Updating the sulcal landscape of the human lateral parieto-occipital junction provides anatomical, functional, and cognitive insights

  1. Ethan H Willbrand
  2. Yi-Heng Tsai
  3. Thomas Gagnant
  4. Kevin S Weiner

  • Curated by eLife

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    eLife assessment

    The present work provides new insights into detailed brain morphology. Using state-of-the-art methods, it provides compelling evidence for the relevance of sucal morphology for the precise localization of brain function. The fundamental findings have great relevance for the fields of imaging neuroscience and individualized medicine as ever-improving techniques improve precision to the point where individual brain anatomy is taking centre stage.

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Abstract

Recent work has uncovered relationships between evolutionarily new small and shallow cerebral indentations, or sulci, and human behavior. Yet, this relationship remains unexplored in the lateral parietal cortex (LPC) and the lateral parieto-occipital junction (LPOJ). After defining thousands of sulci in a young adult cohort, we revised the previous LPC/LPOJ sulcal landscape to include four previously overlooked, small, shallow, and variable sulci. One of these sulci (ventral supralateral occipital sulcus, slocs-v) is present in nearly every hemisphere and is morphologically, architecturally, and functionally dissociable from neighboring sulci. A data-driven, model-based approach, relating sulcal depth to behavior further revealed that the morphology of only a subset of LPC/LPOJ sulci, including the slocs-v, is related to performance on a spatial orientation task. Our findings build on classic neuroanatomical theories and identify new neuroanatomical targets for future “precision imaging” studies exploring the relationship among brain structure, brain function, and cognitive abilities in individual participants.

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  1. Version published to 10.7554/elife.90451.2 on eLife
  2. Version published to 10.7554/elife.90451 on eLife
  3. eLife

    eLife assessment

    The present work provides new insights into detailed brain morphology. Using state-of-the-art methods, it provides compelling evidence for the relevance of sucal morphology for the precise localization of brain function. The fundamental findings have great relevance for the fields of imaging neuroscience and individualized medicine as ever-improving techniques improve precision to the point where individual brain anatomy is taking centre stage.

  4. eLife

    Reviewer #1 (Public Review):

    Summary:
    Ever-improving techniques allow the detailed capture of brain morphology and function to the point where individual brain anatomy becomes an important factor. This study investigated detailed sulcal morphology in the parieto-occipital junction. Using cutting-edge methods, it provides important insights into local anatomy, individual variability, and local brain function. The presented work advances the field and will stimulate future research into this important area.

    Strengths:
    Detailed, very thorough methodology. Multiple raters mapped detailed sulci in a large cohort. The identified sulcal features and their functional and behavioural relevance are then studied using various complementary methods. The results provide compelling evidence for the importance of the described sulcal features and their proposed relationship to cortical brain function.

    Comments on revised version:

    The revised manuscript addresses all my concerns.

  5. eLife

    Reviewer #2 (Public Review):

    Summary:
    After manually labelling 144 human adult hemispheres in the lateral parieto-occipital junction (LPOJ), the authors 1) propose a nomenclature for 4 previously unnamed highly variable sulci located between the temporal and parietal or occipital lobes, 2) focus on one of these newly named sulci, namely the ventral supralateral occipital sulcus (slocs-v) and compare it to neighbouring sulci to demonstrate its specificity (in terms of depth, surface area, gray matter thickness, myelination, and connectivity), 3) relate the morphology of a subgroup of sulci from the region including the slocs-v to the performance in a spatial orientation task, demonstrating behavioural and morphological specificity. In addition to these results, the authors propose an extended reflection on the relationship between these newly named landmarks and previous anatomical studies, a reflection about the slocs-v related to functional and cytoarchitectonic parcellations as well as anatomic connectivity and an insight about potential anatomical mechanisms relating sulcation and behaviour.

    Strengths:
    - To my knowledge, this is the first study addressing the variable tertiary sulci located between the superior temporal sulcus (STS) and intra-parietal sulcus (IPS).
    - This is a very comprehensive study addressing altogether anatomical, architectural, functional and cognitive aspects.
    - The definition of highly variable yet highly reproductible sulci such as the slocs-v feeds the community with new anatomo-functional landmarks (which is emphasized by the provision of a probability map in supp. mat., which in my opinion should be proposed in the main body).
    - The comparison of different features between the slocs-v and similar sulci is useful to demonstrate their difference.
    - The detailed comparison of the present study with state of the art contextualises and strengthens the novel findings.
    - The functional study complements the anatomical description and points towards cognitive specificity related to a subset of sulci from the LPOJ
    - The discussion offers a proposition of theoretical interpretation of the findings
    - The data and code are mostly available online (raw data made available upon request).

    Weaknesses:
    - While the identification of the sulci has been done thoroughly with expert validation, the sulci have not been labelled in a way that enables the demonstration of the reproducibility of the labelling.

    The proposed methodology is convincing in identifying and studying the relationship between highly variable sulci and cognition. This improves our refined understanding of the general anatomical variability in the LPOJ and its potential functional/cognitive correlates. This work is important to the understanding of sulcal variability and its implications on functional and cognitive aspects.

    Comments on revised version:

    Thank you for the elegant and informative work.

  6. eLife

    Reviewer #3 (Public Review):

    Summary:
    72 subjects, and 144 hemispheres, from the Human Connectome Project had their parietal sulci manually traced. This identified the presence of previous undescribed shallow sulci. One of these sulci, the ventral supralateral occipital sulcus (slocs-v), was then demonstrated to have functional specificity in spatial orientation. The discussion furthermore provides an eloquent overview of our understanding of the anatomy of the parietal cortex, situating their new work into the broader field. Finally, this paper stimulates further debate about the relative value of detailed manual anatomy, inherently limited in participant numbers and areas of the brain covered, against fully automated processing that can cover thousands of participants but easily misses the kinds of anatomical details described here.

    Strengths:
    - This is the first paper describing the tertiary sulci of the parietal cortex with this level of detail, identifying novel shallow sulci and mapping them to behaviour and function.
    - It is a very elegantly written paper, situating the current work into the broader field.
    - The combination of detailed anatomy and function and behaviour is superb.

