Mid-Career Mentorship and Research in Imaging-Related Patient-Oriented Research

项目总结/摘要： 背景：NIMH主办的会议（2014年）以及第一届和第二届儿科易怒大会 (Sept 2015年和2017年）强调了更好地理解大脑/行为机制的迫切需要 儿童潜在的易怒-特别是在跨诊断范围抽取的儿童样本中， 易怒，而不是一个单一的DSM障碍。原因是，易怒和由此产生的侵略是 最常见的症状，父母寻求精神病护理，他们的孩子（>40%的艾德案件，>20%， 精神科门诊就诊）。儿童期易怒是成年期损伤的一个重要预测因素， 包括精神病理学、自杀和经济成就下降。职业发展目标 在以患者为导向的研究（POR）中，K24职业中期研究者奖的目的是获得以下方面的专业知识：（1） 计算精神病学技术，包括功能性磁共振成像（fMRI）数据的建模; (2)通过扩散张量成像（DTI）和扩散光谱成像（DSI）的白色物质连通性，以及（3） 教育中的导师制。本次K24奖的研究目标是：（1）确定PFC-杏仁核-纹状体 使用事件相关逆转学习的计算精神病学模型的基于回路的易怒集群 fMRI、静息态fMRI和扩散白色物质连接数据，以及（2）开发、试验和测试一种新的 针对医学和心理学学员和早期职业的成像相关POR的分层导师计划 教师。我的中心假设是所有的易怒并不是由单一的机制引起的;而是独特的 由特定PFC-杏仁核-纹状体回路改变介导认知功能引起的易怒症状群 灵活性.这个K24提案的理由是，在我职业生涯的这个关键时刻，它将使我能够 获得新的成像和指导技能，将其传递给下一代临床医生/科学家。 研究方法：我将通过招募72名青少年的跨诊断样本来验证这一假设。 13-16岁，在易怒的范围内，同时使用双相情感障碍儿童的现有数据 并通常开发控制，以初步学习计算精神病学建模和DTI分析方法 来自我的导师。这K24是创新的，因为它将解决NIMH高优先领域的尖端技术， 成像技术，包括多波段fMRI扫描，以获得更好的fMRI数据时间分辨率， 计算精神病学建模，用于更好地推断/解释这些数据，以及多波段DTI/DSI 扫描可以解决先前的问题，即难以分辨交叉的白色物质束和长扫描 次这K24是重要的，因为它将解决NIMH的高优先级研究领域的儿科 易怒（NIMH战略计划1.1和1.3），而我的导师和创新课程共享计划将 帮助推动下一代临床医生/科学家使用成像相关的POR来帮助他们的患者 从神经精神疾病-在布朗和超越-和一些，从事成像POR。

PROJECT SUMMARY/ABSTRACT: BACKGROUND: NIMH-sponsored meetings (2014) and the 1st and 2nd Congresses on Pediatric Irritability (Sept 2015 and 2017) highlighted the critical need for greater understanding of the brain/behavior mechanisms underlying irritability in children— particularly in trans-diagnostic samples of children drawn across the range of irritability, rather than a single DSM disorder. The reason is that irritability and resultant aggression are the most common symptoms for which parents seek psychiatric care for their children (>40% of ED cases, >20% of psychiatric outpatient visits). Childhood irritability is a significant predictor of impairment in adulthood, including psychopathology, suicide, and decreased financial attainment. The career development objectives of this K24 Midcareer Investigator Award in Patient-Oriented Research (POR) are to gain expertise in (1) computational psychiatry techniques including modeling of functional magnetic resonance imaging (fMRI) data; (2) white matter connectivity via diffusion tensor imaging (DTI) and diffusion spectral imaging (DSI), and (3) mentorship in education. The research objectives of this K24 Award are: (1) identify PFC-amygdala-striatal circuit-based clusters of irritability using computational psychiatry modeling of event-related reversal learning fMRI, resting-state fMRI, and diffusion white matter connectivity data, and (2) to develop, pilot, and test a novel tiered mentorship program for imaging-related POR for medical and psychology trainees and early career faculty. My central hypothesis is that all irritability does not result from a single mechanism; rather unique symptom clusters of irritability result from specific PFC-amygdala-striatal circuit alterations mediating cognitive flexibility. The rationale for this K24 proposal is that, at this critical juncture in my career, it will allow me to acquire new imaging and mentorship skills, passing them on to the next generation of clinician/scientists. Research Method: I will test this hypothesis by enrolling a trans-diagnostic sample of n=72 adolescents ages 13-16 years drawn across the range of irritability, while using extant data from children with bipolar disorder and typically-developing controls to initially learn computational psychiatry modeling and DTI analysis methods from my mentors. This K24 is innovative because it will tackle the NIMH-high priority area with cutting-edge imaging techniques, including multi-band fMRI scanning for better temporal resolution of fMRI data, computational psychiatry modeling for better inference/interpretation of these data, and multi-band DTI/DSI scanning that can address prior concerns of difficulty resolving crossing white matter tracts and long scan times. This K24 is significant because it will address the NIMH high-priority area of research on pediatric irritability (NIMH Strategic Plan 1.1 and 1.3), while my plan for mentorship and innovative curricular sharing will help fuel the next generation of clinician/scientists using imaging-related POR to help their patients suffering from neuropsychiatric illness—at Brown and beyond—and for some, engaging themselves in imaging POR.