PONE-D-24-36525Fiber architecture in the human ventromedial striatum and its relation with the bed nucleus of the stria terminalisPLOS ONE

Dear Dr. Krueger,

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Academic Editor

PLOS ONE

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Outside of the submitted work BB has received consultancies from Medtronic (paid to institution) and is co-founder of AIRAmed GmbH.”

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Additional Editor Comments:

Thanks for the work in putting this manuscript together. It is overall well written and requires minor revisions.

See the reviewer comments and address them accordingly.

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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?

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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: N/A

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Reviewer #1: Yes

Reviewer #2: Yes

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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: This paper utilized polarized light microscopy (PLM) to study their earlier discovery that a pathway from the BST to the orbitofrontal cortex apparently passing directly through the hCN. Moreover, the high-resolution DTI data is used to analyze the differences in fiber density inside the hCN. The applied limitations of PLM and DTI are discussed to show that PLM can be a valuable tool for the verification of unclear or ambiguous DTI fiber tracking results. There are some improved points as follows as

(1) In the Introduction, it is lacked that the current status and application of PLM in brain research. The PLM is primarily used in crystallography for geologists, mineralogists, and chemists. However, in the past few years, the PLM has been employed in biology.

(2) In the 2.4 section, Is your PLM an off-the-shelf instrument or a modified instrument? In the second paragraph, the words “The axis of the upper filter (called analyzer) is arranged orthogonally to the axis of the lower filter (called polarizer) so that, without any sample present between both filters, light transmission is reduced to a minimum” could be confusing. The sample should be placed between both filters. The light first passes the Polarizer, second passes the Birefringent Specimen, and finally passes the Analyzer.

(3) In Results, the caption of Fig.4 is incomplete.

(4) Based on the PLOS Data policy, authors should submit the following data: 1. The values behind the means, standard deviations and other measures reported; 2. The values used to build graphs; 3. The points extracted from images for analysis. So the values of Fig.1(b) may be submitted.

Reviewer #2: The submission concerns a microscopic study of samples of neural tissue from a selected region of CNS. The architecture and organization of white matter in these samples has been observed by the microscope and supported by the MRI of related region. The multi fiber bundles in white matter of diameter 100-250 micrometer were observed. However, neither diameter distribution of particular fibers in bundles, nor the thickness of myelin sheath for particular fibers were assessed. These parameters are of primary significance for the speed of signaling through these paths. Such observations would be beneficial especially in view of recent advances in understanding of the fast saltatory conduction in myelinated axons, which conditions the architecture and organization of neural paths in white matter (including those considered in the submission). The conventional cable model is unable to properly describe signaling in white matter of CNS as the ion diffusion speed is too slow in human axons and the other mechanism of the stimulus in myelinated axons must be considered. The role of myelin is also different than previously thought upon the cable model (cf. e.g., :https://doi.org/10.1103/PhysRevE.109.034401, Neuroscience 505 (2022) 125–156).

Despite the limited range of the study, the paper is probably worth publication. The manuscript is well organized and carefully written. It might be published provided some revision and the supplementation with comments addressed to functionality of studied structures is added, taking into account a present status in understanding of action potential transduction in myelinated axons. The architecture and local organization of white matter is the function of signal transduction mechanism, its velocity, inter-axonal interaction and so on. Some comment towards such problems would enhance the significance of microscopic observations presented in the paper.

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Reviewer #1: No

Reviewer #2: No

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Fiber architecture in the human ventromedial striatum and its relation with the bed nucleus of the stria terminalis

PONE-D-24-36525R1

Dear Dr. Krueger,

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.

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Kind regards,

Stijn Michielse, PhD

Academic Editor

PLOS ONE

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