    Weaknesses:
    - the numbers of subjects are inherently limited both in number as well as in being typically developing young adults.
    - while the paper begins by describing four new sulci, only one is explored further in greater detail.
    - there is some tension between calling the discovered sulci new vs acknowledging they have already been reported, but not named.
    - the anatomy of the sulci, as opposed to their relation to other sulci, could be described in greater detail.

    Overall, to summarize, I greatly enjoyed this paper and believe it to be a highly valued contribution to the field.

  7. eLife

    Author response:

    The following is the authors’ response to the original reviews.

    Public Reviews:

    Reviewer #1 (Public Review):

    Summary:

    Ever-improving techniques allow the detailed capture of brain morphology and function to the point where individual brain anatomy becomes an important factor. This study investigated detailed sulcal morphology in the parieto-occipital junction. Using cutting-edge methods, it provides important insights into local anatomy, individual variability, and local brain function. The presented work advances the field and will stimulate future research into this important area.

    Strengths:

    Detailed, very thorough methodology. Multiple raters mapped detailed sulci in a large cohort. The identified sulcal features and their functional and behavioural relevance are then studied using various complementary methods. The results provide compelling evidence for the importance of the described sulcal features and their proposed relationship to cortical brain function.

    We thank the Reviewer for highlighting the strengths of our methods and findings.

    Weaknesses:

    A detailed description/depiction of the various sulcal patterns is missing.

    We agree that adding these details for the newly described sulci is necessary and have now done so. These details are included in the Results (Page 6):

    “Beyond characterizing the incidence of sulci, it is also common in the neuroanatomical literature to qualitatively characterize sulci on the basis of fractionation and intersection with surrounding sulci (termed “sulcal types”; for examples in other cortical expanses, see Chiavaras & Petrides, 2000; Drudik et al., 2023; Miller et al., 2021; Paus et al., 1996; Weiner et al., 2014; Willbrand, Parker, et al., 2022). All four sulci most commonly did not intersect with other sulci (see Supplementary Tables 1-4 for a summary of the sulcal types of the slocs and pAngs dorsal and ventral components). The sulcal types were also highly comparable between hemispheres (rs > .99 , ps < .001).”

    And in four new Supplementary Tables.

    A possible relationship between sulcal morphology and individual demographics might provide more insight into anatomical variability.

    We have conducted additional analyses to relate sulcal incidence to demographic features (age and gender). These results are included on Pages 5-6:

    “Given that sulcal incidence and patterning is also sometimes related to demographic features (Cachia et al., 2021; Leonard et al., 2009; Wei et al., 2017), subsequent GLMs relating the incidence and patterning of the three more variable sulci (slocs-d, pAngs-v, and pAngs-d) to demographic features (age and gender) revealed no associations for any sulcus (ps > .05).”

    The unique dataset offers an opportunity to provide insights into laterality effects that should be explored.

    We included hemisphere as a factor in all models for this exact reason. Throughout the paper, we have edited the text to ensure that these laterality effects are more apparent to readers.

    Further, we have a Supplementary Results section on hemispheric effects regarding the slocs-v, cSTS3, and lTOS:

    “Hemispheric asymmetries in morphological, architectural, and functional features with regards to the slocs-v, cSTS3, and lTOS comparison

    We observed a sulcus x metric x hemisphere interaction on the morphological and architectural features of the slocs-v (F(4.20, 289.81) = 4.16, η2 = 0.01, p = .002; the cSTS3 is discussed in the next section). Post hoc tests showed that this interaction was driven by the slocs-v being cortically thinner in the left than the right hemisphere (p < .001; Fig. 2a).

    There was also a sulcus x network x hemisphere interaction on the functional connectivity profiles (using functional connectivity parcellations from (Kong et al., 2019)) of the slocs-v and lTOS (F(32, 2144) = 3.99, η2 = 0.06, p < .001; the cSTS3 is discussed in the next section). Post hoc tests showed that this interaction was driven by three effects: (i) the slocs-v overlapped more with the Default C subnetwork in the left than the right hemisphere (p = .013), (ii) the lTOS overlapped more with Visual A subnetwork in the right than the left hemisphere (p = .002), and (iii) the lTOS overlapped more with the Visual B subnetwork in the left than the right hemisphere (p = .002; Fig. 2b).”

    As well as the other STS rami on morphology:

    “It is also worth noting that there was a sulcus x metric x hemisphere interaction (F(4, 284.12) = 6.60, η2 = 0.08, p < .001). Post hoc tests showed that: (i) the cSTS3 was smaller (p < .001) and thinner (p = .025) in the left than the right hemisphere (Supplementary Fig. 8a), (ii) the cSTS2 was shallower (p = .004) and thicker (p < .001) in the right than left hemisphere (Supplementary Fig. 8a), and (iii) the cSTS1 was shallower (p < .001), smaller (p = .002), thinner (p = .001), and less myelinated (p < .001) in the left than the right hemisphere (Supplementary Fig. 8a).”

    And functional connectivity of the STS rami:

    “There was also a sulcus x network x hemisphere interaction (F(32, 2208) = 12.26, η2 = 0.15, p < .001). Post hoc tests showed differences for each cSTS component. Here, the cSTS1 overlapped more with the Auditory network (p < .001), less with the Control B subnetwork (p < .001), more with the Control C subnetwork (p < .001), less with the Default B subnetwork (p < .001), more with the Default C subnetwork (p < .001), more with the Ventral Attention B subnetwork (p < .001), and more with the Visual A subnetwork (p = .024) in the right than in the left hemisphere (Supplementary Fig. 8b). In addition, the cSTS2 overlapped more with the Control B subnetwork (p < .001), more with the Control C subnetwork (p < .001), less with the Default B subnetwork (p < .001), and less with the Temporal-Parietal network (p = .011) in the right than in the left hemisphere (Supplementary Fig. 8b). Finally, the cSTS3 overlapped more with the Control B subnetwork (p = .002), less with the Default B subnetwork (p = .014), more with the Default C subnetwork (p = .022), less with the Ventral Attention B subnetwork (p = .029) in the right than in the left hemisphere (Supplementary Fig. 8b).”

