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

高频 rTMS 对酒精使用障碍中内侧前额皮质的影响

• 批准号: 10630124
• 负责人: Jonathan Wai
• 金额: $ 19.11万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10630124
• 关键词: Adherence; Admission activity; Alcohol consumption; Alcohols; Anterior; Award; Biometry; Brain; Brain region; Clinic; Clinical; Clinical Research; Combination Medication; Data; Decision Making; Development Plans; Devices; Double-Blind Method; Ethics; FDA approved; Feasibility Studies; Fostering; Frequencies; Functional disorder; Funding; Goals; Grant; Guidelines; Hospitals; Hour; Human; Image; Inpatients; Investigation; Israel; K-Series Research Career Programs; Laboratories; Laboratory Study; Magnetic Resonance Spectroscopy; Major Depressive Disorder; Measures; Medial; Mental Depression; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methods; Naltrexone; National Institute on Alcohol Abuse and Alcoholism; Neurotransmitters; Obsessive-Compulsive Disorder; Outcome Study; Participant; Physicians; Pilot Projects; Play; Prefrontal Cortex; Procedures; Randomized; Reporting; Research; Research Design; Research Methodology; Research Personnel; Role; Scanning; Science; Scientist; Self Administration; Severities; Supervision; Symptoms; Testing; Training; Training Programs; Translating; Translational Research; Work; Writing; alcohol abuse therapy; alcohol craving; alcohol seeking behavior; alcohol use disorder; binge drinking; career; cingulate cortex; clinical effect; clinical training; cognitive control; craving; depressed patient; drinking; gamma-Aminobutyric Acid; improved; in vivo; neuroimaging; novel; patient oriented research; reinforcer; repetitive transcranial magnetic stimulation; response; treatment responders; volunteer

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.

项目摘要 乔纳森博士在K23以患者为导向的研究职业发展奖的申请表中 WAI提出了一项全面的临床研究和培训计划，以发展独立研究人员 在基于设备的治疗和酒精使用障碍(AUD)的神经成像方面拥有专业知识。这项建议 旨在研究重复经颅磁刺激(RTMS)对酒精自我给药的影响 以及体内未接受治疗的AUD患者的大脑GABA水平。之前的研究已经 研究表明，AUD与前额叶皮质的广泛功能障碍有关，而且 前额叶GABA浓度。此外，rTMS已被证明在治疗中增加前额叶GABA。 对抑郁症患者的研究表明，GABA的增加与临床改善有关。早期工作 使用rTMS治疗AUD表明，rTMS可以减少饥饿感和报告的酒精使用。因此，rTMS到 前额叶皮质可能是一种潜在的治疗AUD的方法，无论是单独治疗还是作为现有的辅助治疗 治疗。 我们计划进行两个假对照、双盲、随机的人体实验酒精自身 在获奖期间学习行政管理。对于研究1，澳元参与者将被允许参加一项研究 并随机接受活动(n=22)或假(n=22)rTMS。参与者将有一个酒精自我 用药前后的磁共振波谱(MRS)和神经成像 数周的rtms。我们将比较AUD参与者对酒精和大脑GABA水平的选择数量 接收活动rtms与假rtms。研究2(n=20)将是使用相同程序的试验性研究， 活动组和假rTMS组均加入纳曲酮。在进行这项研究和追寻 他的导师(戴安娜·马丁内斯博士、苏泽特·埃文斯博士和克里斯托弗·朱切姆博士)的课程作业和监督 合作者(马库斯·海利格博士、亚伯拉罕·赞根博士和汉加·加尔法维博士)，韦博士将参与 个人化培训计划，以发展1)临床rTMS研究，2)临床研究的专业知识 方法，3)MRS采集和分析方法，4)高级生物统计学，5)赠款撰写和 管理层。