Facilitating self-regulation of cocaine craving with real-time fMRI feedback

描述(由申请人提供)：线索诱导的药物渴求是可卡因依赖中最显著的复发预测因素之一。功能神经成像研究发现，与可卡因渴求有关的中脑边缘奖赏通路存在中断。前扣带回皮质(ACC)被认为是可卡因渴求和动机/寻求毒品的关键区域。因此，ACC活性的调节有可能影响药物渴求和复发。在过去的一年里，我参与了一项研究，使用来自ACC的实时功能磁共振成像(RtfMRI)神经反馈来减少ACC的激活和尼古丁依赖吸烟者的主观渴望。拟议研究项目的总体目标是修改尼古丁rtfMRI方案，并使用来自ACC的rtfMRI反馈来训练可卡因依赖者，以控制与渴望相关的ACC脑活动 可卡因线索。在目标1中，我将开发一个实时视觉反馈信号，表明在与可卡因线索相关的渴望过程中，个性化感兴趣区域的激活程度。现有的rtfMRI方案已用于减少尼古丁依赖吸烟者的自我报告渴望和ACC活动，将根据需要使用先前开发的可卡因线索暴露任务进行测试和修改。任务的初步改进对于确保我们使用脑机接口获取ACC信号并将活动水平传递给参与者的能力至关重要。在目标2中，我将探索来自TH ACC的rtfMRI反馈对20名可卡因依赖者与渴求相关的脑激活和主观渴求的调节效果。与没有神经反馈的减少渴望的指令相比，来自ACC的个性化神经反馈预计会导致该区域大胆信号的减少，并减少自我报告的渴望。据推测，ACC激活的减少将与自我报告的渴望的减少相关。此外，全脑分析将提供必要的洞察，了解与成功或失败的尝试有关的大脑电路，以减少可卡因线索诱导的渴望，无论有没有反馈。这项拟议的研究将探索一种创新的、个性化的治疗可卡因依赖的方法的潜力，并为对照临床试验铺平道路。重要的是，这项拟议的研究解决了NIDA的战略目标，目的是开发有效的行为干预措施来治疗药物滥用和防止复发，此外还有助于NIDA的治疗目标，即“发展导致个性化或定制治疗的知识”。总而言之，这项拟议的研究直接瞄准了一个已知在可卡因渴望和毒品寻找中起重要作用的区域，其方法显示出允许可卡因依赖者获得对与渴望相关的大脑活动的控制的希望。通过拟议的项目，我将接受rtfMRI方案开发、线索反应范例和可卡因依赖临床研究方面的强化指导培训，这对我作为一名成瘾领域的独立科学家的职业生涯至关重要。

DESCRIPTION (provided by applicant): Cue-induced drug craving is one of the most salient predictors of relapse in cocaine dependence. Functional neuroimaging studies have identified disruptions in the mesolimbic reward pathways involved in cocaine craving. The anterior cingulate cortex (ACC) is one region identified as critical in cocaine craving and motivation/drug-seeking. Thus, modulation of ACC activity has the potential to affect drug craving and relapse. Over the past year, I have participated in a study of using real-time functional magnetic resonance imaging (rtfMRI) neurofeedback from the ACC to reduce ACC activation and subjective craving in nicotine-dependent smokers. The overarching goal of the proposed research project is to modify the nicotine rtfMRI protocol and use rtfMRI feedback from the ACC to train cocaine-dependent individuals to control craving-related ACC brain activity in the face of cocaine cues. In Aim 1, I will develop a real-time visual feedback signal that indicates the magnitude of activation in individualized regions of interest during cocaine cue-related craving. The existing rtfMRI protocol that has been used to decrease self-reported craving and ACC activity in nicotine-dependent smokers will be tested and modified, as needed, using a previously developed cocaine-cue exposure task. The initial refinement of the task is critical in ensuring our ability to use the brain-computer interface to acquire ACC signal and relay the activity level to the participant. In Aim 2, I will explore the efficacy of rtfMRI feedback from th ACC in the modulation of craving-related brain activation and subjective craving in 20 cocaine-dependent individuals. Individualized neurofeedback from the ACC is predicted to lead to decreased BOLD signal in that region and decreased self-reported craving compared to instructions to reduce craving without neurofeedback. It is hypothesized that reductions in ACC activation will be correlated with decreases in self-reported craving. Moreover, whole brain analyses will provide needed insight into brain circuitry involved with successful or impaired attempts to reduce cocaine cue-induced craving both with and without feedback. The proposed study will explore the potential of an innovative, individualized approach to the treatment of cocaine dependence and pave the way for controlled clinical trials. Importantly, the proposed research addresses NIDA's strategic goal aimed at developing effective behavioral interventions to treat drug abuse and prevent relapse in addition to contributing to NIDA's treatment objective to "develop the knowledge that leads to personalized or customized treatments". In sum, the proposed research directly targets a region known to be important in cocaine craving and drug-seeking with a methodology that shows promise in allowing cocaine-dependent individuals to gain control over craving-related brain activity. Through the proposed project, I will receive the intensive mentored training in rtfMRI protocol development, cue-reactivity paradigms, and clinical research in cocaine dependence which is essential to my career as an independent scientist in the area of addictions.