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

这份高影响力中心修订后的续签提案整合了一个多学科的科学家小组，以 调查精神疾病易感性的发育起源，重点是受干扰的环境 /感觉信号在敏感的发育期影响大脑回路。它假设，不可预测的， 到发育中的大脑的零散的感觉信号(FRAG)，构成了以前未被认识到的 早期生活中的逆境影响不同物种的大脑回路成熟，引发快感缺乏和脆弱 精神变态。成像核心的首要目标是使中心能够使用成像工具 解决目前尚不清楚的机制途径，即FRAG可能导致快感缺失和其他 易受精神变态影响。核心将与项目1-4合作，进行转化性神经成像 跨物种和群组，通过BCDM核心，它将开发计算和统计模型 提供对FRAG对发育中大脑的影响的电路机制的新见解。 核心将： 1.获取、处理、分析、存储和提供所有高分辨率的结构、功能和扩散 关于人类和啮齿动物队列的核磁共振数据，以支持项目1-4，并解决与成像有关的假说。 2.在结构、功能和连接性方面确定异常的和性别相关的模式和轨迹 快乐/回报回路，将早期生活碎片与快感缺乏和精神病理风险联系起来，使用 跨队列、项目和物种的创新多模式磁共振方法。 3.使用网络连接和工作，开发丰富的全脑成像指标数据集 使用BCDM Core，将这些指标集成到预测快感缺失和精神病理学的统计模型中 大脑回路中与碎片相关的异常。 将使用扩散和静息状态fMRI数据创建全脑功能和结构连接 评估作为分段的功能的动态和稳定的电路重组。网络方法 例如基于结构和功能连接的图论将被用来量化 大脑回路(例如，富人俱乐部和小世界网络)。BCDM和成像核心，由以下专业知识指导 中心顾问Olaf Sporns教授将合作采用这些方法集成到模型中 它考虑了所有其他数据类型，以预测FRAG和 相关的大脑回路改变。这些数据驱动的方法还将允许我们检查 替代假设和次要假设。

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.