Autism: Study Reveals Flaw in Brain Circuit That Affects Social Interest

Autism Spectrum Disorder (ASD) affects the way a person communicates and relates to others. One of the main signs is difficulty paying attention and showing interest in social interactions. This study investigated a possible explanation for this, focusing on a part of the brain called the Superior Colliculus (SC), which helps direct attention to important stimuli, such as faces.

Autism Spectrum Disorder (ASD) is a developmental brain condition that affects the way a person communicates, interacts socially and behaves.

People with ASD often have difficulty engaging with other people and tend to repeat certain behaviors or interests. One of the main challenges faced by those with Autism Spectrum Disorder is a low interest in social interactions, which makes it difficult to form bonds with others.

Many scientists believe that this is linked to a problem in so-called “social motivation”, that is, the natural desire we feel to seek contact with other people and feel pleasure in these relationships.

Social motivation theory suggests that people with ASD have less interest or enjoyment in social interactions. Studies show that they tend to pay less attention to social cues, such as facial expressions or eye contact, and find these types of interactions less rewarding.

This theory has guided many studies and reinforces the importance of identifying autism as early as possible so that children can receive specialized support from an early age.

One tool that has helped scientists understand these behaviors is eye tracking, which allows us to see exactly where a person is looking. These studies have shown that, from a very young age, children with ASD look less at people’s faces or eyes.

When they observe more complex social scenes, these children’s gaze patterns are very different from those of typically developing children. They focus more on areas such as the mouth or outside of the face, ignoring the eyes, an area rich in emotional and social cues.

Additionally, studies show that children with Autism Spectrum Disorder have difficulty shifting their attention, which may be linked to the onset of autism symptoms.

These different behaviors appear very early in childhood, which indicates that there is something different in the brain circuits of these children, especially in the areas involved in perceiving and responding to social stimuli.

One of these circuits involves a region of the brain called the Superior Colliculus (SC), which is located in the brain stem and is responsible for helping to direct attention to important visual stimuli.

In people with Autism Spectrum Disorder, it is believed that the functioning of this region may be altered. Studies in animals have shown that the Superior Colliculus connects with areas of the brain related to motivation and pleasure, such as the Ventral Tegmental Area (VTA), and that these connections help with learning and responding to social interactions.

To investigate further, this study combined research with genetically modified mice (with a mutation in the Shank3 gene, which is associated with autism) and young children diagnosed with ASD.

The researchers, from the University of Geneva, found that both the mice and the children had difficulty paying attention to social stimuli. In the children, imaging studies showed that there was a reduction in communication between the Superior Colliculus and the Ventral Tegmental Area.

In the mice, however, the scientists observed less activity in neurons that connect these two areas. In addition, these changes in the mice’s brains were linked to behaviors similar to those seen in children with ASD.

a) This section shows how the mice were raised and how the social orientation test was performed. This test measures how interested they are in another young mouse placed in front of them.

b) In the top panel, we see heat maps showing where the social stimulus (another mouse) was positioned during the test. In the bottom panel, graphs (in the shape of a “violin”) show how much time mice in two different groups spent looking at the other mouse. Mice with a genetic alteration associated with autism (Shank3−/−) spent less time looking at the social stimulus than typical mice (Shank3+/+), indicating less social interest. This difference was statistically significant.

c) In humans, videos were used to test visual interest in social information (e.g., faces and interactions between people). The graphs show that children with autism (in green) paid less attention to social information than typically developing children (in blue), and this difference was quite clear.

d) In this experiment, children watched more complex social scenes. The proximity index, which shows how close the child’s eyes were to important social elements in the scene, was also lower in children with autism, indicating reduced attention to rich social information.

e-f) These graphs show the severity of behavioral symptoms according to the Autism Diagnostic Observation Scale (ADOS). Children with autism showed more symptoms in both the area of ​​social interaction (e) and repetitive behaviors (f), compared to children with typical development.

g-j) Finally, these parts show the results of tests that measure cognitive development in different areas. Children with autism scored lower on skills such as visual perception (g), fine motor skills (h), language comprehension (i), and speech (j), which shows delays in several areas of development.

Researchers believe these changes may act as a “biological signal” (or biomarker), helping to identify which children may benefit most from specific interventions.

These findings provide new insights into how the brains of people with Autism Spectrum Disorder work and point to possible avenues for more effective treatments that begin as early as possible to improve the social development of these children.

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Translational research approach to social orienting deficits in autism: the role of superior colliculus-ventral tegmental pathway

Alessandro Contestabile, Nada Kojovic, Giulia Casarotto, Farnaz Delavari, Patric Hagmann, Marie Schaer and Camilla Bellone

Molecular Psychiatry. 5 April 2025

DOI: 10.1038/s41380-025-02962-w

Abstract:

Autism Spectrum Disorder (ASD) is characterized by impairments in social interaction and repetitive behaviors. A key characteristic of ASD is a decreased interest in social interactions, which affects individuals’ ability to engage with their social environment. This study explores the neurobiological basis of these social deficits, focusing on the pathway between the Superior Colliculus (SC) and the Ventral Tegmental Area (VTA). Adopting a translational approach, our research used Shank3 knockout mice (Shank3−/−), which parallel a clinical cohort of young children with ASD, to investigate these mechanisms. We observed consistent deficits in social orienting across species. In children with ASD, fMRI analyses revealed a significant decrease in connectivity between the SC and VTA. Additionally, using miniscopes in mice, we identified a reduction in the frequency of calcium transients in SC neurons projecting to the VTA, accompanied by changes in neuronal correlation and intrinsic cellular properties. Notably, the interneuronal correlation in Shank3−/− mice and the functional connectivity of the SC to VTA pathway in children with ASD correlated with the severity of social deficits. Our findings underscore the potential of the SC-VTA pathway as a biomarker for ASD and open new avenues for therapeutic interventions, highlighting the importance of early detection and targeted treatment strategies.