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

影像相关的以患者为导向的研究中的职业中期指导和研究

• 批准号: 10307676
• 负责人: DANIEL P DICKSTEIN
• 金额: $ 18.62万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10307676
• 关键词: Mid; Career; Mentorship; Research; Imaging

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.

项目概要/摘要： 背景：NIMH 主办的会议（2014 年）以及第一届和第二届儿科易激惹大会 （2015 年 9 月和 2017 年）强调了深入了解大脑/行为机制的迫切需要 儿童潜在的烦躁情绪——特别是在跨诊断的儿童样本中 烦躁，而不是单一的 DSM 障碍 原因是烦躁和由此产生的攻击性。 父母为孩子寻求精神治疗的最常见症状（> 40% 的 ED 病例，> 20% 精神科门诊就诊的数量）。 包括精神病理学、自杀和经济成就下降。 K24 职业中期研究者奖以患者为导向的研究 (POR) 的目的是获得 (1) 方面的专业知识 计算精神病学技术，包括功能磁共振成像（fMRI）数据建模； (2) 通过扩散张量成像 (DTI) 和扩散光谱成像 (DSI) 实现白质连接，以及 (3) 该 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基于电路的烦躁集群 fMRI、静息态 fMRI 和扩散白质连接数据，以及 (2) 开发、试点和测试一种新颖的 针对医学和心理学实习生以及早期职业生涯的成像相关 POR 的分层指导计划 我的中心假设是，所有的烦躁情绪都不是由单一机制引起的，而是由一种独特的机制引起的。 烦躁症状群是由介导认知的特定 PFC-杏仁核-纹状体回路改变引起的 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，并将其传授给下一代临床医生/科学家。 研究方法：我将通过招募 n=72 名青少年的跨诊断样本来检验这一假设 使用双相情感障碍儿童的现有数据，绘制了 13-16 岁的易怒范围 以及典型开发的对照，以初步学习计算精神病学建模和 DTI 分析方法 来自我的导师的建议。这个 K24 是创新的，因为它将以尖端技术解决 NIMH 的高度优先领域。 成像技术，包括多波段功能磁共振成像扫描，以提高功能磁共振成像数据的时间分辨率， 计算精神病学建模，以便更好地推断/解释这些数据，以及多频段 DTI/DSI 扫描可以解决先前对解决交叉白质束和长扫描困难的担忧 这次 K24 意义重大，因为它将解决 NIMH 儿科研究的高度优先领域。 烦躁（NIMH 战略计划 1.1 和 1.3），而我的指导和创新课程共享计划将 帮助下一代临床医生/科学家使用成像相关的 POR 来帮助遭受痛苦的患者 一些人因神经精神疾病（在布朗大学及其他大学）而从事 POR 成像。