One key feature of cognitive and behavioral development is the gradual ability to override one behavior in favor of another or to suppress attention to irrelevant information in favor of more relevant information. The proposed studies examine the normal development of this ability and its neural basis. Behavioral paradigms will be used that parametrically manipulate the degree of interfering, irrelevant information, thereby increasing the demands for overriding an attentional or behavioral response (i.e., cognitive control). The investigators will examine the structural and functional connectivity of brain systems including the prefrontal cortex and basal ganglia, assumed to play a role in cognitive control. They propose to use the following methods to address this issue: 1) structural magnetic resonance imaging (MRI) to examine morphometric changes in relevant brain structures; 2) diffusion tensor imaging to examine the extent of myelination of frontostriatal circuitry; and 3) functional MRI in conjunction with well defined cognitive paradigms to examine the functional development of neural systems involved in cognitive control. The investigators will use a cross lag design exploiting both cross-sectional and longitudinal information across the ages of 4 to 30. Further, to understand the neuromodulatory role of dopamine in this developmental process, known polymorphisms in genes that contribute to the neuromodulatory effects of dopamine will be examined via gene association studies. A number of such polymorphisms have been identified that occur relatively frequently in the general population. The investigators will collect DNA samples from the cheek cells of subjects. This DNA will be typed for variation at a particular gene and then correlated with behavioral performance using simple population-based statistical tests. The method is simple, noninvasive, reliable, fast and inexpensive relative to the neuroimaging studies. They will determine if measures of genetic variation predict performance on tasks of cognitive control or relate to measures of structural and functional brain development. This work promises to have significant implications at the behavioral, biological, and ultimately at the genetic level for developmental disorders that have as a core deficit, a problem overriding or suppressing inappropriate thoughts and behaviors like Attention Deficit-Hyperactivity Disorder, Obsessive Compulsive Disorder and Tourette syndrome.
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