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Investigating Brain Changes in Autism Spectrum Disorder

Research reveals key axon differences in autism using machine learning techniques.

Basilis Zikopoulos, A. Yazdanbakhsh, K. Dang, K. Kuang, T. Lian, X. Liu, S. Xie

― 6 min read


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Table of Contents

Autism Spectrum Disorder (ASD) affects how neural connections and communications work in the brain. Studies have found that there are changes in specific areas of the brain related to this condition. These changes include differences in the structures called Axons, which are like wires that carry signals throughout the brain.

Key Findings in Axon Changes

Research shows that in individuals with ASD, there is often an increase in the number of thin axons, while the thicker axons tend to be less dense. This may lead to issues with how signals are transmitted in the brain. Other changes reported include excessive branching of axons due to specific proteins, thinning of the protective layer around axons called myelin, and variations in axon paths.

These differences can affect how quickly signals travel and how strong the connections are, impacting overall brain functions and communications. The location and size of these axons can also provide clues on how they connect to other areas of the brain.

The Role of White Matter

White matter in the brain is important for connections. The superficial white matter (SWM) mainly contains short-range connections, while the deep white matter (DWM) contains long-range connections. The axons in the DWM tend to be thicker than those found in the SWM.

Studying the white matter is essential as it can help us understand brain pathways and how they may be disrupted in autism. Traditional methods to analyze these axons are time-consuming and require expert knowledge, making them challenging for larger studies aimed at identifying issues in ASD.

Machine Learning as a Solution

Machine learning might provide a new way to analyze detailed images of myelinated axons in white matter. Deep neural networks (DNNs) are a type of machine learning tool that has been effective in classifying images. They can help distinguish between images from neurotypical individuals and those with ASD.

For this study, a well-known DNN called GoogLeNet was used. It offered a framework for customizing a model that could differentiate high-resolution images of axons in the brains of individuals with and without ASD.

Targeting the Anterior Cingulate Cortex

The focus was on the white matter below the anterior cingulate cortex (ACC), a part of the brain involved in attention, emotions, and social interactions-areas often impacted in autism. The ACC shows notable activity differences in people with ASD, leading researchers to think that examining its white matter could reveal important insights into the disorder.

Collecting and Analyzing Data

To create the model, researchers used large datasets of images from brain samples. They prepared two types of images: one using Electron Microscopy, which provides detailed structural images, and another using light microscopy. The tissue samples came from post-mortem brains of both neurotypical individuals and those with autism.

The samples were processed and imaged in a specific way to ensure accurate capturing of features. The goal was to create a dataset that could be used to train the machine learning model efficiently.

Preparing the Images for Machine Learning

To optimize the dataset, two methods were applied. The first involved cutting the original images into smaller sections. This way, the model could learn from various parts of each image. The second method used a sliding window to create overlapping sections, increasing the number of images available for training.

Before being inputted into the model, images underwent additional processing to enhance quality and ensure consistency. This included adjusting contrasts and normalizing values, making it easier for the model to learn effectively.

Training the Deep Neural Network

To ensure reliable results, researchers split the images into different sets for training, validation, and testing. They also used techniques to balance the number of images from each class to improve the model's ability to learn.

Transfer learning was employed, using a pre-trained model to help with the new dataset, improving efficiency and accuracy. Different pre-trained models were tested, and the most effective were fine-tuned for the specific task of classifying the axon images.

Evaluating Model Performance

Multiple methods were used to evaluate how well the model performed. Cross-validation techniques ensured that the model learned effectively from different groups of images. Confusion matrices helped visualize how well the model classified different classes and identify areas for improvement.

The study also calculated precision and recall metrics, providing deeper insights into the model's performance. The area under the receiving operating characteristic curve (AUC) was another important measure to assess overall effectiveness.

Using Sensitivity Maps for Insights

To further analyze results, sensitivity maps were generated to highlight which parts of the images influenced the model's decisions. These maps helped identify specific features that contributed to correct and incorrect classifications, offering clues about the underlying differences in brain structure between neurotypical individuals and those with ASD.

DeepDream Images to Visualize Features

DeepDream images were created to illustrate the features learned by the model. These images help visualize patterns and characteristics that are important for the classification tasks. By enhancing specific details from the images, researchers could see distinct features that helped distinguish between different classes.

Findings and Insights

The results showed that the model could classify images from ASD and neurotypical groups with high accuracy. However, distinguishing between different white matter depths was more challenging. The analysis highlighted the difficulty in correctly classifying superficial white matter in individuals with ASD, indicating significant variability in these regions.

The findings pointed to a blending of white matter areas in the brains of people with ASD. This suggests that the structural differences in axons may be more pronounced below the ACC, showing widespread changes that impact how the brain communicates.

Challenges and Future Directions

While the model performed well, various challenges remain. The limited size of the dataset and variability in images can affect the model's ability to generalize to new data. Future studies should focus on expanding datasets and exploring other brain regions to identify more patterns and insights related to ASD.

The approach taken in this study holds promise for understanding brain connectivity in neurotypical individuals and those with mental health disorders. By systematically analyzing images of brain structures and using machine learning, researchers can uncover vital information that may guide future diagnostics and interventions for autism.

Conclusion

The use of machine learning to analyze brain images provides new insights into the structural differences in ASD. This study demonstrates the effectiveness of combining high-resolution imaging with advanced analytical methods. The findings highlight specific axonal features that could be targeted for further research, potentially leading to improved understanding and treatment options for individuals with autism.

Original Source

Title: Artificial intelligence networks combining histopathology and machine learning can extract axon pathology in autism spectrum disorder

Abstract: Axon features that underlie the structural and functional organization of cortical pathways have distinct patterns in the brains of neurotypical controls (CTR) compared to individuals with Autism Spectrum Disorder (ASD). However, detailed axon study demands labor-intensive surveys and time-consuming analysis of microscopic sections from post-mortem human brain tissue, making it challenging to systematically examine large regions of the brain. To address these challenges, we developed an approach that uses machine learning to automatically classify microscopic sections from ASD and CTR brains, while also considering different white matter regions: superficial white matter (SWM), which contains a majority of axons that connect nearby cortical areas, and deep white matter (DWM), which is comprised exclusively by axons that participate in long-range pathways. The result was a deep neural network that can successfully classify the white matter below the anterior cingulate cortex (ACC) of ASD and CTR groups with 98% accuracy, while also distinguishing between DWM and SWM pathway composition with high average accuracy, up to 80%. Multidimensional scaling analysis and sensitivity maps further underscored the reliability of ASD vs CTR classification, based on the consistency of axon pathology, while highlighting the important role of white matter location that constrains pathway dysfunction, based on several shared anatomical markers. Large datasets that can be used to expand training, validation, and testing of this network have the potential to automate high-resolution microscopic analysis of post-mortem brain tissue, so that it can be used to systematically study white matter across brain regions in health and disease. One Sentence StatementHistopathology-trained AI can identify ASD network disruptions and guide development of diagnostics and targeted therapeutics.

Authors: Basilis Zikopoulos, A. Yazdanbakhsh, K. Dang, K. Kuang, T. Lian, X. Liu, S. Xie

Last Update: 2024-10-26 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2024.10.25.620308

Source PDF: https://www.biorxiv.org/content/10.1101/2024.10.25.620308.full.pdf

Licence: https://creativecommons.org/licenses/by/4.0/

Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.

Thank you to biorxiv for use of its open access interoperability.

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