Neuroimaging correlates and feasibility of transcranial magnetic stimulation (TMS) to improve smoking cessation outcomes in veterans with comorbid PTSD

神经影像学相关性和经颅磁刺激 (TMS) 改善患有 PTSD 退伍军人戒烟结果的可行性

• 批准号: 10426251
• 负责人: Jonathan R Young
• 金额: --
• 依托单位: DURHAM VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10426251
• 关键词: Adult; Affect; Biometry; Brain; Cause of Death; Centers for Disease Control and Prevention (U.S.); Cessation Research; Cessation of life; Cigarette; Clinical; Clinical Research; Clinical Trials; Cognitive Therapy; Consumption; Data; Development; Distal; Eligibility Determination; Enrollment; Exclusion; Feasibility Studies; Feedback; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; General Population; Goals; Grant; Health; Health Care Costs; Healthcare; Individual; Instruction; Knowledge; Major Depressive Disorder; Mental Health; Mental disorders; Mentors; Mentorship; Methodology; Methods; Modality; Morbidity - disease rate; Neurobiology; Neuronavigation; Neurosciences; Outcome; Patients; Pharmacotherapy; Physicians; Pilot Projects; Population; Post-Traumatic Stress Disorders; Preparation; Procedures; Protocols documentation; Psychotherapy; Public Health; Randomized, Controlled Trials; Research; Research Design; Research Training; Resistance; Rest; Risk; Scientist; Smoke; Smoker; Smoking; Smoking Cessation Intervention; Special Population; Structure; Structure of postcentral gyrus; Substance Use Disorder; System; Techniques; Therapeutic; Tobacco Use Disorder; Tobacco smoking behavior; Tobacco use; Training; Training Support; Transcranial magnetic stimulation; Trauma; United States; United States Department of Veterans Affairs; United States Food and Drug Administration; Veterans; Work; Writing; acceptability and feasibility; addiction; alternative treatment; career; comorbidity; disability; economic cost; effective therapy; efficacy testing; efficacy trial; evidence base; experience; improved; improved outcome; insight; interest; military veteran; mortality; neural; neural circuit; neuroimaging; neuroregulation; nicotine replacement; noninvasive brain stimulation; novel; novel strategies; open label; patient population; programs; recruit; repetitive transcranial magnetic stimulation; research study; skills; smoking cessation; smoking initiation; study population; substance use; targeted imaging; therapy resistant; trauma exposure

Tobacco use remains the number one preventable cause of death in the United States. Unfortunately, individuals with mental health conditions are disproportionately affected. Tobacco use is also high among US Veterans, and those who have experienced trauma are even more likely to smoke. Successful quitting is especially difficult for individuals who develop posttraumatic stress disorder (PTSD). Despite the efficacy of current evidence-based pharmacotherapies and psychotherapies for smoking cessation, alternative treatments are needed. Neuroimaging techniques such as resting-state functional magnetic resonance imaging (rs-fMRI) have provided insight into the neurocircuitry underlying the neurobiology of tobacco use disorder (TUD) and successful quit attempts. This improved understanding of the TUD pathophysiology at the neural systems-level provides a platform for the use of non-invasive brain stimulation (NIBS) techniques to modulate affected circuitry and improve outcomes. Indeed, the US Food and Drug Administration (FDA) recently cleared a form of NIBS, repetitive transcranial magnetic stimulation (rTMS), as a smoking cessation treatment in adults. However, the vast majority of clinical research trials on rTMS for smoking cessation have been conducted with civilians and excluded individuals with mental health conditions. To improve smoking cessation treatment options for Veterans with PTSD, it is critical to study novel brain stimulation methods such as rTMS in this special population. Similarly, the development of neuroscience-informed techniques to enhance rTMS in this treatment-resistant population are necessary. The application rs-fMRI to develop personalized rTMS targets as a way to precisely modulate the underlying neurocircuitry has been successfully applied to the treatment of major depressive disorder (MDD). This methodology has been demonstrated successfully for smoking cessation, but in civilian subjects making a quit attempt who did not have psychiatric illness. It remains unknown whether Veterans would find a combined neuroimaging-brain stimulation approach acceptable or if it is feasible to apply and study these techniques in a population of Veterans with PTSD. To fill these knowledge gaps, the proposed research aims to develop feasibility data for the therapeutic application of rs-fMRI-targeted rTMS for Veterans with PTSD attempting to quit smoking. Through a single-group, open-label trial, eligible Veterans with PTSD (n=14) seeking smoking cessation will receive rs-fMRI before and after a 5-day course of neuronavigated rTMS the week prior to their quit date, in conjunction with nicotine replacement therapy (NRT) and cognitive behavioral therapy. The scientific aims of the study are to demonstrate recruitment, retention, and acceptability in the study population, as well as feasibility of study procedures. In addition, the training aim is to provide the candidate with mentored clinical research training that supports the completion of the CDA-1 research study and preparation a CDA-2 application. Specifically, the candidate will develop technical proficiency in rTMS therapy and fMRI-based neuronavigation, knowledge of clinical trials, training and experience in clinical research domains relevant to Veteran health including PTSD and smoking cessation, as well as administrative, analytical and grant writing skills. The proposed research study and training plan provide a platform for the candidate to develop and implement a pilot randomized controlled trial (RCT) aimed at quantifying the efficacy of rs-fMRI-guided rTMS for smoking cessation in Veterans with PTSD. Ultimately, this line of research will allow the candidate to establish independence as a physician scientist at the Department of Veterans Affairs and to pursue a career on the development of non-invasive neuromodulation treatments for Veterans with comorbid substance use and psychiatric disorders.

