Structural & Network-Function Correlates of Fragmented Early-Life Across Species

结构性

• 批准号: 9355809
• 负责人: Steven L Small
• 金额: --
• 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 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9355809
• 关键词: Adolescence; Adolescent; Adolescent Behavior; Affect; Age; Anxiety; Area; Behavioral; Brain; Brain imaging; Brain region; Caring; Child; Childhood; Clinical; Cognitive; Complex; Data; Defect; Dendritic Spines; Development; Diffusion Magnetic Resonance Imaging; Disease; Emotional; Equation; Evaluation; Exposure to; Foundations; Functional Magnetic Resonance Imaging; Future; Generations; Genetic; Goals; Health; Hippocampus (Brain); Human; Image; Instruction; Intervention; Learning; Life; Life Experience; Magnetic Resonance; Measures; Mental Depression; Mental disorders; Methodology; Modality; Modeling; Molecular Probes; Molecular Target; Neurobiology; Neurons; Outcome Measure; Output; Pathology; Pathway interactions; Pattern; Perforant Pathway; Physiology; Predictive Value; Process; Psyche structure; Rat-1; Rattus; Resolution; Rest; Rodent; Series; Signal Transduction; Structure; Synapses; Testing; Thick; Time; Trees; Weight; Work; base; behavior measurement; behavioral outcome; cognitive function; cognitive task; cohort; early experience; early life exposure; emotional behavior; experience; gray matter; infancy; innovation; insight; neocortical; novel; postnatal; potential biomarker; predictive marker; predictive modeling; sensory input; statistics; stem; white matter

In concert with Projects 1-3. this revised Project 4 probes the effects of fragmented early life experience on neuronal network structure and function using magnetic resonance brain imaging (MRI) of rats (with Project 1) and humans (with Projects 2-3). The results will be integrated with parameters generated by the other projects to accomplish the Center's goal of generating predictive models and markers of adolescent mental vulnerabilities. We will start by examining whether fragmented early-life experience influences the structure of brain regions and networks that are salient to cognitive and emotional functions. We then define a trajectory of these structural and functional alterations with development, and their correlation with cognitive and emotional behavior, resulting in potential biomarkers of vulnerability to overt cognitive and emotional pathology. The goal of this project is to employ MRI-derived measures to establish predictors of regional brain connectivity (as well as structural changes) that best correlate with developmental and cognitive vulnerabilities as a function of early life exposure to fragmented maternal signals. This novel analysis will identify a series of pathological changes that occur at varying intervals in the pre-symptomatic period that might guide the timing of future interventions "and provide insights into intrinsic compensatory mechanisms. Its significance derives from the crucial importance of the clinical hypothesis: that fragmented patterns of sensory input modulate the function and connectivity of brain networks. The Project innovation stems from (a) The concept of developmentally evolving neuronal networks as the target of fragmented/unpredictable maternal input, (b) from the use of novel methodologies (e.g.. Structural Equation Modeling); (c) from the use of analysis of distributed hippocampal connectivity using multiple modalities across species, and (d) from inclusion of MRI parameters in multivariate models orchestrated by the Computational Core, to generate potentially predictive models for adolescent vulnerabilities.

与项目1-3协调。这项修订后的项目4探讨了支离破碎的早期生活经历对 用核磁共振脑成像(MRI)研究大鼠的神经元网络结构和功能 1)和人类(项目2-3)。结果将与其他生成的参数进行集成 为实现该中心生成青少年心理预测模型和标记的目标而开展的项目 漏洞。我们将首先考察支离破碎的早期生活经历是否会影响结构 大脑中认知和情感功能突出的区域和网络。然后，我们定义一个 这些结构和功能变化与发育的轨迹及其与认知的相关性 和情绪行为，导致潜在的易受公开认知和情绪影响的生物标记物 病理学。 这个项目的目标是使用核磁共振衍生的方法来建立区域大脑的预测因子。 与发展和认知最相关的连通性(以及结构变化) 脆弱性是早年暴露于支离破碎的母体信号的函数。这一新颖的分析将 确定在症状前期以不同的间隔发生的一系列病理变化 可能指导未来干预措施的时机“，并提供对内在补偿机制的洞察。 它的意义来自于临床假说的至关重要：支离破碎的模式 感觉输入调节大脑网络的功能和连通性。项目创新源于 (A)将发育进化的神经元网络作为支离破碎/不可预测的目标的概念 母性投入，(B)使用新的方法(例如.结构方程建模)；(C) 使用跨物种的多种模式分析分布式海马区连接性，以及(D)来自 将MRI参数包括在由计算核心协调的多变量模型中，以生成 青少年脆弱性的潜在预测性模型。