The individuality of shape asymmetries of the human cerebral cortex

  1. Yu-Chi Chen  Is a corresponding author
  2. Aurina Arnatkevičiūtė
  3. Eugene McTavish
  4. James C Pang
  5. Sidhant Chopra
  6. Chao Suo
  7. Alex Fornito
  8. Kevin M Aquino
  9. for the Alzheimer's Disease Neuroimaging Initiative
  1. Monash University, Australia
  2. Yale University, United States
  3. University of Sydney, Australia

Abstract

Asymmetries of the cerebral cortex are found across diverse phyla and are particularly pronounced in humans, with important implications for brain function and disease. However, many prior studies have confounded asymmetries due to size with those due to shape. Here, we introduce a novel approach to characterize asymmetries of the whole cortical shape, independent of size, across different spatial frequencies using magnetic resonance imaging data in three independent datasets. We find that cortical shape asymmetry is highly individualized and robust, akin to a cortical fingerprint, and identifies individuals more accurately than size-based descriptors, such as cortical thickness and surface area, or measures of inter-regional functional coupling of brain activity. Individual identifiability is optimal at coarse spatial scales (~37 mm wavelength), and shape asymmetries show scale-specific associations with sex and cognition, but not handedness. While unihemispheric cortical shape shows significant heritability at coarse scales (~65 mm wavelength), shape asymmetries are determined primarily by subject-specific environmental effects. Thus, coarse-scale shape asymmetries are highly personalized, sexually dimorphic, linked to individual differences in cognition, and are primarily driven by stochastic environmental influences.

Data availability

All data generated or analysed during this study are included in the manuscript. All code and dependent toolboxes used in this study can be found at: https://github.com/cyctbdbw/Shape-Asymmetry-Signature. The code of shape-DNA can be found at: http://reuter.mit.edu/software/shapedna/. The OASIS-3 dataset is available under https://www.oasis-brains.org/. The ADNI dataset is available under https://adni.loni.usc.edu. The HCP dataset is available under https://db.humanconnectome.org/.

The following previously published data sets were used

Article and author information

Author details

  1. Yu-Chi Chen

    Turner Institute for Brain and Mental Health, Monash University, Clayton, Australia
    For correspondence
    yu-chi.chen@monash.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9167-6417
  2. Aurina Arnatkevičiūtė

    Turner Institute for Brain and Mental Health, Monash University, Clayton, Australia
    Competing interests
    No competing interests declared.
  3. Eugene McTavish

    Turner Institute for Brain and Mental Health, Monash University, Clayton, Australia
    Competing interests
    No competing interests declared.
  4. James C Pang

    Turner Institute for Brain and Mental Health, Monash University, Clayton, Australia
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2461-2760
  5. Sidhant Chopra

    Department of Psychology, Yale University, New Haven, United States
    Competing interests
    No competing interests declared.
  6. Chao Suo

    Turner Institute for Brain and Mental Health, Monash University, Clayton, Australia
    Competing interests
    No competing interests declared.
  7. Alex Fornito

    Turner Institute for Brain and Mental Health, Monash University, Clayton, Australia
    Competing interests
    Alex Fornito, Reviewing editor, eLife.
  8. Kevin M Aquino

    Center of Excellence for Integrative Brain Function, University of Sydney, Sydney, Australia
    Competing interests
    Kevin M Aquino, is a scientific advisor and shareholder in BrainKey Inc., a medical image analysis software company..

Funding

Sylvia and Charles Viertel Charitable Foundation (Senior Medical Research Fellowship)

  • Alex Fornito

National Health and Medical Research Council (1197431)

  • Alex Fornito

National Health and Medical Research Council (1146292)

  • Alex Fornito

Australian Research Council (DP200103509)

  • Alex Fornito

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

Ethics

Human subjects: This study only involved subjects from the open-sourced datasets, and all subjects were de-identified by the datasets. Each dataset was approved by its relevant ethics committee and obtained written informed consent from each participant.

Copyright

© 2022, Chen 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

  • 1,668
    views
  • 361
    downloads
  • 22
    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. Yu-Chi Chen
  2. Aurina Arnatkevičiūtė
  3. Eugene McTavish
  4. James C Pang
  5. Sidhant Chopra
  6. Chao Suo
  7. Alex Fornito
  8. Kevin M Aquino
  9. for the Alzheimer's Disease Neuroimaging Initiative
(2022)
The individuality of shape asymmetries of the human cerebral cortex
eLife 11:e75056.
https://doi.org/10.7554/eLife.75056

Share this article

https://doi.org/10.7554/eLife.75056

Further reading

    1. Neuroscience
    Hans Auer, Donna Gift Cabalo ... Jessica Royer
    Research Article

    The amygdala is a subcortical region in the mesiotemporal lobe that plays a key role in emotional and sensory functions. Conventional neuroimaging experiments treat this structure as a single, uniform entity, but there is ample histological evidence for subregional heterogeneity in microstructure and function. The current study characterized subregional structure-function coupling in the human amygdala, integrating post-mortem histology and in vivo MRI at ultra-high fields. Core to our work was a novel neuroinformatics approach that leveraged multiscale texture analysis as well as non-linear dimensionality reduction techniques to identify salient dimensions of microstructural variation in a 3D post-mortem histological reconstruction of the human amygdala. We observed two axes of subregional variation in this region, describing inferior-superior as well as mediolateral trends in microstructural differentiation that in part recapitulated established atlases of amygdala subnuclei. Translating our approach to in vivo MRI data acquired at 7 Tesla, we could demonstrate the generalizability of these spatial trends across 10 healthy adults. We then cross-referenced microstructural axes with functional blood-oxygen-level dependent (BOLD) signal analysis obtained during task-free conditions, and revealed a close association of structural axes with macroscale functional network embedding, notably the temporo-limbic, default mode, and sensory-motor networks. Our novel multiscale approach consolidates descriptions of amygdala anatomy and function obtained from histological and in vivo imaging techniques.

    1. Neuroscience
    Andrea Brenna, Micaela Borsa ... Urs Albrecht
    Research Article

    The circadian clock enables organisms to synchronize biochemical and physiological processes over a 24 hr period. Natural changes in lighting conditions, as well as artificial disruptions like jet lag or shift work, can advance or delay the clock phase to align physiology with the environment. Within the suprachiasmatic nucleus (SCN) of the hypothalamus, circadian timekeeping and resetting rely on both membrane depolarization and intracellular second-messenger signaling. Voltage-gated calcium channels (VGCCs) facilitate calcium influx in both processes, activating intracellular signaling pathways that trigger Period (Per) gene expression. However, the precise mechanism by which these processes are concertedly gated remains unknown. Our study in mice demonstrates that cyclin-dependent kinase 5 (Cdk5) activity is modulated by light and regulates phase shifts of the circadian clock. We observed that knocking down Cdk5 in the SCN of mice affects phase delays but not phase advances. This is linked to uncontrolled calcium influx into SCN neurons and an unregulated protein kinase A (PKA)-calcium/calmodulin-dependent kinase (CaMK)-cAMP response element-binding protein (CREB) signaling pathway. Consequently, genes such as Per1 are not induced by light in the SCN of Cdk5 knock-down mice. Our experiments identified Cdk5 as a crucial light-modulated kinase that influences rapid clock phase adaptation. This finding elucidates how light responsiveness and clock phase coordination adapt activity onset to seasonal changes, jet lag, and shift work.