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.

摘要 在过去的15年里，美国一直受到处方和非法阿片类药物/阿片类药物滥用增加的影响， 上瘾，还有吸毒过量。加强阿片剂/阿片类药物使用个人的治疗选择的研究 障碍(IOUD)显然是一个优先事项。神经科学知情行为疗法的发展可能是 作为辅助手段用于提高药物辅助干预的有效性是国家的优先事项，a 对鸦片类药物危机的反应。为期8周的正念导向恢复增强(更多)减少阿片类药物 误用、渴求和线索反应性，并增强自然奖赏反应，这些效应归因于重组 阿片类药物滥用患者的享乐性失调。功能得到改善，相关大脑灰质增加 在其他8周的正念干预中，已经显示了一些区域[例如，前额叶皮质(PFC)] 上瘾的人。然而，iOUD更相关变化背后的神经机制尚不清楚。 反应抑制和显著归因受损(IRSA)模型强调了 中皮质纹状体区域，包括PFC，与药物相对于自然奖励的显著增强有关 伴随着抑制控制的减少，核心底物是药物成瘾的基础。考虑到这些 在共性方面，我们建议研究IRSA的神经关联，以促进和预测 在iOUD上有更多关于成瘾后果的信息。采用前后随机治疗设计，并进行3个月的随访，我们 我将研究更多的[与常规治疗(TAU)相比，作为美沙酮维持的附加物]对神经的影响 功能和结构可塑性以及临床结果(包括每日生态瞬时评估)， 寻求治疗的吸毒者(主要使用海洛因)。寻求治疗的IOUD将被随机分配到8周的 治疗前和治疗后即刻进行磁共振成像检查。 健康对照将以类似的时间间隔进行扫描。我们假设，与对照组相比，TAU或 在奖励前后，更多的受试者将在以下方面表现出正常化或变化：a)奖励期间的额纹状体功能 加工(即增强的自然奖赏和减少的药物线索加工)和抑制控制；b)中观- 皮质纹状体静息状态的功能连接；以及c)与奖赏加工相关区域的灰质 和抑制性控制。临床结果将在MORE或TAU后的期间、立即和3个月进行评估。我们 假设大脑在更多或更多TAU后发生变化将预测临床改善(治疗 保留、戒断、阿片类药物使用量/频率和渴求)，神经变化越多越好 结果(健康对照提供结果的方向)。在全脑分析中，我们考虑这样一种可能性 复苏还会对弥补赤字的其他网络产生影响。结果将有助于识别个体差异 在支持奖赏处理的大脑区域/回路中，包括线索反应性和抑制控制，以及 可以随着更多的反应而改变，并预测，最终为我们的精准医学做出贡献。