    Reviewer #2 (Public Review):

    Summary: After manually labeling 144 human adult hemispheres in the lateral parieto-occipital junction (LPOJ), the authors 1) propose a nomenclature for 4 previously unnamed highly variable sulci located between the temporal and parietal or occipital lobes, 2) focus on one of these newly named sulci, namely the ventral supralateral occipital sulcus (slocs-v) and compare it to neighboring sulci to demonstrate its specificity (in terms of depth, surface area, gray matter thickness, myelination, and connectivity), 3) relate the morphology of a subgroup of sulci from the region including the slocs-v to the performance in a spatial orientation task, demonstrating behavioral and morphological specificity. In addition to these results, the authors propose an extended reflection on the relationship between these newly named landmarks and previous anatomical studies, a reflection about the slocs-v related to functional and cytoarchitectonic parcellations as well as anatomic connectivity and an insight about potential anatomical mechanisms relating sulcation and behavior.

    Strengths:

    - To my knowledge, this is the first study addressing the variable tertiary sulci located between the superior temporal sulcus (STS) and intraparietal sulcus (IPS).

    - This is a very comprehensive study addressing altogether anatomical, architectural, functional and cognitive aspects.

    - The definition of highly variable yet highly reproducible sulci such as the slocs-v feeds the community with new anatomo-functional landmarks (which is emphasized by the provision of a probability map in supp. mat., which in my opinion should be proposed in the main body).

    - The comparison of different features between the slocs-v and similar sulci is useful to demonstrate their difference.

    - The detailed comparison of the present study with state of the art contextualizes and strengthens the novel findings.

    - The functional study complements the anatomical description and points towards cognitive specificity related to a subset of sulci from the LPOJ

    - The discussion offers a proposition of theoretical interpretation of the findings

    - The data and code are mostly available online (raw data made available upon request).

    We thank the Reviewer for highlighting the strengths of our methods, analyses, and applications of our findings.

    Weaknesses:

    - While three independent raters labeled all hemispheres, one single expert finalized the decision. Because no information is reported on the inter-rater variability, this somehow equates to a single expert labeling the whole cohort, which could result in biased labellings and therefore affect the reproducibility of the new labels.

    Our group does not use an approach amenable to calculating inter-rater agreements to expedite the process of defining thousands of sulci at the individual level in multiple regions. Our method consists of a two-tiered procedure. Here, authors YT and TG defined sulci which were then checked by a trained expert (EHW). These were then checked again by senior author (KSW) . We emphasize that this process has produced reproducible anatomical results in other regions such as posteromedial cortex (Willbrand et al., 2023 Science Advances; Willbrand et al., 2023 Communications Biology; Maboudian et al., 2024 The Journal of Neuroscience), ventral temporal cortex (Weiner et al., 2014 NeuroImage; Miller et al., 2020 Scientific Reports; Parker et al., 2023 Brain Structure and Function), and lateral prefrontal cortex (Miller et al., 2021 The Journal of Neuroscience; Voorhies et al., 2021 Nature Communications; Yao et al., 2022 Cerebral Cortex; Willbrand et al., 2022 Brain Structure and Function; Willbrand et al., 2023 The Journal of Neuroscience) across age groups, species, and clinical populations. Further, in the Supplemental Materials we provide post mortem images showing that these sulci exist outside of cortical reconstructions, supporting this updated sulcal schematic of the lateral parieto-occipital junction. For the present study, by the time the final tier of our method was reached, we emphasize that a very small percentage (~2%) of sulcal definitions were actually modified. We will include an exact percentage in future publications in LPC/LOPJ.

    - 3 out of the 4 newly labeled sulci are only described in the very first part and never reused. This should be emphasized as it is far from obvious at first glance of the article.

    We have edited the Abstract (shown below, on Page 1) and paper throughout to emphasize the emphasis on the slocs-v over the other three sulci.

    “After defining thousands of sulci in a young adult cohort, we revised the previous LPC/LPOJ sulcal landscape to include four previously overlooked, small, shallow, and variable sulci. One of these sulci (ventral supralateral occipital sulcus, slocs-v) is present in nearly every hemisphere and is morphologically, architecturally, and functionally dissociable from neighboring sulci. A data-driven, model-based approach, relating sulcal depth to behavior further revealed that the morphology of only a subset of LPC/LPOJ sulci, including the slocs-v, is related to performance on a spatial orientation task.”

    It is worth noting that we have added additional analyses that include the other three newly-characterized sulci in response to Reviewer 1. We first described the relationship between these sulci and demographic features, alongside analyses on the patterning of these sulci, which are included in the Results (Page 6):

    “Beyond characterizing the incidence of sulci, it is also common in the neuroanatomical literature to qualitatively characterize sulci on the basis of fractionation and intersection with surrounding sulci (termed “sulcal types”; for examples in other cortical expanses, see Chiavaras & Petrides, 2000; Drudik et al., 2023; Miller et al., 2021; Paus et al., 1996; Weiner et al., 2014; Willbrand, Parker, et al., 2022). All four sulci most commonly did not intersect with other sulci (see Supplementary Tables 1-4 for a summary of the sulcal types of the slocs and pAngs dorsal and ventral components). The sulcal types were also highly comparable between hemispheres (rs > .99 , ps < .001). Though we characterize these sulci in this paper for the first time, the location of these four sulci is consistent with the presence of variable “accessory sulci” in this cortical expanse mentioned in prior modern and classic studies (Supplementary Methods). We could also identify these sulci in post-mortem hemispheres (Supplementary Figs. 2, 3), ensuring that these sulci were not an artifact of the cortical reconstruction process.

    Given that sulcal incidence and patterning is also sometimes related to demographic features (Cachia et al., 2021; Leonard et al., 2009; Wei et al., 2017), subsequent GLMs relating the incidence and patterning of the three more variable sulci (slocs-d, pAngs-v, and pAngs-d) to demographic features (age and gender) revealed no associations for any sulcus (ps > .05). Finally, to help guide future research on these newly- and previously-classified LPC/LPOJ sulci, we generated probabilistic maps of each of these 17 sulci and share them with the field with the publication of this paper (Supplementary Fig. 6; Data availability).”

    - The tone of the article suggests a discovery of these 4 sulci when some of them have already been reported (as rightfully highlighted in the article), though not named nor studied specifically. This is slightly misleading as I interpret the first part of the article as a proposition of nomenclature rather than a discovery of sulci.

