Cerebral Polymorphisms for Lateralisation: Modelling the Genetic and Phenotypic Architectures of Multiple Functional Modules
Round 1
Reviewer 1 Report
In this article the author gives a very detailed analysis of the state of the art. This article really extends the original monogenic DC model of hand and language dominance to several functional modules, and also considers in a broad context theories about the specificity of issues in the measurement of laterality, the balance between mutation and selection, and the evolution of brain and visceral asymmetries.
A good addition would be to briefly consider an approach to specifically address the notion of functional interhemispheric asymmetry and activity, which is measured promptly and noninvasively, for example, using dichotic listening with lead-lag paradigm. To this reason, I propose to quote: Does Double Biofeedback Affect Functional Hemispheric Asymmetry and Activity? A Pilot Study (Symmetry 2021, 13(6)).
To enrich the material of this article, we can also mention some theories related to switching between different languages and to the functional modules that provide this. For example, you can see the works of Jubin Abutalebi and others.
All in all, the article is well constructed, has its own logic, and contributes to the development of scientific knowledge.
Author Response
"Please see the attachment."
Author Response File: 
Author Response.docx
Reviewer 2 Report
This manuscript is going to review the author’s theory on functional lateralization as a unique feature of the brain from a theoretical standpoint based on its genetic background. A broad range of topics spanning from terminology and historical evolution of viewpoints, to an application on a specific condition, primary ciliary dyskinesia, is shown.
I recognize the authors’ great efforts; however, a part of the description may impede better understanding for interested readers, if not applicable to all. I hope that the author may consider some points shown below to help disseminate the authors' extensive and insightful work and perspective on this scientific field.
Major concerns
1. While the authors prefer a narrative review style, I believe that some readers may find it to be too redundant if the goal is to better understand the core contents because of the highly mixed descriptions between genetic modelling and functional cerebral lateralization. I think that it may be a good idea to summarize and shorten the manuscript so it's written more concisely, and in paragraph form.
2. Many readers may notice that while they could understand the DC model as an initial condition and functional lateralization as a final representation, there is little discussion on the developmental aspects of the DC model as a so-called endophenotype, indicating susceptibility or the boundary of a self-organizing process. How does the author consider these viewpoints or is there any evidence from either theoretical modelling or disease applicable, like primary ciliary dyskinesia?
3. Recently, many reports have shown the cerebellar lateralization of handedness or language, indicating that not only the cerebrum, but also extracerebral structures significantly contribute to higher order functional lateralization. Although the focus of this manuscript is cerebral polymorphism, considering the lower-order structures of the cerebellum compared to the cerebrum, it may be necessary to consider cerebellar contribution for future perspective or discussion.
Minor points
1. Abstract
The abbreviation "DC" should not be abbreviated.
In summary, the authors should reconsider these points to make the review relevant and show how it can be useful.
Author Response
"Please see the attachment."
Author Response File: Author Response.docx
Round 2
Reviewer 2 Report
Thank you so much for your revision.
