Heterogeneity of White Matter Structure in the Human Brain

Heterogeneity of White Matter Structure in the Human Brain | 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 Biological Sciences - Article Heterogeneity of White Matter Structure in the Human Brain R. Clay Reid, Emily Turschak, Wan-Qing Yu, Kevin Takasaki, Steven Cook, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9285671/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract White-matter, which contains the long-range axons connecting different brain regions, makes up nearly half the human brain, yet the three-dimensional organization of individual axons has not been characterized. While advances in diffusion MRI have enabled macroscopic mapping of major WM pathways, these methods are unable to resolve individual axons: their trajectories, density, and relative orientations. Here, we present a histological and imaging pipeline optimized for post-mortem human white-matter that shows the 3D trajectories of densely stained large (diameter greater than ~1 μm) projection axons. Applying our approach to multiple centimeter-scale WM regions in an adult human brain, we observed striking regional diversity in axonal organization. Specifically, we identified distinct architectural motifs ranging from loosely packed, multi-orientation meshworks (in most superficial white matter), to laminar lattice-like structures (near the basal ganglia), to tightly packed bundles of fibers (e.g. in the corpus callosum). We speculate that these patterns reflect local adaptations to spatial constraints, axonal density, and the diversity of axonal sources and targets, offering region-specific solutions to anatomical optimization problems. These findings offer new insights into the principles shaping brain connectivity and underscore the need for regionally detailed atlases of human WM. Biological sciences/Neuroscience/Neural circuits Biological sciences/Neuroscience/Computational neuroscience/Network models Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Under Review 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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While advances in diffusion MRI have enabled macroscopic mapping of major WM pathways, these methods are unable to resolve individual axons: their trajectories, density, and relative orientations. Here, we present a histological and imaging pipeline optimized for post-mortem human white-matter that shows the 3D trajectories of densely stained large (diameter greater than ~1 μm) projection axons. Applying our approach to multiple centimeter-scale WM regions in an adult human brain, we observed striking regional diversity in axonal organization. Specifically, we identified distinct architectural motifs ranging from loosely packed, multi-orientation meshworks (in most superficial white matter), to laminar lattice-like structures (near the basal ganglia), to tightly packed bundles of fibers (e.g. in the corpus callosum). 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