The central aim of the proposed research is to investigate whether there is a common basis for the numerical cognition deficits associated with three neurogenetic disorders: Turner, Williams, and full mutation fragile X syndromes. Despite many differences, numerical deficits have been consistently reported in individuals with Turner, Williams, full mutation fragile X, and 22q11.2 deletion (velocardiofacial/DiGeorge) syndromes, among others. The investigators hypothesize that some key aspects of visuospatial function are disturbed in each of these syndromes, and characterization of these basic processes will generate explanations of, and possibly indicate treatments for, these numerical deficits. On the other hand, the differences among these genetic syndromes will allow the investigators to control for a range of critical factors such as intelligence level, brain volume, cardiac status, and other cognitive performance domains. This project aims to study seven to fourteen year old children with Williams, Turner, and full mutation fragile X syndromes in parallel with a study of 22q11.2 deletion syndrome children already being carried out by the principal investigator. This will constitute the first parallel study of children with all of these disorders using the same methodology. Thus it has the potential to reveal critical information about a putative """"""""common pathway"""""""" for foundational numerical cognitive competence. Little is known about why a set of neurogenetic disorders that produce such different physical and intellectual outcomes should share what appears to be a common deficit in the numerical cognition domain. The investigators' hypothesis is that the disorders all create some form of anomalous in brain development that affects the parietal lobes, as well as other brain areas, in such a way as to disturb the normal development of visual/spatial cognition. Therefore, the investigators propose a program of research in three genetic disorders: Turner, Williams, full mutation fragile X syndromes with the following aims: (1) Characterize the cognitive deficit with performance tests; (2) Specify the volumetric changes in brains of children with these disorders; (3) Determine, via diffusion tensor imaging, white matter anomalies that might contribute to cognitive dysfunction; and (4) Directly measure, via functional magnetic resonance imaging (fMRI), cortical activity as children attempt visuospatial and numerical cognition tasks. The investigators expect that the results of these studies will provide the first extensive explanation of the similarities and/or differences in foundational numerical cognitive processes that exist among these different disorders. Findings are likely to indicate critical neurocognitive factors in the development of normal and disturbed early numerical ability. It should be possible to use these results to develop interventions for children with numerical disabilities and improved teaching methods in the numerical domain for typically developing children.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD046159-06
Application #
7277608
Study Section
Special Emphasis Panel (ZHD1-MRG-C (31))
Project Start
2005-02-01
Project End
2010-07-31
Budget Start
2007-08-01
Budget End
2010-07-31
Support Year
6
Fiscal Year
2007
Total Cost
$493,062
Indirect Cost
Name
University of California Davis
Department
Psychiatry
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Villalon-Reina, Julio; Jahanshad, Neda; Beaton, Elliott et al. (2013) White matter microstructural abnormalities in girls with chromosome 22q11.2 deletion syndrome, Fragile X or Turner syndrome as evidenced by diffusion tensor imaging. Neuroimage 81:441-454
Simon, Tony J (2011) Clues to the foundations of numerical cognitive impairments: evidence from genetic disorders. Dev Neuropsychol 36:788-805
Awate, Suyash P; Yushkevich, Paul A; Song, Zhuang et al. (2010) Cerebral cortical folding analysis with multivariate modeling and testing: Studies on gender differences and neonatal development. Neuroimage 53:450-9
Beaton, Elliott A; Stoddard, Joel; Lai, Song et al. (2010) Atypical functional brain activation during a multiple object tracking task in girls with Turner syndrome: neurocorrelates of reduced spatiotemporal resolution. Am J Intellect Dev Disabil 115:140-56
Simon, Tony J (2010) Rewards and challenges of cognitive neuroscience studies of persons with intellectual and developmental disabilities. Am J Intellect Dev Disabil 115:79-82
Das, Sandhitsu R; Avants, Brian B; Grossman, Murray et al. (2009) Registration based cortical thickness measurement. Neuroimage 45:867-79
Awate, Suyash P; Yushkevich, Paul; Song, Zhuang et al. (2009) Multivariate high-dimensional cortical folding analysis, combining complexity and shape, in neonates with congenital heart disease. Inf Process Med Imaging 21:552-63
Awate, Suyash P; Yushkevich, Paul; Licht, Daniel et al. (2009) Gender differences in cerebral cortical folding: multivariate complexity-shape analysis with insights into handling brain-volume differences. Med Image Comput Comput Assist Interv 12:200-7
Awate, Suyash P; Win, Lawrence; Yushkevich, Paul et al. (2008) 3D cerebral cortical morphometry in autism: increased folding in children and adolescents in frontal, parietal, and temporal lobes. Med Image Comput Comput Assist Interv 11:559-67
Ramirez-Manzanares, Alonso; Cook, Philip A; Gee, James C (2008) A comparison of methods for recovering intra-voxel white matter fiber architecture from clinical diffusion imaging scans. Med Image Comput Comput Assist Interv 11:305-12

Showing the most recent 10 out of 21 publications