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）：上瘾的个体暴露于与药物使用相关但无法做出反应的提示的提示曝光治疗（CET）表明有效性有限。这可能是由于灭绝学习是 高度背景依赖性-i.e。在动物返回原始学习环境时，在学习范围以外的其他情况下熄灭的行为被重新表达或“更新”。我们的协作研究计划的总体目标是通过将吸烟者现实世界中吸烟环境中的上下文提示纳入治疗，从而防止续订，从而提高CET的功效。但是，为了合理地开发包含个人吸烟环境线索的新型CET，首先有必要牢固地确定这种提示会导致反应性与标准吸烟环境提示和传统使用的近端提示（例如点亮的香烟）不同，并引起吸烟行为（即自我管理）。为了实现这些初步步骤，有78名成年吸烟者将进行大胆的fMRI扫描，而他们查看描述个人和实验者的图片提示产生了标准的吸烟和非吸烟环境，同时观看吸烟和非吸烟的近端线索。个人环境提示将通过培训吸烟者在现实世界中拍摄照片来获得。此外，个人吸烟和非吸烟环境线索对香烟烟雾自我给药和自我报告的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大胆的信号增加外，相对于近端吸烟提示，接触个人吸烟环境线索还将导致药物秘密关联区域（Hippocampus）的激活更大。相对于标准吸烟环境提示，自相关加工区域（MPFC，PCC）的更大激活。我们进一步假设吸烟者将表现出更大的烟雾自我给药（即吸烟的可能性更大，吸烟潜伏期减少，粉扑量更大）以及与非吸烟环境提示相比，响应观看个人吸烟而渴望。此外，我们将探索提示暴露期间连通性的行为与大脑测量之间的关系。如果支持我们的假设，则有必要将个人吸烟环境纳入CET，并可以随后对新型CET的理性发展和评估。此外，NIH投资于开发新型药物治疗，从而增强了CET或破坏激活药物记忆的重新整合；通过纳入更生态有效和个人相关的药物提示，例如在此处提出的研究，这些治疗方法的疗效可以得到改善。最后，尽管有丰富的临床前文献和300多个先前的人类提示反应性研究，但对于人类吸烟行为的决定因素而言，人们对环境的了解很少。因此，除了告知治疗开发外，拟议的研究还将提供有关药物服用和复发的重要机制信息。