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）：冲动问题是多种精神疾病所共有的，包括药物滥用、饮食、赌博、双相情感障碍、注意力缺陷、反社会和边缘性人格障碍，并且可以解释这些疾病的常见同时发生以及他们的高复发率。然而，冲动与旧病复发之间的假定关系尚未得到证实。一项新兴的神经影像学文献表明，冲动可能是禁欲后持续存在的神经紊乱的结果。在之前对戒除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回的区域脑血流（rCBF）的特定中断。这些大脑区域是调节冲动控制的关键。我们还观察到冲动的几种神经认知和自我评估措施存在缺陷，并成功确定了两项冲动任务期间的神经激活（使用功能性磁共振成像或 fMRI）。我们现在建议同时评估可卡因成瘾受试者与冲动相关的神经认知和神经破坏，并检查这些改变与预期复发之间的关系。将研究戒毒两到四周、寻求治疗的可卡因依赖受试者和健康对照。将评估两种与生态相关的冲动神经认知结构——去抑制和决策。 fMRI 将用于评估反应抑制去抑制任务（快速抑制预强反应的能力）和反应逆转决策任务（逆转（或转变）认知和行为策略的能力）期间的神经活动。压制不再适当的行动方针]。还将通过 SPECT 评估受试者的静息 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去抑制和决策。冲动性旧病复发的倾向将通过冲动性旧病复发问卷来衡量，这是一种新的旧病复发方式测量方法。可卡因成瘾者将在住院治疗后进行长达六个月的随访，并评估物质使用复发的时间。我们假设冲动的定量测量以及与去抑制和决策相关的神经缺陷将彼此显着相关，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措施提供框架，以防止已确定的冲动高危患者群体复发。