    We have toned down our language throughout the paper, emphasizing that this paper is updating the sulcal landscape of LPC/LOPJ taking into account these sulci that have not been comprehensively described previously. For example, in the Abstract (Page 1), we now write:

    “After defining thousands of sulci in a young adult cohort, we revised the previous LPC/LPOJ sulcal landscape to include four previously overlooked, small, shallow, and variable sulci. One of these sulci (ventral supralateral occipital sulcus, slocs-v) is present in nearly every hemisphere and is morphologically, architecturally, and functionally dissociable from neighboring sulci. A data-driven, model-based approach, relating sulcal depth to behavior further revealed that the morphology of only a subset of LPC/LPOJ sulci, including the slocs-v, is related to performance on a spatial orientation task. “

    - The article never mentions the concept of merging of sulcal elements and the potential effect it could have on the labeling of the newly named variable sulci.

    We emphasize that we use multiple surfaces (pial, inflated, smoothwm) to help distinguish intersecting sulci from one another. We include extra text in the Methods (Page 21):

    “We defined LPC/LPOJ sulci for each participant based on the most recent schematics of sulcal patterning by Petrides (2019) as well as pial, inflated, and smoothed white matter (smoothwm) FreeSurfer cortical surface reconstructions of each individual. In some cases, the precise start or end point of a sulcus can be difficult to determine on a surface (Borne et al., 2020); however, examining consensus across multiple surfaces allowed us to clearly determine each sulcal boundary in each individual. “

    Further, upon quantifying the patterning of these variable sulci, a majority of the time they are independent (described in the Results on Page 6):

    “Beyond characterizing the incidence of sulci, it is also common in the neuroanatomical literature to qualitatively characterize sulci on the basis of fractionation and intersection with surrounding sulci (termed “sulcal types”; for examples in other cortical expanses, see (Chiavaras & Petrides, 2000; Drudik et al., 2023; Miller et al., 2021; Paus et al., 1996; Weiner et al., 2014; Willbrand, Parker, et al., 2022). All four sulci most commonly did not intersect with other sulci (see Supplementary Tables 1-4 for a summary of the sulcal types of the slocs and pAngs dorsal and ventral components). The sulcal types were also highly comparable between hemispheres (rs > .99 , ps < .001).”

    Thus, merging sulcal elements likely had a minimal impact on the present definitions.

    - The definition of the new sulci is solely based on their localization relative to other sulci which are themselves variable (e.g. the 3rd branch of the STS can show different locations and different orientation, potentially affecting the definition of the slocs-v). This is not addressed in the discussion.

    As displayed in our probabilistic maps of these sulci (Supplementary Fig. 6), the cSTS components (2-4) are actually relatively consistent between individuals, and thus, future investigators can utilize these maps to help define these sulci in new hemispheres.

    Nevertheless, there is, of course, individual variability in the location of these sulci, and we do agree that this point brought up by the Reviewer is important. We have now added text to the Limitations section of the Discussion (Pages 15-16):

    “The main limitation of our study is that presently, the most accurate methodology to define sulci —especially the small, shallow, and variable PTS—requires researchers to manually trace each structure on the cortical surface reconstructions. This method is limited due to the individual variability of cortical sulcal patterning (Fig. 1, Supplementary Fig. 5), which makes it challenging to identify sulci, let alone PTS, without extensive experience and practice. However, we anticipate that our probabilistic maps will provide a starting point and hopefully, expedite the identification of these sulci in new participants. This method is also arduous and time-consuming—which, on the one hand, limits the sample size in terms of number of participants, while on the other, results in thousands of precisely defined sulci. This push-pull relationship reflects a broader conversation in the human brain mapping and cognitive neuroscience fields between a balance of large N studies and “precision imaging” studies in individual participants (Allen et al., 2022; Gratton et al., 2022; Naselaris et al., 2021; Rosenberg and Finn, 2022).”

    - The new sulci are only defined in terms of localization relative to other sulci, and no other property is described (general length, depth, orientation, shape...), making it hard for a new observer to take labeling decisions in case of conflict.

    To help guide future investigators, we now show these metrics for all sulci in Supplemental Figure 7 to help future groups identify these sulci with the assistance of their general morphology.

    - The very assertive tone of the article conveys the idea that these sulci are identifiable certainly in most cases, when by definition these highly variable tertiary sulci are sometimes very difficult to take decisions on.

    The highly variable nature of ¾ of the putative tertiary sulci (slocs-v, slocs-d, pAngs-v, pAngs-d) described here is why we focused on the slocs-v (as it is identifiable in nearly all f hemispheres). However, we have edited our language throughout the text to also emphasize the variability of these sulci. For example, in the Results (Page 5), we now write:

    “In previous research in small sample sizes, neuroanatomists noticed shallow sulci in this cortical expanse (Supplementary Methods and Supplementary Figs. 1-4 for historical details). In the present study, we fully update this sulcal landscape considering these overlooked indentations. In addition to defining the 13 sulci previously described within the LPC/LPOJ, as well as the posterior superior temporal cortex (Methods) (Petrides, 2019) in individual participants, we could also identify as many as four small and shallow PTS situated within the LPC/LPOJ that were highly variable across individuals and uncharted until now (Supplementary Methods and Supplementary Figs. 1-4). Macroanatomically, we could identify two sulci between the cSTS3 and the IPS-PO/lTOS ventrally and two sulci between the cSTS2 and the pips/IPS dorsally. We focus our analyses on the slocs-v since it was identifiable in nearly every hemisphere.”

    - I am not absolutely convinced with the labeling proposed of a previously reported sulcus, namely the posterior intermediate parietal sulcus.

