Effects of amygdala neurofeedback on depressive symptoms and processing biases

描述（申请人提供）：在这份修订后的独立之路奖（K99/R 00）申请书中，Kymberly Young博士要求获得必要的培训，以使自己成为一名独立的研究人员，研究针对重度抑郁症（MDD）的新型神经行为干预措施。特别关注作为MDD症状发作和缓解的生物标志物和治疗靶点的情绪处理偏差。实现这一长期目标需要Young博士发展跨学科的技能，包括MDD的临床神经科学，转化神经科学和功能性神经影像学。她之前的培训和出版记录清楚地表明，杨博士在认知神经科学和抑郁症的生物学基础方面具有专业知识。然而，为了完全实现她的目标，她需要额外的培训， 经验来自于与精神疾病的神经行为治疗和尖端功能性神经影像技术领域的专家合作。为此，Young博士将接受匹兹堡大学医学院认知和情感神经科学项目主任Greg Siegle博士在MDD神经行为治疗方面的指导，他也是情绪障碍治疗和研究项目的执行团队，该项目是西方精神病研究所和诊所的临床试验单位。为了接受尖端功能性神经成像方法的培训，Young博士将与国际知名的MRI物理学家Jerzy Bodurka博士密切合作，他在高级血氧水平依赖（BOLD）fMRI技术和方法学方面具有专业知识，并担任Laureate Institute for Brain Research（LIBR）MRI和EEG设施的首席技术官和主任。培训和相关研究将在LIBR进行，LIBR是一家最先进的独立生物医学研究机构，致力于开展神经影像学研究，其使命是为神经精神疾病开发有效的治疗方法。LIBR附属于Laureate精神病诊所和医院，该诊所和医院为研究提供了特殊的临床人群，特别是MDD患者。通过她的导师和合作者提供的培训，以及LIBR的机构资源，Young博士将能够实现本提案的研究目标，即确定实时功能磁共振成像神经反馈的程度。（rtfMRI-nf）增强对杏仁核神经活动的自主控制，共同调节情绪调节回路中的其他大脑区域，并改变抑郁症状严重程度评级（具体目标1）。她还将确定杏仁核rtfMRI-nf在暴露于情绪化刺激期间恢复规范情绪处理偏差的程度（具体目标2）。最后，这项培训将为Young博士准备该奖项的R 00阶段，她将过渡到独立的学院级研究职位，并调查是否可以通过增加涉及杏仁核活动的rtfMRI-nf来改善症状改善的时间进程和认知行为治疗的整体疗效（具体目标3）。

DESCRIPTION (provided by applicant): In this revised application for a Pathway to Independence Award (K99/R00), Dr. Kymberly Young requests support to acquire the training necessary to establish herself as an independent investigator studying novel neurobehavioral interventions for major depressive disorder (MDD), with a specific focus on emotional processing biases that serve as a biological marker and treatment target both for the onset and remission of MDD symptoms. Accomplishing this long-term goal requires that Dr. Young develop skills that cut across disciplines, including the clinical neuroscience of MDD, translational neuroscience, and functional neuroimaging. Her prior training and publication record clearly indicate that Dr. Young has expertise in cognitive neuroscience and the biological basis of depression. In order to fully attain her goals, however, she needs additional training and experience that comes from working with experts in the field of neurobehavioral treatments of psychiatric disorders and cutting-edge functional neuroimaging techniques. To that end, Dr. Young will receive mentoring in neurobehavioral treatments for MDD from Dr. Greg Siegle, director of the Program in Cognitive and Affective Neuroscience at University of Pittsburgh School of Medicine, who is also on the executive team of the Mood Disorders Treatment and Research Program, which serves as the clinical trials unit for the Western Psychiatric Institute and Clinic. To receive training in cutting-edge functional neuroimaging methods, Dr. Young will work closely with Dr. Jerzy Bodurka, an internationally-renowned MRI physicist with expertise in advanced blood-oxygen level dependent (BOLD) fMRI techniques and methodology, and the Chief Technology Officer and director of the Laureate Institute for Brain Research (LIBR) MRI and EEG facility. The training, and associated research, will take place at LIBR, a state-of-the-art independent biomedical research institute dedicated to conducting neuroimaging research with the mission of developing effective treatments for neuropsychiatric disorders. LIBR is affiliated with the Laureate Psychiatric Clinic and Hospital, which provides exceptional access to clinical populations available for research, particularly patients with MDD. With the training offered by her mentors and collaborators, and institutional resources at LIBR, Dr. Young will be able to achieve the research objectives of this proposal, namely to determine the degree to which real-time fMRI neurofeedback (rtfMRI-nf) enhances voluntary control over amygdala neural activity, co-modulates other brain regions within the emotion regulation circuitry, and alters depressive symptom severity ratings (Specific Aim 1). She also will determine the degree amygdala rtfMRI-nf restores a normative emotional processing bias during exposure to emotionally valenced stimuli (Specific Aim 2). Finally, this training will prepare Dr. Young for th R00 phase of the award in which she will transition to an independent faculty-level research position and investigate whether the time course of symptom improvement and the overall efficacy of cognitive behavioral therapy can be improved by augmenting it with rtfMRI-nf involving amygdala activity (Specific Aim 3).