Neural Basis of Emotion Regulation in Pediatric Post-traumatic Stress Disorder

项目摘要/摘要 这一职业发展奖的目标是为应聘者提供更多的知识和技能 事件相关功能磁共振成像和脑连接的实现和分析。这套知识和技能将 用于探讨健康青少年创伤前后情绪调节的神经基础 青少年创伤后应激障碍(PTSD)的暴露及其功能障碍。创伤后应激障碍是一种令人衰弱的 青少年及其家人容易罹患疾病，而且往往与其他焦虑症和抑郁症并存。成虫 与童年创伤相关的创伤后应激障碍会增加抑郁、焦虑、药物滥用和自杀的风险。 儿童创伤后应激障碍的治疗在很大程度上仅限于心理治疗，显示出中等的效果，留下 许多青年患有顽固性疾病，即使这种治疗是可以获得的。虽然证据有限， 药物治疗对儿童创伤后应激障碍几乎没有好处。鉴于这些因素，非常重要的是 了解创伤后应激障碍如何改变神经发育轨迹，目的是从生物学上建立 知情的早期干预措施，可避免儿童和成年后的负面后果。 儿童创伤后应激障碍的临床和行为特征是情绪调节异常，但很少有研究。 已经检查了这种疾病中情绪调节的神经基础。成人创伤后应激障碍的脑功能研究 提供边缘和前额叶变化的可测试模型，这可能是情绪调节受损的基础。 这包括杏仁核和背侧前扣带回(DACC)皮质的激活增加，这是 促进恐惧反应。同时，前额叶腹内侧皮质的接触受损。 (VmPFC)，它通常会抑制恐惧和焦虑反应。青春期是一种特别敏感的 前额叶皮质发育期，有可能出现更大的前额叶-边缘失衡 与创伤后应激障碍有关。例如，这可以通过前额叶与年龄相关的活动减少来反映出来。 大脑皮层。相比之下，健康的创伤暴露青少年可能表现出与年龄相关的更大的前额叶腹侧 招聘。反过来，对患有创伤后应激障碍的青少年进行成功的治疗可能会产生补偿性或恢复力 在健康的创伤暴露青年中看到的机制。然而，这些模型在很大程度上仍未经过测试。 建议的研究计划将检查内隐情绪调节的功能神经关联 有和没有创伤暴露的健康青年，以及患有创伤后应激障碍的青年，重点是杏仁核和 前额叶皮质区域。这项研究将首先关注基线(治疗前)的大脑差异 以健康青年为对照，纵向随访一年为探索性目标。40个年轻人，12岁- 18人，将为每个小组招聘。将采用经过验证的功能磁共振成像范例和行为测量方法。 功能磁共振成像任务包括两个互补的范式来探索内隐情绪调节，使用情绪 分别是面孔和情感图片。在目标1中，我们预测健康的年轻人会让两个杏仁核 以及情绪调节过程中的前额叶区域，前额叶-杏仁核的连接性将随着 年龄。健康的创伤暴露青年将表现出更大的杏仁核激活，但更大的vmPFC激活和 补偿中的连接。在目标2中，我们预测，与儿童创伤后应激障碍和健康创伤青少年相比 健康、无创伤的年轻人，会表现出杏仁核和dACC的激活增加。然而，儿科创伤后应激障碍 在情绪过程中vmPFC激活和连接性受损，与两个对照组不同 监管。这将反映在创伤后应激障碍患者vmPFC功能随年龄增长的减弱。 探索性分析将检查健康和健康人杏仁核和前额叶功能的纵向变化 创伤后应激障碍青少年，以及随着时间的推移，创伤后应激障碍症状变化与大脑功能变化的相关性。 这位候选人是一位儿科精神病学家和情感神经学家，长期以来一直对压力感兴趣。 引起大脑和行为的改变。他的临床特长包括使用以创伤为中心的认知 行为疗法来治疗受创伤的青年。这位候选人已经对情绪进行了初步的功能磁共振研究 在受创伤的年轻人群体中的规则，在分析区块设计任务方面有经验。 获奖期内的直接职业发展目标包括在以下领域进行功能磁共振成像的额外培训 青年，事件相关功能磁共振分析和功能/有效连接，以及临床试验培训 未来R01功能磁共振治疗研究。掌握这些技能和知识将使应聘者成为 儿童创伤后应激障碍情感神经科学的独立研究员。长期的职业目标包括 在描绘创伤恢复力与创伤的神经发育轨迹方面的专业知识的发展- 与儿童创伤后应激障碍相关的脆弱情绪调节，以及探索治疗的开创性研究- 儿童创伤后应激障碍情绪调节回路的改变。拟议的培训和培训计划 研究将在威斯康星大学麦迪逊分校进行，该大学是 对情绪的神经科学研究，以最先进的神经成像设备和杰出的教师为特色。 其中包括理查德·戴维森博士(导师)和内德·卡林博士(共同导师)，他们都是 研究健康和精神病理学中潜在的情绪调节的神经回路。这个十字架- 因此，学科研究计划允许循序渐进地进入情感神经科学的职业生涯 儿科创伤后应激障碍。

Project Summary/Abstract The goal of this career development award is to provide the candidate with additional knowledge and skills in the implementation and analysis of event-related fMRI and brain connectivity. This knowledge and skill set will be used to explore the neural basis of emotion regulation in healthy adolescents with and without trauma exposure, and its dysfunction in adolescent post-traumatic stress disorder (PTSD). PTSD is a debilitating illness for youth and their families, and is often comorbid with other anxiety disorders and depression. Adult PTSD related to childhood trauma carries additional risk for depression, anxiety, substance abuse, and suicide. Treatment of pediatric PTSD is largely limited to psychotherapy, which shows moderate effect sizes, leaving many youth with persistent illness even when such treatment is accessible. While evidence is limited, medications have shown little benefit for pediatric PTSD. In light of these factors, it is of great importance to understand how PTSD may alter neurodevelopmental trajectories, with the aim of instituting biologically informed, early interventions that may avert negative outcomes in childhood and subsequent adulthood. Pediatric PTSD is characterized clinically and behaviorally by abnormal emotion regulation, but few studies have examined the neural basis of emotion regulation in this illness. Functional brain studies in adult PTSD offer a testable model of limbic and prefrontal changes that that may underlie impaired emotion regulation. This includes increased activation of the amygdala and the dorsal anterior cingulate (dACC) cortex, which promote fear responses. At the same time, there is impaired engagement of the ventromedial prefrontal cortex (vmPFC), which normally suppresses fear and anxiety responses. Adolescence is a particularly sensitive period of prefrontal cortical development, with the potential for even greater