Recent work from our research group shows that school-age children with phenylketonuria (PKU) exhibit impairments in two prefrontally-mediated cognitive abilities of crucial importance to early learning: working memory and strategic processing in long-term memory. These impairments are more evident in older than younger children, suggesting that the impairments are not stable across development but instead may emerge with age. In the proposed research, the developmental trajectory of working memory and strategic memory processing will be charted longitudinally to determine if impairments emerge in individual children. Two neuropathological mechanisms that may underlie impairments in prefrontally-mediated aspects of memory also will be examined. This research has implications for the development of rehabilitation strategies designed to improve learning and memory in children with PKU and other developmental disorders affecting prefrontal function.
The aims and the methods for addressing the aims of this study are as follows: (1) To test the hypothesis that children with PKU exhibit impairments in prefrontally-mediated aspects of memory. To achieve this aim, working memory and strategic memory processing tasks will be administered to children with PKU who range from 7 to 18 years of age. Comparisons will be made with demographically matched, typically developing children. (2) To test the hypothesis that impairments in prefrontally-mediated aspects of memory emerge as children with PKU age. To achieve this aim, working memory and strategic memory processing will be evaluated on a longitudinal basis. By doing so, the developmental trajectory of prefrontally-mediated aspects of memory will be defined at the level of individual children. (3) To test the hypothesis that white matter abnormalities contribute to impairments in prefrontally-mediated aspects of memory in children with early-treated PKU.
This aim will be achieved through the use of diffusion tensor imaging (DTI), a neuroimaging technique permitting refined examination of white matter integrity. Dopamine deficiency also will be examined by assessing blood phenylalanine (a dopamine precursor) levels. Findings from DTI and phenylalanine levels will be examined in relation to findings from the memory tasks. ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD044901-01
Application #
6674511
Study Section
Biobehavioral and Behavioral Processes 3 (BBBP)
Program Officer
Kau, Alice S
Project Start
2003-07-01
Project End
2008-04-30
Budget Start
2003-07-01
Budget End
2004-04-30
Support Year
1
Fiscal Year
2003
Total Cost
$306,441
Indirect Cost
Name
Washington University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Hawks, Zoë W; Strube, Michael J; Johnson, Neco X et al. (2018) Developmental Trajectories of Executive and Verbal Processes in Children with Phenylketonuria. Dev Neuropsychol 43:207-218
Wesonga, Erika; Shimony, Joshua S; Rutlin, Jerrel et al. (2016) Relationship between age and white matter integrity in children with phenylketonuria. Mol Genet Metab Rep 7:45-9
Hood, Anna; Antenor-Dorsey, Jo Ann V; Rutlin, Jerrel et al. (2015) Prolonged exposure to high and variable phenylalanine levels over the lifetime predicts brain white matter integrity in children with phenylketonuria. Mol Genet Metab 114:19-24
Hood, Anna; Grange, Dorothy K; Christ, Shawn E et al. (2014) Variability in phenylalanine control predicts IQ and executive abilities in children with phenylketonuria. Mol Genet Metab 111:445-51
Araujo, Gabriel C; Christ, Shawn E; Grange, Dorothy K et al. (2013) Executive response monitoring and inhibitory control in children with phenylketonuria: effects of expectancy. Dev Neuropsychol 38:139-52
Janos, Alicia L; Grange, Dorothy K; Steiner, Robert D et al. (2012) Processing speed and executive abilities in children with phenylketonuria. Neuropsychology 26:735-43
Banerjee, Pia; Grange, Dorothy K; Steiner, Robert D et al. (2011) Executive strategic processing during verbal fluency performance in children with phenylketonuria. Child Neuropsychol 17:105-17
McAuley, Tara; White, Desirée A (2011) A latent variables examination of processing speed, response inhibition, and working memory during typical development. J Exp Child Psychol 108:453-68
White, Desiree A; Connor, Lisa Tabor; Nardos, Binyam et al. (2010) Age-related decline in the microstructural integrity of white matter in children with early- and continuously-treated PKU: a DTI study of the corpus callosum. Mol Genet Metab 99 Suppl 1:S41-6
Araujo, Gabriel C; Christ, Shawn E; Steiner, Robert D et al. (2009) Response monitoring in children with phenylketonuria. Neuropsychology 23:130-4

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