EFFECTS OF DRUG INDUCED BRAIN INJURY ON COGNITION

药物引起的脑损伤对认知的影响

• 批准号: 7375881
• 负责人: KELVIN O. LIM
• 金额: $ 0.57万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7375881
• 关键词: EFFECTS; DRUG; INDUCED; BRAIN; INJURY

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.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。影像学研究表明，可卡因依赖导致白质损伤，可能继发于可卡因的血管收缩作用。白质损伤会损害大脑皮层的沟通，导致认知和行为的改变。尽管白质为皮层连接提供了物理基础，但可能由于缺乏适当的工具，对白质微观结构的体内研究很少。扩散张量成像（DTI）是一种磁共振成像（MRI）方法，它是唯一适合研究白质。DTI可以在三维上量化组织水流动性（即自扩散）的大小和方向性。白质（WM）中的结构，如髓鞘、轴突膜、细胞骨架元素和白质束，可以作为水流动的障碍，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。当存在水迁移性的方向依赖时，扩散被描述为各向异性。高度规则、有组织的纤维将具有高的各向异性；组织较差的纤维具有较低的各向异性测量值。这种各向异性可以量化，并使用分数各向异性（FA）等标量测量来评估白质纤维的微观结构组织。我们在一系列的临床研究中使用了DTI，并证明了在正常衰老、精神分裂症、酗酒和HIV感染中白质各向异性的改变。此外，我们已经证明了精神分裂症、酒精中毒和HIV感染中白质各向异性与认知测量之间的显著相关性。这种有前景的方法尚未应用于研究可卡因依赖对白质完整性的影响。在这个应用中，我们建议通过MRI和神经认知评估来研究可卡因依赖患者和正常对照。我们的具体目的是：目的1)确定可卡因依赖（CocDep）受试者与对照组（CTRL）相比，白质微观结构是否存在异常。我们的假设是：1)CocDep的白质分数各向异性（FA）比CTRL低。2) codep在额叶区减少FA最多。目的2：确定codep受试者中WM FA与认知障碍之间是否存在关系。我们的假设是：1。与CTRL相比，codep在特定的认知领域会受到损害。根据文献，我们预计最大的缺陷将出现在执行功能领域。2. 异常的神经认知功能将与选定区域的WM FA减少有关。GCRC在该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/测试的额外办公场所。