Electrophysiological Predictors and Indicators of Contingency Management Treatment Response

电生理学方法，包括事件相关电位和功能连接方法， 有很强的潜力来阐明物质使用治疗反应的机制，并表征个体 其中的差异。退伍军人不成比例地受到成瘾性疾病的影响，其中可卡因的使用 疾病（CUD）是特别成问题的，由于高复发率和缺乏批准的药物， 治疗选择。因此，对CUD的行为干预已成为一个重要的焦点， 研究和应急管理（CM）已经成为最受支持和最广泛使用的 approach. CM涉及加强可卡因戒断（通过客观测试建立）， 短期奖励，例如赢得奖品的机会（即，基于奖励的CM或PBCM）。针对大量 经验支持，自2011年以来，VHA倡议一直支持PBCM的国家传播。 然而，PBCM的响应率是可变的，长期效益是有限的-问题被放大， 实施成本与人员配备和奖品有关。基于计量的PBCM方法 实施有很大的希望提高变革管理方案拟订的效力和效率，但 尚未在VA内进行研究或考虑与有前途的神经标志物相关。重要的是，两个 不同版本的PBCM已经在VA站点使用，并且可能对具有不同疾病的个体有不同的益处。 神经认知特征具体来说，VA PBCM计划采用抽象（凭证奖）或具体 （有形奖励）激励，后者可能更有效地激励退伍军人的禁欲， 缺乏前瞻性思维和规划能力。虽然现有PBCM变体之间的选择是 当前由实际考虑驱动（例如，提供商便利），预处理的测量 在这方面，神经认知功能可以有意义地和现实地为临床决策提供信息。 该CDA旨在通过测试一种新的神经认知功能， 的CM模型与直接影响的使用抽象与具体的PBCM激励措施内， 弗吉尼亚具体而言，未来思维决策（FMDM）模型假定CM支架面向未来 目标表征和自我控制，以支持禁欲期间的时刻使用相关的决策。 对于FMDM损伤更严重的个体，具体的、容易获得的激励措施可能更有效 而不是抽象的金钱奖励（例如，需要面向未来的思考和规划来继承 值为了测试该模型，将检查FMDM的神经认知底物作为差异表达的预测因子。 治疗反应的凭证（ChampionerPBCM）与有形奖励（TangiblePBCM）版本的 在VA中使用的干预。神经和认知行为相关因素的治疗相关变化 还将在PBCM中评价FMDM相对于常规治疗（TAU）护理的情况。共有180名退伍军人， CUD将被分配至DicherPBCM（n=70）、TangiblePBCM（n=70）或TAU（n=40）条件， 随访12周治疗间隔。治疗前和治疗后脑电图（EEG）和 认知行为评估将用于测量FMDM相关结构（工作记忆，自我， 控制，未来导向决策，未来奖励表征）和相关的神经标志物。这些 随后，将研究这些指标作为不同治疗反应的预测因子， 对比THBCM。FMDM相关神经基质和认知能力的纵向变化也将 评估神经适应的证据（例如，功能连接的变化）和增强 FMDM通过PBCM发挥作用。拟议的研究将得到以下领域重点培训的支持： 预测分析，（2）EEG数据的功能连接分析，（3） 神经适应机制;（4）临床试验研究。研究和培训目标将共同支持 制定一项独立的研究计划，目标是在VA内精确实施CM。

Electrophysiological methods, including event-related potential and functional connectivity approaches, have strong potential to clarify mechanisms of substance use treatment response and characterize individual differences therein. Veterans are disproportionately affected by disorders of addiction, of which cocaine use disorder (CUD) is particularly problematic due to high relapse rates and the absence of approved pharmaco- therapy treatment options. Behavioral interventions for CUD, have therefore become an important focus of research and Contingency Management (CM) has emerged as the best-supported and most widely used approach. CM involves reinforcing cocaine abstinence (established through objective testing) with reliable, short-term reward, such as chances to win prizes (i.e., Prize-Based CM or PBCM). In response to substantial empirical support, national dissemination of PBCM has been supported by a VHA initiative since 2011. However, PBCM response rates are variable and long-term benefits are limited – problems magnified by the cost of implementation with respect to staffing and prizes. Measurement-based approaches to PBCM implementation have strong promise to improve the effectiveness and efficiency of CM programming but have not yet been investigated within the VA or considered in relation to promising neuromarkers. Importantly, two versions of PBCM are already utilized at VA sites and may differentially benefit individuals with distinct neurocognitive profiles. Specifically, VA PBCM programs employ either abstract (voucher prize) or concrete (tangible prize) incentives, the latter of which may more effectively incentivize abstinence in Veterans with poor future-oriented thinking and planning ability. While selection between existing PBCM variants is currently driven by practical considerations (e.g., provider convenience), measurement of pretreatment neurocognitive functioning could meaningfully and realistically inform clinical decision-making in this regard. This CDA aims to advance measurement-based implementation of CM by testing a novel neurocognitive model of CM with immediate implications for the use of abstract versus concrete PBCM incentives within the VA. Specifically, the future-minded decision-making (FMDM) model posits that CM scaffolds future-oriented goal representation and self-control to support abstinence during in the moment use-related decision-making. For individuals with greater FMDM impairment, concrete, readily-accessible incentives may be more effective than abstract monetary rewards (e.g., vouchers) which require future-oriented thinking and planning to inherit value. To test this model, neurocognitive substrates of FMDM will be examined as predictors of differential treatment response in voucher (VoucherPBCM) versus tangible prize (TangiblePBCM) versions of the intervention used within the VA. Treatment-related change in neural and cognitive-behavioral correlates of FMDM will also be evaluated in PBCM relative to treatment-as-usual (TAU) care. A total of 180 Veterans with CUD will be allocated to VoucherPBCM (n=70), TangiblePBCM (n=70), or TAU (n=40) conditions and followed for a 12 week treatment interval. Pre- and post-treatment electroencephalography (EEG) and cognitive-behavioral assessments will be used to measure FMDM-related constructs (working memory, self- control, future-oriented decision-making, future reward representation) and related neuromarkers. These measures will subsequently be investigated as predictors of differential treatment response in VoucherPBCM versus Tangible PBCM. Longitudinal change in FMDM-related neural substrates and cognitive abilities will also be evaluated for evidence of neuroadaptation (e.g., changes in functional connectivity) and enhancement of FMDM function through PBCM. The proposed research will be supported by focused training in the areas of (1) predictive analytics, (2) functional connectivity analysis of EEG data, (3) longitudinal evaluation of neuroadaptive mechanisms, and (4) clinical trials research. Together, research and training aims will support development of an independent program of research targeting precision implementation of CM within the VA.