Impulsivity, Neural Deficits, and Cocaine Relapse

描述（由申请人提供）：冲动问题在广泛的精神疾病中是共有的，包括物质使用，饮食，赌博，双相情感障碍，注意力缺陷，反社会和边缘型人格障碍，并且可以解释这些疾病的常见共存和高复发率。然而，冲动和复发之间的假定关系尚未得到证实。一项新出现的神经影像学文献表明，冲动可能是持续禁欲的神经中断的结果。在先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）来识别眶额皮质和吻侧前扣带区域脑血流（rCBF）的特定中断。这些大脑区域是控制冲动的关键。我们还观察到冲动性的一些神经认知和自我评估措施的缺陷，并成功地确定了两项冲动性任务中的神经激活（使用功能性磁共振成像或fMRI）。我们现在建议同时评估与可卡因成瘾受试者冲动相关的神经认知和神经中断，并检查这些改变与预期复发之间的关系。两到四周的戒断，寻求治疗的可卡因依赖受试者和健康对照将被研究。两个生态相关的冲动性神经认知结构-去抑制和决策-将被评估。fMRI将用于评估在反应抑制（快速抑制前效反应的能力）和反应逆转（逆转（或转移）认知和行为策略以抑制不再合适的行为过程的能力）的解除抑制任务中的神经活动。受试者还将通过SPECT评估静息时rCBF异常。标准化和实验神经认知测试，以及自我评估措施，将用于评估解除抑制和决策。冲动复吸倾向将通过冲动复吸问卷来测量，这是一种新的复吸方式。可卡因成瘾受试者随后将在住院治疗后进行长达6个月的随访，并评估药物使用复发的时间。我们假设冲动性的定量测量和与去抑制和决策相关的神经缺陷将显着相互关联，并预测药物使用复发的时间。这些研究将大大加强我们对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，以防止确定的冲动高危患者复发。

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.