Abnormal language functioning is one of the primary manifestations of autism. However, to date there has been little research into the underlying neural mechanisms responsible for this language dysfunction. Project III of the program project, """"""""Language and autism: Clinical and Basic Studies,"""""""" will use structural magnetic resonance imaging (MRI) to evaluate the structure of cerebral cortical language regions, and functional MRI (fMRI) techniques to evaluate the cerebral activation responses to language performance tasks, in autistic subjects and matched control groups. fMRI 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 with individual subjects. The structural imaging studies will examine adolescent subjects (age 10-14) over a wide IQ range for gray matter volumes in language-related regions within the cerebral cortex, such as the superior temporal gyrus (STG) and dorsolateral prefrontal cortex (DLPFC). These measures of brain structure will be evaluated for correlation with language performance determined through the Core evaluations. We will also determine whether autistic subjects show abnormal developmental changes in these regions during adolescence by repeating the scanning longitudinally. The fMRI experiments will evaluate adult (age greater than 18), high-functioning autistic subjects and matched control groups for three levels of cognitive processing necessary for language ability: primary sensory stimulation, semantic encoding, and prosody (emotional intonation). There is evidence that each of thee domains may demonstrate abnormality in autism, and we will evaluate the neural activation responses to these activation paradigms through a series of five experimental conditions. Neuroimaging studies in autism to date have primarily examined general measures of brain structure and function, and no prior imaging study has used such a hypothesis-driven approach aimed at deepening our understanding of the neural mechanisms of autistic language dysfunction.
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