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的大脑异常和神经心理学的发现， 通过研究慢性可卡因滥用受试者的冲动性脑机制， 可卡因依赖如初步结果部分所述，我们观察到白色物质 额叶区域的异常，包含已知与冲动控制相关的解剖区域。 我们还观察到在神经认知测试中的去抑制，包括对冲动决策的测量， 可卡因使用者自我报告的冲动特质，由Barratt冲动量表（BIS）测量， 与白色物质完整性相关。在我们的样本中，持续时间较长的可卡因使用者 使用者比使用年数较少者显示更多的白色异常。这些数据一起 这表明可卡因滥用可能与导致冲动增加的大脑变化有关。 在这个项目中，我们将通过收集更具体的冲动性评估， 使用扩散张量将该信息与白色物质完整性的神经成像测量结合联合收割机 磁共振成像（DTI）和GABA（主要抑制性脑神经递质） 波谱学（MRS）。最近的研究结果表明，受损的前额叶抑制控制可能不仅仅是一个 这可能是吸毒的结果，但也可能反映了增加吸毒脆弱性的预先存在的状况 然后上瘾因此，该项目的一个重要目标是直接比较可卡因滥用者 项目3（BED）的参与者，他们不是药物滥用者，但有成瘾行为， 确定可卡因使用者的神经生物学发现是否也存在于非药物受试者中 成瘾行为这将使我们能够区分神经生物学和神经认知标志物， 吸毒的神经生物学和神经认知效应导致的冲动。如果可能，我们 选择我们的任务和措施与项目1中的动物实验重叠， 这将使我们能够解决人类难以研究的问题。拟议中的项目还承诺， 产生了新的发现，涉及大脑GABA水平，白色物质微观结构和神经认知 可卡因滥用者的表现。我们有三个目标：1）测量可卡因滥用者的冲动， 行为任务和自我报告工具。2)使用DTI测量评估额叶白色物质完整性， 与冲动性测量的关系。3)使用MRS，确定可卡因滥用者是否有异常 大脑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.