Phenotyping the neural basis of sensorimotor control of speech in 16p11.2 deletion syndrome

PROJECT SUMMARY Deficits in speech production are highly prevalent in neurodevelopmental disorders (NDDs). They are some of the most debilitating of all deficits because they impair communication and there are not effective and efficient substitutes for speaking. In order to build our mechanistic understanding of the neurodevelopmental causes of speech impairments, we propose to study speech dysfunction in individuals with 16p11.2 deletions, which is one of the most common genetic etiologies of autism and is associated with related conditions such as epilepsy, motor impairment, sensory dysfunction, and most prominently, speech impairments, which affect an estimated 70-100% of individuals with this copy number variant. We will capitalize on data being collected for the ongoing UCSF Speech, Voice, and Communication (SVAC) study of speech in individuals with idiopathic autism for comparison groups, including speech-impaired autistic and typically developing participants, for the proposed cross-sectional study. We will enroll participants with 16p11.2 deletion syndrome and concurrently examine speech abilities, sensorimotor control of speech, and the neural processes that support these functions. This will allow us to build a mechanistic understanding of the potential causes of speech impairments in these populations. Our strong preliminary data suggest distinct mechanisms of impairment in speech-impaired individuals with autism without known genetic etiology and individuals with 16p11.2 deletion syndrome. Contrasting the more genetically and phenotypically homogenous group of individuals with 16p11.2 deletions with the more heterogeneous autism group will allow us to identify differences in neurobiology and sensorimotor control of speech that are specific to genetic impact via the deletion as opposed to being associated with broad neurodevelopmental differences. Thus, the proposed work will build our neurobiological and mechanistic understanding of speech impairments in neurodevelopmental disorders. This knowledge can be applied to uncover potential causal pathways of speech impairments and identify novel targets for intervention.