Augmenting cognitive-behavioral therapy with rTMS of the medial prefrontal and anterior cingulate cortices for the treatment of cocaine use disorder

项目总结/摘要 可卡因使用障碍（CUD）仍然是美国的一个重大公共卫生问题， 需要有效的治疗策略。重复经颅磁刺激（rTMS）是一种非 一种调节特定脑区的侵入性方法，在治疗 CUD。然而，缺乏评估CUD中可卡因消耗的假对照临床试验。 以前的CUD成像研究涉及前额叶皮层的广泛区域，包括 内侧前额叶皮层（mPFC）、前扣带皮层（ACC）和背外侧前额叶皮层（dlPFC）。 连通性和皮质厚度的改变已被证明与CUD的治疗反应相关 在这些大脑区域的不同成像模式中。因此，我们的目标是采用rTMS，使用 H7-线圈，因为该线圈可以同时和双侧刺激mPFC和背侧ACC。 H7-线圈已被FDA批准用于强迫症（OCD），基于其达到这些的能力。 前额叶皮层更深更宽的区域结果，发现了使用H7线圈的治疗中心 在美国（50个州中的42个），这意味着这种线圈的使用可以从实验室 很快就送到了诊所 在本申请中，我们首先提出了一项门诊双盲假对照试验（UG 3期）， 研究H7线圈可行性，使用fMRI的脑行为机制，以及对戒断启动的影响 在认知行为疗法（CBT）之前服用可卡因。如果提议的通过/不通过标准 我们将招募更大的样本，以评估联合rTMS/CBT启动禁欲的有效性 成人CUD（UH 3期）。如果UH 3数据支持治疗效果，这种治疗可以迅速 考虑到精神病人群中H7-螺旋的现有FDA许可（即，强迫症），以及 可能成为FDA批准的第一种治疗CUD的药物。

Project Summary/Abstract Cocaine use disorder (CUD) continues to be a significant public health problem in the U.S. and more effective treatment strategies are needed. Repetitive transcranial magnetic stimulation (rTMS) is a non- invasive method of modulating specific brain regions that has shown preliminary efficacy in the treatment of CUD. However, sham-controlled clinical trials assessing cocaine consumption in CUD are lacking. Previous imaging studies in CUD have implicated broad regions of the prefrontal cortex, including the medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (dlPFC). Alterations in connectivity and cortical thickness have been shown to correlate with treatment response in CUD across different imaging modalities in each of these brain regions. Thus, our goal is to employ rTMS, using the H7-coil, since this coil can simultaneously and bilaterally stimulate the mPFC and dorsal ACC. Additionally, the H7-coil has been FDA-cleared for obsessive-compulsive disorder (OCD), based on its ability to reach these broad, deeper regions within the prefrontal cortex. As a result, treatment centers using the H7-coil are found across the United States (in 42 of 50 states), meaning that the use of this coil could move from the laboratory to the clinic relatively quickly. In this application, we first propose an outpatient double-blind sham-controlled trial (UG3 Phase) to investigate H7-coil feasibility, brain-behavior mechanism(s) using fMRI, and effect on initiation of abstinence from cocaine when administered prior to cognitive behavioral therapy (CBT). If the proposed go/no-go criteria are met, we will recruit a larger sample to evaluate the efficacy of combined rTMS/CBT for abstinence initiation in adults with CUD (UH3 Phase). If the UH3 data support therapeutic efficacy, this treatment could rapidly translate to the clinic given existing FDA-clearance for the H7-coil in psychiatric populations (i.e., OCD), and could become the first FDA-approved therapy for CUD.