Multimodal Neuroimaging of Prosody in Schizophrenia and Developmental Disorders

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DESCRIPTION (provided by applicant): An inability to convey emotion by vocal modulation (prosody) is a major aspect of social cognitive dysfunction for patients afflicted with a variety of neuropsychiatric illnesses such as schizophrenia and autism. The neural mechanisms of these deficits, and how they develop from childhood to adulthood have received remarkably little research attention. This training proposal seeks to prepare the candidate for independent research that addresses both of these issues. In terms of the neural mechanisms of prosody, there is some evidence that prosodic dysfunction is associated with a disruption of interactions between temporal and frontal cortex. The temporal component of this circuit appears to parse the acoustic signal for emotional distinctions, which are subsequently evaluated for emotional meaning by the frontal component. It is likely that this circuit mediates prosodic dysfunction in schizophrenia, which is associated with basic audio-sensory deficits and abnormal temporo-frontal interactions. The research proposed here will employ multimodal neuroimaging approaches to produce the first comprehensive description of this temporo-frontal circuit, in both healthy adults and patients with schizophrenia, by integrating three state-of-the-art neuroimaging techniques. First, magnetoencephalography (MEG) in conjunction with magnetic resonance functional connectivity analysis (fMRI) will be used to determine the time course of processing by the circuit. Then, by applying Diffusion Imaging, these functional estimates will be related to neurostructural estimates of auditory pathway integrity. We expect to demonstrate that neurostructural integrity deficits underpin abnormal temporo-frontal interactions during prosodic processing in schizophrenia. In addition to training the candidate in multimodal neuroimaging, the proposed activities will provide him a background in the developmental psychology of language and auditory neurobiology, as well as a framework to develop and adapt prosodic tasks for children and adolescents. The candidate is an Instructor in Psychiatry at the University of Pennsylvania and has an established interest in social communication. Drs. Timothy Roberts and Ruben Gur will mentor him. Dr. Roberts is an expert in MEG and DTI techniques, with a research focus on the development of auditory and language processing in healthy children and patients with autism. Dr. Gur is an expert in neuropsychological assessment and neuroimaging, whose research concerns emotional and cognitive dysfunction in schizophrenia. These mentors will assure that the experience resulting from the proposed training plan will enable the candidate to establish an independent research program that can make significant contributions in the developmental neuroscience of social communication, and the understanding of how dysfunction in such communication emerges in neuropsychiatric disorders like schizophrenia and autism.