On 2021-02-04 03:36:46, user Sara Sims wrote:
Reviewer #3 (Minor Comments):
P2, ?3. The authors cite To et al. (2011) for the claim that foveal magnification is greater than peripheral magnification. However, to make this claim, To et al. rely on a number of other citations which would be more appropriate here (?2 of their introduction). A clear example of this is Horton and Hoyt (1991). Additionally, it might be more appropriate to describe cortical magnification as having units of square-mm/square-degree rather than only mm/degree. <br />
We appreciate reviewer 3 for her/his suggestion, we cited Horton and Hoyt, 1991; Azzopardi and Cowey 1993 in the third paragraph of Introduction on Page 3.
P2, ?3. Additionally, the final line of this paragraph addresses receptive field size. It might be of interest to review the finding of Harvey and Dumuolin (2011) [10.1523/JNEUROSCI.2572-11.2011], that the product of the pRF size and the cortical magnification factor are approximately constant across human V1 and nearby visual cortex. <br />
We added the information regarding how receptive field size and cortical magnification factor changes as eccentricity increases through V1 constantly in human V1 and near visual areas in the third paragraph of Introduction on Page 3.
P4, continued ?1. in order to understand what the FEF's inclusion in the Dorsal Attention Network means, it might be useful to introduce the Dorsal Attention Network briefly when discussing the DMN and the FPN. <br />
This sentence was reworded for clarity, including removing reference to the Dorsal Attention Network since it was not relevant to the sentence’s main point.
P4, full ?1. Given the amount of work that has been done on the fronto-occipital and inferior longitudinal fasciculi, the following sentence should probably include a citation or three. "Major white matter tracts that connect to the occipital lobe such as the inferior fronto-occipital fasciculus (connects occipital lobe to lateral prefrontal cortex) and the inferior longitudinal fasciculus (connects occipital lobe to anterior temporal lobe) have been well documented using tractography methods in humans." <br />
We have added this citation to the text in the introduction: “Major white matter tracts that connect to the occipital lobe such as the inferior fronto-occipital fasciculus (connects occipital lobe to lateral prefrontal cortex) and the inferior longitudinal fasciculus (connects occipital lobe to anterior temporal lobe) have been well documented using tractography methods in humans (Wu et al., 2016).” <br />
Here is the full citation: Wu, Y., Sun, D., Wang, Y., & Wang, Y. (2016). Subcomponents and Connectivity of the Inferior Fronto-Occipital Fasciculus Revealed by Diffusion Spectrum Imaging Fiber Tracking. Frontiers in Neuroanatomy, 10, 88.
P4, full ?2. This paragraph is a bit hard to follow and might be improved by breaking it up into shorter sentences. In particular, I'm not 100% sure what the authors mean by "direct and indirect structural connections". Additionally, I'm not sure why the end of this sentence follows from its beginning: "Since functional connectivity between two brain regions could come from both direct and indirect structural connections, we used DWI to examine direct connections between regions (Adachi et al., 2012; Honey et al., 2009) that were previously found to show functional connections." <br />
We have changed the wording of this paragraph to the following:<br />
“The goals of the current study are 1) to assess the reproducibility and generalizability of retinotopic effects on functional connections between V1 and functional networks that were found in prior work (Griffis et al., 2017). We aim to extend these findings in a new dataset collected under different task conditions (previous work used blocks of rest during a task with central fixation and the current data was collected as part of a resting-state only scan). 2) Extend prior work on the retinotopic connectivity difference to structural connections between V1 and functional networks. 3) Examine the relationship between functional and structural connections. Since functional connectivity between two brain regions could be derived from measurable structural connections, we used DWI to examine connections between regions (Adachi et al., 2012; Honey et al., 2009).”
P4, full ?3. Again, the concept of a "direct connection" versus an "indirect connection" appears prior to being introduced. Given that this paragraph marks the concept as critical to the point of the paper, the introduction needs to explain what these are. Additionally, it seems that the paper separates the idea of a direct/indirect "structural connection" from that of a direct/indirect "functional connection". This should all be clearer. <br />
In addition to the text added in response to the above comment the following text has been added to the paragraph referenced in this comment: “the pattern of structural and functional connections is similar, suggesting that this lateral frontal functional connection pattern arises from a direct (uni-synaptic) structural connection.” for additional clarification.
