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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH063255-01
Application #
6321622
Study Section
Special Emphasis Panel (ZRG1-BBBP-6 (01))
Program Officer
Anderson, Kathleen C
Project Start
2001-05-01
Project End
2006-04-30
Budget Start
2001-05-01
Budget End
2002-04-30
Support Year
1
Fiscal Year
2001
Total Cost
$315,474
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
201373169
City
New York
State
NY
Country
United States
Zip Code
10065
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Liston, Conor; Watts, Richard; Tottenham, Nim et al. (2006) Frontostriatal microstructure modulates efficient recruitment of cognitive control. Cereb Cortex 16:553-60
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Durston, Sarah; Casey, B J (2006) What have we learned about cognitive development from neuroimaging? Neuropsychologia 44:2149-57
Eigsti, Inge-Marie; Zayas, Vivian; Mischel, Walter et al. (2006) Predicting cognitive control from preschool to late adolescence and young adulthood. Psychol Sci 17:478-84
Kotsoni, Eleni; Byrd, Dana; Casey, B J (2006) Special considerations for functional magnetic resonance imaging of pediatric populations. J Magn Reson Imaging 23:877-86
Scerif, Gaia; Worden, Michael S; Davidson, Matthew et al. (2006) Context modulates early stimulus processing when resolving stimulus-response conflict. J Cogn Neurosci 18:781-92
Nigg, Joel T; Casey, B J (2005) An integrative theory of attention-deficit/ hyperactivity disorder based on the cognitive and affective neurosciences. Dev Psychopathol 17:785-806

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