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

描述（由申请人提供）：最近关于青少年药物滥用的神经认知理论认为，皮层和边缘区域的发育轨迹存在差异，这是导致青少年吸毒增加的原因。越来越多的文献表明，边缘区域的成熟发生在青春期早期，先于皮质区域的成熟，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导致青少年的奖励中心比能够约束它们的额叶区域发展得更快。因此，药物的管理可能会引发强烈的奖励体验，青少年很难管理，因为他们有效的自上而下的控制能力仍然有限。这与目前成人可卡因滥用的模型一致，该模型提出可卡因可能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，并减少执行控制过程。这一观点的一个含义是，重新校准这些改变的奖励敏感性的能力可能作为严重可卡因依赖个体的可行治疗策略。新兴技术，如实时功能磁共振成像（rt-fMRI），提供了向个人提供有关其神经活动当前状态的在线反馈的机会。这项技术的一个有价值的用途可能是为可卡因依赖者提供有关他们对药物相关和非药物相关奖励的神经反应的信息，并利用这种“神经反馈”方法训练参与者控制他们的神经活动，并重新平衡改变的奖励敏感性。我们的团队建议使用R21机制在40名青少年可卡因滥用者的样本中证明rt-fMRI技术的有效性，而他们表现出相当标准的线索引发的渴望范式。在展示药物，非药物和中性图片之前，参与者将被提供听觉指示，以增加，减少或观察，并将被指示尝试增加或减少伏隔核或前扣带的活动。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，参与者将被指示将其作为促进成功神经调节的辅助手段。将收集有关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。主要目的是证明该方案在药物滥用青少年中的可行性，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作为神经调节促进器的可行性的证据将代表着开发针对青少年滥用药物的综合治疗方案的关键一步，并可能作为实现这些治疗目标的未来工作的门户。

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.