The Effect of High Frequency rTMS to the Medial Prefrontal Cortex in Alcohol Use Disorder

项目摘要 在K23指导的以患者为导向的研究职业发展奖的申请中，乔纳森博士 阿威提出了一个全面的临床研究和培训计划，以发展一个独立的研究人员 在酒精使用障碍（AUD）的基于设备的治疗和神经成像方面具有专业知识。这项建议 旨在研究重复经颅磁刺激（rTMS）对酒精自我管理的影响 和体内脑GABA水平在非寻求治疗的人类参与者与AUD。先前的研究 表明AUD与前额叶皮层的广泛功能障碍有关， 前额GABA浓度此外，rTMS已被证明在治疗中增加前额GABA 抑郁症患者的研究，GABA的增加与临床改善相关。早期工作 对AUD使用rTMS表明，rTMS可以减少渴望和报告的酒精使用。因此，rTMS对 前额叶皮质可能作为AUD的潜在治疗，无论是单独还是作为现有治疗的辅助， 治疗。 我们计划进行两个假对照，双盲，随机人类实验室酒精自我， 在获奖期间进行研究。对于研究1，AUD受试者将被允许参加研究 单位，并随机接受活性（n = 22）或假手术（n = 22）rTMS。参与者将有一个酒精自我- 给药期和三次给药前后的磁共振波谱（MRS）神经成像 几周的rTMS。我们将比较AUD参与者的酒精和大脑GABA水平的选择数量 接受活性与假rTMS。研究2（n = 20）将是使用相同程序的初步研究， 在活性和假rTMS组中添加纳洛酮。在进行这项研究和追求 课程和他的导师（戴安娜马丁内斯博士，苏珊特埃文斯和克里斯托弗Juchem）的监督， 合作者（Markus Heilig，Abraham Zangen和Hanga Galfalvy博士），阿威博士将参与一项 个性化的培训计划，以发展1）临床rTMS研究的专业知识，2）临床研究 方法，3）MRS采集和分析方法，4）先进的生物统计学，和5）格兰特写作和 管理

Project Summary In this application for a K23 Mentored Patient Oriented Research Career Development Award, Dr. Jonathan Wai proposes a comprehensive clinical study and training plan for development of an independent researcher with expertise in device-based treatments and neuroimaging for alcohol use disorder (AUD). This proposal seeks to study the effects of repetitive transcranial magnetic stimulation (rTMS) on alcohol self-administration and in vivo brain GABA levels in non-treatment seeking human participants with AUD. Previous studies have shown that AUD is associated with broad dysfunction in the prefrontal cortices, as well as decreased prefrontal GABA concentrations. Additionally, rTMS has been shown to increase prefrontal GABA in treatment studies with depressed patients, with the increase in GABA associated with clinical improvement. Early work using rTMS for AUD has shown that rTMS can decrease craving and reported alcohol use. Thus, rTMS to the prefrontal cortex may serve as a potential treatment for AUD, either alone or as an adjunct to existing treatments. We plan to conduct two sham-controlled, double-blinded, randomized human laboratory alcohol self- administration studies during the award period. For Study 1, AUD participants will be admitted to a research unit and randomized to receive active (n=22) or sham (n=22) rTMS. Participants will have an alcohol self- administration session and neuroimaging with magnetic resonance spectroscopy (MRS) before and after three weeks of rTMS. We will compare the number of choices for alcohol and brain GABA levels in AUD participants receiving active vs. sham rTMS. Study 2 (n=20) will be a pilot study using the same procedures, with the addition of naltrexone in both active and sham rTMS groups. In conducting this study and pursuing coursework and supervision from his mentors (Drs. Diana Martinez, Suzette Evans, and Christoph Juchem) and collaborators (Drs. Markus Heilig, Abraham Zangen, and Hanga Galfalvy), Dr. Wai will engage in an individualized training program to develop expertise in 1) Research with clinical rTMS, 2) Clinical research methods, 3) MRS acquisition and analysis methods, 4) Advanced biostatistics, and 5) Grant writing and management.