Reconnection of Neural Networks and Cognitive Recovery after Pediatric TBI

描述(由申请人提供)：中到重度非穿透性儿童创伤性脑损伤(TBI)通过破坏轴突连接而损害分布式神经网络，从而导致认知障碍。与急性期相比，绝大多数儿童脑外伤幸存者的认知功能在脑外伤后第一年有显著改善。有证据表明，在脑外伤后的第一年，神经连接得到了恢复。这一建议的中心假设是，儿童非穿透性脑损伤后的认知障碍反映了脑白质损伤和连接中断，认知恢复伴随着神经网络连接的恢复。连接性将使用结构脑成像(MRI和DTI)和功能(电生理、功能磁共振和神经心理学)方法进行评估。我们将研究大脑系统的结构和功能，这些系统特别容易受到脑外伤造成的脑白质(WM)干扰的影响。本研究将研究作为脑外伤破坏神经网络的样例的胼胝体(CC)和辅助空间工作记忆的额叶-颞叶-顶叶(Ftp)网络。来自行为神经科学和神经成像的创新方法将被用来评估这些网络的功能，包括单独测量前部和后部CC功能。将使用包括MRI和DTI在内的结构性措施来评估区域WM变化。功能和结构措施将在60名中/重度颅脑损伤儿童和60名年龄和性别匹配的对照组中纵向实施。我们将对儿童进行急性研究(TB I后2-4个月)和慢性研究(受伤后12个月)，以验证脑外伤后神经认知恢复与WM连接性和容量增加相关的假设。这个项目将开发研究脑外伤后CC中大脑/行为关系的方法，这些方法可以转化为对小动物的实验研究，以帮助开发新的治疗方法。通过阐明自然发生的白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：中重度创伤性脑损伤的儿童将在损伤后2-4个月和12个月进行研究，以检验脑损伤后神经认知恢复与脑白质连接性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脑外伤后大脑结构和功能的变化。通过阐明自然发生的白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。

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.