HUMAN STUDY: BRAIN MECHANISMS OF IMPULSIVITY IN COCAINE USERS

这个项目的总体目标是扩展我们最近在大脑异常和神经心理学方面的发现。 慢性可卡因滥用受试者的缺陷通过对大脑冲动机制的研究 可卡因依赖。如初步发现部分所述，我们观察到白质 包含已知与冲动控制相关的解剖区域的额部区域的异常。 我们还观察到神经认知测试中的去抑制作用，包括一项衡量冲动决策的指标 可卡因使用者。用Barratt冲动量表(BIS)测量的自我报告的冲动性特征， 与脑白质完整性的测量有关。在我们的样本中，吸食可卡因的人持续时间较长 与使用年限较短的人相比，使用年限较短的人表现出更多的白质异常。总而言之，这些数据 这表明，可卡因滥用可能与大脑的变化有关，这些变化导致冲动增加。 在这个项目中，我们将在前期工作的基础上，收集更具体的冲动评估和 将此信息与使用扩散张量的脑白质完整性的神经成像测量相结合 磁共振成像(DTI)和主要抑制性脑神经递质GABA 波谱(MRS)。最近的发现表明，前额叶抑制控制受损可能不仅仅是 药物使用的结果，但也可能反映了增加使用药物易感性的先前存在的状况 变得上瘾。因此，该项目的一个重要目标是直接比较可卡因滥用者 与项目3(床)的参与者，他们不是物质滥用者，但有成瘾行为，以 确定在可卡因使用者中出现的神经生物学结果是否也在非药物使用者中发现 上瘾的行为。这将使我们能够区分神经生物学和神经认知标志物 由于药物使用的神经生物学和神经认知影响而产生的冲动。在可能的地方，我们有 选择我们的任务和措施与项目1中正在进行的动物实验相重叠， 这将使我们能够解决在人类身上难以研究的问题。拟议的项目还承诺 产生与大脑GABA水平、白质微结构和神经认知相关的新发现 在可卡因滥用者中的表现。我们有三个目标：1)测量使用可卡因滥用者的冲动 行为任务和自我报告工具。2)使用DTI测量评估额叶白质完整性和 它与冲动指标的关系。3)使用MRS，确定可卡因滥用者是否在 大脑中的GABA水平。

The general goal of this project is to extend our recent findings of brain abnormalities and neuropsychological deficits in chronic cocaine abusing subjects through the study of putative brain mechanisms of impulsivity in cocaine dependence. As described in the Preliminary Findings section, we observed white matter abnormalities in frontal areas that contain anatomical regions known to be associated with impulse control. We also observed disinhibition on neurocognitive tests including a measure of impulsive decision-making in the cocaine users. Self-reported impulsivity traits, as measured by the Barratt Impulsiveness Scale (BIS), were associated with measures of white matter integrity. In our sample, cocaine users with longer duration of use showed more white matter abnormalities than those with fewer years of use. Together, these data suggest that cocaine abuse may be associated with changes in the brain that result in increased impulsivity. In this project we will build on this preliminary work by collecting more specific assessments of impulsivity and combine this information with neuroimaging measures of white matter integrity using Diffusion Tensor Imaging(DTI) and GABA, the major inhibitory brain neurotransmitter, using Magnetic Resonance Spectroscopy(MRS). Recent findings suggest that impaired prefrontal inhibitory control may not be solely a result of drug use, but may also reflect a preexisting condition that increases the vulnerability to using drugs and becoming addicted. Accordingly, an important goal of this project is to compare cocaine abusers directly with participants in Project 3 (BED), who are not substance abusers yet have an addictive behavior, to determine whether neurobiological findings present in cocaine users are also found in subjects with non-drug addictive behavior. This will allow us to differentiate neurobiological and neurocognitive markers of impulsivity from the neurobiological and neurocognitive effects of drug use. Where possible, we have selected our tasks and measures to overlap with what is being done in the Animal experiments in Project 1, which will allow us address questions difficult to study in humans.The proposed project also promises to generate new findings relating brain GABA levels, white matter microstructure and neurocognitive performance in cocaine abusers. We have three aims: 1) Measure impulsivity in cocaine abusers using behavioral tasks and self-report instruments. 2) Use DTI measures to assess frontal white matter integrity and its relationship to impulsivity measures. 3) Using MRS, determine if cocaine abusers have abnormalities in brain GABA levels.