Impulsivity, Neural Deficits, and Cocaine Relapse

冲动、神经缺陷和可卡因复吸

• 批准号: 7456489
• 负责人: BRYON H. ADINOFF
• 金额: $ 30.77万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7456489
• 关键词: Abstinence; Alcohol or Other Drugs use; Anterior; Area; Attention; Behavioral; Biological; Borderline Personality Disorder; Brain; Brain region; Cerebrovascular Circulation; Cocaine; Cognitive; Decision Making; Disease; Disinhibition; Disruption; Drug usage; Eating; Eating Disorders; Etiology; Failure; Functional Magnetic Resonance Imaging; Gambling; Human; Hyperactive behavior; Impairment; Impulsive Behavior; Impulsivity; Inferior; Intervention; Laboratory Study; Left; Literature; Measures; Mental disorders; Nervous System Physiology; Neuraxis; Neurocognition; Neurocognitive; Neurons; Patient Self-Report; Patients; Pattern; Performance; Personality; Phenotype; Population; Prefrontal Cortex; Process; Questionnaires; Rate; Regulation; Relapse; Research Personnel; Residential Treatment; Rest; Risk; Score; Self Assessment; Self-Administered; Substance Use Disorder; Task Performances; Thinking; Time; Validity of Self Report; Week; anti social; follow-up; instrument; neurobehavioral; neurocognitive test; neuroimaging; neuromechanism; novel; peer; preclinical study; prevent; programs; prospective; relating to nervous system; response; single photon emission computed tomography; sound; trait

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.

描述（由申请人提供）：冲动性问题在各种精神疾病中共享，包括药物使用，饮食，赌博，双相情感障碍，注意力不足，反社会和边缘性人格障碍，并可以解释这些疾病的常见共同发生及其这些疾病的共同出现及其较高的复发率。但是，尚未证明冲动与复发之间的假定关系。新兴的神经影像学文献表明，冲动性可能是由于戒酒而持续存在的神经干扰的结果。在先前对戒除可卡因的受试者的研究中，我们使用了单个光子发射计算机断层扫描（SPECT）来确定轨道额叶皮层和前鼻部扣带回的区域脑血流（RCBF）中的特定干扰。这些大脑区域是脉冲控制调节的关键。我们还观察到了冲动性的几种神经认知和自我评估度量的缺陷，并在两项冲动性任务中成功确定了神经激活（使用功能磁共振成像或fMRI）。现在，我们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干扰，并检查这些改变与前瞻性复发之间的关系。将研究两到四周戒酒，寻求治疗的可卡因受试者和健康对照。将评估两种在生态相关的神经认知结构 - 抑制和决策。 fMRI将用于评估抑制反应抑制任务（迅速抑制预测前反应的能力）和反应反转的决策任务[逆转（或移动）认知和行为策略抑制不再适当的行动方案的决策任务]）。还将评估受试者与SPECT静止的RCBF异常。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抑制和决策。冲动复发的趋势将通过冲动复发问卷（一种新颖的复发方式衡量）来衡量。住院治疗后最多六个月，可卡因成瘾的受试者将随后遵循，并评估有时间使用物质使用复发。我们假设，冲动性的定量度量和与抑制和决策相关的神经缺陷都将显着相关，并预测物质使用复发的时间。这些研究将显着加强我们对与冲动性和复发有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措施提供框架，以防止识别出冲动性的高危患者的复发。