One out of every 150 people in the United States is affected by autism. Autistic individuals are severely impaired in their ability to process the subtle cues used in everyday communication and social interactions. Recent functional imaging studies have revealed serious deficits in speech sound discrimination in both children and adults with autism. The latency increase of speech evoked neural responses is well correlated with the degree of cognitive and language impairments. Unfortunately, the poor resolution of human imaging techniques obscures the neural basis of the impairment. We propose to evaluate speech sound coding in the valproic acid (VPA) animal model of autism, and quantify the beneficial effects of two common autism therapies: auditory training and environmental enrichment. Speech sounds evoke specific spatiotemporal patterns of cell firing in the central auditory system of normal rats.
The first aim of the project is to determine the consequence of VPA exposure on the collicular and cortical representations of speech sounds. Our preliminary results indicate that in utero VPA exposure severely degrades the precise spatiotemporal patterns evoked by speech sounds in auditory cortex. As in autism, the longer latency in our animal model is significantly greater for speech sounds compared to tones.
The second aim of the project is to determine the behavioral consequences of VPA exposure on speech sound discrimination. If the neural spatiotemporal representations of speech sounds are degraded, then it is possible that certain speech sounds may not be distinguishable in VPA treated rats. We therefore predict that speech sound discrimination will be impaired in VPA exposed rats.
The third aim i s to determine the effects of speech training and environmental enrichment on speech evoked activity in VPA exposed rats. Based on previous studies, we predict that both speech training and environmental enrichment will relieve the degradation of the cortical responses to speech sounds and restore speech sound discrimination to control levels in VPA treated rats. The results of the proposed studies will add to our understanding of the neural mechanisms that are associated with speech sound coding. Insights derived from these studies may influence the development of new behavioral and sensory techniques to treat the communication impairments in autism that result in part from degraded speech sound discrimination.
Although individuals with autism are known to have significant communication problems, the neural mechanisms responsible for impaired communication are poorly understood. The proposed animal model for autism will identify a potential cause of speech sound discrimination impairments and quantify the beneficial effects of two common autism therapies: auditory training and environmental enrichment. A better understanding of these mechanisms may aid the design of improved behavioral and sensory therapies to reduce communication impairments in autism.
|Engineer, Crystal T; Rahebi, Kimiya C; Borland, Michael S et al. (2018) Shank3-deficient rats exhibit degraded cortical responses to sound. Autism Res 11:59-68|
|Engineer, Crystal T; Hays, Seth A; Kilgard, Michael P (2017) Vagus nerve stimulation as a potential adjuvant to behavioral therapy for autism and other neurodevelopmental disorders. J Neurodev Disord 9:20|
|Engineer, Crystal T; Shetake, Jai A; Engineer, Navzer D et al. (2017) Temporal plasticity in auditory cortex improves neural discrimination of speech sounds. Brain Stimul 10:543-552|
|Pruitt, David T; Schmid, Ariel N; Danaphongse, Tanya T et al. (2016) Forelimb training drives transient map reorganization in ipsilateral motor cortex. Behav Brain Res 313:10-16|
|Centanni, Tracy Michelle; Booker, Anne B; Chen, Fuyi et al. (2016) Knockdown of Dyslexia-Gene Dcdc2 Interferes with Speech Sound Discrimination in Continuous Streams. J Neurosci 36:4895-906|
|Hays, Seth A; Ruiz, Andrea; Bethea, Thelma et al. (2016) Vagus nerve stimulation during rehabilitative training enhances recovery of forelimb function after ischemic stroke in aged rats. Neurobiol Aging 43:111-8|
|Meyers, Eric; Sindhurakar, Anil; Choi, Rachel et al. (2016) The supination assessment task: An automated method for quantifying forelimb rotational function in rats. J Neurosci Methods 266:11-20|
|Hulsey, Daniel R; Hays, Seth A; Khodaparast, Navid et al. (2016) Reorganization of Motor Cortex by Vagus Nerve Stimulation Requires Cholinergic Innervation. Brain Stimul 9:174-81|
|Khodaparast, Navid; Kilgard, Michael P; Casavant, Reema et al. (2016) Vagus Nerve Stimulation During Rehabilitative Training Improves Forelimb Recovery After Chronic Ischemic Stroke in Rats. Neurorehabil Neural Repair 30:676-84|
|Engineer, Crystal T; Rahebi, Kimiya C; Borland, Michael S et al. (2015) Degraded neural and behavioral processing of speech sounds in a rat model of Rett syndrome. Neurobiol Dis 83:26-34|
Showing the most recent 10 out of 34 publications