在美国，烟草的使用仍然是可预防的死亡原因。不幸的是，个人 在心理健康状况下受到不成比例的影响。美国退伍军人中的烟草使用也很高， 那些经历过创伤的人更有可能吸烟。成功退出特别困难 患有创伤后应激障碍（PTSD）的个体。尽管当前基于证据的功效 需要戒烟的药物治疗和心理治疗，需要替代治疗。神经影像学 诸如静止状态功能磁共振成像（RS-FMRI）之类的技术提供了深入的见解 烟草使用障碍神经生物学（TUD）和成功戒烟尝试的神经通路。这 对神经系统级的TUD病理生理学的了解得以提高，为使用的平台提供了一个平台 非侵入性大脑刺激（NIB）技术以调节受影响的电路并改善预后。确实， 美国食品药品监督管理局（FDA）最近清除了一种笔尖，重复的经颅磁刺激形式 （RTMS），作为成人的戒烟治疗。但是，大多数RTMS的临床研究试验 为了戒烟，已经与平民进行了戒烟，并排除了具有心理健康状况的人。 为了改善具有PTSD退伍军人的戒烟治疗选择，研究新颖的大脑刺激至关重要 该特殊人群中的RTMS等方法。同样，神经科学知识技术的发展 为了增强这种抗药性人群的RTM。应用程序RS-FMRI开发 个性化的RTMS目标是精确调节基本神经通路的一种方式 应用于重度抑郁症（MDD）的治疗。该方法已成功证明 为了戒烟，但在平民中，没有精神病的企图。它仍然存在 未知退伍军人是否会发现可以接受的神经影像学 - 脑刺激方法或是否可以接受 可行的，可以在具有PTSD的退伍军人人群中应用和研究这些技术。为了填补这些知识空白， 拟议的研究旨在为RS-FMRI靶向RTMS的治疗应用开发可行性数据 有PTSD的退伍军人试图戒烟。通过单一的开放标签试验，合格的退伍军人 PTSD（n = 14）寻求戒烟将在5天的神经元过程之前和之后获得RS-FMRI RTM在退出日期之前的一周以及尼古丁替代疗法（NRT）和认知 行为疗法。该研究的科学目的是证明招聘，保留和可接受性 研究人群以及研究程序的可行性。此外，培训目的是为候选人提供 通过指导的临床研究培训，支持CDA-1研究和准备的完成 CDA-2应用程序。具体而言，候选人将在RTMS疗法和基于fMRI的技术方面发展技术水平 与退伍军人有关 健康，包括PTSD和戒烟，以及行政，分析和授予写作技巧。这 拟议的研究和培训计划为候选人提供了一个平台，以开发和实施飞行员 随机对照试验（RCT）旨在量化RS-FMRI引导的RTMS在戒烟中的疗效 具有PTSD的退伍军人。最终，这一研究将使候选人能够建立独立性 退伍军人事务部的医师科学家，并从事非侵入性发展的职业 具有合并药物使用和精神疾病的退伍军人的神经调节治疗。

项目成果

Transcranial Magnetic Stimulation Treatment for Smoking Cessation: An Introduction for Primary Care Clinicians.

• DOI: 10.1016/j.amjmed.2021.06.037
• 发表时间: 2021-11
• 期刊: The American journal of medicine
• 作者: Young JR;Galla JT;Appelbaum LG
• 通讯作者: Appelbaum LG

Ketamine for treatment of mood disorders and suicidality: A narrative review of recent progress.

• DOI: 10.12788/acp.0048
• 发表时间: 2022-03
• 期刊: ANNALS OF CLINICAL PSYCHIATRY
• 影响因子: 1.3
• 作者: Kritzer, Michael D.;Mischel, Nicholas A.;Young, Jonathan R.;Lai, Christopher S.;Masand, Prakash S.;Szabo, Steven T.;Mathew, Sanjay J.
• 通讯作者: Mathew, Sanjay J.

Diversifying the Bioethics Funding Landscape: The Case of TMS.

• DOI: 10.1080/15265161.2021.2001106
• 发表时间: 2022-01
• 期刊: AMERICAN JOURNAL OF BIOETHICS
• 影响因子: 13.4
• 作者: Dubljevic, Veljko;Young, Jonathan R.;Appelbaum, L. Gregory
• 通讯作者: Appelbaum, L. Gregory