We propose to extend our developments with magnetic resonance imaging (MRI) for tracking neuronal fibers in the lining human brain. The method, called diffusion tensor tracking (DTT), reconstructs continuous threedimensional trajectories of neuronal fiber bundles from diffusion tensor-encoded MRI data (DT-MRI). Compared to other methods, the MR procedure is non-invasive, capable of studying connectional anatomy unique to humans, and amenable to direct correlation with fMRI activations in the same individual subjects, which potentially will uncover the neuronal connections used for human tasks. Noninvasive DTT methods are especially important for revealing connections in humans associated with cognitive functions like language that cannot be extrapolated from non-human primate studies.
For Aim I we will further enhance current computations of three- dimensional whole-brain fiber trajectories from DT-MRI data and develop and refine methods for selecting different fiber groups, especially including connections between regions defined by fMRI.
For Aim II we will evaluate the accuracy and precision of DTT fiber trajectories by computer simulation and test-retest evaluation of experimental data.
In Aim III we will assess the ability of DTT to determine the connectivity between fMRI-defined primary sensory and higher-order regions in the somatosensory and visual systems using known monkey neuroanatomy as a standard. The visual studies will involve retinotopic fMRI mapping to identify higher visual areas and to select functional subsets of the geniculocalcarine tract, and motion perception studies to activate remote cognitive regions outside the visual cortex.
For Aim I V we will examine the potential clinical utility of DTT to characterize the functional effects of white matter lesions by correlating the lesion-to-cortex DTT projections with cortical defects in retinotopic fMRI and with visual field defects in patients with focal lesions of the geniculocalcarine tract.
In Aim V, we will compare visual cortex connections in sighted, early- and late-blind subjects to assess the effects of age of blindness on the development and organization of the visual system. Successful completion of the proposed research will provide a set of tested tools for interrogating the development, functional organization, and reorganization of the human brain in normal and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS039538-04
Application #
6700859
Study Section
Diagnostic Radiology Study Section (RNM)
Program Officer
Babcock, Debra J
Project Start
2001-01-27
Project End
2005-12-31
Budget Start
2004-01-01
Budget End
2004-12-31
Support Year
4
Fiscal Year
2004
Total Cost
$417,456
Indirect Cost
Name
Washington University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Salminen, Lauren E; Schofield, Peter R; Pierce, Kerrie D et al. (2017) Vulnerability of white matter tracts and cognition to the SOD2 polymorphism: A preliminary study of antioxidant defense genes in brain aging. Behav Brain Res 329:111-119
Salminen, Lauren E; Conturo, Thomas E; Bolzenius, Jacob D et al. (2016) REDUCING CSF PARTIAL VOLUME EFFECTS TO ENHANCE DIFFUSION TENSOR IMAGING METRICS OF BRAIN MICROSTRUCTURE. Technol Innov 18:5-20
Baker, Laurie M; Cabeen, Ryan P; Cooley, Sarah et al. (2016) APPLICATION OF A NOVEL QUANTITATIVE TRACTOGRAPHY-BASED ANALYSIS OF DIFFUSION TENSOR IMAGING TO EXAMINE FIBER BUNDLE LENGTH IN HUMAN CEREBRAL WHITE MATTER. Technol Innov 18:21-29
Salminen, Lauren E; Conturo, Thomas E; Laidlaw, David H et al. (2016) Regional age differences in gray matter diffusivity among healthy older adults. Brain Imaging Behav 10:203-11
Salminen, Lauren E; Schofield, Peter R; Pierce, Kerrie D et al. (2016) Neuromarkers of the common angiotensinogen polymorphism in healthy older adults: A comprehensive assessment of white matter integrity and cognition. Behav Brain Res 296:85-93
Behrman-Lay, Ashley M; Usher, Christina; Conturo, Thomas E et al. (2015) Fiber bundle length and cognition: a length-based tractography MRI study. Brain Imaging Behav 9:765-75
Cooley, Sarah A; Heaps, Jodi M; Bolzenius, Jacob D et al. (2015) Longitudinal Change in Performance on the Montreal Cognitive Assessment in Older Adults. Clin Neuropsychol 29:824-35
Cooley, Sarah A; Cabeen, Ryan P; Laidlaw, David H et al. (2015) Posterior brain white matter abnormalities in older adults with probable mild cognitive impairment. J Clin Exp Neuropsychol 37:61-9
Bolzenius, Jacob D; Laidlaw, David H; Cabeen, Ryan P et al. (2015) Brain structure and cognitive correlates of body mass index in healthy older adults. Behav Brain Res 278:342-7
Salminen, Lauren E; Paul, Robert H (2014) Oxidative stress and genetic markers of suboptimal antioxidant defense in the aging brain: a theoretical review. Rev Neurosci 25:805-19

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