Plasticity of Aversive Salience in Opioid Use Disorder

摘要/项目总结 NOT-DA-20-012 鉴于与阿片类药物成瘾有关的死亡人数在美国处于历史最高水平， 一个关键的需要，了解大脑机制阻碍与促进恢复，一个过程 以长期禁欲和使用内部/外部资源来解决毒品问题为特点 问题这项提议的主要目的是了解大脑回路是如何参与 厌恶性内部（身体信号）和外部（压力，损失）刺激轨迹的显着性 阿片类药物成瘾者内部和之间的康复，以（1）为未来的目标提供信息， 干预（例如，脑神经反馈）;（2）帮助个体化治疗的发展 减少与毒品有关的死亡。在治疗的三个月内，50%的药物使用者 复发，服用药物以避免与渴望、戒断和压力有关的令人厌恶的身体状态。 我们的初步数据表明，阿片类药物使用者表现出更大的负面影响， 内部感觉，和更快的疼痛反应比健康对照，配对较低的显着性- 在注意身体信号和预期金钱损失时的相关大脑反应 然而，目前还不清楚与厌恶性显著性相关的大脑回路是否会改善和跟踪 在脆弱的前三个月治疗期间恢复。具体目标是 一项提案测试了200名寻求治疗的人之间基于显着性的大脑回路的差异 阿片类药物使用障碍的个体和50名健康个体在早期阶段的四个时间点 阿片类药物恢复（2周和1，2和3个月），确定自我报告，行为， 大脑变量可用于识别阿片类药物使用者复发的高风险， 保持禁欲。功能性磁共振成像（fMRI）范式涉及身体 意识，金钱赢/输，压力/药物线索，物质使用评估和NIDA 将在每个时间点收集自我报告/行为表型组合。一旦 建议的目标完成后，将对该数据集的结果进行评估，以确定 这些预测指标是否可以在其他寻求治疗的样本中得到验证。

ABSTRACT/PROJECT SUMMARY NOT-DA-20-012 Given that deaths linked to opioid addiction are at an all-time high in the United States, there is a crucial need to understand brain mechanisms impeding versus promoting recovery, a process marked by prolonged abstinence and use of internal/external resources to resolve drug problems. The broad aims of this proposal are to understand how brain circuitry implicated in the salience of aversive internal (bodily signals) and external (stressful, loss) stimuli tracks recovery within and across individuals with opioid addiction to (1) inform future targets for intervention (e.g., brain neurofeedback); and (2) aid the development of individualized treatment to reduce drug-related deaths. Within three months of treatment, 50% of substance users relapse, taking drugs to avoid aversive bodily states linked to craving, withdrawal, and stress. Our preliminary data suggest that opioid users show greater negative affect, higher intensity of internal sensations, and faster pain reactivity than healthy controls, paired with lower salience- relevant brain responses during attention to bodily signals and anticipation of monetary losses However, it is unclear whether aversive salience-related brain circuitry improves and tracks recovery during the vulnerable first three months during treatment. The specific aims of this proposal test how salience-based brain circuitry differs between 200 treatment-seeking individuals with opioid use disorder and 50 healthy individuals at four timepoints during early opioid recovery (2 weeks and 1, 2, and 3 months), identifying what self-report, behavioral, and brain variables can be used to identify opioid users at high risk for relapse versus those who maintain abstinence. Functional magnetic resonance imaging (fMRI) paradigms involving bodily awareness, monetary win/loss, and stress/drug cues, substance use assessments, and NIDA self-report/behavioral phenotyping batteries will be collected at each timepoint. Once the proposed aims are completed, the findings from this dataset will be evaluated to determine whether these prediction metrics can be validated in additional treatment-seeking samples.