Tracing the development and lifespan change of population-level structural asymmetry in the cerebral cortex
- University of Oslo, Norway
- University of Bordeaux, France
- Research Centre Jülich, Germany
- Max Planck Institute for Psycholinguistics, Netherlands
Abstract
Cortical asymmetry is a ubiquitous feature of brain organization that is subtly altered in some neurodevelopmental disorders, yet we lack knowledge of how its development proceeds across life in health. Achieving consensus on the precise cortical asymmetries in humans is necessary to uncover the developmental timing of asymmetry and extent to which it arises through genetic and later influences in childhood. Here, we delineate population-level asymmetry in cortical thickness and surface area vertex-wise in 7 datasets and chart asymmetry trajectories longitudinally across life (4-89 years; observations = 3937; 70% longitudinal). We find replicable asymmetry interrelationships, heritability maps, and test asymmetry associations in large-scale data. Cortical asymmetry was robust across datasets. Whereas areal asymmetry is predominantly stable across life, thickness asymmetry grows in childhood and peaks in early adulthood. Areal asymmetry is low-moderately heritable (max h2SNP ~19%) and correlates phenotypically and genetically in specific regions, indicating coordinated development of asymmetries partly through genes. In contrast, thickness asymmetry is globally interrelated across the cortex in a pattern suggesting highly left-lateralized individuals tend towards left-lateralization also in population-level right-asymmetric regions (and vice versa), and exhibits low or absent heritability. We find less areal asymmetry in the most consistently lateralized region in humans associates with subtly lower cognitive ability, and confirm small handedness and sex effects. Results suggest areal asymmetry is developmentally stable and arises early in life through genetic but mainly subject-specific stochastic effects, whereas childhood developmental growth shapes thickness asymmetry and may lead to directional variability of global thickness lateralization in the population.
Data availability
All summary-level maps are available in Supplementary file 2. All code underlying the main analyses is available at https://github.com/jamesmroe/PopAsym and on the Open Science Framework (OSF; https://osf.io/dv9um/). Derived source data underlying figures is also available on the OSF. All datasets used in this work are openly available, with the exception of LCBC where participants, which include many children, have not consented to share their data publicly online. Other datasets used in this work are available without restrictions and are not subject to application approval (DLBS; https://fcon_1000.projects.nitrc.org/indi/retro/dlbs.html; CC BY-NC; SALD; http://fcon_1000.projects.nitrc.org/indi/retro/sald.html; CC BY-NC; IXI; https://brain-development.org/ixi-dataset; CC BY-SA 3.0). Accordingly, we have made the individual-level data for these samples available and our code can be used to reproduce vertex-wise analyses in these samples. Individual-level data for the remaining samples (LCBC; Cam-CAN, HCP; UKB) may be available upon reasonable request, given appropriate ethical, data protection, and data-sharing agreements where applicable. Requests must be submitted and approved via the relevant channel (details are provided in Supplementary File 1).
Article and author information
Author details
Didac Vidal-Pineiro
Michel Thiebaut de Schotten
Kristine B Walhovd
Funding
European Research Council (283634)
- Anders M Fjell
European Research Council (725025)
- Anders M Fjell
European Research Council (313440)
- Kristine B Walhovd
Norwegian Research Council (249931)
- Anders M Fjell
Norwegian Research Council (249931)
- Kristine B Walhovd
Norwegian Research Council (302854)
- Yunpeng Wang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: All studies were conducted in accordance with the Declaration of Helsinki. Ethical approval was obtained from the relevant authorities, and all participants provided informed consent. Studies conducted at the Center for Lifespan Changes in Brain and Cognition (LCBC) were approved by the Regional Ethical Committee of South-East Norway (2017/653) and complied with all relevant ethical regulations. Ethical approval for the other datasets was granted by the relevant authorities (Supplementary File 1M).
Copyright
© 2023, Roe 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
-
- 1,352
- views
-
- 194
- downloads
-
- 17
- 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)
Tracing the development and lifespan change of population-level structural asymmetry in the cerebral cortex
eLife 12:e84685.
https://doi.org/10.7554/eLife.84685
Further reading
-
- Neuroscience
Cerebellar dysfunction leads to postural instability. Recent work in freely moving rodents has transformed investigations of cerebellar contributions to posture. However, the combined complexity of terrestrial locomotion and the rodent cerebellum motivate new approaches to perturb cerebellar function in simpler vertebrates. Here, we adapted a validated chemogenetic tool (TRPV1/capsaicin) to describe the role of Purkinje cells — the output neurons of the cerebellar cortex — as larval zebrafish swam freely in depth. We achieved both bidirectional control (activation and ablation) of Purkinje cells while performing quantitative high-throughput assessment of posture and locomotion. Activation modified postural control in the pitch (nose-up/nose-down) axis. Similarly, ablations disrupted pitch-axis posture and fin-body coordination responsible for climbs. Postural disruption was more widespread in older larvae, offering a window into emergent roles for the developing cerebellum in the control of posture. Finally, we found that activity in Purkinje cells could individually and collectively encode tilt direction, a key feature of postural control neurons. Our findings delineate an expected role for the cerebellum in postural control and vestibular sensation in larval zebrafish, establishing the validity of TRPV1/capsaicin-mediated perturbations in a simple, genetically tractable vertebrate. Moreover, by comparing the contributions of Purkinje cell ablations to posture in time, we uncover signatures of emerging cerebellar control of posture across early development. This work takes a major step towards understanding an ancestral role of the cerebellum in regulating postural maturation.
-
- Neuroscience
When holding visual information temporarily in working memory (WM), the neural representation of the memorandum is distributed across various cortical regions, including visual and frontal cortices. However, the role of stimulus representation in visual and frontal cortices during WM has been controversial. Here, we tested the hypothesis that stimulus representation persists in the frontal cortex to facilitate flexible control demands in WM. During functional MRI, participants flexibly switched between simple WM maintenance of visual stimulus or more complex rule-based categorization of maintained stimulus on a trial-by-trial basis. Our results demonstrated enhanced stimulus representation in the frontal cortex that tracked demands for active WM control and enhanced stimulus representation in the visual cortex that tracked demands for precise WM maintenance. This differential frontal stimulus representation traded off with the newly-generated category representation with varying control demands. Simulation using multi-module recurrent neural networks replicated human neural patterns when stimulus information was preserved for network readout. Altogether, these findings help reconcile the long-standing debate in WM research, and provide empirical and computational evidence that flexible stimulus representation in the frontal cortex during WM serves as a potential neural coding scheme to accommodate the ever-changing environment.
