Autism, a condition more familiar to many thanks to the popular drama Extraordinary Attorney Woo, is characterized by neurological and behavioral symptoms. In the show, the protagonist WOO Young-woo exhibits hypersensitivity to the texture of food, leading her to eat only gimbap. This portrayal reflects real-life cases of autism where individuals often show extreme sensitivity to certain stimuli.

Researchers at the IBS Center for Synaptic Brain Dysfunctions have focused on sensory hypersensitivity, a common feature in individuals with autism spectrum disorder (ASD).

1. The Anterior Cingulate Cortex and Brain Connectivity

The anterior cingulate cortex (ACC) is a brain region involved in processing emotions, cognition, decision-making, and pain perception. Located in the middle of the cerebral cortex, it interacts with other brain regions to perform various functions.

The brain operates through interactions between different regions, allowing us to think, feel, and act. Neurological health depends on the organization and functioning of these neural networks. Abnormal brain connectivity has been clinically observed in patients with neurodevelopmental disorders, cognitive impairments, and other psychiatric conditions.

2. The Importance of Research on Autism Spectrum Disorder

Autism is a neurodevelopmental disorder affecting approximately 1 in 36 individuals, characterized by challenges in social interaction, communication deficits, and repetitive behaviors. Another hallmark symptom is sensory abnormalities, particularly hypersensitivity. This heightened reaction to everyday stimuli such as sound, light, or touch often causes significant stress and lowers quality of life for those affected. Sensory hypersensitivity is observed in 90% of individuals with autism, yet its causes and mechanisms remain poorly understood.

3. Why Everyday Stimuli Can Be Overwhelming for Individuals with Autism

The research team investigated sensory hypersensitivity in a mouse model of autism caused by the deletion of the Grin2b gene, which is associated not only with ASD but also with developmental delays and obsessive-compulsive disorder. These mice exhibited autism-like hypersensitivity to mechanical, electrical, and thermal stimuli, showing increased avoidance and heightened responses compared to controls. Interestingly, when the genetic mutation was limited to the spinal cord and peripheral nervous system, sensory hypersensitivity did not occur, indicating the central role of the brain in this mechanism.

To identify specific brain regions involved, the researchers used c-fos imaging to visualize brain responses to sensory stimuli and functional magnetic resonance imaging (fMRI) to monitor neural activity and analyze connectivity in real-time.

The results revealed that the ACC, associated with higher cognitive functions, was excessively activated in response to stimuli. This overactivation led to heightened excitatory neural transmission and excessive connectivity between the ACC and other brain regions.

Remarkably, when the researchers suppressed the overactivation of ACC neurons using chemogenetic methods, both the ACC hyperactivity and sensory hypersensitivity normalized. This suggests that ACC overactivation is a primary cause of sensory hypersensitivity in autism.

4. Future Research Directions

The team plans to further investigate how overconnectivity between higher-order brain regions and other areas induces sensory hypersensitivity and explore methods to regulate the activity of these regions. Additionally, they will study whether activation of higher-order brain regions is linked to sensory abnormalities in other autism gene models.

[Figure] Recovery of Sensory Hypersensitivity via ACC Inhibition
(Left) A mouse model carrying the same genetic mutation observed in autistic individuals exhibits sensory hypersensitivity, ACC hyperactivation, and overconnectivity in associated neural circuits.
(Right) Suppression of ACC activity restores overconnectivity and sensory hypersensitivity to levels similar to those of normal mice.