Fragmented early-life experiences, aberrant circuit maturation, emotional vulnerabilities

破碎的早期生活经历、异常的电路成熟、情感脆弱

• 批准号: 10379272
• 负责人: Michael A Yassa
• 金额: $ 46.05万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-17 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10379272
• 关键词: Address; Adult; Amygdaloid structure; Anhedonia; Animals; Brain; Brain imaging; Cohort Studies; Computer Models; Data; Data Set; Data Storage and Retrieval; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Dimensions; Emotional; Functional Magnetic Resonance Imaging; Goals; Hippocampus (Brain); Human; Image; Imaging Device; Imaging Techniques; Lead; Life; Life Experience; Link; MRI Scans; Magnetic Resonance Imaging; Mental disorders; Methods; Modeling; Pathway interactions; Pattern; Phase; Population; Process; Psyche structure; Psychopathology; Quality Control; Rattus; Resolution; Rest; Rewards; Risk; Rodent; Scanning; Scientist; Security; Sensory; Signal Transduction; Statistical Models; Structure; System; Testing; Thick; Work; base; brain circuitry; cohort; connectome; early life adversity; graph theory; high risk; imaging facilities; innovation; insight; low socioeconomic status; maternal depression; multidisciplinary; multimodality; neuroimaging; neuropsychiatric disorder; novel; pleasure; predictive modeling; prisma; resilience; reward circuitry; sex; young adult

This high-impact Center revised renewal proposal integrates a multidisciplinary group of scientists to investigate the developmental origins of vulnerability to mental illness, with a focus on perturbed environmental / sensory signals impacting brain circuits during sensitive developmental periods. It posits that unpredictable, fragmented sensory signals to the developing brain (FRAG), constitute a previously unrecognized indicator of early-life adversity that impacts brain circuit maturation across species, provoking anhedonia and vulnerability to psychopathology. The overarching goal of the Imaging Core is to enable the Center to use imaging tools to address the as yet unknown mechanistic pathways by which FRAG may lead to anhedonia and other vulnerabilities to psychopathology. The Core will work with Projects 1-4 to conduct translational neuroimaging across species and cohorts, and with the BCDM core it will develop computational and statistical models to provide novel insights into circuit mechanisms that underlie the impact of FRAG on the developing brain. The core will: 1. Acquire, process, analyze, store, and make available all high-resolution structural, functional, and diffusion MRI data on human and rodent cohorts, in support of Projects 1-4 and to address imaging-related hypotheses. 2. Identify aberrant and sex-specific patterns and trajectories in structure, function, and connectivity of pleasure/reward circuitry that link early life FRAG to anhedonia and risk for psychopathology, using innovative multimodal MRI approaches across cohorts, projects, and species. 3. Develop a rich dataset of whole-brain-derived imaging metrics using network connectomics and, working with the BCDM Core, integrate these metrics in statistical models that predict anhedonia and psychopathology from FRAG-associated aberrations in brain circuitry. Whole brain functional and structural connectomes will be created using diffusion and resting state fMRI data to assess dynamic and stable reorganization of circuits as a function of FRAG. Network approaches such as graph theory based on structural and functional connectomes will be used to quantify overall shifts in brain circuits (e.g. rich club and small world networks). The BCDM and Imaging cores, guided by expertise of Center consultant, Prof. Olaf Sporns, will collaborate on employing these methods for integration into models that take into account all other data types to predict anhedonia and psychopathology from FRAG and the associated brain circuitry alterations. These data-driven approaches will additionally allow us to examine alternative and secondary hypotheses.

这个高影响力的中心修订的更新提案整合了一个多学科的科学家小组， 调查易患精神疾病的发展根源，重点是受干扰的环境 /在敏感的发育时期影响大脑回路的感觉信号。它假定不可预测， 碎片化的感觉信号到发育中的大脑（FRAG），构成了一个以前未被认识到的指标， 生命早期的逆境影响了不同物种的脑回路成熟，引发了快感缺失和脆弱性 到精神病理学。成像核心的首要目标是使中心能够使用成像工具， 解决FRAG可能导致快感缺乏和其他 易受精神病理学影响核心将与项目1-4合作进行翻译神经成像 跨物种和队列，并与BCDM核心，它将开发计算和统计模型， 提供了新的见解电路机制的基础上的影响FRAG的大脑发育。 核心将： 1.获取、处理、分析、存储并提供所有高分辨率的结构、功能和扩散 人类和啮齿动物队列的MRI数据，支持项目1-4，并解决成像相关假设。 2.识别异常和性别特异性的模式和轨迹的结构，功能和连接， 快乐/奖励回路，将早期生活FRAG与快感缺乏和精神病理学风险联系起来，使用 跨队列、项目和物种的创新多模式MRI方法。 3.使用网络连接组学开发全脑衍生成像指标的丰富数据集， 使用BCDM核心，将这些指标整合到预测快感缺乏和精神病理学的统计模型中 与FRAG相关的脑回路畸变 全脑功能和结构连接体将使用扩散和静息状态fMRI数据创建 以评估动态和稳定的重组电路作为功能的FRAG。网络方法 例如基于结构和功能连接体的图论将用于量化 大脑回路（例如富人俱乐部和小世界网络）。BCDM和成像核心，由专业知识指导， 中心顾问Olaf Sporns教授将合作采用这些方法集成到模型中 该模型考虑了所有其他数据类型来预测FRAG的快感缺失和精神病理学，并且 相关的脑回路改变。这些数据驱动的方法还将使我们能够检查 替代和次要假设。