Plasticity of Aversive Salience in Opioid Use Disorder

阿片类药物使用障碍中厌恶显着性的可塑性

• 批准号: 10360677
• 负责人: Jennifer Lorraine Stewart
• 金额: $ 64.61万
• 依托单位: LAUREATE INSTITUTE FOR BRAIN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10360677
• 关键词: Abstinence; Affect; Age; Anterior; Attention; Automobile Driving; Awareness; Base of the Brain; Behavioral; Biological Process; Brain; Brain region; Cardiac; Categories; Cessation of life; Chronic; Corpus striatum structure; Cues; Data; Data Set; Development; Dimensions; Drug usage; Emotions; Esthesia; Ethics; Functional Magnetic Resonance Imaging; Future; Impairment; Individual; Insula of Reil; Intervention; Knowledge; Link; Measures; National Institute of Drug Abuse; Negative Reinforcements; Opiate Addiction; Opioid; Pain; Pain interference; Participant; Patient Self-Report; Pattern; Persons; Pharmaceutical Preparations; Process; Public Health; Punishment; Recording of previous events; Recovery; Relapse; Research; Resources; Rewards; Sampling; Signal Transduction; Stimulus; Stress; Stressful Event; System; Testing; Time; United States; Urine; Visit; Withdrawal; Withdrawal Symptom; Woman; addiction; anxiety sensitivity; behavioral phenotyping; biobehavior; biological sex; bodily sensation; brain circuitry; brain dysfunction; cingulate cortex; craving; cue reactivity; depressive symptoms; dimensional analysis; directed attention; disorder later incidence prevention; drug craving; drug withdrawal; early detection biomarkers; follow-up; high risk; improved; individualized medicine; longitudinal design; men; mindfulness-based stress reduction; mortality; negative affect; neurofeedback; neuroimaging; novel; opioid use disorder; opioid user; persistent symptom; precision medicine; prospective; recruit; relapse risk; response; rumination; stimulant use disorder; stress reactivity; substance use; substance user

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.

摘要/项目摘要 NOT-DA-20-012 鉴于美国与阿片类药物成瘾相关的死亡人数处于历史最高水平， 迫切需要了解阻碍与促进康复的大脑机制，这是一个过程 其特点是长期戒毒并使用内部/外部资源来解决毒品问题 问题。该提案的主要目标是了解大脑回路如何参与 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（1）为未来的目标提供信息 干预（例如大脑神经反馈）； (2) 帮助开发个体化治疗 以减少与毒品相关的死亡。在接受治疗的三个月内，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，更高的强度 与健康对照组相比，内部感觉和更快的疼痛反应，以及较低的显着性- 注意身体信号和预期金钱损失时的相关大脑反应 然而，目前尚不清楚与厌恶显着性相关的大脑回路是否会改善和跟踪 弱势群体在治疗期间的前三个月内康复。本次活动的具体目标 提案测试 200 名寻求治疗的人之间基于显着性的大脑回路有何不同 早期四个时间点的阿片类药物使用障碍个体和 50 名健康个体 阿片类药物恢复（2 周以及 1、2 和 3 个月），确定自我报告、行为和 大脑变量可用于识别阿片类药物使用者与那些复发风险高的使用者 保持禁欲。涉及身体的功能磁共振成像 (fMRI) 范式 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/行为表型电池。一旦 拟议的目标已完成，将评估该数据集的结果以确定 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。