Longitudinal Mapping of Maturational Change in Brain Function-Structure Relations

本研究的总体目标是纵向研究在正常发育过程中，经典脑语言区以灰质厚度增加的形式观察到的结构变化的功能和行为意义。我们还将评估非语言额叶区域的功能激活（已经观察到皮层变薄），以评估我们在早期大脑结构成熟研究中观察到的动态变化的认知/功能意义和区域特异性。通过描述语言发展、执行功能发展、大脑功能和大脑结构之间的关系，本研究将弥合正常发育的大脑中语言和额叶功能的神经基础上的信息鸿沟。我们将使用功能和结构磁共振成像以及详细的神经认知评估来评估以下具体目标：1)量化纵向研究儿童的功能和结构信号的变化；2)研究功能信号随时间的变化是否与脑基础结构的变化有关；3)将行为语言和额叶功能的变化与大脑结构和功能的变化联系起来。我们建议研究5 - 9岁的儿童（重复评估间隔2年），因为这个年龄段的儿童的许多语言和额叶功能都在迅速变化，与这些认知领域相关的大脑结构也在迅速变化。提出的纵向项目将强调如何将行为、功能和结构数据相结合的综合方法可能对大脑-行为相互作用的复杂本质产生重要的新见解。据我们所知，这将是首次利用功能性和结构性MRI来纵向检查同一个体中与语言处理（即阅读）相关的神经网络，并将语言处理相关的神经网络的正常发育变化（用功能磁共振成像观察到）与大脑形态测量学的年龄相关变化（用结构磁共振成像评估）联系起来的研究。类似的评估将通过额叶功能测试进行，从而评估语言和非语言大脑区域变化模式之间的关系。从拟议的纵向研究项目中收集的数据应该使我们能够更充分地阐明与正常发育儿童成熟语言和额叶能力出现相关的神经发育。此外，这些发育方面的发现将为评估在各种发育障碍（如阅读障碍、自闭症、多动症）中观察到的与语言、交际和额叶损伤相关的脑功能障碍模式提供规范性数据。

The overarching goal of the proposed studies is to longitudinally investigate the functional and behavioral significance of structural change in the form of gray matter thickness increases recently observed in classical brain language regions during the process of normal development. We will also assess functional activation in non-language frontal lobe regions (where cortical thinning has been observed) to evaluate the cognitive/functional significance and regional specificity of dynamic changes observed in our earlier studies of structural brain maturation. By delineating the relationship among language developments, executive function development, brain function, and brain structure, this study will bridge the informational gap on the neural basis of language and frontal function in the normally developing brain. We will use functional and structural magnetic resonance imaging and detailed neurocognitive assessments to assess the following specific aims: 1) To quantify change in functional and structural signal within children studied longitudinally; 2) To investigate whether change in functional signal across time is related to change in the underlying brain structure; and 3) To relate behavioral language and frontal lobe functioning change to changes in brain structure and function. We propose to study children between the ages of 5 and 9 years (with 2 years between repeat evaluations) when so many language and frontal lobe functions are rapidly changing as are brain structures related to these cognitive domains. The proposed longitudinal project will highlight how an integrated approach relating behavioral, functional, and structural data might yield important new insights on the complex nature of brain- behavior interactions. To our knowledge, this will be the first study to undertake such challenges by using both functional and structural MRI to examine, longitudinally, the neural networks associated with language processing (i.e., reading), within the same individuals, and to relate the normal developmental changes in the neural networks subserving language processing (as observed with fMRI) to age-related changes in brain morphometry (as assessed by structural MRI). Similar evaluations will be made with tests of frontal lobe functioning allowing assessment of relationships between patterns of change in language and non-language brain regions. The data gathered from the proposed longitudinal research program should enable us to more fully elucidate the neural developments associated with the emergence of mature linguistic and frontal lobe competence in normally developing children. Furthermore, these developmental findings will provide normative data for evaluating the patterns of brain dysfunction associated with the linguistic, communicative, and frontal lobe impairments observed in a variety of developmental disorders (e.g., dyslexia, autism, ADHD).