Reconnection of Neural Networks and Cognitive Recovery after Pediatric TBI

描述（由申请人提供）：中度至重度非穿透性儿童创伤性脑损伤（TBI）通过破坏轴突连接导致认知障碍，损害分布式神经网络。相对于急性期，绝大多数儿童创伤性脑损伤幸存者的认知功能在创伤后的第一年显著改善。有证据表明，在创伤性脑损伤后的第一年，神经连通性得到了恢复。该建议的中心假设是，非穿透性儿童脑外伤后的认知缺陷反映了白质损伤和断开，认知恢复与神经网络连接的恢复同时发生。连接将使用结构脑成像（MRI和DTI）和功能（电生理、功能磁共振成像和神经心理学）方法进行评估。我们将研究脑系统的结构和功能，这些系统特别容易受到脑外伤引起的白质（WM）破坏的影响。胼胝体（CC）和支持空间工作记忆的额-颞-顶叶（FTP）网络将作为脑外伤破坏神经网络的例子进行研究。来自行为神经科学和神经影像学的创新方法将被用于评估这些网络的功能，包括单独测量前部和后部CC功能。结构性措施，包括MRI和DTI，将用于评估区域WM变化。功能和结构措施将在60名中度/重度TBI儿童和60名年龄和性别匹配的对照组中进行纵向管理。儿童将在急性期（1型结核病后2-4个月）和慢性期（损伤后12个月）进行研究，以检验脑损伤后神经认知恢复与脑皮层连通性和容量增加有关的假设。该项目将开发研究脑外伤后CC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。

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.