The goals of the proposed research are three:(1) to test children with brain damage localized to frontal cortex on tests (a) which have been linked specifically to frontal cortex function through neuroanatomical and behavioral studies with infant and adult monkeys and (b) on which we know the normal developmental progression in children. Important aspects of this work will be to look for converging evidence from diverse tests all linked to the same subregion of frontal cortex, and to attempt to dissociate performance on these tests from performance on tests linked to other neural circuits. The goal is to develop non-invasive tests capable of detecting frontal cortex damage in infants and young children. Presently such damage often goes undetected for many years because of the lack of such tests. (2) to investigate the relationship of dopamine levels to performance on these tasks, and to begin to investigate the hypothesis that the fundamental maturational change which underlies the emergence of cognitive abilities dependent on frontal cortex during infancy is increasing levels of frontal cortex dopamine. To do this, children with early-treated PKU, who have no known structural brain damage but who are vulnerable to reduced levels of dopamine will be tested. Because their general cognitive functioning is good, if deficits are found they are likely to be selective. If they are selectively impaired on tests of frontal cortex function, this will be the first demonstration in humans of a cognitive deficit on frontal cortex tasks from dopamine depletion alone. Because L-dopa and the dopamine precursor, tyrosine, can be taken orally, there is an excellent chance that if deficits are found, therapeutic interventions will be possible to alleviate any impairments. (3) to better understand the abilities required for success on tasks that depend on frontal cortex function. Hypotheses will be considered that suggest that memory for space, and/or time, or for relational information in general is dissociable from memory for other information and dependent upon frontal cortex function.
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