Project 1 brings together the Principal Investigator's previous research on development of communication and social behavior in autism with research by Co-PI Jocelyne H. Bachevalier on the developmental consequences of lesions on the medial temporal lobe in infant rhesus macaques. Dr. Bachevalier's research has led to the hypothesis that developmental impairment of the orbitofrontal-limbic circuit of the brain, including the medial-orbitofrontal cortex and amygdala, is a biological marker for autism and that the characteristic socio-emotional deficits of persons with autism are related to developmental impairment of this circuit. A secondary hypothesis derived from Dr. Bachevalier's research will also be addressed: that the degree of intellectual impairment in individuals with autism is related to impairment of the dorsolateral prefrontal-hippocampal circuit of the brain, including the dorsolateral prefrontal cortex and the hippocampus. All components of the Program Project will address these two hypotheses. Children and adolescents with Autistic Disorder (DSM-IV) (N=72) aged 7 to 19 and a comparison group of comparable ages and IQs without autism will be compared cross-sectionally.
Aims are as follows:
Aim 1 : to compare the performance of children and adolescents with and without autism, using neuropsychological tasks measuring the functioning of the orbitoprefrontal-amygdalar circuit of the dorsolateral prefrontal- hippocampal circuit.
Aim 2 : to compare performance on tasks measuring the functioning of the orbitoprefrontal-amygdalar circuit or the dorsolateral prefrontal-hippocampal circuit.
Aim 2 : to compare performance on tasks measuring the functioning of the orbitoprefrontal- amygdalar and dorsolateral prefrontal-hippocampal circuits of the brain with performance on tasks measuring socio-emotional cognition and behavior, and with clinical measures of the symptoms of autism.
Aim 3 : to carry out comparisons of Project I findings with those of other Program Project components. Because they share a common participant sample and design, direct comparisons between the neuroimaging data collected in Project II and neuropsychological and behavioral data collected in Project I will be possible. In addition, a core set of shared neuropsychological tasks will be given both to human participants in Project I and to rhesus monkeys in Project III that have received highly specific early lesions of the orbitoprefrontal cortex or amygdala, allowing exploratory comparisons between human and animal results. In confirmed, our hypotheses have the potential to help explain the neurodevelopmental disorder. As a component of the Program Project, Project I provides a necessary link between human behavior and a possible animal model of autism.
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