1. Neuroscience

Heritability and cross-species comparisons of human cortical functional organization asymmetry

  1. Bin Wan  Is a corresponding author
  2. Şeyma Bayrak
  3. Ting Ting Xu
  4. H Lina Schaare
  5. Richard AI Bethlehem
  6. Boris C Bernhardt
  7. Sofie Louise Valk  Is a corresponding author
  1. Max Planck Institute for Human Cognitive and Brain Sciences, Germany
  2. Child Mind Institute, United States
  3. University of Cambridge, United Kingdom
  4. McGill University, Canada
https://doi.org/10.7554/eLife.77215
Share this article
Cite this article
  1. Bin Wan
  2. Şeyma Bayrak
  3. Ting Ting Xu
  4. H Lina Schaare
  5. Richard AI Bethlehem
  6. Boris C Bernhardt
  7. Sofie Louise Valk
(2022)
Heritability and cross-species comparisons of human cortical functional organization asymmetry
eLife 11:e77215.
https://doi.org/10.7554/eLife.77215
  2. Download BibTeX
  3. Download .RIS

Abstract

The human cerebral cortex is symmetrically organized along large-scale axes but also presents inter-hemispheric differences in structure and function. The quantified contralateral homologous difference, i.e., asymmetry, is a key feature of the human brain left-right axis supporting functional processes, such as language. Here, we assessed whether the asymmetry of cortical functional organization is heritable and phylogenetically conserved between humans and macaques. Our findings indicate asymmetric organization along an axis describing a functional trajectory from perceptual/action to abstract cognition. Whereas language network showed leftward asymmetric organization, frontoparietal network showed rightward asymmetric organization in humans. These asymmetries were heritable in humans and showed a similar spatial distribution with macaques, in the case of intra-hemispheric asymmetry of functional hierarchy. This suggests (phylo)genetic conservation. However, both language and frontoparietal networks showed a qualitatively larger asymmetry in humans relative to macaques. Overall, our findings suggest a genetic basis for asymmetry in intrinsic functional organization, linked to higher-order cognitive functions uniquely developed in humans.

Data availability

All human data analyzed in this manuscript were obtained from the open-access HCP youngadult sample (HCP; www.humanconnectome.org/), UK Biobank (UKB,https://www.ukbiobank.ac.uk/). Macaque data came from PRIME-DE(http://fcon_1000.projects.nitrc.org/indi/indiPRIME.html). Full statistical scripts can be found at https://bit.ly/3sAJ1bP.

The following previously published data sets were used

Article and author information

Author details

  1. Bin Wan

    Otto Hahn Group Cognitive Neurogenetics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
    For correspondence
    wanb.psych@outlook.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9077-3354

  2. Şeyma Bayrak

    Otto Hahn Group Cognitive Neurogenetics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
    Competing interests
    The authors declare that no competing interests exist.

  3. Ting Ting Xu

    Center for the Developing Brain, Child Mind Institute, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. H Lina Schaare

    Otto Hahn Group Cognitive Neurogenetics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
    Competing interests
    The authors declare that no competing interests exist.

  5. Richard AI Bethlehem

    Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0714-0685

  6. Boris C Bernhardt

    McConnell Brain Imaging Centre, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9256-6041

  7. Sofie Louise Valk

    Otto Hahn Group Cognitive Neurogenetics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
    For correspondence
    valk@cbs.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2998-6849

Funding

Max Planck Gesellschaft

  • Sofie Louise Valk

Sick Kids Foundation (NI17-039)

  • Boris C Bernhardt

National Sciences and Engineering Research Council of Canada (Discovery-1304413)

  • Boris C Bernhardt

Canadian Institute of Health Research (FDN154298)

  • Boris C Bernhardt

Azrieli Center for Autism Research

  • Boris C Bernhardt

Canada First Research Excellence Fund

  • Boris C Bernhardt
  • Sofie Louise Valk

International Max Planck Research School on Neuroscience of Communication: Function, Structure, and Plasticity

  • Bin Wan

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The current research complies with all relevant ethical regulations as set by The Independent Research Ethics Committee at the Medical Faculty of the Heinrich-Heine-University of Duesseldorf (study number 2018-317).