    In defining previously-identified LPC sulci, we followed the previous labeling procedure by Petrides (2019) alongside historical definitions (detailed in Supplementary Figures 1-4). Nevertheless, future deep learning algorithms using these and others data can be used to rectify discrepancies in labeling (e.g., Borne et al., 2020 Medical Image Analysis; Lyu et al., 2021 NeuroImage). We discuss these points in the Limitations section of the Discussion (Pages 16-17):

    “The main limitation of our study is that presently, the most accurate methodology to define sulci —especially the small, shallow, and variable PTS—requires researchers to manually trace each structure on the cortical surface reconstructions. This method is limited due to the individual variability of cortical sulcal patterning (Fig. 1, Supplementary Fig. 5), which makes it challenging to identify sulci without extensive experience and practice. However, we anticipate that our probabilistic maps will provide a starting point and hopefully, expedite the identification of these sulci in new participants. This should accelerate the process of subsequent studies confirming the accuracy of our updated schematic of LPC/LOPJ. This manual method is also arduous and time-consuming, which, on the one hand, limits the sample size in terms of number of participants, while on the other, results in thousands of precisely defined sulci. This push-pull relationship reflects a broader conversation in the human brain mapping and cognitive neuroscience fields between a balance of large N studies and “precision imaging” studies in individual participants (Allen et al., 2022; Gratton et al., 2022; Naselaris et al., 2021; Rosenberg & Finn, 2022). Though our sample size is comparable to other studies that produced reliable results relating sulcal morphology to brain function and cognition (e.g., (Cachia et al., 2021; Garrison et al., 2015; Lopez-Persem et al., 2019; Miller et al., 2021; Roell et al., 2021; Voorhies et al., 2021; Weiner, 2019; Willbrand, Parker, et al., 2022; Willbrand, Voorhies, et al., 2022; Yao et al., 2022), ongoing work that uses deep learning algorithms to automatically define sulci should result in much larger sample sizes in future studies (Borne et al., 2020; Lyu et al., 2021). Finally, the time-consuming manual definitions of primary, secondary, and PTS also limit the cortical expanse explored in each study, thus, restricting the present study to LPC/LPOJ. “

    Assuming that the labelling of all sulci reported in the article is reproducible, the different results are convincing and in general, this study achieves its aims in defining more precisely the sulcation of the LPOJ and looking into its functional/cognitive value. This work clearly offers a finer understanding of sulcal pattern in this region, and lacks only little for the new markers to be convincingly demonstrated. An overall coherence of the labelling can still be inferred from the supplementary material which support the results and therefore the conclusions, yet, addressing some of the weaknesses listed above would greatly enhance the impact of this work. This work is important to the understanding of sulcal variability and its implications on functional and cognitive aspects.

    We thank the Reviewer for their positive remarks on the implications of this work.

    Reviewer #3 (Public Review):

    Summary: 72 subjects, and 144 hemispheres, from the Human Connectome Project had their parietal sulci manually traced. This identified the presence of previously undescribed shallow sulci. One of these sulci, the ventral supralateral occipital sulcus (slocs-v), was then demonstrated to have functional specificity in spatial orientation. The discussion furthermore provides an eloquent overview of our understanding of the anatomy of the parietal cortex, situating their new work into the broader field. Finally, this paper stimulates further debate about the relative value of detailed manual anatomy, inherently limited in participant numbers and areas of the brain covered, against fully automated processing that can cover thousands of participants but easily misses the kinds of anatomical details described here.

    Strengths:

    - This is the first paper describing the tertiary sulci of the parietal cortex with this level of detail, identifying novel shallow sulci and mapping them to behaviour and function.

    - It is a very elegantly written paper, situating the current work into the broader field.

    - The combination of detailed anatomy and function and behaviour is superb.

    We thank the Reviewer for their positive remarks on paper and our findings.

    Weaknesses:

    - The numbers of subjects are inherently limited both in number as well as in typically developing young adults.

    We emphasize that the sample size is limited due to the arduous nature of manually defining sulci; however, we provide probabilistic maps with the publication of this work to help expedite this process for future investigators. Further, with improved deep learning algorithms, the sample sizes in future neuroanatomical studies should be enhanced. We discuss these points in the Limitations section of the Discussion (Pages 16-17):

    “The main limitation of our study is that presently, the most accurate methodology to define sulci —especially the small, shallow, and variable PTS—requires researchers to manually trace each structure on the cortical surface reconstructions. This method is limited due to the individual variability of cortical sulcal patterning (Fig. 1, Supplementary Fig. 5), which makes it challenging to identify sulci without extensive experience and practice. However, we anticipate that our probabilistic maps will provide a starting point and hopefully, expedite the identification of these sulci in new participants. This should accelerate the process of subsequent studies confirming the accuracy of our updated schematic of LPC/LOPJ. This manual method is also arduous and time-consuming, which, on the one hand, limits the sample size in terms of number of participants, while on the other, results in thousands of precisely defined sulci. This push-pull relationship reflects a broader conversation in the human brain mapping and cognitive neuroscience fields between a balance of large N studies and “precision imaging” studies in individual participants (Allen et al., 2022; Gratton et al., 2022; Naselaris et al., 2021; Rosenberg & Finn, 2022). Though our sample size is comparable to other studies that produced reliable results relating sulcal morphology to brain function and cognition (e.g., (Cachia et al., 2021; Garrison et al., 2015; Lopez-Persem et al., 2019; Miller et al., 2021; Roell et al., 2021; Voorhies et al., 2021; Weiner, 2019; Willbrand, Parker, et al., 2022; Willbrand, Voorhies, et al., 2022; Yao et al., 2022), ongoing work that uses deep learning algorithms to automatically define sulci should result in much larger sample sizes in future studies (Borne et al., 2020; Lyu et al., 2021). The time-consuming manual definitions of primary, secondary, and PTS also limit the cortical expanse explored in each study, thus restricting the present study to LPC/LPOJ.”

    - While the paper begins by describing four new sulci, only one is explored further in greater detail.

    Due to the increased variability of three of the four newly-classified sulci, we chose to only focus on the slocs-v given that it was present in nearly all hemispheres. In response to other reviewers, we have conducted additional analyses that also describe these new sulci and potential factors related to their incidence (Page 6):

    “Given that sulcal incidence and patterning is also sometimes related to demographic features (Cachia et al., 2021; Leonard et al., 2009; Wei et al., 2017), subsequent GLMs relating the incidence and patterning of the three more variable sulci (slocs-d, pAngs-v, and pAngs-d) to demographic features (age and gender) revealed no associations for any sulcus (ps > .05).”

