This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.One finding emerging from our research program is that insult to the medial temporal lobe in monkeys, and more specifically the amygdala, results in an array of behavioral changes that mimic in many ways the behavioral disturbances seen in autistic people. The goal of the present project is to pursue investigation of this putative animal model of autism by testing the effects of early versus late lesions of a neural network that includes the amygdala and orbitofrontal cortex. All monkeys that had received selective lesions of the amygdala and orbital frontal cortex and their sham-operated controls have completed the behavioral testing and we are in the process of evaluating the extent of their lesions. The monkeys that had received the same lesions in infancy are being behaviorally trained at different time points from infancy through adulthood in tasks measuring recognition memory, stimulus-reward associations, working memory, social interactions, and emotional reactivity. These studies provide the unique opportunity to examine in the same animals cognitive functions, regulation of emotions, and formation and maintenance of social bonds. Through, such research, principles of the brain's response to damage will ultimately advance our understanding of the basic developmental processes that follow early dysfunction of the orbitofrontal-limbic circuit in primates, its implication for developmental disorders, such as autism, and leads eventually to discovery of ways by which such effects can be alleviated or even eliminated.
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