PONE-D-19-19654

Axial variation of deoxyhemoglobin density as a source of BOLD low-frequency time lag structure.

PLOS ONE

Dear Dr Aso,

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.

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Quan Jiang, Ph,D.

Academic Editor

PLOS ONE

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Reviewers' comments:

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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: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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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: No

Reviewer #2: Yes

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

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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: The research is original. Experiments are well designed and the conclusions are supported by the data. I appreciated the extensive use of citations to back up the introduction and discussion sections.

Minor comments:

Although all the details of the figures are given in the text and in the legends, some figures would benefit from a few additions:

Fig1: There could be a confusion in Part A between the spatial extent of vasculature and the time variations in 1-3. It would be clearer if the time arrows were bigger. I didn’t understand the usefulness of the second schematic in gray area.

Fig2: Putting a legend related to the colorlines in partB woud help.

Fig3: Part A. This was especially difficult to follow. The colorbars are missing as well as the axis names. I would remove the resampling part and add graphs about instantaneous phase differences times series and the corresponding averages. Part B. There is no colorbar to explain the different line colors.

Some references are not properly cited:

Hoge R, Atkinson J, Gill B, Crelier G & Marrett S (1999). Investigation of BOLD signal

dependence on cerebral blood flow and oxygen consumption: The …. Magnetic

Resonance in Medicine 863, 849–863. Misssing part of the title

Kennerley AJ, Berwick J, Martindale J, Johnston D, Papadakis 868 N & Mayhew JE (2005).

Concurrent fMRI and Optical Measures for the Investigation of the Hemodynamic

Response Function. 365, 354–365. No Journal title

Willie CK, Tzeng Y-C, Fisher JA & Ainslie PN (2014). Integrative regulation of human

brain blood flow: Integrative regulation of human brain blood flow. The Journal of

Physiology 592, 841–859. repetition in the title

Reviewer #2: This is an important and exciting contribution that not only acknowledges the vascular-derived lag-based structure inherent in the BOLD response but proposes a thoughtful method for combining this information with an optimized global signal regression approach that shows promise in reducing inter-individual variation while preserving task-based BOLD responses to visuomotor and respiratory tasks. The analyses and statistical approach was rigorously conducted with appropriate treatment of multiple comparisons. I did not find any methodological errors or unreasonable interpretations of the data that should slow publication of what could be a new technical standard in treatment of fMRI signal data.

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Reviewer #1: No

Reviewer #2: Yes: Jeffrey S Anderson

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[EXSCINDED]

Axial variation of deoxyhemoglobin density as a source of the low-frequency time lag structure in blood oxygenation level-dependent signals

PONE-D-19-19654R1

Dear Dr. Aso,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

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With kind regards,

Quan Jiang, Ph,D.

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 #1: All comments have been addressed

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 #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

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 #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. 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: (No Response)

Reviewer #2: Authors have appropriately addressed reviewer concerns. I have no further concerns that require addressing.

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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 #1: No

Reviewer #2: No