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

基本信息

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
项目类别：
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

项目摘要

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 15 年中，美国受到处方药和非法阿片/阿片类药物滥用增加的影响，成瘾和过量。研究加强阿片/阿片类药物使用个体的治疗选择疾病（iOUD）显然是一个优先事项。基于神经科学的行为疗法的发展可以用作辅助手段以提高 iOUD 药物辅助干预措施的有效性是国家优先事项，应对鸦片危机。为期 8 周的正念导向恢复增强 (MORE) 减少阿片类药物的使用误用、渴望和提示反应性，并增强自然奖励反应性，归因于重组的影响阿片类药物滥用患者的享乐失调。改善相关大脑的功能并增加灰质其他为期 8 周的正念干预已显示出对非上瘾的人。然而，iOUD 中 MORE 相关变化背后的神经机制尚不清楚。反应抑制和显着归因受损 (iRISA) 模型强调了中皮质纹状体区域，包括 PFC，以增强药物相对于自然奖励的显着性伴随着抑制控制的降低，药物成瘾的核心底物。鉴于这些的共性，我们建议研究 iRISA 的神经相关性，以促进和预测影响更多关于 iOUD 成瘾结果的信息。我们采用前后随机治疗设计并进行 3 个月的随访将检查“更多”[与“更多”]的影响照常治疗（TAU），作为美沙酮维持的附加疗法] 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 iOUD（主要使用海洛因）。寻求治疗的 iOUD 将被随机分为 8 周的治疗组 MORE 或社会心理 TAU 并在治疗前后立即使用磁共振成像进行扫描。健康对照将以相似的时间间隔进行扫描。我们假设与对照组相比，TAU 或 MORE 前、MORE 后受试者将表现出以下方面的正常化或变化：a) 奖励期间的额纹状体功能处理（即增强自然奖赏和减少药物线索处理）和抑制控制； b) 中观- 皮质纹状体静息态功能连接； c) 与奖励处理相关的区域的灰质和抑制控制。临床结果将在 MORE 或 TAU 期间、立即和之后 3 个月进行评估。我们假设 MORE 后>MORE 或 TAU 前的大脑变化将预测临床改善（治疗保留、戒断、阿片类药物使用量/频率和渴望），神经变化越多越好结果（健康的控制提供结果的方向）。在全脑分析中，我们考虑以下可能性：复苏会对其他网络产生影响，以弥补赤字。结果将有助于识别个体差异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控制可以随着 MORE 的反应而改变并预测 MORE 的反应，最终有助于 OUD 的精准医疗。