Even individuals with autism spectrum disorders (ASD) who develop fluent use of spoken language often sustain problems with the suprasegmental aspects of speech (prosody). ASD individuals' difficulties with prosody can affect receptive as well as expressive language. Prosody contributes significantly to the `personal' information conveyed by speech communication that enables individuals to participate in the joint construction of socially meaningful and effective discourse. Difficulties in perception of prosody in ASD may be related to the same neurodevelopmental deficits that result in other symptomatic domains of the autistic syndrome. A currently popular view is that these deficits in ASD may involve abnormalities in long-range neural connectivity. Importantly, all current biological theories of prosody view understanding prosody as depending upon the dynamic integration of processes in widely- separated brain regions. We propose that difficulties in understanding prosody in ASD may, in fact, be related to underlying abnormalities in connectivity among brain regions required for its processing. Limited research has been done on understanding prosody in ASD to date, however, particularly with regard to individuals' abilities to perceive affective prosodic cues (the 'emotion' in speech) and understand their significance. The goals of the research in this proposal are: 1) to better characterize the perceptual impairment in understanding affective prosody in high-functioning autistic individuals (HFA), 2) to identify the functional neuroanatomy of an affective prosody perceptual task that significantly distinguishes HFA from control subjects, 3) to determine whether abnormalities in neural connectivity may explain the differences in functional neuroanatomy identified in (2), and 4) to potentially contribute to the development of a useful endophenotypic marker that may aid in identification of genetic and neurobiological causes of autism. To achieve these goals, in this two-year project we will use behavioral testing and functional magnetic resonance imaging (fMRI) to assess the responses of sib-pairs recruited from an established ASD research subject pool as well as those of control subjects as they make perceptual judgments on speech stimuli varying in their affective prosody. In addition to more conventional assessments of brain activation within the fMRI data, we will for the first time in a study of autism assess distinct response types (transient vs. sustained responses) and jointly apply three separate techniques for assessing brain structure, functional connectivity and white matter tract integrity in brain networks engaged by our subjects. The strength of correspondence between functional and connectional 'abnormalities' identified with these techniques will be determined. Our sib-pair experimental design will also offer the opportunity for preliminarily identifying possible `markers' that aggregate in families, which may be important for future genetic evaluations. An overarching goal of this two-year brain imaging project is to determine whether abnormal connections in the brain may account for some of the communication impairments in autism, particularly those involved in the understanding of verbally expressed emotion between individuals. Results of this project, however, may also enrich our understanding of how emotion and other personal aspects of verbal communication are understood by normal individuals, and clarify mechanisms by which these processes can be disrupted in the human brain. [unreadable] [unreadable] [unreadable] [unreadable]