Remediating Emotion Deficits in PTSD: Probing and Modulating Neurocircuits

补救 PTSD 中的情绪缺陷：探测和调节神经回路

• 批准号: 9278018
• 负责人: Lisa M McTeague
• 金额: $ 19.73万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9278018
• 关键词: Affective; Amygdaloid structure; Anxiety Disorders; Arousal; Base of the Brain; Brain; Brain Diseases; Brain region; Chronic; Clinical; Cognitive; Cognitive Therapy; Comorbidity; Desire for food; Diagnosis; Diagnostic; Distal; Distress; Doctor of Philosophy; Emotional; Emotions; Ensure; Equilibrium; Fright; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Grant; Heterogeneity; Imagery; Impairment; Intervention; K-Series Research Career Programs; Light; Maps; Medicine; Memory; Mental Depression; Mentored Patient-Oriented Research Career Development Award; Mentors; Neurobiology; Outcome; Participant; Patients; Phase; Physiologic pulse; Physiological; Post-Traumatic Stress Disorders; Process; Psychiatry; Psychologist; Psychophysiology; Psychotherapy; Publishing; Recruitment Activity; Reflex action; Regulation; Research; Science; Series; Services; Suggestion; Syndrome; Techniques; Testing; Training; Transcranial magnetic stimulation; Translating; Trauma; Treatment outcome; Universities; attenuation; base; career; emotion regulation; emotional experience; experience; habituation; imaging modality; innovation; instructor; multimodality; neural circuit; neuroimaging; neuromechanism; post-traumatic stress; psychosocial; public health relevance; relating to nervous system; remediation; repetitive transcranial magnetic stimulation; response; tool

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).

描述（由申请人提供）：这是 Lisa M. McTeague 博士的 K23 职业发展奖申请，她是斯坦福大学精神病学系的临床心理学家和讲师。 McTeague 博士的长期职业目标是了解严重情感疾病中情绪反应性损伤的神经基础，以便确定多模式方法来更好地补救这些缺陷。该 K23 奖项将使 McTeague 博士能够熟练掌握 1) 尖端功能神经影像 (fMRI)、2) 经颅磁刺激 (TMS) 作为研究完整和紊乱大脑激活的直接工具、3) 将“实验医学”原理转化为心理社会治疗，以改善情绪功能障碍，以及 4) 结合她所建立的技术利用这些新技术 认知行为治疗和心理生理学方面的专业知识，用于提交一系列赠款，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），它是一种具有明显情绪缺陷的综合征，可能容易受到外源刺激（即 TMS）的影响，而这反过来又可以用来增强传统心理治疗的效果。以创伤为重点的暴露疗法是 PTSD 的一线治疗方法，但完成后有一半患者符合诊断标准。暴露的一个基本组成部分是主观和客观上彻底的情感投入的过程，以确保最终的习惯体验是最强大的。 McTeague 博士之前观察到，慢性 PTSD 的特点是防御性动员明显减弱，最重要的是厌恶意象期间的惊吓反射反应，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 名遭受创伤的健康参与者在中性和厌恶以及同样高的激发食欲意象时的大脑激活和自主反应。纳入后者将有助于了解 PTSD 是否以情感网络的核心缺陷为标志，而不是战略性回避——这两种结果都是干预计划的组成部分（目标 1）。为了评估边缘系统和前额叶回路之间异常的、状态依赖性的相互作用是否是 PTSD 的特征，在意象过程中将 TMS 的单脉冲施加到两个前额叶区域（目标 2）。最后，接受单次（非治疗性）rTMS 治疗的患者的前额叶边缘回路将被兴奋，以评估在随后的意象治疗中对情绪处理的（潜在正常化）影响（目标 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).

项目成果

COGNITION-CHILDHOOD MALTREATMENT INTERACTIONS IN THE PREDICTION OF ANTIDEPRESSANT OUTCOMES IN MAJOR DEPRESSIVE DISORDER PATIENTS: RESULTS FROM THE iSPOT-D TRIAL.

认知-童年虐待治疗相互作用在预测重度抑郁症患者抗抑郁药效果中的作用：iSPOT-D 试验的结果。

• DOI: 10.1002/da.22368
• 发表时间: 2015
• 期刊: Depression and anxiety
• 影响因子: 7.4
• 作者: Miller,Shefali;McTeague,LisaM;Gyurak,Anett;Patenaude,Brian;Williams,LeanneM;Grieve,StuartM;Korgaonkar,MayureshS;Etkin,Amit
• 通讯作者: Etkin,Amit

Transdiagnostic impairment of cognitive control in mental illness.

• DOI: 10.1016/j.jpsychires.2016.08.001
• 发表时间: 2016-12
• 期刊: JOURNAL OF PSYCHIATRIC RESEARCH
• 影响因子: 4.8
• 作者: McTeague, Lisa M.;Goodkind, Madeleine S.;Etkin, Amit
• 通讯作者: Etkin, Amit

Reconciling RDoC and DSM approaches in clinical psychophysiology and neuroscience.

协调临床心理生理学和神经科学中的 RDoC 和 DSM 方法。

• DOI: 10.1111/psyp.12602
• 发表时间: 2016
• 期刊: Psychophysiology
• 影响因子: 3.7
• 作者: McTeague,LisaM