Advanced imaging from the ABCD study revealed that children with autism have lower neuron density in regions associated with memory and problem-solving, while regions such as the amygdala showed higher neuron density. These differences were specific to autism and were not seen in children with other psychiatric conditions, indicating a distinct neurological profile. These findings may increase our understanding of the development of autism and potentially guide targeted therapies for children on the spectrum.
The brains of people with autism spectrum disorder (ASD) exhibit some structural differences compared to neurotypical brains. Studies have shown abnormalities in neuronal cytoarchitecture, particularly in areas such as the cortex, cerebellum, and limbic networks.
These changes include narrower neural minicolumns and variations in neuron density, which may affect communication between different brain regions.
In addition, magnetic resonance imaging (MRI) studies suggest changes in neurite density and abnormal patterns of water diffusion in brain tissue, revealing different neural connectivity. These structural differences are related to aspects of perception, behavior, and information processing in autism.
Researchers at the Del Monte Institute for Neuroscience at the University of Rochester have found that in some areas of the brain, the density of neurons varies in children with autism compared to the general population. They investigated changes in the brain structure of individuals with autism using an advanced imaging technology called diffusion-weighted MRI (DWI).
The central idea is that people with autism may have differences in the organization of brain cells, called “neural cytoarchitecture,” that are difficult to study in postmortem brains. Until recently, scientists have struggled to collect enough samples of postmortem brains to identify clear patterns, and that’s where DWI provided an important breakthrough.
Diffusion-weighted MRI (DWI) allows scientists to look at the brains of living people. In this study, 142 individuals diagnosed with autism were compared to a much larger group of 8,971 people without autism using a technique called Restriction Spectrum Imaging (RSI).
This technique can measure the density and organization of “neurites” — tiny extensions of neurons (brain cells) that help cells communicate with each other.
The results showed that in people with autism, the total neurite density (TND) was significantly lower in a specific area of the brain called the right cerebellar cortex. This means there were fewer of these connections between neurons in this region, which may be linked to the symptoms of autism.
In addition, the researchers found a different pattern of water diffusion in various regions of the brain, which may reflect changes in the organization and function of neurons.
This type of discovery is crucial because it suggests that there are structural differences in the brains of people with autism that can be detected in life, without the need for autopsies. These findings also indicate that future studies should consider these differences in cytoarchitecture as important variables, which may help improve the understanding and treatment of autism.
Regions that had significantly different restricted normalized directional (RND) measures when comparing the autism spectrum disorder (ASD) and nASD groups. Regions where ASD had higher RND are in red and regions where ASD had lower RND are in blue.
In short, using this advanced brain imaging technology allows scientists to explore structural differences in the brain noninvasively, shedding light on how these changes may contribute to the development of disorders like autism.
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Autism is associated with in vivo changes in gray matter neurite architecture
Zachary P. Christensen, Edward G. Freedman, John J. Foxe
Autism Research. 2024; 1–17 doi.org/10.1002/aur.3239
Abstract:
Postmortem investigations in autism have identified anomalies in neural cytoarchitecture across limbic, cerebellar, and neocortical networks. These anomalies include narrow cell mini-columns and variable neuron density. However, difficulty obtaining sufficient post-mortem samples has often prevented investigations from converging on reproducible measures. Recent advances in processing magnetic resonance diffusion-weighted images (DWI) make in vivo characterization of neuronal cytoarchitecture a potential alternative to post-mortem studies. Using extensive DWI data from the Adolescent Brain Cognitive Development (ABCD®) study 142 individuals with an autism diagnosis were compared with 8971 controls using a restriction spectrum imaging (RSI) framework that characterized total neurite density (TND), its component restricted normalized directional diffusion (RND), and restricted normalized isotropic diffusion (RNI). A significant decrease in TND was observed in autism in the right cerebellar cortex (β = −0.005, SE =0.0015, p = 0.0267), with significant decreases in RNI and significant increases in RND found diffusely throughout posterior and anterior aspects of the brain, respectively. Furthermore, these regions remained significant in post-hoc analysis when the autism sample was compared against a subset of 1404 individuals with other psychiatric conditions (pulled from the original 8971). These findings highlight the importance of characterizing neuron cytoarchitecture in autism and the significance of their incorporation as physiological covariates in future studies.
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