Copyright

© 2022, Wan et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 3,235
    views
  • 793
    downloads
  • 25
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Bin Wan
  2. Şeyma Bayrak
  3. Ting Ting Xu
  4. H Lina Schaare
  5. Richard AI Bethlehem
  6. Boris C Bernhardt
  7. Sofie Louise Valk
(2022)
Heritability and cross-species comparisons of human cortical functional organization asymmetry
eLife 11:e77215.
https://doi.org/10.7554/eLife.77215

Share this article

https://doi.org/10.7554/eLife.77215

Categories and tags

Research organisms

Further reading

    1. Cell Biology
    2. Neuroscience

    Projection neurons are necessary for the maintenance of the mouse olfactory circuit

    Luis Sánchez-Guardado, Peyman Callejas Razavi ... Carlos Lois
    Research Article

    The assembly and maintenance of neural circuits is crucial for proper brain function. Although the assembly of brain circuits has been extensively studied, much less is understood about the mechanisms controlling their maintenance as animals mature. In the olfactory system, the axons of olfactory sensory neurons (OSNs) expressing the same odor receptor converge into discrete synaptic structures of the olfactory bulb (OB) called glomeruli, forming a stereotypic odor map. The OB projection neurons, called mitral and tufted cells (M/Ts), have a single dendrite that branches into a single glomerulus, where they make synapses with OSNs. We used a genetic method to progressively eliminate the vast majority of M/T cells in early postnatal mice, and observed that the assembly of the OB bulb circuits proceeded normally. However, as the animals became adults the apical dendrite of remaining M/Ts grew multiple branches that innervated several glomeruli, and OSNs expressing single odor receptors projected their axons into multiple glomeruli, disrupting the olfactory sensory map. Moreover, ablating the M/Ts in adult animals also resulted in similar structural changes in the projections of remaining M/Ts and axons from OSNs. Interestingly, the ability of these mice to detect odors was relatively preserved despite only having 1–5% of projection neurons transmitting odorant information to the brain, and having highly disrupted circuits in the OB. These results indicate that a reduced number of projection neurons does not affect the normal assembly of the olfactory circuit, but induces structural instability of the olfactory circuitry of adult animals.

    1. Neuroscience

    Single-cell transcriptomics of vomeronasal neuroepithelium reveals a differential endoplasmic reticulum environment amongst neuronal subtypes

    GVS Devakinandan, Mark Terasaki, Adish Dani
    Research Article

    Specialized chemosensory signals elicit innate social behaviors in individuals of several vertebrate species, a process that is mediated via the accessory olfactory system (AOS). The AOS comprising the peripheral sensory vomeronasal organ has evolved elaborate molecular and cellular mechanisms to detect chemo signals. To gain insight into the cell types, developmental gene expression patterns, and functional differences amongst neurons, we performed single-cell transcriptomics of the mouse vomeronasal sensory epithelium. Our analysis reveals diverse cell types with gene expression patterns specific to each, which we made available as a searchable web resource accessed from https://www.scvnoexplorer.com. Pseudo-time developmental analysis indicates that neurons originating from common progenitors diverge in their gene expression during maturation with transient and persistent transcription factor expression at critical branch points. Comparative analysis across two of the major neuronal subtypes that express divergent GPCR families and the G-protein subunits Gnai2 or Gnao1, reveals significantly higher expression of endoplasmic reticulum (ER) associated genes within Gnao1 neurons. In addition, differences in ER content and prevalence of cubic membrane ER ultrastructure revealed by electron microscopy, indicate fundamental differences in ER function.

    1. Medicine
    2. Neuroscience

    Human birth tissue products as a non-opioid medicine to inhibit post-surgical pain

    Chi Zhang, Qian Huang ... Yun Guan
    Research Article

    Pain after surgery causes significant suffering. Opioid analgesics cause severe side effects and accidental death. Therefore, there is an urgent need to develop non-opioid therapies for managing post-surgical pain. Local application of Clarix Flo (FLO), a human amniotic membrane (AM) product, attenuated established post-surgical pain hypersensitivity without exhibiting known side effects of opioid use in mice. This effect was achieved through direct inhibition of nociceptive dorsal root ganglion (DRG) neurons via CD44-dependent pathways. We further purified the major matrix component, the heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) from human AM that has greater purity and water solubility than FLO. HC-HA/PTX3 replicated FLO-induced neuronal and pain inhibition. Mechanistically, HC-HA/PTX3-induced cytoskeleton rearrangements to inhibit sodium current and high-voltage activated calcium current on nociceptive DRG neurons, suggesting it is a key bioactive component mediating pain relief. Collectively, our findings highlight the potential of naturally derived biologics from human birth tissues as an effective non-opioid treatment for post-surgical pain. Moreover, we unravel the underlying neuronal mechanisms of pain inhibition induced by FLO and HC-HA/PTX3.