Resting State Functional Connectivity and Addiction at Duke (RAD) Repository

杜克大学 (RAD) 存储库的静息状态功能连接和成瘾

• 批准号: 8526624
• 负责人: Francis Joseph McClernon
• 金额: $ 8.36万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-15 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8526624
• 关键词: Accounting; Address; Adult; Amygdaloid structure; Animals; Area; Behavior; Behavioral; Brain; Brain region; Cause of Death; Cigarette; Cues; Data; Development; Drug usage; Effectiveness; Environment; Evaluation; Exhibits; Exposure to; Functional Magnetic Resonance Imaging; Goals; Hippocampus (Brain); Human; Image; Individual; Investigation; Lead; Learning; Link; Literature; Measures; Medial; Memory; Patient Self-Report; Pharmaceutical Preparations; Pharmacotherapy; Prefrontal Cortex; Probability; Process; Relapse; Relative (related person); Reporting; Research; Rest; Scanning; Self Administration; Signal Transduction; Smoke; Smoker; Smoking; Smoking Behavior; Stimulus; Substance abuse problem; Techniques; Training; Translating; Treatment Efficacy; United States National Institutes of Health; Ventral Striatum; addiction; behavior measurement; cigarette smoking; cigarette smoking; cingulate cortex; craving; cue reactivity; disability; improved; indexing; information processing; learning extinction; neuroimaging; novel; pre-clinical; prevent; programs; repository; response; therapy design; therapy development

DESCRIPTION (provided by applicant): Cue-exposure treatments (CETs) in which addicted individuals are exposed to cues associated with drug use, but prevented from responding, have demonstrated limited effectiveness. This is potentially due to the fact that extinction learning is highly context dependent-i.e. behavior extinguished in a context other than the one in which it was learned, is re-expressed or 'renewed' when the animal returns to the original learning context. The overarching goal of our collaborative research program is to increase the efficacy of CETs by incorporating contextual cues from the smoker's real-world smoking environment into treatment, thereby preventing renewal. However, in order to rationally develop novel CETs that incorporate personal smoking environment cues, it is first necessary to firmly establish that such cues result in reactivity distinct from standard smoking environment cues and traditionally used proximal cues (e.g. lit cigarette) and that they provoke smoking behavior (i.e. self- administration). In order to achieve these initial steps, seventy-eight (n=78) adult smokers will undergo BOLD fMRI scanning while they view picture cues depicting personal and experimenter generated standard smoking and nonsmoking environments and while viewing smoking and nonsmoking proximal cues. Personal environment cues will be acquired by training smokers to take pictures in real-world settings. In addition, the effects of personal smoking and nonsmoking environment cues on cigarette smoke self-administration and self-reported craving will be assessed in two lab sessions. We hypothesize that in addition to increased BOLD signal in cue-reactivity areas, exposure to personal smoking environment cues will result in greater activation of a drug-context association area (hippocampus) relative to proximal smoking cues; and greater activation of self-relevance processing areas (mPFC, PCC) relative to standard smoking environment cues. We further hypothesize that smokers will exhibit greater smoke self-administration (i.e. greater probability of smoking, decreased latency to smoke, greater puff volume) and craving in response to viewing personal smoking as compared to nonsmoking environment cues. Additionally, we will explore relations between behavioral and brain measures of connectivity during cue-exposure. If our hypotheses are supported, then the incorporation of personal smoking environments into CET is warranted and the rational development and evaluation of novel CETs can follow. In addition, the NIH is invested in the development of novel pharmacotherapies that enhance CET or disrupt reconsolidation of activated drug memories; the efficacy of these treatments can potentially be improved by incorporating more ecologically valid and personally relevant drug cues such as those proposed for study here. Finally, despite a rich preclinical literature and over 300 prior human cue-reactivity studies, very little is known regarding the environment as a determinant of smoking behavior in humans. As such, the proposed research, in addition to informing treatment development, will provide novel mechanism information regarding an important, yet understudied, determinant of drug taking and relapse.

描述（由申请人提供）：提示暴露治疗（CET）已证明效果有限，其中成瘾者暴露于与吸毒相关的提示，但阻止其做出反应。这可能是由于灭绝学习是 高度依赖上下文——即当动物回到原来的学习环境时，在不同于学习环境的环境中消失的行为会被重新表达或“更新”。我们合作研究计划的总体目标是通过将吸烟者真实吸烟环境的背景线索纳入治疗中来提高 CET 的功效，从而防止更新。然而，为了合理地开发包含个人吸烟环境线索的新型CET，首先必须牢固地确定此类线索会导致与标准吸烟环境线索和传统使用的近端线索（例如点燃香烟）不同的反应，并且它们会引发吸烟行为（即自我管理）。为了实现这些初始步骤，七十八名 (n=78) 成年吸烟者将接受大胆的功能磁共振成像扫描，同时他们查看描绘个人和实验者生成的标准吸烟和非吸烟环境的图片线索，并同时查看吸烟和非吸烟的近端线索。通过训练吸烟者在现实环境中拍照来获取个人环境线索。此外，个人吸烟和非吸烟环境线索对香烟烟雾自我管理和自我报告渴望的影响将在两个实验室会议中进行评估。我们假设，除了提示反应区域中 BOLD 信号增加之外，暴露于个人吸烟环境提示将导致药物关联区域（海马体）相对于邻近吸烟提示的更大激活；相对于标准吸烟环境线索，自我相关处理区域（mPFC、PCC）的激活程度更高。我们进一步假设，与非吸烟环境线索相比，吸烟者将表现出更大的烟雾自我管理（即吸烟的可能性更大、吸烟潜伏期缩短、吸烟量更大）和对观看个人吸烟的渴望。此外，我们将探讨线索暴露期间行为和大脑连接测量之间的关系。如果我们的假设得到支持，那么将个人吸烟环境纳入 CET 是有道理的，并且可以对新型 CET 进行合理的开发和评估。此外，NIH 还投资开发新型药物疗法，以增强 CET 或破坏激活药物记忆的重新巩固；通过纳入更生态有效且与个人相关的药物线索（例如本文建议研究的药物线索），可以潜在地提高这些治疗的功效。最后，尽管有丰富的临床前文献和 300 多项先前的人类线索反应研究，但人们对环境作为人类吸烟行为的决定因素知之甚少。因此，拟议的研究除了为治疗开发提供信息外，还将提供有关吸毒和复发的重要但尚未充分研究的决定因素的新机制信息。