P6, ?3. "Previous work has shown that cortical anatomy is a reliable predictor of the retinotopic organization of V1 (O. Hinds et al., 2009; O. P. Hinds et al., 2008) so that the more posterior parts of the visual cortex represent more central portions of the visual field." At the risk of splitting hairs, the publications by Oliver Hinds show mainly that the V1 *boundaries* are reliably predicted by anatomy. A better citation for the V1 *retinotopic organization* is Benson et al. (2012) [10.1016/j.cub.2012.09.014], wherein we actually assessed the retinotopic maps and not just the boundaries. <br />
This citation has been added.
P6, ?3. "The average eccentricity of each segment was estimated from Benson and colleagues' probabilistic retinotopy template (Benson et al., 2012)..." The correct citation for the retinotopic template is Benson et al. (2014) [10.1371/journal.pcbi.1003538], along with Benson and Winawer (2018) [10.7554/eLife.40224] assuming you are using a recent version of the template, which appears to be the case based on Figure 2 (though given that you are using the FreeSurfer V1 boundary also, I can't really tell). Additionally, it isn't technically correct to call this a probabilistic template (such as might be said correctly of the visual area atlas by Wang et al., 2015). The retinotopic template is more accurately a model of retinotopic organization fit to the average retinotopic organization across many subjects-it does not explicitly express or depend on probabilities. <br />
Wording has been changed to retinotopic template.
P6, ?3. "These ROIs were defined in the gray matter on the cortical sheet for the freesurfer template, then moved into the individual anatomical space for each participant." I believe that the authors' intent here is to state that ROIs were defined on FreeSurfer's fsaverage brain using the eccentricity of the retinotopic template (which is also defined on the fsaverage brain) then were interpolated over to individual subject cortical surfaces using FreeSurfer's anatomical registration. However, I don't have a good prior for what the "freesurfer template" is here or what the "gray matter on the cortical sheet" of it might be, so this may all be wrong. Perhaps the implication is that the ROIs were hand-drawn in the voxels of the fsaverage subject's "ribbon," but if so, is the interpolation back to the individual subject done on the surface or using FreeSurfer's newish diffeomorphic volumetric alignment? <br />
The following text has been revised to further clarify for the reviewer: “These V1 eccentricity segment ROIs were defined on FreeSurfer's fsaverage brain using the eccentricity of the retinotopic template then were interpolated to individual subject cortical surfaces using FreeSurfer's anatomical registration. To avoid the potential for artifacts due to differences in ROI size when comparing probabilistic tractography results, the number of vertices were kept similar (on the Freesurfer fsaverage brain) between eccentricity segments.”
P6, ?3. "To avoid the potential for artifacts due to differences in ROI size, the number of segments per eccentricity region were assigned to more evenly distribute ROI size." Again, this is not at all clear. Earlier text in this paragraph implies that the segments *are* eccentricity regions. Does this sentence indicate that the segments were adjusted in each individual subject to be of a similar size? Or that the ROIs were split into several segments each before interpolation? Is there a material difference between what was done and simply starting with a larger number of segments? It's not clear to my why the process is described in terms of three segments whose eccentricities are reported then redescribed in terms of more segments whose eccentricities are not reported. <br />
We acknowledge that the reporting of the V1 ROI eccentricity segments was unclear. We have simplified the text to be more clear so that it now reads: “Based on this template, 3 retinotopic regions were identified: central vision (mean eccentricity estimates of 0-2.2 degrees visual angle), mid-peripheral vision (mean eccentricity estimates of 4.1-7.3 degrees visual angle) and far-peripheral vision (mean eccentricity estimates of 14.1-25.5 degrees visual angle) (Figure 2).”
