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Difficulties in social situations experienced by boys with autism may be related to how certain brain networks communicate with each other, a new study suggests. Scientists at the A*STAR Institute for Human Development and Potential have found that variations in the connections between brain networks involved in attention and self-reflection were associated with challenges in social awareness, communication, and understanding social cues. The research was published in Developmental Cognitive Neuroscience.
Scientists have long been working to understand the complexities of autism spectrum disorder, a condition that affects social interaction and behavior. Autism is known to be incredibly diverse, with individuals experiencing a wide range of symptoms and challenges. This variability makes it difficult to pinpoint the underlying biological reasons for the condition and develop effective, personalized treatments. While it’s understood that early differences in behavior can be signs of autism, these early signs are not always specific to autism and can be subtle.
The research team believed that by studying the way large areas of the brain connect during rest, they could pinpoint specific differences that might explain the social challenges seen in autism spectrum disorder. They also wanted to see if differences in higher-level thinking skills, such as the ability to switch between tasks or hold information in mind, played a role in linking these brain connection differences to behavior.
“Autism spectrum disorder is highly heterogeneous at both the phenotypic and neural levels,” explained first authors Shi Yu Chan and senior author Tan Ai Peng. “Previous research has suggested that variations in resting state functional connectivity (rsFC) between functional networks may underlie the symptoms of social impairments in individuals with autism . Hence, in this study, we employed normative modelling to examine the link between functional connectivity alterations and social behavior at an individual level in a large cohort of male children with autism. Normative modelling is a technique that models a typically developing trajectory and calculates an individual’s deviation from the norm.”
To conduct their study, the researchers used brain scan data from a large, publicly available database called the Autism Brain Imaging Data Exchange. This database includes brain scans and behavioral information from many individuals with and without autism. The researchers focused on data from 816 boys between the ages of 5 and 14. Because autism is more common in boys, and because brain development can differ between boys and girls, the researchers chose to focus specifically on males to ensure a more consistent study group.
First, the researchers established what typical brain connectivity development looks like in boys without autism. They used brain scans from 321 boys without autism to create a model of how communication between different brain networks changes with age. They looked at the connections between seven major brain networks: the visual network (for seeing), the somatomotor network (for movement and sensation), the dorsal attention network (for focused attention), the ventral attention network (for noticing important things), the limbic network (for emotions), the frontoparietal network (for higher-level thinking), and the default mode network (for self-reflection).
For each boy, they measured the strength of communication between each pair of these networks while the boys were resting in the scanner. This allowed them to create a ‘typical’ developmental pattern for brain network communication in boys as they grow from childhood to adolescence.
Next, the researchers applied this ‘typical’ pattern to a group of 418 boys with autism and a separate group of 77 boys without autism. For each boy, they calculated a ‘deviation score’ for each brain network connection. This score represented how much an individual boy’s brain connectivity differed from the ‘typical’ pattern they had established. A higher score meant a greater difference from the typical pattern.
To understand how these brain connectivity deviations related to social behavior, the researchers used the Social Responsiveness Scale, a questionnaire completed by parents that measures different aspects of social behavior. This scale assesses social awareness, social communication, social understanding, social motivation, and unusual mannerisms.
Finally, the researchers investigated whether executive functions, or higher-level thinking skills, played a role in the relationship between brain connectivity deviations and social difficulties. Executive functions include skills like cognitive flexibility (being able to switch between tasks or ideas) and working memory (holding information in mind to use it). They used the Behavior Rating Inventory of Executive Function, another parent questionnaire, to measure these skills in a subset of the boys with autism.
The results showed that deviations in communication patterns between certain brain networks were indeed linked to specific aspects of social behavior problems in boys with autism. Specifically, differences in connectivity involving the default mode network, ventral attention network, frontoparietal network, and somatomotor network were related to different dimensions of social difficulties.
Interestingly, deviations in the communication between the ventral attention network and the default mode network were found to be particularly relevant and were associated with challenges in social awareness, social communication, and social understanding. This suggests that when these networks don’t communicate in a typical way, it may impact a person’s ability to understand social cues, communicate effectively, and grasp social situations.
Furthermore, the study found that cognitive flexibility and working memory played a mediating role in the connection between deviations in ventral attention network and default mode network communication and social behavior problems. This means that boys with autism who had greater deviations in this brain network communication and who also had weaker cognitive flexibility and working memory skills tended to have more pronounced social difficulties. This finding suggests that these thinking skills might be a pathway through which brain connectivity differences impact social behavior in autism.
“Normative modelling is a promising method to map alterations in functional connectivity to behavior at the individual level,” Chan and Peng told PsyPost. “This is critical for the implementation of precision diagnosis and intervention. Specifically in male children with autism, the deviations of the functional connectivity between the ventral attention network and default mode network from a normative trajectory mapped to multiple domains of social behavior. Notably, executive function mediates the association between functional connectivity deviation and social behavior, highlighting executive function as a potential intervention target for improving social functioning in children with autism.”
The researchers acknowledged some caveats. “Our normative trajectories were modelled only with cross-sectional data from a publicly available dataset (the ABIDE I/II consortium),” the researchers said. “We included only males in the study, so we cannot draw any conclusions about the associations between functional connectivity deviations and social behavior in females. In addition, we were interested in neurodevelopment over childhood, so the age range of our study is from 5.9 to 13.9 years. However, a large proportion of the study cohort are between ages 9 to 12 years. Hence, our findings are most relevant for that age group.
Future research could analyze multiple brain scans collected over time to get a more precise picture of brain development in autism. Studies could also explore the influence of genetics and environment and investigate whether these findings are similar in girls with autism. Moving forward, this method of comparing individual brain patterns to a typical developmental trajectory holds promise for understanding the diverse nature of autism and other conditions.
“We aim to validate our study findings using a normative model built on longitudinal neuroimaging data,” Chan and Peng explained. “We will also apply the normative modelling approach used in our study to identify neural biomarkers for other neurodevelopmental disorders such as ADHD and dyslexia.”
The study, “Social behavior in ASD males: The interplay between cognitive flexibility, working memory, and functional connectivity deviations,” was authored by Shi Yu Chan, Jasmine Si Min Chuah, Pei Huang, and Ai Peng Tan.
