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1-3一致。修订后的项目4探讨了碎片化的早期生活经历对心理健康的影响