    In addition, given that sulcal variability is cognitively (e.g., Amiez et al., 2018 Scientific Reports; Cachia et al., 2021 Frontiers in Neuroanatomy; Garrison et al., 2015 Nature Communications; Willbrand et al., 2022, 2023 Brain Structure & Function), anatomically (e.g., Amiez et al., 2021 Communications Biology; Vogt et al., 1995 Journal of Comparative Neurology), functionally (e.g., Lopez Persem et al., 2019 The Journal of Neuroscience), and translationally (e.g., Yucel et al., 2002 Biological Psychiatry) relevant, future research can investigate these relationships regarding the slocs-d and pAngs components. We have added text to the Limitations section of the Discussion (Pages 17-18) to discuss this:

    “Finally, although we did not focus on the relationship between the other three PTS (slocs-d, pAngs-v, and pAngs-d) to anatomical and functional features of LPC and cognition, given that variability in sulcal incidence is cognitively (Amiez et al., 2018; Cachia et al., 2021; Garrison et al., 2015; Willbrand, Jackson, et al., 2023; Willbrand, Voorhies, et al., 2022), anatomically (Amiez et al., 2021; Vogt et al., 1995), functionally (Lopez-Persem et al., 2019), and translationally (Clark et al., 2010; Le Provost et al., 2003; Meredith et al., 2012; Nakamura et al., 2020; Yücel et al., 2002, 2003) relevant, future work can also examine the relationship between the more variable slocs-d, pAngs-v, and pAngs-d and these features.”

    - There is some tension between calling the discovered sulci new vs acknowledging they have already been reported, but not named.

    We have edited the manuscript throughout to emphasize our primary focus on revising the LPC/LOPJ sulcal landscape to include these often overlooked small, shallow, and variable putative tertiary sulci, rather than using the terms “discovered sulci” and “new.”

    - The anatomy of the sulci, as opposed to their relation to other sulci, could be described in greater detail.

    Beyond the radar plots in the main text which compare specific groupings of sulci, we now show the morphological metrics for all sulci investigated in the present work in Supplemental Figure 7.

    Overall, to summarize, I greatly enjoyed this paper and believe it to be a highly valued contribution to the field.

    We are glad the Reviewer enjoyed reading our paper and thank them for their positive thoughts on the potential impact of this work on the field.

    Recommendations for the authors:

    Reviewer #1 (Recommendations For The Authors):

    (1) The slocs-v is found in 71 subjects left and right. Is that the same subject?

    No, these are different subjects.

    (2) How were the 72 subjects chosen?

    The subjects were randomly selected from the HCP database as describe in the methods (Page 18):

    “Here, we used 72 randomly-selected participants, balanced for gender (following the terminology of the HCP data dictionary), from the HCP database (50% female, 22-36 years old, and 90% right-handed; there was no effect of handedness on our behavioral tasks; Supplementary materials) that were also analyzed in several prior studies (Hathaway et al., 2023; Miller et al., 2021, 2020; Willbrand et al., 2023b, 2023c, 2022a).”

    (3) Are there effects of laterality on sulcal pattern? Table?

    We now include sulcal pattern results in the Results section and Supplementary Materials; although there were no laterality effects regarding the sulcal pattern .

    (4) Depiction/description of common sulcal patterns

    We now include sulcal pattern results in the Results section and Supplementary Materials.

    (5) Is there a relationship between sulcal patterns and demographic features?

    We now include analyses on this in the Results section. There is no relationship between sulcal patterns and demographic features.

    (6) Just for clarity, the sulcal features are studied and extracted in native space?

    Yes, sulcal features are studied and extracted in native space, as described in the Methods section (Page 19):

    “Anatomical T1-weighted (T1-w) MRI scans (0.8 mm voxel resolution) were obtained in native space from the HCP database. Reconstructions of the cortical surfaces of each participant were generated using FreeSurfer (v6.0.0), a software package used for processing and analyzing human brain MRI images (surfer.nmr.mgh.harvard.edu) (Dale et al., 1999; Fischl et al., 1999). All subsequent sulcal labeling and extraction of anatomical metrics were calculated from these native space reconstructions generated through the HCP’s version of the FreeSurfer pipeline (Glasser et al., 2013).”

    (7) The authors use "Gender". Are they referring to biological sex (female/male) or socially defined characteristics (man/woman etc.)?

    The term gender is referred to socially defined characteristics, as used by the HCP data dictionary (Methods page 18):

    “Here, we used 72 randomly-selected participants, balanced for gender (following the terminology of the HCP data dictionary), from the HCP database (50% female, 22-36 years old, and 90% right-handed; there was no effect of handedness on our behavioral tasks; Supplementary materials) that were also analyzed in several prior studies (Hathaway et al., 2023; Miller et al., 2021, 2020; Willbrand et al., 2023b, 2023c, 2022a).”

    (8) Fig 2. Grey is poorly visible compared to green and blue.

    The shade of gray has been edited to be more distinguishable.

    (9) The relationship between behavior and sulcal features is significant but weak.

    We acknowledge that the morphological-behavioral relationship identified in the present study explains a modest amount of variance; however, the more important aspect of the finding is that multiple sulci identified in the model are recently-characterized sulci in LPC/LOPJ identified by our group and others (Petrides, 2019), and thus, the relationship would have been overlooked or lost if these sulci were not identified. We have added text to the Limitations section of the Discussion (Pages 17-18) to emphasize this point:

    “It is also worth noting that the morphological-behavioral relationship identified in the present study explains a modest amount of variance; however, the more important aspect of our findings is that multiple sulci identified in our model-based approach are recently-characterized sulci in LPC/LOPJ identified by our group and others (Petrides, 2019), and thus, the relationship would have been overlooked or lost if these sulci were not identified. “

    (10) The Limitation section could be expanded.