prefrontal-limbic imbalance associated with PTSD. This could be reflected, for example, by diminished age-related activity in the prefrontal cortex. In contrast, healthy trauma-exposed adolescents may show even greater age-related ventral prefrontal recruitment. Successful treatment, in turn, for youth with PTSD may engage compensatory or resilient mechanisms seen in healthy trauma-exposed youth. However, these models remain largely untested. The proposed research plan will examine the functional neural correlates of implicit emotion regulation in healthy youth with and without trauma exposure, and youth with PTSD, with an emphasis on amygdala and prefrontal cortical regions. This research will focus on initially on baseline (pre-treatment) brain differences compared to healthy youth, with a longitudinal one-year follow up as an exploratory aim. Forty youth, ages 12- 18, will be recruited for each group. Validated fMRI paradigms and behavioral measures will be employed. The fMRI tasks include two complementary paradigms to explore implicit emotion regulation, using emotional faces and emotional pictures, respectively. In Aim 1, we predict that healthy youth will engage both amygdala and prefrontal areas during emotion regulation, and that prefrontal-amygdala connectivity will increase with age. Healthy trauma-exposed youth will show greater amygdala activation, but greater vmPFC activation and connectivity in compensation. In Aim 2, we predict that pediatric PTSD and healthy trauma youth, compared to healthy non-trauma youth, will show increased amygdala and dACC activation. However pediatric PTSD will be differentiated from both comparison groups by impaired vmPFC activation and connectivity during emotion regulation. This will be reflected by diminished age-associated increases in vmPFC function in PTSD. Exploratory analyses will examine longitudinal changes in amygdala and prefrontal function in healthy and PTSD adolescents, and how PTSD symptom changes correlate with brain function change over time. The candidate is a pediatric psychiatrist and affective neuroscientist, with a long-standing interest in stress- induced changes in brain and behavior. His clinical specialization includes the use of trauma-focused cognitive behavioral therapy to treat traumatized youth. The candidate has conducted initial fMRI studies of emotion regulation in a traumatized, young adult population, with experience in the analysis of block design tasks. Immediate career development goals during the award period include additional training in conducting fMRI in youth, analysis of event related fMRI and functional/effective connectivity, and training in clinical trials for a future R01 fMRI treatment study. Acquisition of these skills and knowledge will allow the candidate to become an independent investigator in the affective neuroscience of pediatric PTSD. Long-term career goals include the development of expertise in delineating neurodevelopmental trajectories of trauma-resilient vs. trauma- vulnerable emotion regulation as related to pediatric PTSD, and pioneering research exploring treatment- induced changes in emotion regulation circuitry in pediatric PTSD. The proposed program of training and research will be conducted at the University of Wisconsin-Madison, which is a leading institution in the neuroscientific study of emotion, featuring state-of-the art neuroimaging facilities and distinguished faculty. These include Drs. Richard Davidson (mentor) and Ned Kalin (co-mentor), both of whom are pioneers in the study of the neural circuitry underlying emotion regulation in health and psychopathology. This cross- disciplinary research plan therefore allows for a stepwise approach to a career in the affective neuroscience of pediatric PTSD.