Connectional asymmetry of the inferior parietal lobule shapes hemispheric specialization in humans, chimpanzees, and rhesus macaques

Reviewer #1:

[…] 1) The tract-wise approach shows unclear results which should be further discussed. There is a lack of concordance between ROIs connectivity and tract connectivity. Notably, in humans, C1 shows some ROIs based connectivity asymmetry, but no significant leftward asymmetry in the tracts connectivity. And in chimps, there is no significant tract-wise leftward asymmetry in any subregion of the IPL while it exists in the ROI-wise connectivity. It raises other intriguing questions such as: why are human SLF3 and arcuate left lateralized in C2 and right lateralized in C3? Or why do C3 show ROI-wise lateralization for but no tract-wise lateralization at all?

The results are what they are but an effort to link tract-wise connectivity to ROI-wise connectivity and to explain eventual discrepancies between them would benefit to the manuscript. Some of those somehow unexpected results could be biologically relevant, some might reveal limitations of a tract-based approach and make a case for a multiple approaches study like this one.

Thank you for your comment and suggestion. The human C1 showed ROI-wise connectivity asymmetry with the precentral gyrus and insula but no significant asymmetry in the tract-wise connectivity. Some potential reasons are: First, the ROI-wise connectivity is not completely overlapped with the predefined tracts. For example, the precentral gyrus is mainly connected to C1 subregion with SLFII and SLFIII, but the SLFIII is mainly connected C1 with the precentral gyrus and the IFG (De Schotten et al., 2011; Kamali et al., 2014). Second, subcomponents are present in brain regions and major fiber tracts, a concept which is supported by recent work suggesting that the SLF2, SLF3, and AF could be separated into dorsal and ventral branches (Barbeau et al., 2020), as could the ILF (Jones et al., 2013), uncinate fasciculus (Hau et al., 2017), and cingulum bundle (Latini et al., 2017). Hence, the measured connectivity of the SLF3 in the present study may only include a portion of the actual connectivity. Although the SLF3 was shown to be asymmetric (De Schotten et al., 2011), its laterality effect may be diluted, leading to no asymmetry in the tract-wise analysis. This is also the case in chimpanzees and the human C4.

The human SLF3 and AF were found to be left-lateralized in the C2 and right-lateralized in the C3, which seems to be contradictory but reasonable. The two connectivity asymmetries matched well in the ROI-wise and tract-wise analyses. The leftward connectivity asymmetry between the human C2 and the SLF3 and AF using the tract-wise approach corresponds to that between the human C2 and the IFG and precentral gyrus using the ROI-wise approach. The rightward connectivity asymmetry between the human C3 and the SLF3 and AF using the tract-wise approach corresponds to that between the human C3 and the IFG using the ROI-wise approach. These two connectivity findings were consistent with previous studies using invasive tract-tracing in macaque monkeys and resting-state functional connectivity in humans to study the frontal and parietal connectivity (Petrides and Pandya, 2009; Margulies and Petrides, 2013). Our results also provided more information showing that the two connectivities have different asymmetric patterns.

We have added some relevant text in the Discussion section as follows.

“Methodological considerations

The three levels of analyses, i.e., the vertex-wise, ROI-wise, and tract-wise analyses, were performed to provide a full description of the connectivity asymmetry. […] The creation of a finer tract atlas should be a priority for future work because this would help to map the tract-wise connectivity asymmetry at a higher resolution.”

Furthermore, because it only shows a relative lateralization index, Figure 4 does not allow to tell whether a null value is the result of symmetry, or if it simply comes from the absence of connectivity.

Thanks for your question. To clarify this, we have added appendix figures indicating the connectivity values for each subregion for each species (Figure 4—figure supplements 1 and 2).

2) The discussion focuses heavily on the chimpanzee-human distinction. I think the macaque difference with both apes species is a big story and should be equally highlighted as it is relevant to the question of the origin itself of the hemispheric lateralization. Which functional and behavioural features appeared when apes diverged from monkeys as their hemispheres began to specialize is of particular interest.

Thank you for your wonderful suggestion, we have added some text to highlight the differences between macaques and humans and chimpanzees as follows.

In the second paragraph of the “Connectional asymmetries underlying human language and complex tool use” of the Discussion – “[…], while macaques showed symmetric connections between the IPL and temporal cortex. […] This sequence may support the emergence of language and language-related functions.”

In the first paragraph of the “Human unique asymmetric connectivity of IPL subregions” of the Discussion – “A more recent study reported that, in olive baboons, contralateral hemispheric sulcus depth asymmetry of the central sulcus related to the motor hand area is correlated with the direction and degree of hand preference, as measured by a bimanual coordinated tube task, but only about 41% of them were classified as right-handed and 33% were classified as left-handed (Margiotoudi et al., 2019).”

3) I think the manuscript is missing a figure carrying the central message of the study. To improve the impact, I recommend to add a graphical summary highlighting the main findings and putting them into the evolutionary context. It could be a schematic view of IPL and its projections in the 3 species, or/and a simplified phylogenic tree displaying the main evolutionary changes (for example, similar to figure 2. in Stout et al. [1]).

Thank you for your suggestion. We have added a graphical abstract summarizing the main results in the present study (See Author response image 1).

Author response image 1

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Reviewer #2:

[…] The paper is well written, robustly analysed, compelling and the shared results will be extremely useful for the neuroscientific community. The only potential issue that I grappled with is the clustering of the IPL into 4 regions in each species using the similarity analyses. As they note current human, ape and macaque histological atlases for the IPL are difficult to compare and it is not clear which anatomical regions correspond across the species. The spectral similarity clustering approach is well suited for the paper, but the authors, again as they note, need to select an ideal cluster size, which could range from 1-12. However, in my view they selected a good cluster size value of 4 because with 5 the additional IPL cluster is in the wrong dorsal/ventral location in humans/chimpanzees, which would be very difficult to understand from an evolutionary perspective. So, the authors do a fair job dealing with my concern. Still it would be good for the shared results to ensure that they can be easily cross-referenced to atlases in each of the species, or the results taken forward by the authors or others in the future with other parcellation schemes.

Thank you for your positive comments. We are planning to share the results including the parcellation schemes in the present study. They will be available from the Brainnetome Atlas website (https://atlas.brainnetome.org/index.html) and github (https://github.com/LuqiCheng/IPL_Connectional_Asymmetry).

References:

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