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脑底物：一项初步研究NIDA PAR-09-073 R03影像科学轨道研究过渡奖（I/START）情感失调在酒精和药物成瘾中普遍存在，是公认的可卡因成瘾复发的危险因素。对于可卡因依赖患者来说，他们在调节情绪方面的困难可能是由于负责调节涉及情绪唤醒的边缘结构的前额皮质脑区（PFC）的结构和功能缺陷。我们的初步数据显示，在暴露于情感唤起刺激的可卡因依赖患者中，PFC和杏仁核之间的功能连接减弱。然而，目前还没有研究描述可卡因依赖患者在试图调节情绪时的大脑活动。本研究的目的是展示情感调节范式在研究情感调节的神经机制方面的效用。我们将对25名可卡因依赖患者实施该范式，这些患者正在参加nida资助的三个正在进行的神经影像学方案。将招募25名非成瘾对照组来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pi的试点数据她的第一个独立资助的研究：对影响失调的神经基质和对药物复发的易感性之间联系的调查。我们的最终目标是确定与情感失调有关的神经解剖回路，并将异常作为可卡因成瘾复发和治疗反应的预测因子。具体目的：利用情感调节范式，我们的目标是：1)在可卡因和非成瘾对照组中表征与情感调节相关的脑底物，并假设调节尝试将招募两组的PFC系统（即PFC激活增加）；2)比较可卡因患者与对照组与情绪调节相关的pfc -边缘连通性。我们假设对照组将比可卡因患者表现出更大的功能连接。相关性和意义：在我们的临床样本中使用这种具有良好特征的范式是一种研究成瘾中情感失调作用的新方法。考虑到各种成瘾障碍（如可卡因依赖、饮食失调、赌博）和共病精神疾病（如抑郁、焦虑）中情感失调的患病率，拟议的研究将具有广泛的临床相关性。此外，它将为这些临床疾病中情绪失调的神经机制以及行为和药物干预的关键治疗靶点提供重要的见解。

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.