MRI signatures of cortical microstructure in human development align with oligodendrocyte cell-type expression

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Abstract Neuroanatomical changes to the cortex during adolescence have been well documented using MRI, revealing ongoing cortical thinning and volume loss with age. However, the underlying cellular mechanisms remain elusive with conventional neuroimaging. Recent advances in MRI hardware and new biophysical models of tissue informed by diffusion MRI data hold promise for identifying the cellular changes driving these morphological observations. This study used ultra-strong gradient MRI to obtain high-resolution, in vivo estimates of cortical neurite and soma microstructure in sample of typically developing children and adolescents. Cortical neurite signal fraction, attributed to neuronal and glial processes, increased with age (mean R2fneurite=.53, p<3.3e-11, 11.91% increase over age), while apparent soma radius decreased (mean R2Rsoma=.48, p<4.4e-10, 1% decrease over age) across domain-specific networks. To complement these findings, developmental patterns of cortical gene expression in two independent post-mortem databases were analysed. This revealed increased expression of genes expressed in oligodendrocytes, and excitatory neurons, alongside a relative decrease in expression of genes expressed in astrocyte, microglia and endothelial cell-types. Age-related genes were significantly enriched in cortical oligodendrocytes, oligodendrocyte progenitors and Layer 5-6 neurons (pFDR<.001) and prominently expressed in adolescence and young adulthood. The spatial and temporal alignment of oligodendrocyte cell-type gene expression with neurite and soma microstructural changes suggest that ongoing cortical myelination processes contribute to adolescent cortical development. These findings highlight the role of intra-cortical myelination in cortical maturation during adolescence and into adulthood.
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MRI signatures of cortical microstructure in human development align with oligodendrocyte cell-type expression | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article MRI signatures of cortical microstructure in human development align with oligodendrocyte cell-type expression Sila Genc, Gareth Ball, Maxime Chamberland, Erika Raven, Chantal Tax, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4883534/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 07 Apr, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Neuroanatomical changes to the cortex during adolescence have been well documented using MRI, revealing ongoing cortical thinning and volume loss with age. However, the underlying cellular mechanisms remain elusive with conventional neuroimaging. Recent advances in MRI hardware and new biophysical models of tissue informed by diffusion MRI data hold promise for identifying the cellular changes driving these morphological observations. This study used ultra-strong gradient MRI to obtain high-resolution, in vivo estimates of cortical neurite and soma microstructure in sample of typically developing children and adolescents. Cortical neurite signal fraction, attributed to neuronal and glial processes, increased with age (mean R 2 f neurite =.53, p<3.3e-11, 11.91% increase over age), while apparent soma radius decreased (mean R 2 R soma =.48, p<4.4e-10, 1% decrease over age) across domain-specific networks. To complement these findings, developmental patterns of cortical gene expression in two independent post-mortem databases were analysed. This revealed increased expression of genes expressed in oligodendrocytes, and excitatory neurons, alongside a relative decrease in expression of genes expressed in astrocyte, microglia and endothelial cell-types. Age-related genes were significantly enriched in cortical oligodendrocytes, oligodendrocyte progenitors and Layer 5-6 neurons (p FDR <.001) and prominently expressed in adolescence and young adulthood. The spatial and temporal alignment of oligodendrocyte cell-type gene expression with neurite and soma microstructural changes suggest that ongoing cortical myelination processes contribute to adolescent cortical development. These findings highlight the role of intra-cortical myelination in cortical maturation during adolescence and into adulthood. Biological sciences/Neuroscience/Computational neuroscience/Biophysical models Biological sciences/Computational biology and bioinformatics/Image processing Biological sciences/Neuroscience/Development of the nervous system Full Text Additional Declarations There is NO Competing Interest. Supplementary Files GencSANDINatCommssupplementary.pdf Cite Share Download PDF Status: Published Journal Publication published 07 Apr, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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