- Awarded: 2018
- Award Type: Explorer
- Award #: 579068
During early life, the auditory system normally undergoes tremendous development and plasticity; however, this typical maturation is perturbed in individuals with autism spectrum disorder (ASD). The ability to accurately process sound and encode rapidly changing temporal features is key for the proper development of the auditory system. Long-term consequences of developmental auditory deficits can be profound, often extending from disruptions in reflexive, pre-attentive auditory behavior to deficits in perceptual tasks and impaired language development.
Over the past decade, neuroimaging studies have begun to characterize the structural and functional differences in the brains of individuals with and without ASD, and sensory processing deficits have been gaining increasingly more attention. At the same time, a variety of rodent models have been developed in an attempt to uncover the cellular mechanisms that may underlie particular autism-related phenotypes. For example, Susanne Schmid’s laboratory recently uncovered alterations in auditory processing, filtering and reactivity in Cntnap2 knockout rat model of ASD1. Despite these separate advances, very little progress has been made in the direct translation between such mechanistic studies in rodents and the complex behavioral profiles observed in individuals with ASD. Consequently, we are far from understanding the cellular mechanisms that contribute to sensory processing and higher-order deficits observed in ASD. Schmid contends that this significant gap in knowledge translation exists largely because researchers have been unable to directly relate the findings in rodents with those in humans (and vice versa) due to incompatibility in the experimental protocols used to screen for the various behavioral phenotypes.
The goal of this project is to establish a highly translational behavioral platform, where the exact same pre-attentive and perceptual auditory behavioral paradigms are tested in children with ASD and in a Cntnap2 deficient rat model of ASD with the expectation of uncovering similar perturbations in auditory temporal processing.
Once Schmid has established this highly translational behavioral platform, future projects will:
1) examine to what extent perturbed auditory processing during development correlates with cognitive dysfunction, such as language impairments, deficits in social behavior and increased anxiety in both animal models and individuals with ASD;
2) explore the mechanistic causes of impaired auditory temporal processing using in vivo and in vitro (patch-clamp) electrophysiology in animal models, as well as functional imaging studies in both animals and humans;
3) evaluate the potential of both pharmacological intervention (informed by results in (2) and research of others) and behavioral therapy (i.e., exposure to a multimodal sensory-enriched environment to ameliorate the developmental auditory processing deficits and associated cognitive impairment).