An expanding manifold in transmodal regions characterizes adolescent reconfiguration of structural connectome organization
- Inha University, Republic of Korea
- University of Cambridge, United Kingdom
- McGill University, Canada
Abstract
Adolescence is a critical time for the continued maturation of brain networks. Here, we assessed structural connectome development in a large longitudinal sample ranging from childhood to young adulthood. By projecting high-dimensional connectomes into compact manifold spaces, we identified a marked expansion of structural connectomes with the strongest effects in transmodal regions during adolescence. Findings reflected increased within-module connectivity together with increased segregation, indicating increasing differentiation of higher-order association networks from the rest of the brain. Projection of subcortico-cortical connectivity patterns into these manifolds showed parallel alterations in pathways centered on the caudate and thalamus. Connectome findings were contextualized via spatial transcriptome association analysis, highlighting genes enriched in cortex, thalamus, and striatum. Statistical learning of cortical and subcortical manifold features at baseline and their maturational change predicted measures of intelligence at follow-up. Our findings demonstrate that connectome manifold learning can bridge the conceptual and empirical gaps between macroscale network reconfigurations, microscale processes, and cognitive outcomes in adolescent development.
Data availability
The imaging and phenotypic data were provided by the Neuroscience in Psychiatry Network (NSPN) 2400 cohort. As stated in https://doi.org/10.1093/ije/dyx117, the NSPN project is committed to make the anonymised dataset fully available to the research community, and participants have consented to their de-identified data being made available to other researchers. A data request can be made to openNSPN@medschl.cam.ac.uk. Codes for connectome manifold generation are available at https://github.com/MICA-MNI/BrainSpace and those for calculating manifold eccentricity and subcortical-weighted manifold, as well as performing linear mixed effect modeling to assess age-effects on these features at https://github.com/MICA-MNI/micaopen/tree/master/manifold_features.
Article and author information
Author details
Richard AI Bethlehem
Funding
Canada Research Chairs
- Boris C Bernhardt
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.The Neuroscience and Psychiatry Network (NSPN) study was funded by a Wellcome Trust award to the University of Cambridge and University College London. The data were curated and analyzed using a computational facility funded by an MRC research infra-structure award (MR/M009041/1) and supported by the NIHR Cambridge Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.
Ethics
Human subjects: Participants provided informed written consent for each aspect of the study, and parental consent was obtained for those aged 14-15 y old. Ethical approval was granted for this study by the NHS NRES Committee East of England-Cambridge Central (project ID 97546). The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.
Copyright
© 2021, Park 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
-
- 2,686
- views
-
- 371
- downloads
-
- 56
- 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)
An expanding manifold in transmodal regions characterizes adolescent reconfiguration of structural connectome organization
eLife 10:e64694.
https://doi.org/10.7554/eLife.64694
Further reading
-
- Neuroscience
γ-Secretase plays a pivotal role in the central nervous system. Our recent development of genetically encoded Förster resonance energy transfer (FRET)-based biosensors has enabled the spatiotemporal recording of γ-secretase activity on a cell-by-cell basis in live neurons in culture. Nevertheless, how γ-secretase activity is regulated in vivo remains unclear. Here, we employ the near-infrared (NIR) C99 720–670 biosensor and NIR confocal microscopy to quantitatively record γ-secretase activity in individual neurons in living mouse brains. Intriguingly, we uncovered that γ-secretase activity may influence the activity of γ-secretase in neighboring neurons, suggesting a potential ‘cell non-autonomous’ regulation of γ-secretase in mouse brains. Given that γ-secretase plays critical roles in important biological events and various diseases, our new assay in vivo would become a new platform that enables dissecting the essential roles of γ-secretase in normal health and diseases.
-
- Neuroscience
The neurotransmitter dopamine helps form long-term memories by increasing the production of proteins through a unique signaling pathway.
