This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.There is evidence from imaging studies that white matter is injured in cocaine dependence, possibly secondary to the vasoconstrictive effects of cocaine. White matter injury can impair coritcal communication resulting in cognitive and behavioral alterations. Although white matter provides the physical foundation for cortical connectivity, there has been little in vivo study of white matter microstructure, perhaps because of a lack of appropriate tools. Diffusion Tensor Imaging (DTI) is a magnetic resonance imaging (MRI) method which is uniquely suited to the study of white matter. DTI can be used to quantify the magnitude and directionality of tissue water mobility (i.e, 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 that are perpendicular to these fibers. When there is a directional dependence of water mobility, the diffusion is described as being anisotropic. Highly regular, organized fibers will have high anisotropy; less well-organized fibers will have lower anisotropy measures. This anisotropy can be quantified and used to assess the microstructural organization of white matter fibers using scalar measures such as fractional anistropy (FA). We have used DTI in a series of clincial research studies and have demonstrated alterations in white matter anisotropy in normal aging, schizophrenia, alcoholism, and HIV infection. In addition, we have demonstrated significant correlations between white matter anisotropy and cognitive measures in schizophrenia, alcoholism and HIV infection. This promising method has not yet been applied for studying the effects of cocaine dependence on white matter integrity.In this application, we propose to study cocaine dependent patients and normal controls with MRI and neurocognitive assessments.
Our specific aims are to:
Aim 1) Determine if there are abnormalities in white matter microstructure in cocaine dependent (CocDep) subjects compared with controls (CTRL). Our hyoptheses are: 1) CocDep will have lower white matter fractional anisotropy (FA) than CTRL. 2) CocDep will have greatest FA reduction in frontal regions.
Aim 2 : Determine if there is a relationship between WM FA and cognitive impairment in CocDep subjects. Our hypotheses are: 1. CocDep compared with CTRL will be impaired in specific cognitive domains. Based on the literature, we anticipate the greatest deficits will be in the executive function domain. 2. Abnormal neurocognitive functioning will be associated with reduced WM FA in selected regions. The role of the GCRC in this project will be to provide the standardized clinical interview assessments for diagnostic purposes and additional office space where interview/testing can be performed.
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