Impulsivity, Neural Deficits, and Cocaine Relapse

描述(由申请人提供)：冲动问题在一系列精神障碍中都有，包括药物使用、进食、赌博、躁郁症、注意力缺陷、反社会和边缘人格障碍，这可能解释了这些障碍常见的共生现象及其高复发率。然而，冲动和复发之间的假设关系还没有得到证实。一项新出现的神经成像文献表明，冲动可能是禁欲持续的神经紊乱的结果。在之前对戒断可卡因成瘾受试者的研究中，我们使用单光子发射计算机断层扫描(SPECT)来识别眼眶额叶皮质和头端前扣带回局部脑血流(RCBF)的特定干扰。这些脑区是调节冲动控制的关键。我们还观察到了冲动的几个神经认知和自我评估指标的缺陷，并成功地确定了在两个冲动任务中的神经激活(使用功能磁共振成像，或fMRI)。我们现在建议同时评估与可卡因成瘾受试者的冲动相关的神经认知和神经障碍，并检查这些改变与未来复发之间的关系。两到四周的戒酒、寻求治疗的可卡因依赖者和健康对照将被研究。我们将评估冲动的两个生态相关的神经认知结构--去抑制和决策。FMRI将被用来评估在反应抑制(快速抑制预先有效的反应的能力)的去抑制任务和反应逆转的决策任务(逆转(或改变)认知和行为策略以抑制不再合适的行动过程的能力)期间的神经活动。受试者还将接受SPECT对静息rCBF异常的评估。标准化和实验性神经认知测试以及自我评估措施将用于评估去抑制和决策。冲动复发的倾向将通过冲动复发问卷来衡量，这是一种衡量复发风格的新指标。可卡因成瘾者随后将在住院治疗后接受长达六个月的跟踪，并评估药物使用复发的时间。我们假设，冲动的定量测量和与去抑制和决策相关的神经缺陷都将显著相互关联，并预测物质使用复发的时间。这些研究将大大加强我们对与冲动和复发相关的神经生物学和神经认知机制的理解，并为有针对性的干预提供框架，以防止在已确定的冲动高危患者群体中复发。

DESCRIPTION (provided by applicant): Problems with impulsivity are shared across a wide spectrum of psychiatric disorders, including substance use, eating, gambling, bipolar, attention deficit, antisocial and borderline personality disorders, and may explain the common co-occurrence of these disorders and their high rates of relapse. However, the putative relationship between impulsivity and relapse has not been demonstrated. An emerging neuroimaging literature suggests that impulsivity may be a result of neural disruptions that persist with abstinence. In previous studies with abstinent cocaine-addicted subjects, we have used single photon emission computed tomography (SPECT) to identify specific disruptions in the regional cerebral blood flow (rCBF) of the orbitofrontal cortex and rostral anterior cingulate. These brain areas are key in the regulation of impulse control. We have also observed deficits in several neurocognitive and self-assessment measures of impulsivity, and have successfully determined neural activation (using functional magnetic resonance imaging, or fMRI) during two tasks of impulsivity. We now propose to concurrently assess the neurocognitive and neural disruptions associated with impulsiveness in cocaine-addicted subjects, and examine the relationship between these alterations and prospective relapse. Two- to four-week abstinent, treatment-seeking cocaine dependent subjects and healthy controls will be studied. Two ecologically relevant neurocognitive constructs of impulsivity - disinhibition and decision-making - will be assessed. fMRI will be used to assess neural activity during a disinhibition task of response inhibition (the ability to rapidly inhibit a pre-potent response) and a decision-making task of response reversal [the ability to reverse (or shift) cognitive and behavioral strategies to suppress a course of action that is no longer appropriate]. Subjects will also be assessed for resting rCBF abnormalities with SPECT. Standardized and experimental neurocognitive tests, as well as self-assessment measures, will be used to assess disinhibition and decision- making. The tendency to relapse impulsively will be measured by the Impulsive Relapse Questionnaire, a novel measure of relapse style. Cocaine-addicted subjects will subsequently be followed for up to six months following residential treatment and assessed for time to substance use relapse. We hypothesize that both quantitative measures of impulsivity and the neural deficits associated with disinhibition and decision-making will significantly correlate with each other and predict time to substance use relapse. These studies will significantly strengthen our understanding of the neurobiologic and neurocognitive mechanisms related to impulsivity and relapse, and provide the framework for targeted interventions to prevent relapse in an identified population of impulsive, at-risk patients.