Novel insights into axon diameter and myelin content in late childhood and adolescence

Genc, Sila; Raven, Erika P.; Drakesmith, Mark; Blakemore, Sarah‐Jayne; Jones, Derek K.

doi:10.1093/cercor/bhac515

Cited by 16 publications

(12 citation statements)

References 107 publications

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“…Individuals with ASD also had significantly thinner myelin sheaths in all sizes of axon 50 . Though this histological experiment was performed in adults instead of the adolescents in this study, given these two factors, a bias toward smaller diameter axons and thinner myelin, it is likely that the results reported here confirm this prior finding, as the aggregate g-ratio in this adolescent cohort is overall lower than expected in adults due to insufficiently developed myelin, and thus the TD group can be interpreted as nearer to developed myelin and thus higher g- ratio closer to optimum values 52,84,94,95 . It has also been reported that children with ASD have lower conduction velocity using magnetoencephalography 96,97 and in peripheral neurons 98 , potentially due to reduced axonal diameter and the prevalence of small fibers.…”

Section: Discussionsupporting

confidence: 79%

“…12, the aggregate g-ratio can be lowered if both AVF and MVF are reduced, especially unequally. In absolute terms, it is possible that this adolescent cohort is overall lower than expected in adults due to insufficiently developed myelin and smaller axonal diameters, and thus the TD group can be interpreted as nearer to developed myelin/axonal volumes and thus the initially paradoxical seeming greater g-ratio compared to the ASD group is actually the result of higher axonal diameter[52,81,83,94]. Further comparison of these metrics to age shows that aggregate g-ratio has a negative relationship with age while aggregate conduction velocity has a positive relationship with age during this developmental period (Fig.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Conduction Velocity, G-ratio, and Extracellular Water as Microstructural Characteristics of Autism Spectrum Disorder

Newman

Jacokes

Venkadesh

et al. 2023

Preprint

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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 novel metric 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 T1/T2 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. This study is the first to reveal that ASD involves differences of myelin and axonal development with implications for neuronal function. We also introduce a novel neuroimaging metric, 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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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Conduction Velocity, G-ratio, and Extracellular Water as Microstructural Characteristics of Autism Spectrum Disorder

Newman

Jacokes

Venkadesh

et al. 2023

Preprint

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“…As illustrated in Fig 12 , the aggregate g-ratio can be lowered if both AVF and MVF are reduced, especially unequally. In absolute terms, it is possible that this adolescent cohort is overall lower than expected in adults due to insufficiently developed myelin and smaller axonal diameters, and thus the TD group can be interpreted as nearer to developed myelin/axonal volumes and thus the initially paradoxical seeming higher g-ratio compared to the ASD group is actually closer to optimum values [ 52 , 81 , 83 , 103 ]. It has also been reported that children with ASD have lower conduction velocity using magnetoencephalography [ 104 , 105 ] and in peripheral neurons [ 106 ], potentially due to reduced axonal diameter and the prevalence of small fibers.…”

Section: Discussionmentioning

confidence: 99%

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

Newman,

Jacokes,

Venkadesh

et al. 2024

PLoS ONE

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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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“…In fact, correlation between white matter changes and cognitive function over the course of human life establishes a link between myelin development and cognitive development. Longitudinal brain imaging studies have shown that white matter volume—reflecting the myelin content and axonal caliber [ 81 ]—has a linear increase throughout childhood and adolescence ([ 82 ] reviews such findings while discussing various myelin imaging techniques and their shortcomings). As first reported by fractional anisotropy, a measure of white matter volume in diffusion tensor imaging (DTI), an increase of myelin thickness in frontal white matter positively correlates with increased working memory scope in children [ 83 ].…”

Section: Myelin In Cognitive Processingmentioning

confidence: 99%

Functional myelin in cognition and neurodevelopmental disorders

Khelfaoui,

Ibaceta-Gonzalez,

Angulo

2024

Cell. Mol. Life Sci.

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In vertebrates, oligodendrocytes (OLs) are glial cells of the central nervous system (CNS) responsible for the formation of the myelin sheath that surrounds the axons of neurons. The myelin sheath plays a crucial role in the transmission of neuronal information by promoting the rapid saltatory conduction of action potentials and providing neurons with structural and metabolic support. Saltatory conduction, first described in the peripheral nervous system (PNS), is now generally recognized as a universal evolutionary innovation to respond quickly to the environment: myelin helps us think and act fast. Nevertheless, the role of myelin in the central nervous system, especially in the brain, may not be primarily focused on accelerating conduction speed but rather on ensuring precision. Its principal function could be to coordinate various neuronal networks, promoting their synchronization through oscillations (or rhythms) relevant for specific information processing tasks. Interestingly, myelin has been directly involved in different types of cognitive processes relying on brain oscillations, and myelin plasticity is currently considered to be part of the fundamental mechanisms for memory formation and maintenance. However, despite ample evidence showing the involvement of myelin in cognition and neurodevelopmental disorders characterized by cognitive impairments, the link between myelin, brain oscillations, cognition and disease is not yet fully understood. In this review, we aim to highlight what is known and what remains to be explored to understand the role of myelin in high order brain processes.

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Novel insights into axon diameter and myelin content in late childhood and adolescence

Cited by 16 publications

References 107 publications

Conduction Velocity, G-ratio, and Extracellular Water as Microstructural Characteristics of Autism Spectrum Disorder

Conduction Velocity, G-ratio, and Extracellular Water as Microstructural Characteristics of Autism Spectrum Disorder

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

Functional myelin in cognition and neurodevelopmental disorders

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