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

自然动态刺激期间的脑对脑神经反馈可减少海洛因成瘾的渴望

• 批准号: 10725836
• 负责人: Rita Z Goldstein
• 金额: $ 25.35万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10725836
• 关键词: Abstinence; Alcohols; Attention; Brain; Brain region; COVID-19 pandemic; Cannabis; Characteristics; Chronic; Complex; Coupling; Cues; Data; Development; Disease; Drug Addiction; Drug usage; Early treatment; Environment; Feedback; Functional Magnetic Resonance Imaging; Goals; Habits; Heroin; Heroin Dependence; Human; Individual; Inpatients; Intervention; Knowledge; Learning; Longitudinal Studies; Measures; Memory; Morbidity - disease rate; Neurobiology; Neurocognitive; Neurons; Neurosciences; Opioid; Overdose; Participant; Pattern; Permeability; Persons; Pharmaceutical Preparations; Process; Protocols documentation; Public Health; Recovery; Relapse; Rewards; Sampling; Self Direction; Signal Induction; Signal Transduction; Smoker; Stimulant; Stimulus; Substance Use Disorder; Synaptic Transmission; Testing; Time; Training; Work; addiction; alcohol use disorder; behavioral study; brain based; brain behavior; craving; cue reactivity; drug craving; drug of abuse; executive function; experience; heroin use; imaging study; improved; improved outcome; innovation; interest; medication-assisted treatment; mortality; movie; neural; neural circuit; neural patterning; neurofeedback; non-drug; novel; opioid epidemic; opioid overdose; opioid use disorder; overdose death; recruit; reinforcer; response; scaffold; successful intervention

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.

阿片类药物流行仍然是美国的一个重大公共卫生危机，其复发率和用药过量有关 然而，对患有此类疾病的个体进行可行干预措施的机制探索仍在继续。 阿片类药物使用障碍特别罕见，在这里我们将探索一种新颖的基于大脑的干预措施。 在早期治疗中减少海洛因使用障碍（iHUD）患者的渴望是药物的核心特征。 成瘾是对药物相关线索的反应性增强，以及自然环境中其他强化物的加工减少。 正如在众多大脑网络中可靠观察到的那样，环境与增强的渴望有关（a 我们最近在 iHUD 中的研究表明，这种大脑行为线索是诱发的。 偏见模式随着禁欲/治疗而改善，因此，我们将测试是否先发制人地改变这种情况。 神经线索反应性可以通过减少药物渴望来加速恢复过程。 我们认为训练可以帮助 iHUD 实现对其提示反应信号的有意调节。 自己的大脑信号，实时功能磁共振成像神经反馈（rt-fMRI NF）允许参与者进行意志调节 吸烟者和酗酒者的目标大脑区域的大脑活动可有效减少 药物提示神经反应，与戒断/渴望减少有关，但是，这种反应的渗透性。 方法并不统一，这里我们第一次测试是否可以通过使用 来增强 NF 效果。 具体来说，这是我们的第一个目标。 最前沿的探索性应用是识别区分早期（戒除）的大脑区域 <1 个月）与较晚（禁欲 >3 个月）的 iHUD 治疗时间相比，我们的第二个目标是使用 iHUD。 神经纤维瘤治疗后产生的独特的多变量神经模式提供给新招募的样本 iHUD 处于早期治疗中，目的是增加两组之间的神经耦合。 生态有效性并更好地接近 iHUD 中的实际现实世界体验，刺激是动态的， 我们的工作假设是，与早期治疗中的 iHUD 相比。 药物提示反应更加自动且更难控制（影响非药物加工），恢复 个人能够更好地对其进行调节，从而减少对毒品的渴望（并减少或完全消除毒品） 因此，在 rt-fMRI NF 期间，我们预计会有更好的恢复（并且）。 在治疗早期的 iHUD 新样本中，表现出最神经性的人 简而言之，在这个创新的 R21 提案中，与后期恢复中的神经模式耦合/对齐。 我们将回答以下问题：成瘾个体在后期康复中的神经模式是否可以使用 在治疗早期为新生的恢复过程提供支架，帮助减少渴望？ 这项概念验证研究可用于以后的纵向研究，以开发基于 NF 的实时训练 改善 iHUD 的结果，可推广到其他物质使用障碍。