Neural Circuit Defect Linked to Social Behavior Deficits in Autism
Researchers find a neural circuit defect in ASD, impairing attention-shifting and social behavior.
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Researchers from the University of Geneva (UNIGE) have identified a neural circuit defect in individuals with autism spectrum disorders (ASD) that affects the ability to redirect attention, an essential aspect of social interaction. This discovery, published in Molecular Psychiatry, could lead to more targeted interventions for ASD.
The role of attention in social development
Human survival depends on the ability to engage with others from birth. This skill, crucial for early development, is often impaired in children with ASD, who show limited interest in social stimuli early in life. While the impact of this social deficit on cognitive development is well-documented, the underlying neurobiological causes have remained unclear.
Approximately 1 in 36 children is diagnosed with an autism spectrum disorder, and ~1/3 of these children are at risk for cognitive impairments.
‘‘In the children who show a delay, the cognitive difficulties are the consequence of a lack of understanding of social interactions,’’ said Dr. Camilla Bellone, an associate professor at UNIGE’s Department of Basic Neurosciences.
She notes that social learning is critical, and without early interaction with others, children with ASD struggle to acquire the skills needed to navigate the social world.
Findings from animal models
To better understand the neural mechanisms of social behavior, researchers at UNIGE used mouse models, specifically mice lacking the Shank3 gene, a common genetic cause of ASD in humans. These mice exhibited social behavior deficits similar to those observed in children with ASD, providing an appropriate model for studying the disorder.
The team focused on the communication between two brain areas involved in social behavior: the superior colliculus and the ventral tegmental area. The superior colliculus is involved in directing attention, including to social cues, while the ventral tegmental area is connected to the brain's reward system. Through in vivo imaging with miniaturized microscopes, the researchers observed that a lack of synchrony in the neurons of the superior colliculus disrupted communication between these areas, resulting in impaired social behavior.
Superior colliculus
A brain structure involved in orienting attention toward visual and social stimuli, crucial for interpreting the environment.
Ventral tegmental area
A part of the brain associated with the reward system, influencing motivation and the processing of rewarding stimuli, including social interactions.
Neural synchrony
The coordinated firing of neurons in the brain, essential for effective communication between brain regions and proper cognitive function.
Implications for human development
To explore these findings in humans, the researchers adapted their approach to work with young children. Led by Nada Kojovic, the team developed a protocol to obtain high-quality brain MRIs of children aged 2 to 5 years without sedation. This method, which allowed children to fall asleep naturally during the scan, successfully provided valuable MRI data for over 90% of the participants.
The results in children mirrored those observed in the mouse models. The connectivity of the neural circuit between the superior colliculus and the ventral tegmental area in the brain was predictive of cognitive development in the following year. This finding opens the door to earlier interventions, particularly those aimed at improving the ability of children with ASD to rapidly shift attention between stimuli, a key skill in social learning.
The potential for intervention
While direct intervention on this neural circuit is not yet possible, the discovery provides valuable guidance for behavioral interventions. Programs aimed at strengthening attention-switching abilities in young children with ASD could help mitigate developmental delays. One such intervention, which involves 20 hours of therapy per week for 2 years, has shown promising results in increasing IQ scores by 20 points in some children. Notably, 75% of children who underwent this treatment were able to transition to regular schooling.
Reference: Contestabile A, Kojovic N, Casarotto G, et al. Translational research approach to social orienting deficits in autism: the role of superior colliculus-ventral tegmental pathway. Mol Psychiatry. 2025. doi: 10.1038/s41380-025-02962-w
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