Using Real-Time fRMI to Facilitate Neuromodulation to Drug-Cues in Adolescent Abu

描述（由申请人提供）：青少年药物滥用的最新神经认知理论认为，皮质和边缘系统区域发育轨迹的差异有助于青少年期间开始使用药物的增加。越来越多的文献表明，边缘系统区域的成熟发生在青春期早期，并且先于皮质区域，皮质区域在青春期和成年早期继续发育。这些不同的成熟轨迹可能会导致青少年的奖励中心比能够限制它们的额叶区域发展得更快。因此，药物的管理可能会引起强烈的有益的经验，青少年有一个困难的时间管理，他们仍然有限的能力，有效的自上而下的控制。这与目前成人可卡因滥用的模型相吻合，该模型提出可卡因可能会改变中皮质边缘的敏感性，导致对药物相关奖励的敏感性增加，但对非药物相关奖励的敏感性降低，以及执行控制过程减少。这种观点的一个含义是，重新调整这些改变的奖励敏感性的能力可能会成为严重可卡因依赖者的可行治疗策略。新兴的技术，如实时功能性磁共振成像（rt-fMRI），提供了机会，为个人提供在线反馈有关他们的神经活动的当前状态。这项技术的一个有价值的用途可能是提供可卡因依赖者的信息，他们的神经反应药物相关和非药物相关的奖励，并利用这种“神经反馈”的方法来训练参与者获得控制他们的神经活动，并重新平衡改变奖励的敏感性。我们的团队建议使用R21机制来证明rt-fMRI技术在40名青少年可卡因滥用者的样本中的有效性，同时他们执行相当标准的线索引发的渴望范式。在呈现药物、非药物和中性图片之前，将向受试者提供增加、减少或观看的听觉指导，并指导受试者尝试增加或减少丘脑核或前扣带回内的活动。屏幕上的“温度计”将向参与者显示感兴趣区域内的当前活动状态，参与者将被指示使用该状态作为促进成功神经调节的辅助手段。将收集关于奖励和渴望的主观水平以及所采用的神经调节策略的详细数据。主要目的是证明该协议在物质滥用青少年的可行性，同时增加我们对可能影响这种神经调节过程的发育特征的理解。支持rt-fMRI作为神经调节促进剂的可行性的证据将代表为青少年滥用者制定全面的药物滥用治疗计划的关键一步，并可能作为未来工作的门户，以实现这些治疗目标。 公共卫生相关性：最近的药物滥用模型认为，药物滥用者可能会经历减少神经活动的非药物奖励，但增加神经活动的药物奖励。特别是青少年滥用者，可能特别容易受到这种不平衡的影响，这是由于能够调节这些奖励冲动的皮层区域不完全成熟。本研究将利用实时功能磁共振成像测试的可行性，“神经反馈”的方法，以促进青少年可卡因滥用者的奖励相关的神经活动的自愿调制。进行这种自愿神经调节的能力可能被证明是药物滥用障碍的可行治疗选择。目前的工作将提供对这一新兴技术的基本评估，并将作为未来在药物滥用人群中进行大规模临床研究的门户。

DESCRIPTION (provided by applicant): Recent neurocognitive theories of adolescent substance abuse posit differences in the developmental trajectories of cortical and limbic regions as contributing to the increased initiation of drug use during adolescence. A growing literature indicates that maturation of limbic regions occurs early in adolescence, and precedes that of cortical regions, which continue to develop through adolescence and into early adulthood. These differing maturation trajectories may lead the adolescent's reward centers to develop faster than the frontal regions capable of constraining them. As such, the administration of drugs may elicit an intensely rewarding experience, that the adolescent has a difficult time managing, with their still limited capacity for effective top-down control. This coincides with current models of cocaine abuse in adults, which propose that cocaine may alter sensitivity within mesocorticolimbic, leading to increased sensitivity to drug-related reward, yet decreased sensitivity to nondrug-related reward, and decreased executive control processes. One implication of this perspective is that the ability to recalibrate these altered reward sensitivities may serve as a viable treatment strategy for individuals with serious cocaine dependency. Emerging technology, such as real-time functional magnetic resonance imaging (rt-fMRI), affords the opportunity to provide individuals with online feedback regarding the current state of their neural activity. One valuable use of this technology may be to provide cocaine-dependent individuals with information regarding their neural response to drug-related and nondrug-related reward, and to utilize this "neuro-feedback" approach to train participants to gain control over their neural activity, and to rebalance altered reward sensitivities. Our team proposes to use the R21 mechanism to demonstrate efficacy of rt-fMRI technology within a sample of 40 adolescent cocaine-abusers while they perform a fairly standard cue-elicited craving paradigm. Prior to presentation of drug, nondrug and neutral pictures, participants will be provided with an aural instruction to either INCREASE, DECREASE, or WATCH, and will be instructed to try to increase or decrease activity within either nucleus accumbens or anterior cingulate. An on-screen "thermometer" will display to participants the current state of activity within the region of interest, which participants will be instructed to use as an aid for facilitating successful neuromodulation. Detailed data regarding subjective levels of reward and craving, and of the neuromodulatory strategies employed, will be collected. The primary aim is to demonstrate feasibility of this protocol in substance abusing adolescents, while simultaneously increasing our understanding of developmental characteristics that could influence this neuromodulatory process. Evidence supporting feasibility of rt-fMRI as a facilitator of neuromodulation would represent a critical step toward development of comprehensive substance abuse treatment programs for adolescent abusers, and may serve as a gateway for future work to achieve these treatment goals. PUBLIC HEALTH RELEVANCE: Recent models of substance abuse argue that the substance abuser may experience decreased neural activity in response to nondrug rewards, yet increased neural activity in response to drug rewards. Adolescent abusers, in particular, may be particularly susceptible to this imbalance, due to incomplete maturation of cortical regions capable of regulating these rewarding impulses. The present study will utilize rt-fMRI to test the feasibility of a "neurofeedback" approach for facilitating voluntary modulation of reward-related neural activity in adolescent cocaine abusers. The ability to undertake such voluntary neuromodulate may prove a viable treatment option for substance abuse disorders. The present work will provide a fundamental evaluation of this emerging technology, and will serve as a gateway for future work to conduct larger-scale clinical studies in substance-abusing populations.