    We have added additional text to flesh out the Limitations section of the Discussion (Pages 17-18):

    “It is also worth noting that the morphological-behavioral relationship identified in the present study explains a modest amount of variance; however, the more important aspect of our findings is that multiple sulci identified in our model-based approach are recently-characterized sulci in LPC/LOPJ identified by our group and others (Petrides, 2019), and thus, the relationship would have been overlooked or lost if these sulci were not identified. Finally, although we did not focus on the relationship between the other three PTS (slocs-d, pAngs-v, and pAngs-d) to anatomical and functional features of LPC and cognition, given that variability in sulcal incidence is cognitively (Amiez et al., 2018; Cachia et al., 2021; Garrison et al., 2015; Willbrand, Jackson, et al., 2023; Willbrand, Voorhies, et al., 2022), anatomically (Amiez et al., 2021; Vogt et al., 1995), functionally (Lopez-Persem et al., 2019), and translationally (Clark et al., 2010; Le Provost et al., 2003; Meredith et al., 2012; Nakamura et al., 2020; Yücel et al., 2002, 2003) relevant, future work can also examine the relationship between the more variable slocs-d, pAngs-v, and pAngs-d and these features. “

    Reviewer #2 (Recommendations For The Authors):

    First, I would like to thank the authors for their important contribution to the field of sulcal studies and anatomo-functional correlates. My main comments about the work are treated in the public review, and I will only address details in this section. I have detected a number of typos which are harder to report from a document in which lines are not numbered. Could you please submit a numbered document for the next iteration?

    - p2. "hominoid-specific, shallow indentations, or sulci" - can lead to misunderstanding that sulci are hominoid-specific and shallow

    Sentence has been rewritten:

    “Of all the neuroanatomical features to target, recent work shows that morphological features of the shallower, later developing, hominoid-specific indentations of the cerebral cortex (also known as putative tertiary sulci, PTS) are not only functionally and cognitively meaningful, but also are particularly impacted by multiple brain-related disorders and aging (Amiez et al., 2019, 2018; Ammons et al., 2021; Cachia et al., 2021; Fornito et al., 2004; Garrison et al., 2015; Harper et al., 2022; Hathaway et al., 2023; Lopez-Persem et al., 2019; Miller et al., 2021, 2020; Nakamura et al., 2020; Parker et al., 2023; Voorhies et al., 2021; Weiner, 2019; Willbrand et al., 2023b, 2023c, 2022a, 2022b; Yao et al., 2022).”

    - p2. next sentence (starting with "The combination [...]": not clear that you are addressing tertiary sulci here, maybe introduce the concept beforehand?

    The previous sentence (just above) has been edited to introduce putative tertiary sulci beforehand.

    - p5. error in numbering of sulci relative to Fig1. (5,6,7,8 -> 6,7,8,9)

    Sulcal numbering has been fixed.

    -p5. reference to supp mat -> I would have expected the nomenclature used in Borne et al. 2020 to be discussed alongside with the state of the art. How would you relate F.I.P.r.int.1 and F.I.P.r.int.2 to the sulci you describe?

    We thank the Reviewer for bringing up this relevant literature. The F.I.P.r.int. 1 and 2 are described as rami of the IPS, whereas the slocs and pAngs are independent, small indentations near the IPS, but not part of the complex. Nevertheless, future work should integrate these two schematics together to establish the most comprehensive sulcal map of LPC/LOPJ. We have added text to the Supplementary Methods detailing the differences between the F.I.P.r.int.1 and F.I.P.r.int.2 and slocs-/pAngs:

    “slocs/pAng vs. F.I.P.r.int.1 and F.I.P.r.int.2

    Recent work (Borne et al., 2020; Perrot et al., 2011) identified two intermediate rami of the IPS (F.I.P.r.int.1 and F.I.P.r.int.2) that were not defined in the present investigation. Crucially, the newly classified sulci here (slocs and pAngs) are distinguishable from the two F.I.P.r.int. in that the F.I.P.r.int. are branches coming off the main body of the IPS (Borne et al., 2020; Perrot et al., 2011), whereas the slocs/pAngs are predominantly non-intersecting (“free”) structures that never intersected with the IPS (Supplementary Tables 1-4).”

    - p6. Fig 1.a. labelling discrepancy between line 1 and 2, column 4: the labels 10 and 11 from the inflated hemisphere do not match the labels 10 and 11 in the pial surface. Fig 1.b. swapped label 2 and 3 in the 4th hemisphere

    These aspects of Figure 1 have been edited accordingly.

    - p7. "(iii) the slocs-v was thicker than both the cSTS3 and lTOS" -> the slocs-v showed thicker gray matter?

    The sentence has been adjusted (Page 7):

    “(iii) the slocs-v showed thicker gray matter than both the cSTS3 and lTOS (ps < .001), “

    - p9. Six left hemisphere LPC/LPOJ sulci were related to spatial orientation task performance -> missing

    Fixed (Page 9):

    “Six left hemisphere LPC/LPOJ sulci were related to spatial orientation task performance (Fig. 3a, b). “

    - p14. "Steel and colleagues" -> missing space

    Fixed (Page 14):

    “Furthermore, the slocs-v appears to lie at the junction of scene-perception and place-memory activity (a transition that also consistently co-localizes with the HCP-MMP area PGp) as identified by Steel and colleagues (2021).”

    - p20. Probability maps "we share these maps with the field" -> specify link to data availability

    The link to data availability has been added (Page 21):

    “To aid future studies interested in investigating LPC/LPOJ sulci, we share these maps with the field (Data availability). “

    Reviewer #3 (Recommendations For The Authors):

    No detailed recommendations not already present in the rest of the review.

  8. Version published to 10.1101/2023.06.08.544284v5 on bioRxiv
  9. Version published to 10.7554/elife.90451.1 on eLife
  10. eLife

    eLife assessment

    This is an important study that provides detailed insights into the morphology of the lateral parietal cortex. Through this work new shallow sulci in the parietal cortex were identified and linked to function and behaviour. The evidence presented is convincing, even though some claims about the definition of highly variable sulci should be tampered down, and some important precisions about the labelling process are lacking to secure reproducibility. The present work both advances our understanding of the parietal cortex while also stimulating further debate on precise, detailed manual anatomy vs large scale automated data processing.

  11. eLife

    Reviewer #1 (Public Review):

    Summary:
    Ever-improving techniques allow the detailed capture of brain morphology and function to the point where individual brain anatomy becomes an important factor. This study investigated detailed sulcal morphology in the parieto-occipital junction. Using cutting-edge methods, it provides important insights into local anatomy, individual variability, and local brain function. The presented work advances the field and will stimulate future research into this important area.