P7, ?1. "... voxels within the white matter corresponding to the network ROIs were used as track seeds." I found this initially confusing as immediately prior to this section, "ROI" refers to the ROIs of V1, which should have no truck with the white-matter (i.e., a white-matter voxel predicted to be in an ROI derived from the FreeSurfer's V1 label or the retinotopic template must by definition be erroneous). However, I suspect that this is intended to be about a separate set of network ROIs? This should be clearer. <br />
Yes, there are two sets of ROIs, the V1 ROIs and the Network ROIs. The “network ROIs” has been changed to “network-ROIs” to emphasize this point further. Also, whenever the term “ROI” is used, the name of the set of ROIs being referred to is now stated.
P7, Data Analysis. Again, citing the analysis methods is well and good, but this section should make very clear up front which data were collected/analyzed by the authors and which data were collected/analyzed by the HCP. I should be able to easily tell both what analysis steps were performed *and* which set of authors performed each step. <br />
See response to Reviewer #3 Major Comment #2.
P7, ?2. "Next, right-to-left and left-to-right acquisitions were concatenated into a single 4D volume for the functional connectivity analysis." While I understand from this sentence that the preprocessed images were transformed into single 4D volume files, I do not follow the significance of "right-to-left" and "left-to-right" in this context. <br />
The text of the article has been changed to clarify this: “Next, both the acquisitions (those collected right-to-left and those collected left-to-right) were concatenated into a single 4D volume for the functional connectivity analysis.”
P8, ?4. The text references a "2mm2 Gaussian kernel". Is this supposed to be 2 mm (not squared)? If so, does it refer to the FWHM or to the HWHM or to the parameter ?? It says the "surface maps" were smoothed, but was this done on the FreeSurfer cortical sphere (in which case, mm is a curious unit)? Volumetrically? Something else? <br />
This was a typo it has been changed to “2mm” and the text now reads “Surface maps of the track termination probabilities were smoothed using a 2mm FWHM Gaussian filter and averaged across all subjects.”. This was done with mri_glmfit “fwhm” flag.
P9, ?1. More information is needed about the t-tests that were used. Were these tests one-tailed or two-tailed? Corrected for multiple comparisons or not? How was mri_glmfit used to perform these tests? The help-file for mri_glmfit mentions t-tests only in the context that a certain use-case reduces to a t-test in some circumstances. <br />
We have added “two-tailed” to the text. The mri_glmfit function can be used as a t-test under one sample group mean test with the --osgm flag. We did not correct for multiple comparisons due to the analysis’s design with specific, planned comparisons.
P9, Comparison of Functional and Structural Connectivity. Was only one correlation coefficient calculated? Were the authors not interested in these correlations for the non-central V1 regions? It seems irregular that only one of these would be examined given the experimental setup and the hypotheses of the manuscript. <br />
We have now included dice coefficients, per the reviewer’s suggestion, as well as adding non-central V1 regions in this new analysis.
Methods, generally. In a couple of places, the authors refer to commands like "mri_vol2surf" (P8, ?1). It would be ideal if the command lines or scripts were also provided with the manuscript. <br />
The code has now been added to the code repository.
P9, ?4. "The t-test comparing functional connectivity to different eccentricity segments in V1 revealed significant effects (p<.001) and brain regions belonging to FP, CO, and DMN functional networks (Figure 3)" is the "and" here supposed to be "in"? <br />
This edit has been made.
P9, ?4. It's not clear to me how "preference" was evaluated here. For example, "central representing V1 was preferentially connected (over mid-peripheral and far-peripheral V1) to regions associated with the FP network". Was this assessed by visual inspection? A good quantitative metric would be nice to have here, such as the dice coefficient for each ROI-network pair. <br />
We have added dice coefficients to the analysis. See Tables 1 & 2.
P9, ?4. "Those previous results had also shown differences in connectivity between mid-peripheral-representing regions and far-peripheral representing regions, which were not observed here, (Figure 3)" <br />
This text has been reworded for clarity: “However our results differ in that mid-peripheral-representing regions and far-peripheral representing regions differences were not observed here (Figure 3).”
