Reconnection of Neural Networks and Cognitive Recovery after Pediatric TBI

儿童创伤性脑损伤后神经网络的重新连接和认知恢复

• 批准号: 7890678
• 负责人: ROBERT F ASARNOW
• 金额: $ 53.42万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-09 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7890678
• 关键词: Acute; Address; Adverse effects; Age; Animals; Anterior; Behavioral; Bilateral; Biological Neural Networks; Brain; Brain imaging; Child; Childhood; Cognitive deficits; Corpus Callosum; Development; Functional Magnetic Resonance Imaging; Gender; Impaired cognition; Impairment; Injury; Magnetic Resonance Imaging; Measures; Memory; Methods; Neurocognitive; Neurosciences; Parietal; Parietal Lobe; Performance; Process; Recovery; Relative (related person); Sampling; Short-Term Memory; Signal Transduction; Structure; Survivors; System; Testing; Time; Translating; Traumatic Brain Injury; age related; brain behavior; cognitive function; cognitive recovery; gray matter; improved; improved functioning; injury and repair; innovation; neuroimaging; neuropsychological; novel; processing speed; public health relevance; relating to nervous system; research study; restoration; therapy design; transmission process; white matter; white matter change; white matter injury

DESCRIPTION (provided by applicant): Moderate to severe non-penetrating pediatric traumatic brain injury (TBI) compromises distributed neural networks by disrupting axonal connections contributing to cognitive impairments. Cognitive functioning improves significantly over the first year post-TBI relative to the post-acute period in the vast majority of pediatric TBI survivors. There is evidence of restitution of neural connectivity over the first year post-TBI. The central hypothesis of this proposal is that cognitive deficits after non-penetrating pediatric TBI reflect white matter injury and disconnection, and that cognitive recovery occurs in conjunction with the restoration of neural network connectivity. Connectivity will be assessed using both structural brain imaging (MRI and DTI) and functional (electrophysiological, fMRI and neuropsychological) methods. We will study the structure and function of brain systems that are particularly vulnerable to white matter (WM) disruptions caused by TBI. The corpus callosum (CC) and a frontal-temporal-parietal (FTP) network that subserves spatial working memory will be studied as exemplars of neural networks disrupted by TBI. Innovative methods from behavioral neuroscience and neuroimaging will be used to assess the function of these networks, including separate measures of anterior and posterior CC function. Structural measures, including MRI and DTI, will be used to assess regional WM changes. The functional and structural measures will be administered longitudinally in 60 children with moderate/severe TBI and 60 age and gender matched controls. Children will be studied post-acutely (2-4 months post-TB I) and chronically (12 months post injury) to test the hypothesis that neurocognitive recovery following TBI is associated with increased WM connectivity and volume. This project will develop methods for studying brain/behavior relations in the CC following TBI that can be translated into experimental studies of small animals to help develop novel therapies. By explicating mechanisms that underlie naturally-occurring white matter injury and repair, the proposed project will identify potential new targets for interventions designed to accelerate the process of neurocognitive recovery. PUBLIC HEALTH RELEVANCE: Children with moderate-severe traumatic brain injuries will be studied 2-4 months and at 12 months post-injury to test the hypothesis that neurocognitive recovery following TBI is associated with increased white matter connectivity and volume. Innovative brain imaging and behavioral neuroscience methods will be used to assess changes in brain structure and function following pediatric TBI. By explicating mechanisms that underlie naturally-occurring white matter injury and repair, the proposed project will identify potential new targets for interventions designed to accelerate the process of neurocognitive recovery.

描述（由申请人提供）：中度至重度非穿透性小儿创伤性脑损伤（TBI）通过破坏轴突连接损害分布式神经网络，导致认知障碍。在绝大多数儿童TBI幸存者中，相对于急性期后，TBI后第一年的认知功能显著改善。有证据表明，在TBI后的第一年神经连接恢复。该提议的中心假设是，非穿透性小儿TBI后的认知缺陷反映了白色物质损伤和断开，并且认知恢复与神经网络连接的恢复一起发生。将使用脑结构成像（MRI和DTI）和功能（电生理学、fMRI和神经心理学）方法评估连通性。我们将研究脑系统的结构和功能，特别容易受到由TBI引起的白色物质（WM）破坏。胼胝体（CC）和额颞顶叶（FTP）的网络，使空间工作记忆将被研究的神经网络被TBI破坏的范例。行为神经科学和神经影像学的创新方法将用于评估这些网络的功能，包括前后CC功能的单独测量。结构测量，包括MRI和DTI，将用于评估区域WM变化。将在60名中度/重度TBI儿童和60名年龄和性别匹配的对照组中纵向实施功能和结构测量。将对儿童进行急性（TB I后2-4个月）和慢性（损伤后12个月）研究，以检验TBI后神经认知恢复与WM连接和体积增加相关的假设。该项目将开发用于研究TBI后CC中大脑/行为关系的方法，这些方法可以转化为小动物的实验研究，以帮助开发新的疗法。通过阐明自然发生的白色物质损伤和修复的机制，拟议的项目将确定旨在加速神经认知恢复过程的干预措施的潜在新目标。 公共卫生相关性：将对患有中重度创伤性脑损伤的儿童进行2-4个月和伤后12个月的研究，以检验TBI后神经认知恢复与白色连接和体积增加相关的假设。创新的脑成像和行为神经科学方法将用于评估儿童TBI后大脑结构和功能的变化。通过阐明自然发生的白色物质损伤和修复的机制，拟议的项目将确定旨在加速神经认知恢复过程的干预措施的潜在新目标。