Conduction velocity, G-ratio, and extracellular water as microstructural characteristics of autism spectrum disorder.

The neuronal differences contributing to the etiology of autism spectrum disorder (ASD) are still not well defined. Previous studies have suggested that myelin and axons are disrupted during development in ASD. By combining structural and diffusion MRI techniques, myelin and axons can be assessed us...

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Main Authors: Benjamin T Newman, Zachary Jacokes, Siva Venkadesh, Sara J Webb, Natalia M Kleinhans, James C McPartland, T Jason Druzgal, Kevin A Pelphrey, John Darrell Van Horn, GENDAAR Research Consortium
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0301964&type=printable
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author Benjamin T Newman
Zachary Jacokes
Siva Venkadesh
Sara J Webb
Natalia M Kleinhans
James C McPartland
T Jason Druzgal
Kevin A Pelphrey
John Darrell Van Horn
GENDAAR Research Consortium
author_facet Benjamin T Newman
Zachary Jacokes
Siva Venkadesh
Sara J Webb
Natalia M Kleinhans
James C McPartland
T Jason Druzgal
Kevin A Pelphrey
John Darrell Van Horn
GENDAAR Research Consortium
author_sort Benjamin T Newman
collection DOAJ
description The neuronal differences contributing to the etiology of autism spectrum disorder (ASD) are still not well defined. Previous studies have suggested that myelin and axons are disrupted during development in ASD. By combining structural and diffusion MRI techniques, myelin and axons can be assessed using extracellular water, aggregate g-ratio, and a new approach to calculating axonal conduction velocity termed aggregate conduction velocity, which is related to the capacity of the axon to carry information. In this study, several innovative cellular microstructural methods, as measured from magnetic resonance imaging (MRI), are combined to characterize differences between ASD and typically developing adolescent participants in a large cohort. We first examine the relationship between each metric, including microstructural measurements of axonal and intracellular diffusion and the T1w/T2w ratio. We then demonstrate the sensitivity of these metrics by characterizing differences between ASD and neurotypical participants, finding widespread increases in extracellular water in the cortex and decreases in aggregate g-ratio and aggregate conduction velocity throughout the cortex, subcortex, and white matter skeleton. We finally provide evidence that these microstructural differences are associated with higher scores on the Social Communication Questionnaire (SCQ) a commonly used diagnostic tool to assess ASD. This study is the first to reveal that ASD involves MRI-measurable in vivo differences of myelin and axonal development with implications for neuronal and behavioral function. We also introduce a novel formulation for calculating aggregate conduction velocity, that is highly sensitive to these changes. We conclude that ASD may be characterized by otherwise intact structural connectivity but that functional connectivity may be attenuated by network properties affecting neural transmission speed. This effect may explain the putative reliance on local connectivity in contrast to more distal connectivity observed in ASD.
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spelling doaj-art-1e2d0f866b1447d381571d3d494042e82024-12-10T05:32:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01194e030196410.1371/journal.pone.0301964Conduction velocity, G-ratio, and extracellular water as microstructural characteristics of autism spectrum disorder.Benjamin T NewmanZachary JacokesSiva VenkadeshSara J WebbNatalia M KleinhansJames C McPartlandT Jason DruzgalKevin A PelphreyJohn Darrell Van HornGENDAAR Research ConsortiumThe neuronal differences contributing to the etiology of autism spectrum disorder (ASD) are still not well defined. Previous studies have suggested that myelin and axons are disrupted during development in ASD. By combining structural and diffusion MRI techniques, myelin and axons can be assessed using extracellular water, aggregate g-ratio, and a new approach to calculating axonal conduction velocity termed aggregate conduction velocity, which is related to the capacity of the axon to carry information. In this study, several innovative cellular microstructural methods, as measured from magnetic resonance imaging (MRI), are combined to characterize differences between ASD and typically developing adolescent participants in a large cohort. We first examine the relationship between each metric, including microstructural measurements of axonal and intracellular diffusion and the T1w/T2w ratio. We then demonstrate the sensitivity of these metrics by characterizing differences between ASD and neurotypical participants, finding widespread increases in extracellular water in the cortex and decreases in aggregate g-ratio and aggregate conduction velocity throughout the cortex, subcortex, and white matter skeleton. We finally provide evidence that these microstructural differences are associated with higher scores on the Social Communication Questionnaire (SCQ) a commonly used diagnostic tool to assess ASD. This study is the first to reveal that ASD involves MRI-measurable in vivo differences of myelin and axonal development with implications for neuronal and behavioral function. We also introduce a novel formulation for calculating aggregate conduction velocity, that is highly sensitive to these changes. We conclude that ASD may be characterized by otherwise intact structural connectivity but that functional connectivity may be attenuated by network properties affecting neural transmission speed. This effect may explain the putative reliance on local connectivity in contrast to more distal connectivity observed in ASD.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0301964&type=printable
spellingShingle Benjamin T Newman
Zachary Jacokes
Siva Venkadesh
Sara J Webb
Natalia M Kleinhans
James C McPartland
T Jason Druzgal
Kevin A Pelphrey
John Darrell Van Horn
GENDAAR Research Consortium
Conduction velocity, G-ratio, and extracellular water as microstructural characteristics of autism spectrum disorder.
PLoS ONE
title Conduction velocity, G-ratio, and extracellular water as microstructural characteristics of autism spectrum disorder.
title_full Conduction velocity, G-ratio, and extracellular water as microstructural characteristics of autism spectrum disorder.
title_fullStr Conduction velocity, G-ratio, and extracellular water as microstructural characteristics of autism spectrum disorder.
title_full_unstemmed Conduction velocity, G-ratio, and extracellular water as microstructural characteristics of autism spectrum disorder.
title_short Conduction velocity, G-ratio, and extracellular water as microstructural characteristics of autism spectrum disorder.
title_sort conduction velocity g ratio and extracellular water as microstructural characteristics of autism spectrum disorder
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0301964&type=printable
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