Deficits in language and social-communication functioning represent one of the primary manifestations of 'autism. However, to date there has been little research into the underlying neural mechanisms responsible for language and social-communication dysfunction in autism. Project Ill of the program project, 'Language in autism: Clinical and Basic Studies,' will use structural magnetic resonance imaging (MRI) and functional MRI (fMRI) techniques to evaluate the anatomy and physiology of brain regions and tasks related to language and Social-communication in autism. Subjects will include adolescent (age 10-1 6) autistic, specific language impaired (SLI), and matched control groups. fMRl is ideally suited for the functional studies in this project because it is non-invasive, and does not use ionizing radiation, allowing multiple experimental conditions to be evaluated within individual subjects. The structural imaging studies will examine gray matter volumes in language and social-communication-related regions within the cerebral cortex using segmentation, parcellation, and voxel-based morphometry (VBM) methods. White matter and cerebellum have also been implicated in autism, and so structural analyses will also include cerebellar and white matter parcellation and diffusion-tensor imaging (DTI) of white matter organization. Measures of brain structure will be evaluated for correlation with language performance determined through the Core evaluations. The fMRl experiments will evaluate high-functioning autistic subjects and matched control groups under five experimental conditions: lexical-semantic encoding, past tense processing, phonological processing, processing facial expressions linked to eyes vs. mouths, and activation related to direct vs. averted eye gaze. The three language fMRl tasks relate to experiments and findings from Project II (language), while the two social-communication tasks relate directly to Project I experiments and findings (social-communication). There is evidence that each of these domains demonstrates abnormality in autism, and we will evaluate the neural activation responses to these activation paradigms through a series of five experimental conditions.
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