P10, Figure 3. "There, vertices in yellow showed stronger (z>3) connectivity to central V1 than to both Far peripheral and mid-peripheral regions." I do not understand the significance of "(z>3)" in this caption. Additionally, what is the significance of the gray color shown on all brains in the bottom row? <br />
Clarification has been added to the Figure legend, including “The grey regions indicate the location of the other networks.”
P11, ?1. "... we performed pairwise comparisons of functional connections... Results indicate that ... there are preferential connections between central V1 ..." Again, I'm not clear how preference is being assessed here, or what is being compared pairwise. Pairwise comparisons between segments and networks? What values exactly were compared? If these are referring to visual inspection, that is fine, but the language seems to suggest something more programatic, and what that might be is not clear. <br />
The text has been clarified to now state “We performed statistical comparisons (t-test) of functional connections between central vs far-peripheral eccentricity segments of V1 and the FPN (Figure 4).”
P11, Figure 4. Please tell us what exactly is being plotted. What value minus what value? <br />
The values being subtracted have now been added to all figures.
P14, ?2. "A comparison between structure and function showed overall agreement, indicating that the functional connections are likely mediated by direct structural connections (Figure 6, right column)." Depending on what the authors mean by "mediate" I'm not sure that this follows. Please elaborate. <br />
We acknowledge that this wording is unclear. We have therefore changed the wording of this statement to the following: “These relationships indicate that the overall pattern of connectivity of central V1 greater than far peripheral V1 is consistent across modalities with an especially high overlap within the FPN.”
P14, Figure 6. "Far-peripheral and central V1 are statistically different within the FPN..." How was statistical difference within the FPN assessed? <br />
Please refer to the following section:<br />
“Tractography Analysis <br />
To test the hypothesis that patterns of functional connections previously found in V1 (Griffis et al., 2017) are similar to patterns of structural connections, comparisons were made between the central and far-peripheral eccentricity segments of V1 connectivity patterns to the FPN. Differences in track probabilities corresponding to V1 eccentricity segments connections were compared by paired, two-tailed t-test (using Freesurfer’s mri_glmfit with a one sample group mean test). “
Style/Aesthetic Comments <br />
Throughout the manuscript, starting on P3, full ?1, there are several mismatched parentheses that are distracting. These typically look like this: "some claim is made here (e.g., (Someone et al., 2010) then continues here". Almost all of these could be fixed by removing the "(e.g. ". That said, the use of "e.g., "makes me think that there are other citations that *should* appear here, but haven't been filled in yet, especially given that many of these are broad statements somewhat outside my particular expertise, such as "The fronto-parietal network (FPN) directs attentional control (e.g., (Zanto & Gazzaley, 2013)".
P4, L8. "Markov et. al," should be "Markov et al.," <br />
This edit has been made.
P4, full ?2-3. The authors mix the style "Something listable: (1) first thing, (2) second thing..." and the style "Something listable: 1) first thing, 2) second thing." <br />
This formatting has been changed.
P7, ?1. The acronyms "FP" and "CO" were previously reported as "FPN" and "CON". This needs to be fixed throughout. I get that at times the intention is to represent the deduplication of the word "network," i.e., "the fronto-parietal and default mode network" becomes "the FP and DMN". I think this usage is less clear to readers than "the FPN and DMN" and, besides, the text sometimes says "the FP and DMN networks" (P8?3L3, P9?4L4). Alternately, introduce FP et al. as separate acronyms on P7: "Fronto-parietal (FP), cingulo-opercular (CO), and default mode (DM) networks...". <br />
Abbreviations have been edited for consistency.
Reviewer #3 (Additional data files and statistical comments):
As mentioned in the Major and Minor comments, most if not all of the statistical tests need to be more explicitly described. I could not currently reproduce the exact tests from the manuscript, even if I had the data.
Additionally, because the project is a reanalysis of a large dataset, it would be particularly valuable to have the source code used for analysis. It is nearly impossible to reproduce or assess a project like this without such code.
The code for the analysis has now been added to a repository and it is referenced in the paper.