FUNCTIONAL MAGNETIC RESONANCE IMAGING

功能磁共振成像

• 批准号: 6104128
• 负责人: STEVEN E. HYMAN
• 金额: $ 18.48万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6104128
• 关键词: brain circulation; brain mapping; cocaine; functional magnetic resonance imaging; image processing; in situ hybridization; laboratory rat; neuropharmacology; neurotoxins; pharmacokinetics; regulatory gene

In Project 3, we propose to use a rat model to characterize the neural substrates of cocaine-induced alterations in fMRI signals. An animal model is required because the invasive methods used cannot be applied to human subjects. The proposed experiments will characterize the underlying biological processes that contribute to the fMRI signal, including an analysis of contributions due to the direct effects of cocaine on the vascular versus its direct effects on target neurons. We then plan to investigate the postsynaptic correlates of the fMRI signal by comparing patterns of regional brain activation obtained by fMRI with in situ hybridization for the immediate early genes (IEGs) c-fos and zif268. We propose this approach because mapping of IEG induction is the best current functional neuroanatomic tool to investigate circuits, cells, and neurotransmitter receptors involved in cocaine action. In addition we propose to identify basic mechanisms by which cocaine induces both fMRI and IEG 'signals' by a series of studies in which the monoamine systems acted upon by cocaine are lesioned. The experiments proposed in Project 3 directly impact our interpretation of the human data obtained in Project 1. Project 3 is designed to rigorously test hypotheses concerning the biological significance of fMRI signals produced by cocaine administration. At the same time it should produce significant data on the neural substrates of cocaine dependence.

在项目 3 中，我们建议使用大鼠模型来表征神经网络 可卡因引起的功能磁共振成像信号改变的底物。 一只动物 需要模型，因为所使用的侵入性方法不能应用于 人类受试者。 所提出的实验将表征 有助于功能磁共振成像信号的潜在生物过程， 包括对由于直接影响而做出的贡献进行分析 可卡因对血管的影响与对目标神经元的直接影响。 我们 然后计划研究功能磁共振成像信号的突触后相关性 通过比较功能磁共振成像（fMRI）获得的区域大脑激活模式 立即早期基因 (IEG) c-fos 和 zif268。 我们提出这种方法是因为 IEG 感应的映射是 目前最好的功能性神经解剖学工具来研究回路， 细胞和参与可卡因作用的神经递质受体。 在 此外，我们建议确定可卡因诱发的基本机制 通过一系列研究，fMRI 和 IEG 均发出“信号”，其中单胺 可卡因作用的系统受到损害。 提出的实验 项目 3 直接影响我们对人类数据的解释 项目1中获得。项目3旨在严格测试 关于功能磁共振成像信号的生物学意义的假设 由可卡因管理产生。 同时它应该产生 关于可卡因依赖的神经基质的重要数据。