Remediating Emotion Deficits in PTSD: Probing and Modulating Neurocircuits

描述（由申请人提供）：这是一个K23职业发展奖申请丽莎M。麦克蒂格博士，临床心理学家，斯坦福大学精神病学系讲师。McTeague博士的长期职业目标是了解严重情感疾病中情绪反应障碍的神经基础，以确定多模式方法来更好地弥补这些缺陷。这个K23奖项将使McTeague博士能够熟练掌握1）尖端的功能性神经成像（fMRI），2）经颅磁刺激（TMS）作为研究完整和紊乱的大脑激活的直接工具，3）将“实验医学”的原则转化为改善情绪功能障碍的心理社会治疗，以及4）利用这些新技术与她在认知行为治疗和心理生理学方面的既定专业知识，进行一系列的拨款申请，以帮助巩固她的独立性。 该项目的重点是创伤后应激障碍（PTSD）作为一种具有良好特征的情绪缺陷的综合征，可能容易受到外源性刺激（即，TMS），这反过来又可以用来提高传统的心理治疗效果。以创伤为中心的基于创伤的治疗是PTSD的一线治疗方法，但一半的患者在完成治疗后符合诊断标准。暴露的一个基本组成部分是彻底的情感表达过程，包括主观和客观的，以确保习惯化的最终体验是最佳的。McTeague博士先前观察到，慢性PTSD的特征是防御性动员明显迟钝，最重要的是在厌恶性图像期间的惊吓反射反应，这表明边缘系统（和相关网络）激活不足。 为了有意义地推进这些结论并指出干预目标，McTeague博士建议评估40名PTSD患者和20名创伤暴露的健康参与者在中性和厌恶以及同样高的唤起食欲图像期间的大脑激活和自主反应。包括后者将告知是否PTSD的特点是核心缺陷的情绪网络，而不是战略性回避，无论是结果不可或缺的干预计划（目标1）。为了评估边缘系统和前额叶回路之间的异常、状态依赖性相互作用是否表征PTSD，将在成像期间向两个前额叶区域施用TMS的单脉冲（目的2）。最后，将在患者中用单次（非治疗性）rTMS刺激前额叶边缘回路，以评估（潜在正常化）对随后立即进行的图像会话中情绪处理的影响（目标3）。成功完成将为McTeague博士先前观察到的迟钝反应提供更复杂的神经生物学回路理解，同时为使用TMS增强情绪反应和调节神经回路的可行性提供必要的指导，作为PTSD想象暴露的序言（计划的R01应用）。

DESCRIPTION (provided by applicant): This is a K23 Career Development Award application for Lisa M. McTeague, Ph.D., a clinical psychologist and Instructor in the Department of Psychiatry at Stanford University. Dr. McTeague's long-term career goal is to understand the neural basis of emotional reactivity impairments in severe affective illness in the service of identifying multimodal approaches to better remediate these deficits. This K23 award would enable Dr. McTeague to gain proficiency in 1) cutting-edge functional neuroimaging (fMRI), 2) transcranial magnetic stimulation (TMS) as a direct tool for investigating intact and disordered brain activation, 3) translating the principles of "experimental medicine" to psychosocial treatment toward ameliorating emotional dysfunction, and 4) leveraging these new techniques in conjunction with her established expertise in cognitive- behavioral treatment and psychophysiology for a series of grant submissions to help solidify her independence. This project focuses on posttraumatic stress disorder (PTSD) as a syndrome with well-characterized emotion deficits that may be susceptible to exogenous stimulation (i.e., TMS), which could, in turn, be utilized to enhance conventional psychotherapy outcomes. Trauma-focused exposure-based therapies are the first-line treatments for PTSD but half of patients meet diagnostic criteria upon completion. A fundamental component of exposure is the process of thorough emotional engagement-both subjectively and objectively-ensuring that the ultimate experience of habituation is optimally powerful. Dr. McTeague previously observed that chronic PTSD is marked by stark blunting of defensive mobilization, foremost in startle reflex responding during aversive imagery, suggestive of deficient limbic (and associated network) activation. To meaningfully advance these conclusions and point to intervention targets, Dr. McTeague proposes to assess brain activation and autonomic responding in 40 patients with PTSD and 20 trauma-exposed healthy participants during neutral and aversive as well as equally high arousing appetitive imagery. The inclusion of the latter will inform on whether PTSD is marked by core deficiencies in emotion networks as opposed to strategic avoidance-either outcome integral to intervention planning (Aim 1). To assess whether aberrant, state-dependent, interactions between limbic and prefrontal circuitry characterize PTSD, single pulses of TMS will be administered to two prefrontal regions during imagery (Aim 2). Finally, prefrontal-limbic circuits will be excited in patients with a single (non-therapeutic) session of rTMS to assess for (potentially normalizing) effects on emotional processing in an immediately subsequent imagery session (Aim 3). Successful completion would provide a more sophisticated neurobiological circuit understanding to Dr. McTeague's prior observation of blunted responding while furnishing essential guidance on the feasibility of using TMS to enhance emotional reactivity and regulation neurocircuitry as a preamble to imaginal exposure for PTSD (planned R01 application).