Biology subjects

Pelphrey, K. A.

Publications and source records attributed to Pelphrey, K. A..

6 recordsLinked to original sources

bioRxiv2026

Altered biological aging-related brain profile in adolescents with autism: A neuroimaging study based on DunedinPACNI

Individuals with Autism Spectrum Disorder (ASD) show increased rates of physical health conditions across major organ systems, some of which are commonly linked with aging, suggesting that body-wide biological profiles may be altered compared to neurotypical controls. Since brain structure associates with peripheral physiology and biomarkers of aging, it may inform understanding of broader biological differences and physical health risks in ASD. Here, we assessed this possibility using DunedinPACNI, a neuroimaging-based model that estimates the pace of longitudinal aging in peripheral organ systems from brain structural information, in 329 adolescents (8-18 years) from the Autism Centers of Excellence network, with replication in an independent age-matched sample of comparable size from the Autism Brain Imaging Data Exchange. Across both datasets and sensitivity analyses, autistic individuals showed significantly larger DunedinPACNI values than controls, consistent with brain structural features that align with patterns associated with a faster pace of biological aging in adults. Group differences were mainly driven by the volume of the 3rd ventricle, cortical thickness of the left entorhinal cortex, grey matter volume of the right entorhinal cortex and grey-to-white matter ratio in the left temporal pole. No association between DunedinPACNI and core autistic traits was found. Our results provide novel evidence for a possible altered brain-body profile in ASD, motivating future studies combining neuroimaging with peripheral biomarkers to better understand the neurobiology of physical health conditions in autism.

neuroscience↗

bioRxiv2025

Brain morphology network alterations in adolescents with autism spectrum disorder: a sex-stratified study

Neuroimaging studies based on altered functional and structural networks have contributed to better characterizing males and females with Autism Spectrum Disorder (ASD), advancing our understanding of the male prevalence in diagnosis. However, much less is known about how brain networks are altered from a morphological perspective, and whether these alterations may help explain sex-related characteristics in ASD. Here, we used structural MRI from a sex- and diagnosis-balanced sample of 337 individuals in typical neurodevelopmental ages (8-18 years) from the Autism Center of Excellence to elucidate sex-specific alterations in morphology-based connectivity, calculated as the similarity between region-wise multivariate morphological signatures. Network-based statistics showed that ASD males had significantly increased connectivity involving the fusiform gyrus, medial orbitofrontal, entorhinal, and parahippocampal cortices. This network profile was further linked to a core social-communication trait within the autistic group. In females with ASD, increased connectivity was found in a subnetwork primarily implicating the entorhinal cortex, followed by the inferior parietal lobule and lateral occipital cortex. In contrast to males, females fusiform gyrus showed decreased connectivity with the superior temporal sulcus. No overlap between male- and female-specific profiles was found. Together, these findings offer new insights into the neurobiology underlying sex differences in autism.

neuroscience↗

bioRxiv2025

ALE Meta-Analysis Reveals Neural Substrates for the Impact of Prematurity on Executive Functioning in Children and Adults

Premature birth has known impacts on brain development, leading to sustained differences in cognitive function throughout the lifespan. Despite known deficits in executive functioning (EF) within individuals born premature, the extent to which neural engagement during executive functioning tasks differs between those born preterm and full-term is not fully understood. Additionally, it is unknown whether regions of differential engagement are the same in children and adults. This meta-analysis synthesizes fMRI results of activation differences between preterm and full-term subjects during executive functioning tasks in adult and child groups separately. Our results indicate that differences in neural engagement during EF tasks differ between pre-term (PT) and full term (FT) individuals in both age groups. Moreover, the regions affected contribute to well-known brain networks, including the fronto-striatal circuitry, the default mode network (DMN), and the salience network, all of which subserve broad EF capabilities. We found no differences between child and adult maps in a direct contrast, suggesting that effects of prematurity on executive functioning may persist from childhood into adulthood, although these findings should be interpreted in context of methodological limitations and potential confounding factors. This meta-analysis provides greater insight into the neural mechanisms behind EF disruption following premature birth. HighlightsO_LIDifferences in neural activation during executive function tasks exist in both children and adults with a history of premature birth. C_LIO_LIPT children show hyperactivity in fronto-striatal regions while PT adults show differential engagement of default mode network regions. C_LI

neuroscience↗

bioRxiv2025

Structural Determinants of Signal Speed: A Multimodal Investigation of Face Processing in Autism Spectrum Disorder

It has not previously been possible to investigate the fundamental relationship between axonal structure - which dictates action potential transmission - and human neuronal function in vivo. Here, we introduce a novel metric of axonal signal speed, estimated axonal latency (EAL), derived from the relationship between axonal diameter, myelination, and length measured via MRI. We validate EAL along two pathways of the face processing network by relating it to N170 latency, an electrophysiological marker of face processing speed measured via EEG. Our results show that EAL along these pathways predicts N170 latency specifically during face processing. Moreover, we demonstrate that individuals with and without autism rely upon different pathways, potentially providing a structural account for autism-related face processing differences. By establishing this relationship between EEG-based electrical function and MRI-based axonal microstructure, we provide a non-invasive, spatially detailed estimate of neuronal processing speed that can inform our understanding of brain function, development, and disorder. TeaserEstimated axonal latency is a non-invasive, spatially detailed measure of neuronal speed to inform brain function and disorder.

neuroscience↗

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↗