EFFECTS OF DRUG INDUCED BRAIN INJURY ON COGNITION

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。影像学研究表明，可卡因依赖时白色物质受损，可能继发于可卡因的血管收缩作用。白色物质损伤可损害皮质通讯，导致认知和行为改变。虽然白色物质提供了皮质连接的物理基础，但白色物质微观结构的体内研究很少，可能是因为缺乏适当的工具。 扩散张量成像（DTI）是一种磁共振成像（MRI）方法，特别适合于研究白色物质。DTI可用于量化三维组织水流动性（即自扩散）的大小和方向性。白色（WM）中的结构，如髓鞘，轴突膜，细胞骨架元件和白色束，可以作为水流动性的障碍，导致水分子沿着平行于纤维的路径移动得更远，而不是垂直于这些纤维的路径。当存在水流动性的方向依赖性时，扩散被描述为各向异性的。高度规则、有序的纤维将具有高的各向异性;不太有序的纤维将具有较低的各向异性测量。这种各向异性可以被量化，并用于评估的微观结构组织的白色物质纤维使用标量措施，如分数各向异性（FA）。 我们已经在一系列临床研究中使用了DTI，并证明了正常衰老、精神分裂症、酒精中毒和HIV感染中白色物质各向异性的改变。此外，我们已经证明了精神分裂症、酗酒和HIV感染的白色物质各向异性和认知测量之间的显著相关性。这种有前途的方法尚未应用于研究可卡因依赖对白色物质完整性的影响。 在这个应用中，我们建议研究可卡因依赖患者和正常对照与MRI和神经认知评估。我们的具体目标是：目的1）确定与对照组（CTRL）相比，可卡因依赖（CocDep）受试者中的白色微结构是否存在异常。我们的假设是：1）CocDep将有较低的白色物质分数各向异性（FA）比CTRL。2)CocDep将在额叶区域具有最大的FA减少。 目的2：确定CocDep受试者中WM FA和认知障碍之间是否存在关系。我们的假设是：1.与CTRL相比，CocDep将在特定的认知领域受损。根据文献，我们预计最大的缺陷将在执行功能领域。2.异常的神经认知功能将与选定区域的WM FA减少相关。 GCRC在本项目中的作用将是提供用于诊断目的的标准化临床面谈评估，并提供可进行面谈/测试的额外办公空间。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for 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.