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.

项目概要 在这份 K23 指导患者导向研究职业发展奖申请中，乔纳森博士 韦提出了一个全面的临床研究和培训计划，以培养独立研究人员 拥有针对酒精使用障碍 (AUD) 的基于设备的治疗和神经影像学方面的专业知识。这个提议 旨在研究重复经颅磁刺激 (rTMS) 对酒精自我管理的影响 以及未接受治疗的 AUD 人类参与者的体内大脑 GABA 水平。之前的研究有 研究表明，AUD 与前额皮质的广泛功能障碍有关，并且与 前额叶 GABA 浓度。此外，rTMS 已被证明可以在治疗中增加前额 GABA 对抑郁症患者的研究表明，GABA 的增加与临床改善相关。早期工作 使用 rTMS 治疗 AUD 表明，rTMS 可以减少对酒精的渴望和报告的饮酒量。因此，rTMS 前额叶皮层可能作为 AUD 的潜在治疗方法，无论是单独使用还是作为现有治疗的辅助方法 治疗。 我们计划进行两项假对照、双盲、随机的人类实验室酒精自我测试 奖励期间的管理研究。对于研究 1，AUD 参与者将被录取参加研究 单位并随机接受主动（n = 22）或假（n = 22）rTMS。参与者将进行酒精自我测试 给药疗程以及三周前后的磁共振波谱 (MRS) 神经影像学检查 数周的 rTMS。我们将比较 AUD 参与者的酒精选择数量和大脑 GABA 水平 接受主动 rTMS 与假 rTMS。研究 2 (n=20) 将是一项使用相同程序的试点研究，其中 在活性 rTMS 组和假 rTMS 组中添加纳曲酮。在进行这项研究和追求 导师（Diana Martinez 博士、Suzette Evans 和 Christoph Juchem 博士）的课程作业和监督 Wai 博士的合作者（Markus Heilig 博士、Abraham Zangen 博士和 Hanga Galfalvy）将参与一项 个性化培训计划，以发展 1) 临床 rTMS 研究，2) 临床研究方面的专业知识 方法，3) MRS 采集和分析方法，4) 高级生物统计学，以及 5) 拨款写作和 管理。