There is increasing evidence that white matter is injured in cocaine dependence (CD). Cocaine and its metabolites have potent vasoconstrictive and neurotoxic properties. White matter lesions in CD subjects have been observed with magnetic resonance imaging (MRI). Brain perfusion defects are present even after several months of abstinence. Chronic hypoperfusion in animal models has been shown to result in white matter injury and learning impairment. White matter injury can impair cortical communication resulting in cognitive and behavioral alterations. Although white matter provides the physical foundation for cortical connectivity, there has been iime in vivo study of white matter, perhaps because of a lack of appropriate tools. Diffusion Tensor Imaging (DTI) is an MRI method which is uniquely suited to the study of white matter because it can be used to quantify the magnitude and directionality of tissue water mobility (ie., self-diffusion) in three dimensions. Structures in white matter (WM), such as myelin sheaths, axon membranes, cytoskeletal elements and white matter tracts, can act as barriers to water mobility, causing the water molecules to move farther along paths that are parallel to fibers rather than those mat are perpendicular to these fibers. When there is a directional dependence of water mobility, the diffusion is described as being anisotropic. This anisotropy can be quantified in a scalar value, fractional anisotropy (FA) and used to assess the microstructural organization of white matter fibers. Highly regular, organized fibers will have high anisotropy; less well-organized fibers will have lower anisotropy measures. We have used DTJ in a series of clinical research studies and have demonstrated differences in white matter anisotropy due to normal aging, schizophrenia, and alcoholism. In addition, we have demonstrated significant correlations between white matter anisotropy and cognitive measures in schizophrenia and alcoholism. In this application, we propose to study cocaine dependent patients and normal controls with DTI and neurocognitive assessments.
Our Specific Aims are to: 1 ) Determine if there are abnormalities in WM FA in cocaine dependent (CD) subjects compared with controls (NC) 2) Determine if there is a relationship between WM FA and cognitive impairment in CD subjects.
| Lim, Kelvin O; Wozniak, Jeffrey R; Mueller, Bryon A et al. (2008) Brain macrostructural and microstructural abnormalities in cocaine dependence. Drug Alcohol Depend 92:164-72 |
