Language Development Following Early Focal Brain Injury

描述（由申请人提供）：我们提出了从出生到5岁的早期脑损伤和语言发育之间关系的前瞻性纵向研究，建立在15年先天性左半球或右半球损伤（主要由于产前或围产期中风）儿童语言和认知结果的研究基础上，使用最先进的结构成像和病变-症状映射方法。后者包括称为基于体素的病变症状映射的新方法（VLSM，Bates等人，性质：Neuroscience，2003），它允许行为测量和病变部位之间的关系的分级彩色地图，首次应用于儿童病变。新的弥散张量成像（DTI）方法将用于检查可能归因于早期脑损伤和随后重组的连通性变化。语言和相关的非语言功能的纵向研究将从8个月到60个月进行，这是大部分语言获得的时期，从牙牙学语的第一个迹象到掌握语法和话语。我们以前的研究表明，这一时期是一个“可塑性窗口”，在此期间，大多数早期单侧损伤的儿童开始严重延迟，但在语言测量上进入正常到低正常范围。在患有先天性单侧病变的儿童中，我们将尝试扩展一系列重要且令人惊讶的发现，这些发现涉及与牙牙学语、单词理解、手势、单词产生和语法的初始延迟相关的特定病变部位，并检查早期局灶性脑损伤儿童的语言和视觉空间发育轨迹。将基于三维病变重建、VLSM和DTI建立里程碑、轨迹、延迟和延迟恢复的神经解剖学相关性。对于所有脑损伤儿童，将在两个时间点进行扫描：进入研究时（6至36个月）和5岁时。这两个数据点将允许对系统的初始状态进行受试者内分析，其中神经解剖结构的任何变化可能与病变类型和/或语言发育的成功或失败程度相关。在5岁时还将获得年龄和性别匹配的对照组的扫描，允许评估由于早期损伤和随后的重组而引起的结构改变，这些改变也可能与语言成功的程度和时间相关。从这些研究中获得的新信息将增强我们对与发育中的神经系统的可塑性相关的变化的时间的理解，以及定义语言和视觉空间发育中的关联和解离。这项研究中获得的知识可能成为更有效的干预措施的基础，以帮助改善未来脑损伤儿童的神经发育结果。

DESCRIPTION (provided by applicant): We propose prospective, longitudinal studies of the relationship between early brain injury and language development from birth to age 5, building on 15 years of research on language and cognitive outcomes in children with congenital left- or right hemisphere injuries (due primarily to pre- or perinatal stroke), using state-of-the-art methods for structural imaging and lesion-symptom mapping. The latter include a new method called Voxel-based Lesion Symptom Mapping (VLSM, Bates et al., Nature: Neuroscience, 2003) developed in our laboratories, which permits graded color maps of the relationship between behavioral measures and lesion sites, applied for the first time to children with lesions. New diffusion-tensor imaging (DTI) methods will be used to examine changes in connectivity that may be attributable to early brain injury and subsequent reorganization. Longitudinal studies of language and related non-linguistic functions will be conducted from 8 to 60 months of age, the period in which most of language is acquired, from the first signs of babbling to the mastery of grammar and discourse. Our previous studies suggest that this period is a "window of plasticity", in which most children with early unilateral injuries start with serious delays, but move into the normal to low-normal range on language measures. In children with congenital, unilateral lesions, we will attempt to extend a series of important and surprising findings regarding the specific lesion sites associated with initial delays in babbling, word comprehension, gesture, word production, and grammar, and to examine the trajectories of language and visual spatial development in children with early focal brain damage. Neuroanatomical correlates of milestones, trajectories, delays and recovery from delay will be established based on 3-dimensional lesion reconstruction, VLSM and DTI. For all children with brain injuries, scans will be obtained at two points: on entry into the study (between 6 and 36 months), and at 5 years of age. These two data points will permit within-subject analyses of the initial state of the system with any changes in neuroanatomy that may be related to lesion type and/or to degrees of success or failure in language development. Scans will also be obtained for age- and gender-matched controls at age 5, permitting an assessment of structural alterations due to early injury and subsequent reorganization, alterations which also may correlate with degree and timing of success in language. The new information gained from these studies will enhance our understanding of the timing of changes associated with plasticity in the developing nervous system, as well as defining associations and dissociations in linguistic and visual spatial development. Knowledge gained in this study may form the basis for more effective interventions to help improve neurodevelopmental outcome of children with brain damage in the future.