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

描述（由申请人提供）：暗示诱导的药物渴望是可卡因依赖复发的最显着预测因素之一。功能性神经影像学研究已经确定了参与可卡因渴望的中脑边缘奖赏通路的中断。前扣带皮层（ACC）是一个被确定为对可卡因渴望和动机/药物寻求至关重要的区域。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的实时功能性磁共振成像（rtfMRI）神经反馈来减少尼古丁依赖吸烟者的ACC激活和主观渴望。拟议研究项目的总体目标是修改尼古丁rtfMRI协议，并使用来自ACC的rtfMRI反馈来训练可卡因依赖个体在面对成瘾时控制与渴望相关的ACC大脑活动。 可卡因线索在目标1中，我将开发一个实时视觉反馈信号，指示可卡因线索相关渴望期间感兴趣的个性化区域的激活程度。现有的rtfMRI协议已被用于减少尼古丁依赖性吸烟者自我报告的渴望和ACC活性，将进行测试和修改，根据需要，使用以前开发的可卡因线索暴露任务。任务的初始细化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。目的二：探讨20名可卡因依赖者大脑前扣带回的rtfMRI反馈对渴求相关脑激活和主观渴求的调节作用。与没有神经反馈的减少渴望的指令相比，来自ACC的个体化神经反馈预计会导致该区域的BOLD信号减少，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减少相关。此外，全脑分析将提供所需的洞察力，以成功或受损的尝试，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、个性化的方法来治疗可卡因依赖的潜力，并为对照临床试验铺平道路。重要的是，拟议的研究解决了NIDA的战略目标，旨在制定有效的行为干预措施，以治疗药物滥用和预防复发，以及促进NIDA的治疗目标，以“开发导致个性化或定制治疗的知识”。总之，拟议的研究直接针对一个已知在可卡因渴望和药物寻求中很重要的区域，其方法显示出允许可卡因依赖者控制与渴望相关的大脑活动的希望。通过拟议的项目，我将接受rtfMRI协议开发，线索反应范式和可卡因依赖的临床研究的强化指导培训，这对我作为成瘾领域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.