Kleinhans, N. M. | Search bioRxiv

bioRxiv2024

Widespread Associations between Behavioral Metrics and Brain Microstructure in ASD

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and repetitive behaviors. Our lab has previously found that g-ratio, the proportion of axon width to myelin diameter, and axonal conduction velocity, which is associated with the capacity of an axon to carry information, are both decreased in ASD individuals. By associating these differences with performance on cognitive and behavioral tests, this study aims to first associate a broad array of behavioral metrics with neuroimaging markers of ASD, and to explore the prevalence of ASD subtypes using a neuroimaging driven perspective. Analyzing 273 participants (148 with ASD) ages 8 to 17 through an NIH-sponsored Autism Centers of Excellence network (MH100028), we observe widespread associations between behavioral and cognitive evaluations of autism and between behavioral and microstructural metrics, alongside different directional correlations between different behavioral metrics. Stronger associations with individual subcategories from each test rather than summary scores suggest that different neuronal profiles may be masked by composite test scores. Machine learning cluster analyses applied to neuroimaging data reinforce the association between neuroimaging and behavioral metrics and suggest that age-related maturation of brain metrics may drive changes in ASD behavior. This suggests that if ASD can be definitively subtyped, these subtypes may show different behavioral trajectories across the developmental period. Clustering identified a pattern of restrictive and repetitive behavior in some participants and a second group that was defined by high sensory sensitivity and language performance.

neuroscience↗

bioRxiv2023

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 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 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 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.

neuroscience↗