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

总结/摘要 戒烟是困难的，尽管几种药物已经证明有效， 认知行为疗法这可能是由于不平衡的神经回路，包括功能性升高， 驱动-回报回路（内侧眶额叶皮层[mOFC]到丘脑核[NAc]）的连接， 执行控制回路（背外侧前额叶皮层[ DLPFC]至 NAc）。重复经颅磁刺激（rTMS）是一种新的治疗方法， 显示出产生新的，非药物干预神经精神疾病的显着潜力， 紊乱先前的研究报告说，rTMS减少线索渴望，减少香烟消费， 增加了烟草使用障碍（TUD）的戒烟率。然而，治疗参数和 rTMS提高戒烟率的确切机制有待进一步研究。UG 3/UH 3的目标是 该应用的目的是进一步开发用于戒烟的基于电路的精确rTMS疗法。在2年 UG 3阶段，我们将招募45名TUD。参与者将接受基线线索暴露功能磁共振成像和抵抗- 吸烟功能磁共振成像参与者将被随机分为三组：1）左侧mOFC上的假rTMS或 左后外侧前额叶皮层2)在左侧mOFC（1 Hz，900个脉冲，E- 场建模，15分钟，吸烟提示暴露fMRI引导的目标）。或3）主动高频rTMS（HF- rTMS）在左侧DLPFC（10 Hz，3000个脉冲，电场建模，15分钟，抗烟fMRI引导 目标）。我们将在三周内完成15次rTMS，之后我们将获得功能磁共振成像扫描。 Go/No-Go：要在UH 3阶段移动，UG 3必须在左侧mOFC上证明（1）每日1 Hz TMS 在每天减少3支或更多支香烟的香烟消耗方面显示出不同的临床效果， 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支香烟的香烟消耗）， 显著的脑连接变化（p < 0.05）（减少NAc和mOFC之间的连接， 增加DLPFC和NAc之间的连接）。在3年的UH 3阶段，我们将测试治疗 4周主动rTMS的影响（UG 3在左侧mOFC上1 Hz rTMS或在左侧DLPFC上10 Hz rTMS 阶段）与假rTMS在64个TUD，并遵循参与者的结果为4个月治疗后。我们还将 测试治疗前后4周的驱动奖励和执行控制的不平衡功能， 比较各组间的功能不平衡。

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.