HUMAN BRAIN FUNCTION AND DRUG ABUSE

该项目旨在确定导致药物依赖的大脑功能异常，并为开发新的治疗模式提供线索。我们的策略包括通过正电子发射断层扫描(PET)和[F-18]氟脱氧葡萄糖来评估可卡因滥用者的可卡因渴求和脑功能以及冒险行为和脑功能之间的关系；使用PET和[O-15]水来评估冒险行为和脑功能以及抑制不当反应的能力和脑功能之间的关系；以及使用[0-15]水PET测量脑血流量来确定尼古丁对大脑功能的认知影响。与药物滥用者前额叶总体积比对照组小的发现一致，我们发现，在对人类眼眶额叶损伤敏感的冒险任务中，多药滥用者(n=30)的表现明显比对照组(n=24)差，但在威斯康星卡分类任务(一种标准的额叶皮质功能神经心理测试)上表现不佳。此外，在PET研究中，在冒险任务执行期间测量大脑激活的研究中，吸毒者眼眶额叶皮质的激活程度低于对照受试者。这些数据表明，多药滥用与前额叶皮质特定部分的功能缺陷有关。一项用[O-15]-水进行正电子发射计算机断层扫描(PET)测量的尼古丁对大脑功能影响的评估表明，12名戒烟者(12小时)的记忆表现似乎由不同的神经底物介导，这表明长期接触尼古丁会改变认知策略或辅助记忆的神经系统。在对照组中，尼古丁增加了工作记忆任务(N-back测试)中的区域激活，而在吸烟者中则没有，这表明耐受性的发展。

This project aims to identify abnormalities in brain function that contribute to dependence on drugs, and to offer leads in developing new treatment modalities. Our strategies include evaluating the relationship between cocaine craving and brain function and between risk taking and brain function in cocaine abusers as measured by positron emission tomography (PET) and [F-18]fluorodeoxyglucose; the relationship between risk taking and brain function and between the ability to inhibit inappropriate responses and brain function using PET and [O-15]water; and determining cognitive effects of nicotine on brain function using the [0-15]-water PET to measure cerebral blood flow. Consistent with findings of a smaller total volume of the prefrontal lobe in substance abusers compared to controls, we found that polydrug abusers (n=30) performed significantly more poorly than controls (n=24) on a risk taking task that is sensitive to orbitofrontal damage in humans, but not on the Wisconsin Card Sorting Task, a standard neuropsychological test of frontal cortical function. Furthermore, in PET studies measuring brain activation during the performance of the risk taking task, drug abusers show less activation in the orbital frontal cortex than control subjects. These data suggest that polydrug abuse is associated with functional deficits in specific portions of the prefrontal cortex. An evaluation of the effects of nicotine on brain function, as measured by PET with [O-15]-water showed that memory performance in 12 abstinent (12 h) nicotine-dependent smokers seems to be mediated by different neural substrates than those in 12 non-dependent controls, suggesting that chronic exposure to nicotine alters cognitive strategies or neural systems subserving memory. Regional activation during performance of a working memory task (N-Back test) was increased by nicotine in controls, but not in smokers, suggesting the development of tolerance.