Brain Substrates of Affect Dysregulation in Cocaine Addiction: A Pilot Study

描述（由申请人提供）：可卡因成瘾中情感失调的大脑基质：一项试点研究NIDA PAR-09-073 R 03成像科学跟踪研究过渡奖（I/START）情感失调在酒精和药物成瘾中普遍存在，是可卡因成瘾复发的公认风险因素。对于可卡因依赖患者，他们在调节情绪方面的困难可能是由于前额叶皮质脑区（PFC）的结构和功能缺陷，该脑区负责调节涉及情绪唤起的边缘结构。我们的初步数据显示，可卡因依赖患者暴露于情绪唤起刺激时，PFC和杏仁核之间的功能联系减弱。然而，在这个时候，还没有研究描述可卡因依赖患者的大脑活动，同时实际上试图调节他们的情绪。目前的建议的目的是证明效用的影响调节范式，以检查的神经机制的影响调节。我们将对25名可卡因依赖患者进行范式管理，这些患者正在参与三项正在进行的NIDA资助的神经影像学方案。将招募25名非成瘾对照，以获得比较神经影像学数据。根据I/START的目的，成像结果将用作P.I.的第一个独立资助的研究：一个调查之间的联系神经基板的影响失调和脆弱性药物复发。我们的最终目标是确定神经解剖回路参与影响失调，并使用异常作为可卡因成瘾复发和治疗反应的预测。具体目标：使用情感调节范式，我们的目标是：1）描述可卡因和非成瘾对照组中与情感调节相关的大脑底物，假设调节尝试将招募PFC系统（即，PFC激活增加）; 2）比较与可卡因患者和对照组之间的情感调节相关的PFC-边缘系统连接。我们假设，对照组将显示出更大的功能连接比可卡因患者。相关性和意义：在我们的临床样本中使用这种良好表征的范例是一种新的方法来检查成瘾中情感失调的作用。考虑到各种成瘾性疾病（例如，可卡因依赖、饮食失调、赌博）和共病精神病（例如，抑郁、焦虑）。此外，它将为这些临床疾病中情感失调的神经机制以及行为和药物干预的关键治疗目标提供重要见解。 公共卫生相关性：拟议的试点项目将使用认知策略来检查情感调节的神经机制。根据I/START的目的，试点成像结果将用于制定更广泛的研究提案，以调查情感失调的神经基质与药物复吸的脆弱性之间的联系。拟议的研究与公共卫生有关，因为这些发现将为物质成瘾中影响失调的神经机制提供重要见解，并将为行为和药理干预提供直接治疗目标。

DESCRIPTION (provided by applicant): Brain Substrates of Affect Dysregulation in Cocaine Addiction: A Pilot Study NIDA PAR-09-073 R03 Imaging-Science Track Award for Research Transition (I/START) Affect dysregulation is pervasive in alcohol and drug addiction, and is a recognized risk factor for relapse in cocaine addiction. For cocaine-dependent patients, their difficulties in modulating emotions may be due to the documented structural and functional deficits in the prefrontal cortical brain regions (PFC) responsible for regulating limbic structures involved in emotional arousal. Our preliminary data reveals attenuated functional connection between the PFC and the amygdala in cocaine-dependent patients who were exposed to emotionally evocative stimuli. At this time, however, no studies have characterized the brain activity in cocaine-dependent patients while actually attempting to regulate their emotions. The objective of the current proposal is to demonstrate the utility of an affect regulation paradigm to examine the neural mechanisms of affect regulation. We will administer the paradigm to 25 cocaine-dependent patients who are participating in three ongoing NIDA-funded neuroimaging protocols. Twenty-five non-addicted controls will be recruited to obtain comparison neuroimaging data. In line with the purpose of I/START, the imaging results will be used as pilot data for the P.I.'s first independently-funded research: An investigation of the link between neural substrates of affect dysregulation and vulnerability to drug relapse. Our ultimate goals are to identify the neuroanatomical circuits involved in affect dysregulation and to use the anomalies as a predictor of relapse and treatment response in cocaine addiction. Specific Aims: Using the affect regulation paradigm, we aim: 1) To characterize the brain substrates associated with affect regulation within cocaine and non-addicted control groups, with an hypothesis that regulatory attempts will recruit the PFC system (i.e., increase in PFC activation) in both groups; and 2) To compare the PFC-limbic connectivity associated with affect regulation between cocaine patients and controls. We hypothesize that the control group will show greater functional connectivity than the cocaine patients. Relevance and Significance: Using this well-characterized paradigm in our clinical sample is a novel approach to examine the role of affect dysregulation in addiction. The proposed research will have wide clinical relevance given the prevalence of affect dysregulation in various addiction disorders (e.g., cocaine dependence, eating disorder, gambling) and comorbid psychiatric conditions (e.g., depression, anxiety). Further, it will provide significant insights into the neural mechanisms of affect dysregulation in these clinical disorders, as well as critical treatment targets for behavioral and pharmacological interventions. PUBLIC HEALTH RELEVANCE: The proposed pilot project will examine the neural mechanisms of affect regulation using cognitive strategies. In line with the purpose of the I/START, the pilot imaging results will be used to develop a more extensive research proposal, to investigate the link between neural substrates of affect dysregulation and vulnerability to drug relapse. The proposed research has relevance to public health because the findings will provide critical insights into the neural mechanisms of affect dysregulation in substance addiction, and will provide direct treatment targets for behavioral and pharmacological interventions.