Fragile X, ASD children have distinct brain network patterns
MRI study: Assessment scores also differed between two groups
Children with Fragile X syndrome (FXS) share some traits with those with autism spectrum disorder (ASD), but exhibit several differences in terms of brain’s traffic patterns, according to an MRI study.
Associations between certain brain traffic patterns, which reflect different connections between brain regions that actively work together, and scores on ASD assessments also differed between the two groups, data showed.
Importantly, higher levels of methylation, a process responsible for silencing the gene that’s defective in fragile X patients, were significantly associated with a less active and connected region within the brain’s cerebellum.
“This finding may offer evidence for linking cerebellar dysfunction and methylation with cognitive impairment in FXS since recent research has highlighted the cerebellum’s involvement in various cognitive and emotional processes,” researchers wrote. “These findings shed light on the variability of the FXS [clinical profile], … offering insights into the underlying mechanisms driving cognitive and behavioral outcomes in FXS.”
The study, “Distinct and shared intrinsic resting-state functional networks in children with idiopathic autism spectrum disorder and fragile X syndrome,” was published in Molecular Psychiatry by a team of researchers in China.
Team conducted resting-state fMRI studies, collected behavioral data
Fragile X is a genetic condition marked by a variety of cognitive, developmental, and behavioral symptoms, as well as physical features. It’s also the most common cause of inherited intellectual disability and autism spectrum disorder, a collection of behaviors that include communication and social difficulties, poor eye contact, and repetitive movements.
Functional MRI (fMRI) is an imaging technique that measures brain activity by detecting changes in blood flow, either at rest or during specific tasks, which serve as a proxy for nerve cell activity. It can identify brain traffic patterns, or functional connectivity patterns, either within brain regions or between regions that work together.
However, “little is known about the functional patterns underlying the cognitive and behavioral characteristics of FXS and ASD,” the researchers wrote.
With this in mind, the team of researchers used fMRI to identify functional networks in the brains of 37 young children with fragile X and 70 age-matched children with idiopathic ASD, or ASD without a known genetic cause. The study also included 43 typically developing children who served as a control group.
In addition to resting-state fMRI studies, the team collected behavioral data from the participants.
Little is known about the functional patterns underlying the cognitive and behavioral characteristics of FXS and ASD.
The fMRI analysis revealed that children with fragile X had significantly decreased functional connectivity within the default mode network, a brain network that is active during rest and periods of self-directed thought, relative to the ASD and control groups.
ASD children, in contrast, showed significantly decreased functional connectivity between the default mode network and the cerebellum network, a brain region often affected in fragile X and ASD, relative to controls.
Fragile X and ASD groups showed significantly reduced functional connectivity within the cerebellum network relative to controls. Both groups also showed significantly reduced connectivity between the cerebellum network and networks involved in processing visual information (visual network) and in combining sensory information to guide motor responses (sensorimotor network).
There were also network differences within several brain regions between the three groups, with ASD children showing the most significantly reduced activity, including in two areas within the cerebellum (crus I and lobule IV-V). Children with fragile X also showed significantly lower connectivity in the crus I region relative to controls.
Changes in brain networks linked to process responsible for silencing key gene
The researchers then evaluated potential links between changes in fMRI functional connectivity and scores on the Autism Diagnostic Observation Schedule, second edition (ADOS-2), a standardized assessment tool for evaluating ASD.
In fragile X children, the team found that the mean functional connectivity between the cerebellum network and other networks, like the default mode, the visual, and the sensorimotor networks, were each significantly associated with ADOS-2 scores.
These correlations, which differed from those observed in the ASD group, applied to two ADOS-2 subscales: the Ccalibrated Severity Score of Social Affect and the Repeated and Repetitive Behavior score.
Lastly, the researchers examined whether changes in brain networks were linked to methylation, a process that silences FMR1, the gene that’s defective in fragile X patients. Results showed that higher levels of methylation, reflecting greater gene suppression, were significantly associated with reduced functional connectivity in the crus I region within the cerebellum, reflecting a less active and connected region.
“Our study represents the first to identify such a genetic-specific neural pattern within the FXS population,” the researchers wrote.
Overall, the findings demonstrated “both distinct and shared patterns of resting-state functional connectivity and brain-behavior associations in young children with FXS and ASD,” the team wrote. “These findings add to the growing evidence that FXS and ASD, though sharing common [characteristics], are mainly characterized by distinctly different functional network patterns.”
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