    Strengths:
    Detailed, very thorough methodology. Multiple raters mapped detailed sulci in a large cohort. The identified sulcal features and their functional and behavioural relevance are then studied using various complementary methods. The results provide compelling evidence for the importance of the described sulcal features and their proposed relationship to cortical brain function.

    Weaknesses:
    A detailed description/depiction of the various sulcal patterns is missing. A possible relationship between sucal morphology and individual demographics might provide more insight into anatomical variability. The unique dataset offers to opportunity to provide insights into laterality effects that should be explored.

  12. eLife

    Reviewer #2 (Public Review):

    Summary: After manually labelling 144 human adult hemispheres in the lateral parieto-occipital junction (LPOJ), the authors 1) propose a nomenclature for 4 previously unnamed highly variable sulci located between the temporal and parietal or occipital lobes, 2) focus on one of these newly named sulci, namely the ventral supralateral occipital sulcus (slocs-v) and compare it to neighbouring sulci to demonstrate its specificity (in terms of depth, surface area, gray matter thickness, myelination, and connectivity), 3) relate the morphology of a subgroup of sulci from the region including the slocs-v to the performance in a spatial orientation task, demonstrating behavioural and morphological specificity. In addition to these results, the authors propose an extended reflection on the relationship between these newly named landmarks and previous anatomical studies, a reflection about the slocs-v related to functional and cytoarchitectonic parcellations as well as anatomic connectivity and an insight about potential anatomical mechanisms relating sulcation and behaviour.

    Strengths:
    - To my knowledge, this is the first study addressing the variable tertiary sulci located between the superior temporal sulcus (STS) and intra-parietal sulcus (IPS).
    - This is a very comprehensive study addressing altogether anatomical, architectural, functional and cognitive aspects.
    - The definition of highly variable yet highly reproducible sulci such as the slocs-v feeds the community with new anatomo-functional landmarks (which is emphasized by the provision of a probability map in supp. mat., which in my opinion should be proposed in the main body).
    - The comparison of different features between the slocs-v and similar sulci is useful to demonstrate their difference.
    - The detailed comparison of the present study with state of the art contextualises and strengthens the novel findings.
    - The functional study complements the anatomical description and points towards cognitive specificity related to a subset of sulci from the LPOJ
    - The discussion offers a proposition of theoretical interpretation of the findings
    - The data and code are mostly available online (raw data made available upon request).

    Weaknesses:
    - While three independent raters labelled all hemispheres, one single expert finalized the decision. Because no information is reported on the inter-rater variability, this somehow equates to a single expert labelling the whole cohort, which could result in biased labellings and therefore affect the reproducibility of the new labels.
    - 3 out of the 4 newly labelled sulci are only described in the very first part and never reused. This should be emphasized as it is far from obvious at first glance of the article.
    - The tone of the article suggests a discovery of these 4 sulci when some of them have already been reported (as rightfully highlighted in the article), though not named nor studied specifically. This is slightly misleading as I interpret the first part of the article as a proposition of nomenclature rather than a discovery of sulci.
    - The article never mentions the concept of merging of sulcal elements and the potential effect it could have on the labelling of the newly named variable sulci.
    - The definition of the new sulci is solely based on their localization relative to other sulci which are themselves variable (e.g. the 3rd branch of the STS can show different locations and different orientation, potentially affecting the definition of the slocs-v). This is not addressed in the discussion.
    - The new sulci are only defined in terms of localization relative to other sulci, and no other property is described (general length, depth, orientation, shape...), making it hard for a new observer to take labelling decisions in case of conflict.
    - The very assertive tone of the article conveys the idea that these sulci are identifiable certainly in most cases, when by definition these highly variable tertiary sulci are sometimes very difficult to take decisions on.
    - I am not absolutely convinced with the labelling proposed of a previously reported sulcus, namely the posterior intermediate parietal sulcus.

    Assuming that the labelling of all sulci reported in the article is reproducible, the different results are convincing and in general, this study achieves its aims in defining more precisely the sulcation of the LPOJ and looking into its functional/cognitive value. This work clearly offers a finer understanding of sulcal pattern in this region, and lacks only little for the new markers to be convincingly demonstrated. An overall coherence of the labelling can still be inferred from the supplementary material which support the results and therefore the conclusions, yet, addressing some of the weaknesses listed above would greatly enhance the impact of this work. This work is important to the understanding of sulcal variability and its implications on functional and cognitive aspects.

  13. eLife

    Reviewer #3 (Public Review):

    Summary: 72 subjects, and 144 hemispheres, from the Human Connectome Project had their parietal sulci manually traced. This identified the presence of previously undescribed shallow sulci. One of these sulci, the ventral supralateral occipital sulcus (slocs-v), was then demonstrated to have functional specificity in spatial orientation. The discussion furthermore provides an eloquent overview of our understanding of the anatomy of the parietal cortex, situating their new work into the broader field. Finally, this paper stimulates further debate about the relative value of detailed manual anatomy, inherently limited in participant numbers and areas of the brain covered, against fully automated processing that can cover thousands of participants but easily misses the kinds of anatomical details described here.

    Strengths:
    - This is the first paper describing the tertiary sulci of the parietal cortex with this level of detail, identifying novel shallow sulci and mapping them to behaviour and function.
    - It is a very elegantly written paper, situating the current work into the broader field.
    - The combination of detailed anatomy and function and behaviour is superb.

    Weaknesses:
    - the numbers of subjects are inherently limited both in number as well as in being typically developing young adults.
    - while the paper begins by describing four new sulci, only one is explored further in greater detail.
    - there is some tension between calling the discovered sulci new vs acknowledging they have already been reported, but not named.
    - the anatomy of the sulci, as opposed to their relation to other sulci, could be described in greater detail.

    Overall, to summarize, I greatly enjoyed this paper and believe it to be a highly valued contribution to the field.

  14. Version published to 10.1101/2023.06.08.544284v4 on bioRxiv
  15. Version published to 10.1101/2023.06.08.544284v2 on bioRxiv
  16. Version published to 10.1101/2023.06.08.544284v3 on bioRxiv
  17. Version published to 10.1101/2023.06.08.544284v1 on bioRxiv