Brain-to-brain neurofeedback during naturalistic dynamic stimuli to reduce craving in heroin addiction

阿片类药物流行仍然是美国的一个主要公共卫生危机，复发率和过量相关 死亡人数继续上升。然而，对患有糖尿病的个体进行可行干预的机械探索 阿片类药物使用障碍特别罕见。在这里，我们将探索一种新的基于大脑的干预， 在早期治疗中减少海洛因使用障碍（iHUD）患者的渴望。毒品的一个核心特征 成瘾是一种对药物相关线索的反应增强，而对自然界中其他物质的处理减少。 环境，正如在许多大脑网络中可靠地观察到的那样，与增强的渴望有关（a 实验室外药物使用的预测器）。我们最近对iHUD的研究表明，这种大脑行为线索诱导的 偏差模式随着禁欲/治疗而改善。因此，我们将测试是否先发制人地改变这种 神经线索反应性可以加速恢复过程，如用减少的药物渴望所测量的。具体地说， 我们假设训练可以帮助iHUD实现对他们的线索反应信号的有意调制。使用 一个人自己的大脑信号，实时功能磁共振成像神经反馈（rt-fMRI NF）允许参与者自愿调节 在吸烟者和酗酒者中显示的目标大脑区域的大脑活动有效地减少了 药物提示神经反应，与戒断/减少渴望有关。然而，这种渗透性 方法并不统一。在这里，我们将第一次测试是否可以通过使用 从其他人的大脑导出的信号（即，脑-脑神经传输）。具体来说，我们的第一个目标是， 尖端的探索性应用是确定大脑区域，区分早期（禁欲）， <1个月）与iHUD中较晚（禁欲>3个月）的治疗时间相比。我们的第二个目标是利用 独特的多元神经模式，后来在治疗中作为NF提供给一个新招募的样本， 在早期治疗中使用iHUD，目的是增加两组之间的神经元耦合。增加 生态有效性和更好地近似实际的现实世界的经验，在iHUD的刺激是一个动态的， 以叙事为基础，背景丰富的电影。我们的工作假设是，与早期治疗中的iHUD相比， 其中药物线索反应性更自动且更难控制（影响非药物处理）， 个人能够更好地调节它，使他们能够减少渴望（并减少，或完全消除，药物- 即使在与毒品有关的情况下。因此，在rt-fMRI NF过程中，我们预计会有更大的恢复（以及 较低的线索诱导的渴望），在治疗早期的iHUD新样本中， 与那些在后期恢复中的神经模式耦合/对齐。简而言之，在这个创新的R21提案中， 我们将回答以下问题：成瘾个体在后期恢复中的神经模式是否可以用于 在治疗的早期为新生的恢复过程提供支架，帮助减少渴望？结果 这种概念验证研究可用于以后的纵向研究，以开发基于NF的实时培训， iHUD改善结局可推广至其他物质使用障碍。

The opioid epidemic remains a major public health crisis in the US, with relapse rates and overdose-related fatalities continuing to rise. However, the mechanistic explorations of viable interventions in individuals with opioid use disorder have been particularly scarce. Here we will explore a novel brain-based intervention to decrease craving in individuals with heroin use disorder (iHUD) in early treatment. A core characteristic of drug addiction is an enhanced reactivity to drug related cues and reduced processing of other reinforcers in the natural environment, as reliably observed across numerous brain networks and associated with enhanced craving (a predictor of drug use outside the lab). Our recent studies in iHUD suggest that this brain-behavior cue-induced biased pattern improves with abstinence/treatment. Therefore, we will test whether preemptively changing such neural cue reactivity could expedite the recovery process as measured with reduced drug craving. Specifically, we hypothesize that training can help iHUD achieve an intentional modulation of their cue reactivity signal. Using one’s own brain signal, real-time fMRI neurofeedback (rt-fMRI NF) allows participants to volitionally modulate brain activity in targeted brain regions shown in smokers and heavy alcohol drinkers to be effective in reducing drug cue neural reactivity, as associated with abstinence/decreases in craving. However, the permeability of this approach is not uniform. Here for the first time, we will test whether the NF effect can be enhanced by using the signal derived from the brains of others (i.e., brain-to-brain neural transmission). Specifically, our first aim in this cutting-edge exploratory application is to identify the brain regions that distinguish between early (abstinent for <1 month) as compared to later (abstinent for >3 months) time-in-treatment in iHUD. Our second aim is to use the unique multivariate neural patterns derived later in treatment as NF provided to a newly recruited sample of iHUD in early treatment, with the goal of increasing neuronal coupling between both groups. To increase ecological validity and better approximate actual real-world experiences in iHUD, the stimulus is a dynamic, narrative-based, and context-rich movie. Our working hypothesis is that, as compared to iHUD in early treatment where drug cue reactivity is more automatic and harder to control (impacting non drug processing), recovering individuals are better able to regulate it allowing them to reduce craving (and curtail, or entirely eliminate, drug- seeking) even in potent drug-related situations. Therefore, during rt-fMRI NF, we expect greater recovery (and lower cue-induced craving) in the new sample of iHUD early in treatment who show the most neural coupling/alignment with the neural patterns of those in later recovery. In short, in this innovative R21 proposal we will answer the following question: Can the neural patterns of addicted individuals in later recovery be used to provide scaffolding for the nascent recovery process early in treatment, helping to reduce craving? Results of this proof-of-concept study can be used in later longitudinal studies to develop real-time NF-based training to improve outcomes in iHUD as generalizable to other substance use disorders.