maunsell, 2010) and cognitive processes, such as attention (Fries et al., 2001; Bosman et al., 2012) and working memory (Pesaran et al., 2002). And a second type of high-gamma range (from 60 to 150 Hz) activity is observed in invasive (e.g., Brovelli et al., 2005; Crone et al., 2006; Jerbi et al., 2009) and noninvasive (MEG) studies. This second type of gamma band activity is broadband rather than purely oscillatory. I think it would be better to specify which type of gamma activity the manuscript is focusing on and whether it is possible to discern the two.

The introduction still contains the presentation of several results. I would move these paragraphs from the introduction to the results section. Lines 143 - 167 for example.

RESULTS

If the labelling of the different oscillatory bands is modified according to the novel nomenclature (first point above), I would suggest revising the figures.

CODE

The data and code underlying the findings described in their manuscript should be fully available without restriction. The repository is very limited and it could contain some additional script for the analysis and visualisation of the resutls. Maybe some exemplar notebook could help. I leave this point to the authors.

Reviewer #2: minor revision attachment

**********

Have the authors made all data and (if applicable) computational code underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data and code 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 and code 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 or code —e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No: Only the core code to similate the model. I asked for a mode detailed code in the revision.

Reviewer #2: Yes

**********

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: Pinzuti Edoardo

Figure 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. 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 us at figures@plos.org.

Data Requirements:

Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example in PLOS Biology see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5.

Reproducibility:

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

References:

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.

Attachments

Attachment

Submitted filename: Minor_revision_plosComp2024.doc

Dear Mister Mereles Menesse,

We are pleased to inform you that your manuscript 'Information dynamics of in silico EEG Brain Waves: Insights into oscillations and functions' has been provisionally accepted for publication in PLOS Computational Biology.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.

Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS.

Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Computational Biology. 

Best regards,

Daniele Marinazzo

Section Editor

PLOS Computational Biology

Daniele Marinazzo

Section Editor

PLOS Computational Biology

***********************************************************