How the Brain Learns to Ignore Noise, and Why This Mechanism Fails in Autism-Related Disorders
2026 Award: $109,932
Many individuals with autism experience sensory overload, where everyday sounds such as traffic or cafeteria noise can remain intrusive, making it hard to follow speech in noise. In this project, we will study how the brain learns to filter out irrelevant background sound, and how these mechanisms may be disrupted in a mouse model related to autism. Findings in the simple mouse brain should provide a first step toward understanding, and ultimately treating, the sensory difficulties that affect daily life for people with autism.
Need/Problem: Around 90% of individuals with ASD experience atypical sensory responses, and difficulty understanding speech in noise can be especially disabling. To develop future interventions, we need to understand the brain mechanisms that normally allow us to filter out irrelevant background noise and how these mechanisms may be altered in ASD.
Grant Summary: To identify brain circuit alterations underlying hearing-in-noise difficulties in ASD, we will study a mouse model of Angelman syndrome, a neurodevelopmental disorder with strong overlap with autism. Using cellular-level neural recording and behavioral testing, we will examine whether impaired experience-dependent noise filtering contributes to sound-processing difficulties in autism-related disorders.
Goals & Projected Outcomes: This study will reveal how a top-down brain circuit from the orbitofrontal cortex to the auditory cortex supports filtering of background sounds, and how this circuit is altered in ASD-related diseases. Data from this study will support a future NIH R01 proposal to test the generalizability of these findings across multiple ASD models.
Hiroyuki Kato, PhD
Grant Details: Atypical sensory processing affects around 90% of individuals with ASD, and difficulty understanding speech in noisy environments is among the most disruptive symptoms. Our recent work identified a brain circuit that builds an experience-dependent “noise filter”: top-down projections from the orbitofrontal cortex to the auditory cortex suppress responses to repeated, predictable sounds. This project will test whether this learned filtering is impaired in mice lacking a maternal copy of the Ube3a gene, a model of Angelman syndrome with high ASD comorbidity. Using two-photon calcium imaging, we will track activity of the same auditory cortex neurons across days of noise exposure, and relate these neural measurements to behavioral performance on hearing-in-noise tasks. Our preliminary data show that habituation to repeated noise is reduced in Ube3a mutant mice, consistent with a failure of predictive filtering. Findings in this mouse model should provide a first step toward identifying therapeutic targets for sensory symptoms in ASD.
