Auditory brainstem responses in an animal model of autism spectrum disorder: Audiograms, sex differences and...

Atypical processing of sound is a common feature of autism spectrum disorder (ASD). This impairment is present at birth, ranges in severity and can impact language and cognitive ability. As such, early diagnosis and intervention is paramount. The auditory brainstem response (ABR) is a simple, non-invasive tool that reveals synchronized electrical activity along the ascending auditory pathway in response to simple sounds and numerous studies have reported significant changes in ABR latency and amplitude in individuals with ASD. Additionally, neuropathological studies reveal fewer auditory brainstem neurons in ASD. Together, these findings implicate brainstem dysfunction as a root cause of atypical sound processing in ASD. In utero exposure to the antiepileptic drug valproic acid (VPA) significantly increases the risk of an ASD diagnosis in humans. As such, in utero exposure to VPA is a clinically relevant and validated animal model of ASD. Previous studies have shown that animals exposed to VPA in utero have significantly fewer neurons in the auditory brainstem, thalamus and cerebral cortex, reduced ascending projections to the inferior colliculus and medial geniculate, decreased cortical projections to the inferior colliculus and poorly organized tonotopic maps. Consistent with these structural changes, male rats exposed to VPA in utero have significant changes in ABR latency in response to broadband clicks. In this study, we aimed to further characterize the ABR in a repeated oral VPA exposure model of ASD. Specifically, we hypothesized that VPA exposure would result in significant hearing differences in both male and female animals in response to both broadband clicks and pure tone pips. We also hypothesized that ABR latency might provide a quantitative screening tool for ASD. Our results indicate that repeated oral exposure to VPA results in atypical click and tone-evoked ABRs in both male and female rats and that wave V latency may provide a highly sensitivity metric for neurodevelopmental brainstem dysfunction. Together, these results further characterize hearing impairment in an animal model of ASD and illustrate the utility of the ABR in screening for neurodevelopmental conditions.