Neuroimaging response inhibition and salience attribution changes during mindfulness-based treatment of human heroin addiction

基于正念的人类海洛因成瘾治疗过程中神经影像反应抑制和显着性归因的变化

• 批准号: 10646215
• 负责人: Rita Z Goldstein
• 金额: $ 74.43万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10646215
• 关键词: Abstinence; Affect; Aftercare; American; Anterior; Attention; Behavior; Behavior Therapy; Brain; Brain region; Clinical; Clinical assessments; Cognitive Therapy; Compensation; Corpus striatum structure; Cues; Development; Disease model; Dorsal; Drug Addiction; Drug usage; Ecological momentary assessment; Effectiveness; Emotions; Equilibrium; Frequencies; Goals; Heroin; Heroin Dependence; Human; Impairment; Individual; Individual Differences; Inferior frontal gyrus; Informal Social Control; Infrastructure; Intervention; Knowledge; Letters; Magnetic Resonance Imaging; Medial; Methods; Mindfulness Training; Modeling; Morbidity - disease rate; Morphology; Nature; Neurosciences; Opiate Addiction; Opioid; Outcome; Overdose; Parkinson Disease; Patients; Pharmaceutical Preparations; Pharmacological Treatment; Population; Prefrontal Cortex; Process; Psychiatry; Publishing; Randomized; Recovery; Research; Rest; Rewards; Scanning; Statistical Data Interpretation; Stress; Testing; Urine; Visit; addiction; aged; anxious; brain based; brain circuitry; chronic pain patient; cingulate cortex; clinical predictors; comparison control; craving; cue reactivity; emotion regulation; endophenotype; evidence base; follow-up; functional MRI scan; functional improvement; gray matter; hedonic; heroin use; illicit opioid; improved; indexing; individual variation; insight; intervention effect; methadone treatment; mindfulness; mindfulness intervention; mortality; neural; neural correlate; neural network; neuroimaging; neuromechanism; opioid abuse; opioid epidemic; opioid misuse; opioid use; opioid use disorder; overdose death; precision medicine; predict clinical outcome; prescription opioid; prescription opioid misuse; psychosocial; randomized, clinical trials; response; reward processing; standard of care; stress reactivity; substance use; therapy design; time interval; treatment as usual

ABSTRACT Over the past 15 years, the US has been affected by increasing prescription and illicit opiate/opioid abuse, addiction, and overdose. Research into the enhancement of treatment options for individuals with opiate/opioid use disorder (iOUD) is clearly a priority. The development of neuroscience-informed behavioral therapies that could be used as adjuncts to improve effectiveness of medication-assisted interventions in iOUD is a national priority, a response to the opiate crisis. The 8-week Mindfulness-Oriented Recovery Enhancement (MORE) decreases opioid misuse, craving, and cue-reactivity, and enhances natural reward responsiveness, effects attributed to restructuring of hedonic dysregulation, in opioid misusing patients. Improved function and increased gray matter in relevant brain regions [e.g., the prefrontal cortex (PFC)] have been shown with other 8-week mindfulness interventions in non- addicted individuals. However, the neural mechanisms underlying MORE-related changes in iOUD are unknown. The Impaired Response Inhibition and Salience Attribution (iRISA) model highlights the importance of mesocorticostriatal regions, including the PFC, to enhanced salience of drugs relative to natural rewards concomitant with decreased inhibitory control, core substrates underlying drug addiction. Given these commonalities, we propose to study the neural correlates of iRISA as contributing to and predictive of the impact of MORE on addiction outcome in iOUD. Using a pre-post randomized treatment design with a 3-months follow-up, we will examine the impact of MORE [vs. treatment-as-usual (TAU), as add-ons to methadone maintenance] on neural functional and structural plasticity, and clinical outcomes (including daily ecological momentary assessments), in treatment-seeking iOUD (with primary use of heroin). Treatment-seeking iOUD will be randomized to 8-weeks of MORE or psychosocial TAU and scanned with magnetic resonance imaging immediately before and after treatment. Healthy controls will be scanned at similar time intervals. We hypothesize that compared with the controls, TAU or pre-MORE, post-MORE subjects will show normalizations or changes in: a) frontostriatal function during reward processing (i.e., enhanced natural reward and reduced drug cue processing) and inhibitory control; b) meso- corticostriatal resting-state functional connectivity; and c) gray matter in regions associated with reward processing and inhibitory control. Clinical outcome will be assessed during, immediately and 3-months after MORE or TAU. We hypothesize that brain changes post-MORE>pre-MORE or TAU will predict clinical improvement (treatment retention, abstinence, amount/frequency of opiate use and craving) such that the more the neural change, the better the outcomes (healthy controls provide direction of results). In whole-brain analyses we consider the possibility that recovery entails effects in other networks that compensate for deficits. Results will help identify individual variability in the brain regions/circuits that support reward processing, including cue reactivity, and inhibitory control and that could change with, and predict, response to MORE, ultimately contributing to precision medicine in OUD.

抽象的 在过去的15年中，美国受到了增加的处方和非法鸦片/阿片类药物的影响， 成瘾和过量。研究鸦片/阿片类药物使用的人的治疗选择增强 疾病（IOUD）显然是当务之急。可能是神经科学知识的行为疗法的发展 用作提高IOUD药物辅助干预措施有效性的辅助手段是国家优先事项，一个 对鸦片危机的反应。为期8周的正念恢复增强（更多）减少了阿片类药物 滥用，渴望和提示反应性并增强自然奖励响应能力，效果归因于重组 阿片类药物滥用患者的享乐功能障碍。相关大脑的功能改善和灰质增加 区域[例如，前额叶皮层（PFC）]在非 - 上瘾的人。但是，IOUD中与更加相关的更改的神经机制尚不清楚。 响应抑制和显着归因（IRISA）模型的障碍障碍强调了 包括PFC在内的中皮层区域相对于自然奖励增强了药物的显着性 伴随着抑制性控制的降低，核心底物是药物成瘾的基础。鉴于这些 共同点，我们建议研究IRISA的神经相关性，以促进并预测 有关IOUD成瘾结果的更多信息。使用3个月的随访前的前随机治疗设计，我们 将检查更多[Vs的影响在神经上的美沙酮维持的附加组件作为治疗 - 与众不同（tau） 功能性和结构可塑性以及临床结果（包括每日生态时刻评估） 寻求治疗的IOUD（主要使用海洛因）。寻求治疗的IOUD将被随机分为8周 在治疗前后，更多或心理社会tau并用磁共振成像进行扫描。 健康对照将以类似的时间间隔进行扫描。我们假设与对照，tau或 预科，后的受试者将显示：a）奖励期间额叶功能的正常化或变化 加工（即增强的自然奖励和减少药物提示处理）和抑制控制； b）中索 - 皮层静止状态功能连通性； c）与奖励处理相关地区的灰质 和抑制控制。在或多tau之后，将立即评估临床结果。我们 假设大脑在物体后变化>预测或tau将预测临床改善（治疗 保留，禁欲，数量/鸦片使用和渴望的频率）使神经变化越多，越好 结果（健康对照提供了结果的方向）。在全脑分析中，我们考虑了可能性 恢复需要补偿缺陷的其他网络中的效果。结果将有助于确定个体可变性 在支持奖励处理的大脑区域/电路中，包括提示反应性和抑制性控制， 可以随着更多的方式而改变并预测对更多的反应，最终导致OUD的精密医学。