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RTMS manipulates imbalanced drive-reward and executive control circuitry for smoking cessation

RTMS 操纵不平衡的驱动奖励和执行控制电路来戒烟

基本信息

批准号：
10400944
负责人：
Xingbao Li
金额：
$ 35.51万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-15 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10400944
关键词：
Abstinence Active Sites Aftercare Automobile Driving Brain Cigarette Clinical Clinical Trials Cognitive Therapy Consumption Cues Double-Blind Method Frequencies Functional Magnetic Resonance Imaging Goals Intervention Left Magnetic Resonance Imaging Measures Medial Modeling Nucleus Accumbens Outcome Outcome Measure Participant Pharmaceutical Preparations Pharmacotherapy Phase Physiologic pulse Prefrontal Cortex Public Health Randomized Reporting Rewards Signal Transduction Smoke Smoker Study Section Testing Therapeutic Therapeutic Effect Tobacco Use Disorder active method base blood oxygen level dependent cigarette smoking clinical effect comparative efficacy craving executive function follow-up frontal lobe functional MRI scan innovation neuronal circuitry neuropsychiatric disorder neuroregulation novel overtreatment placebo group recruit repetitive transcranial magnetic stimulation response smoking cessation smoking cue therapeutic evaluation tobacco abstinence

项目摘要

SUMMARY/ABSTRACT Smoking cessation is difficult, despite the demonstrated efficacy of several pharmacotherapeutic agents and cognitive behavioral therapies. This may be due to imbalanced neuronal circuits, including elevated functional connectivity in the drive-reward circuit (medial orbital frontal cortex [mOFC] to nucleus accumbens [NAc]) and decreased functional connectivity in the executive control circuit (dorsolateral prefrontal cortex[ DLPFC] to NAc). Repetitive transcranial magnetic stimulation (rTMS) is a new class of therapeutics that has already displayed remarkable potential for producing novel, non-pharmacological interventions for neuropsychiatric disorders. Previous studies have reported that rTMS decreased cue craving, reduced cigarette consumption, and increased smoking quit rate in tobacco use disorders(TUDs). However, the treatment parameters and exact mechanism for rTMS increasing smoking quit rate need further refinement. The goal of this UG3/UH3 application is to develop a circuit-based precision rTMS therapy for smoking cessation further. In the 2-year UG3 phase, we will recruit 45 TUDs. Participants will undergo a baseline cue-exposure fMRI and a resisting-to smoke fMRI session. Participants will be randomized into three groups: 1) Sham rTMS over the left mOFC or the left DLPFC. 2) Active, inhibitory low-frequency rTMS (LF-rTMS) over the left mOFC (1 Hz, 900 pulses, E- field modeling, 15 minutes, smoking cue exposure fMRI-guided target). Or 3) Active, high-frequency rTMS (HF- rTMS) over the left DLPFC (10 Hz, 3000 pulses, E-field modeling,15 minutes, resisting-to-smoke fMRI guided target). Fifteen sessions of rTMS will be completed over three weeks, after which we will acquire fMRI scans. Go/No-Go: To move on the UH3 phase, the UG3 must demonstrate (1) daily 1-Hz TMS over the left mOFC shows a different clinical effect in the reduction of cigarette consumption by 3 or more cigarette per day, compared to daily 10-Hz over the left DLPFC (2) compared to sham, one of the active site/frequency combinations shows relative clinical improvement (reduces cigarette consumption by 5 cigarettes per day) and significant brain connectivity changes (p < 0.05) (decreases the connection between NAc and mOFC, and increases the connection between DLPFC and NAc). In the 3-year UH3 phase, we will test the therapeutic effects of 4 weeks of active rTMS (1 Hz rTMS over the left mOFC or 10 Hz over the left DLPFC by the UG3 phase) vs sham rTMS in 64 TUDs and follow participant outcomes for 4 months post-treatment. We will also test the imbalanced function of drive-reward and executive control before and after 4 weeks of treatments to compare the imbalanced function between groups.

摘要/摘要尽管多种药物治疗剂和药物已被证明有效，但戒烟仍然很困难。认知行为疗法。这可能是由于神经元回路不平衡，包括功能升高驱动奖励回路（内侧眶额皮质 [mOFC] 到伏隔核 [NAc]）的连接性执行控制回路（背外侧前额皮质[DLPFC]至 NAc）。重复经颅磁刺激 (rTMS) 是一种新型疗法，已经显示出针对神经精神科产生新颖的非药物干预措施的巨大潜力失调。先前的研究报告称，rTMS 降低了对线索的渴望，减少了香烟的消费，烟草使用障碍（TUD）的戒烟率增加。然而，治疗参数和 rTMS 提高戒烟率的确切机制需要进一步完善。本次UG3/UH3的目标该应用程序是为了进一步开发一种基于电路的精确 rTMS 戒烟疗法。在2年内 UG3阶段，我们将招募45名TUD。参与者将接受基线提示暴露功能磁共振成像和抵抗测试烟雾功能磁共振成像会议。参与者将被随机分为三组：1）在左侧 mOFC 上进行假 rTMS 或左 DLPFC。 2) 左侧 mOFC 上的主动抑制性低频 rTMS (LF-rTMS)（1 Hz，900 脉冲，E- 现场建模，15 分钟，吸烟提示暴露 fMRI 引导目标）。或 3) 主动、高频 rTMS (HF- rTMS）在左侧 DLPFC 上（10 Hz，3000 个脉冲，电场建模，15 分钟，抗烟功能磁共振成像引导目标）。十五次 rTMS 将在三周内完成，之后我们将获得功能磁共振成像扫描。 Go/No-Go：要进入 UH3 阶段，UG3 必须在左侧 mOFC 上展示 (1) 每日 1-Hz TMS 在每天减少 3 支或更多支香烟方面表现出不同的临床效果，与左侧 DLPFC 每日 10 Hz 相比 (2) 与假手术相比，活动部位/频率之一组合显示出相对的临床改善（每天减少 5 支香烟的消费量）并且显着的大脑连接变化 (p < 0.05)（NAc 和 mOFC 之间的连接减少，并且增加 DLPFC 和 NAc 之间的连接）。在为期3年的UH3阶段，我们将测试治疗效果 4 周主动 rTMS 的影响（UG3 对左侧 mOFC 进行 1 Hz rTMS 或对左侧 DLPFC 进行 10 Hz rTMS）阶段）与 64 个 TUD 中的假 rTMS 相比，并在治疗后 4 个月内跟踪参与者的结果。我们还将在治疗 4 周之前和之后测试驱动奖励和执行控制的不平衡功能比较组间功能的不平衡。