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: 10540788
• 负责人: Jennifer Lorraine Stewart
• 金额: $ 65.36万
• 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/10540788
• 关键词: Abstinence; Affect; Age; Anterior; Attention; Automobile Driving; Awareness; Behavioral; Biological Process; Brain; Brain region; Cardiac; 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 based; brain circuitry; brain dysfunction; cingulate cortex; craving; cue reactivity; depressive symptoms; dimensional analysis; directed attention; 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; prolonged abstinence; prospective; recruit; relapse prevention; relapse risk; response; rumination; stimulant use disorder; stress reactivity; substance use; substance user; Abstinence; Affect; Age; Anterior; Attention; Automobile Driving; Awareness; Behavioral; Biological Process; Brain; Brain region; Cardiac; 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 based; brain circuitry; brain dysfunction; cingulate cortex; craving; cue reactivity; depressive symptoms; dimensional analysis; directed attention; 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; prolonged abstinence; prospective; recruit; relapse prevention; 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 非DA-20-012 鉴于与阿片类药物成瘾有关的死亡在美国的历史高 了解障碍与促进恢复的大脑机制的关键需求，这是一个过程 以长期禁欲和使用内部/外部资源来解决药物的标志 问题。该提案的广泛目的是了解大脑电路如何与 厌恶性内部（身体信号）和外部（压力，损失）刺激的显着性 阿片类药物成瘾的人内外的恢复到（1）告知未来目标 干预（例如，脑神经反馈）； （2）帮助开发个性化治疗 减少与药物有关的死亡。在治疗的三个月内，有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身体状态。 我们的初步数据表明，阿片类药物使用者显示出更大的负面影响，更高的强度 内部感觉和比健康对照更快的疼痛反应性，与较低的显着性配对 关注身体信号和预期金钱损失时相关的大脑反应 但是，目前尚不清楚厌恶性显着性相关的脑电路是否会改善和轨道 在治疗期间的前三个月中恢复。这个特定的目的 提案测试基于显着性的脑电路在200个寻求治疗之间有何不同 早期的四个时间点，患有阿片类药物使用障碍和50个健康个体的人 阿片类药物恢复（2周，1、2和3个月），确定自我报告，行为和 大脑变量可用于识别复发高风险的阿片类药物使用者 保持禁欲。涉及身体的功能磁共振成像（fMRI）范例 意识，货币胜利/损失以及压力/药物提示，药物使用评估和NIDA 每个时间点都会收集自我报告/行为表型电池。一旦 拟议的目标已完成，将评估该数据集的发现以确定 这些预测指标是否可以在其他寻求治疗样本中得到验证。