Examination and Comparison of Theta Band Connectivity in Left- and Right-Hand Dominant Individuals throughout a Motor Skill Acquisition

Round 1

Reviewer 1 Report

This is a particularly interesting study by J. McDonnell et al. which aims at filling the gap of motor control literature devoted to the left-hand dominant individuals. Specifically, the authors address the issue of the difference in brain activation during skill acquisition between right- and left-hand dominant populations using functional connectivity analysis and graph-theoretical metrics.

First, I would like to acknowledge an exceptionally interesting research design which accounts for several factors of interest: hand dominance, type of the task, and time. Subjects selection also raises no questions. However, I have strong concerns regarding the sensor-level analysis of functional connectivity and its statistical justification.

As I understand, for each trial the authors have calculated subject-specific connectivity matrices in which elements represent the values of imaginary coherence between all possible pairs of sensors averaged over the frequency band (4-7 Hz), and trial duration (approx. 21 sec.). Then the individual connectivity matrices comprised of statistically significant links have been estimated via a nonparametric statistical test. The overall conclusions are built upon the statistical analysis of the difference matrices between conditions using similar statistical technique. Taking into account the multifactorial nature of the study (more than 2 factors), this approach seems to be not completely correct and hard for further interpretation since it does not account for the interaction between some of the factors of interest. 

I would recommend the authors reconsidering their methodology in the following fashion: 

1. Calculate weighted all-to-all connectivity matrices for each trial in each group/experimental condition.
2. Compute weighted graph-theoretical metrics which quantify overall connectivity matrix, e.g. clustering coefficient, global efficiency, and degree.
3. Evaluate the effect of factors of interest on the estimated weighted graph metrics using the mixed-design ANOVA, and provide a post-hoc test where allowed by ANOVA results.
4. Finally, support the mixed-design ANOVA results by considering the within-group connectivity matrices and difference matrices thresholded via appropriate statistical methods (I recommend Network-Based Statistics, see Zalesky et al. 2010) where allowed by ANOVA results. By the latter, I mean considering the difference in functional connectivity only between the factors exhibiting statistically significant changes of the graph metrics.

If the authors do not agree, they should justify in detail in their response how rigor is a pairwise comparison for each possible combination of factors about the hierarchy of factors and multiple-comparison problem.

Minor issue:

1. In subsection 2.1 'Subjects and Experimental Design', 4 females in RH group are reported, however, Fig. 1 illustrates only 3 of them. Please correct. 

Reference list:

Zalesky A, Fornito A, Bullmore ET (2010) NeuroImage 53:1197-207.

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Review of “Examination and comparison of theta band connectivity in left- and right-hand dominant individuals throughout a motor skill acquisition”

 

In their manuscript entitled  “Examination and comparison of theta band connectivity in left- and right-hand dominant individuals throughout a motor skill acquisition”, McDonnel et al. investigate handedness effects on theta band connectivity during motor skill acquisition. This is an interesting and well-written article that is very well in line with the thematic scope of Symmetry. A couple of relevant references are missing and there are some open questions, but most of them should be remedied by standard revisions.

I therefore recommend:

Major revision

 

Specific comments:

Abstract:

• The statement “The majority of the population identifies as right-hand dominant, with a 12-16% minority identifying as left-hand dominant.” This is not correct. The largest meta-analysis on human handedness indicates that 10.6% of people are left-handed (Papadatou-Pastou et al., 2020). Please correct.

Reference:

Papadatou-Pastou M, et al. (2020) Human handedness: A meta-analysis. Psychol Bull. 2020 Jun;146(6):481-524. doi: 10.1037/bul0000229

 

Introduction:

 

• Statement “Hand dominance is now understood to influence fundamental interactions with the environment.” Please support the statement with appropriate citation, e.g.

Reference:

Schmitz J, et al.. Beyond the genome-Towards an epigenetic understanding of handedness ontogenesis. Prog Neurobiol. 2017 Dec;159:69-89. doi: 10.1016/j.pneurobio.2017.10.005

 

• The statement “Structurally, hand dominance is associated with a comparatively larger volume of the hand motor cortical area contralateral to the dominant hand.” Not correct, the largest study on this topic did not find any significant difference, see Guadalupe et al. (2014).

Reference:

Guadalupe T, Willems RM, Zwiers MP, Arias Vasquez A, Hoogman M, Hagoort P, Fernandez G, Buitelaar J, Franke B, Fisher SE, Francks C. Differences in cerebral cortical anatomy of left- and right-handers. Front Psychol. 2014 Mar 28;5:261.

• The statement “Another study with left and right-hand 53 dominant participants observing images of left and right hands executing a motor task found clear differences in neural activation patterns” please describe the pattern

 

Methods:

 

• Gender patterns were reversed for left- and right-handers which might be a problem since gender effects for hemispheric asymmetries have been reported. Please mention this as a limitation and discuss potential effects on results.
• How was the sample size determined?
• Figure 1: “Handiness” might be a typo, do the authors mean “handedness”?
• How was the number of trials determined?

 

Results:

• Please support statements in the results with p-values etc. Just referring to the figures is not enough, E.g. statements like “Differences between LH and RH groups executing the motor task are clear when looking within the theta frequency band.” Need to be supported by proper statistics.
• Please include effect sizes
• Figure 4-6: Please indicate what the error bars indicate

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

In their response, the authors have addressed the issues raised in the review report and dispelled the concerns on the methodology of functional connectivity analysis. Thus, I find the manuscript suitable for publishing in the Symmetry journal.

One final remark that has been missed in the first review report regards the "Data availability statement". Following the Open Science standards, the statement "The data presented in this study are available upon request from the corresponding author" is highly undesirable. For reproducibility purposes, which a modern field of neuroscience suffers from, it's highly demanded to support the original research papers with the analyzed datasets shared in open-access repositories.

Author Response

The authors agree fully with the reviewer’s comments regarding the importance of data availability and we appreciate the stress placed on reproducibility purposes. We ask for a bit of patience as the data remains under continued analysis at the present time and cannot be parsed out in its rawest form. The authors chose the journal for its open-access standards and intend to uphold the principles. We thank the reviewer for their thoughtful comments and review and hope they find the current statement of data availability suitable for the time being.

Reviewer 2 Report

The authors did a great job in improving the paper and reacting to my comments. From my perspective, the paper can be accepted now.

Author Response

We thank you for your efforts in improving the paper.