Development of White Matter Language Tracts after Early Life Epilepsy and Stroke

早期癫痫和中风后白质语言束的发育

• 批准号: 10606337
• 负责人: Madeline Marcelle
• 金额: $ 3.41万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10606337
• 关键词: Ablation; Adult; Affect; Anisotropy; Aphasia; Area; Behavioral; Birth; Brain; Brain Injuries; Child; Chronic; Clinical; Cognitive; Communication impairment; Complex; Comprehension; Data; Development; Diffuse; Diffusion Magnetic Resonance Imaging; Disease; Dorsal; Epilepsy; Feedback; Functional Magnetic Resonance Imaging; Future; Image; Impairment; Infant; Injury; Instruction; Intervention; Language; Language Development; Language Disorders; Learning; Left; Lesion; Life; Linguistics; Link; Literature; Long-Term Effects; Measures; Modeling; Names; National Institute on Deafness and Other Communication Disorders; Partial Epilepsies; Pathology; Pathway interactions; Patients; Pattern; Play; Population; Process; Production; Recording of previous events; Role; Seizures; Speech; Stroke; Temporal Lobe; Voice; acute stroke; brain behavior; connectome; early experience; early onset; frontal lobe; insight; language impairment; language processing; myelination; perinatal stroke; programs; rate of change; relating to nervous system; response; response to injury; trend; white matter; white matter change; white matter damage

PROJECT SUMMARY/ABSTRACT Language acquisition at the neural level requires the maturation and engagement of speech comprehension and speech production centers in the frontal and temporal lobes. The structural connections (white matter, WM) between these centers must therefore play an important role in children’s ability to learn speech with rapid proficiency and without explicit instruction. However, an important question is: does maturation of WM tracts (through increased myelination or efficiency of connections) precede the acquisition of increasingly complex components of language, setting up the developing brain to acquire language? Or does language acquisition simply reinforce ongoing WM development in an activity-dependent manner? Little is known about the typical developmental trends in WM maturation with respect to the known stages of language acquisition, despite the importance of these connections in mature language functioning. This proposal aims first to clarify the relationship between WM connectivity and language acquisition in typically developing infants by examining the timing of WM changes with emerging language functions. Our hypothesis is that rapid maturation of WM tracts enables infants to learn increasingly complex aspects of language through iterative feedback between frontal and temporal language centers. The importance of WM is further reinforced when considering language deficits seen in pathologies that damage WM connections as well as cortical speech centers. WM damage in adults can result in deficits ranging from problems in naming and verbal fluency to aphasia, but infants have a remarkable ability to acquire language normally when WM tracts are similarly affected, raising questions about WM plasticity in the developing brain. The second aim of this proposal is to examine WM tracts after early-onset focal epilepsy (L-EPI) and perinatal stroke (L-PSP) in the left hemisphere and to characterize how differences in their microstructure impact overall language processing. Our hypothesis here is that disruption of typical WM maturation due to either an acute stroke or chronic epilepsy differentially impairs tract organization such that chronic seizure activity disrupts typical myelination of WM tracts in the language network in L-EPIs, impairing communication between cortical language centers without leading to hemispheric reorganization. In contrast, early ablation of WM in L-PSPs disinhibits right hemisphere tract development, allowing language acquisition and function to proceed normally. This proposal aims to characterize the brain-behavior relationships of key WM pathways in the language network in typically developing infants and young children that are acquiring language (Aim 1) (NIDCD Voice, Speech, and Language Program: Language, Understanding Normal Function); and aims to understand how disruptions to these key WM tracts due to either L-EPI or L-PSP affect long-term WM organization and linguistic function (Aim 2) (NIDCD Voice, Speech, and Language Program: Language, Understanding Diseases and Disorders).

项目摘要/摘要 神经层面的语言获取需要语音理解的成熟和参与 语音生产中心以额叶和临时爱心为中心。结构连接（白奇，WM） 因此，在这些中心之间必须在儿童快速学习语音的能力中发挥重要作用 熟练程度，没有明确的指示。但是，一个重要的问题是：WM界的成熟是否成熟 （通过提高髓鞘形成或连接效率）先于逐渐复杂的获取 语言的组成部分，建立发展中的大脑以获取语言？或进行语言获取 只需以活动依赖性的方式加强正在进行的WM开发？关于典型的知之甚少 关于语言获取的已知阶段，WM成熟的发展趋势，Dospite 这些连接在成熟语言功能中的重要性。该建议旨在首先澄清 WM连通性与语言获取之间的关系是通过检查典型发展婴儿的 WM的时机随着新兴语言功能而变化。我们的假设是WM段的快速成熟 使婴儿能够通过额叶之间的迭代反馈来学习越来越复杂的语言方面 和临时语言中心。 当考虑语言定义的病理学中，WM的重要性将进一步加强 损坏WM连接以及皮质语音中心。成人的WM损害可能导致缺陷范围 从命名和口头流利性的问题到失语症，但婴儿具有出色的获取语言的能力 通常，当WM区域类似地影响WM时，就提出了有关发育中大脑中WM可塑性的问题。 该提案的第二个目的是检查早发局灶性癫痫（L-EPI）和围产期后的WM区域 左半球的中风（L-PSP），以表征其微观结构的差异总体影响 语言处理。我们在这里的假设是典型的WM成熟的破坏是由于急性的 中风或慢性癫痫会损害道路组织，以使慢性癫痫活性破坏典型 L-EPIS语言网络中WM的髓鞘化，损害皮质语言之间的交流 中心没有导致半球重组。相比之下，L-PSPS中的WM早期消融 右半球区的发展，允许语言获取和功能正常进行。 该建议旨在表征语言中关键WM途径的脑行为关系 网络中通常发展接受语言的婴儿和幼儿的网络（AIM 1）（NIDCD声音， 语音和语言程序：语言，了解正常功能）；并旨在了解如何 由于L-EPI或L-PSP导致的这些关键WM的破坏会影响长期WM组织和语言 功能（AIM 2）（NIDCD语音，语音和语言程序：语言，理解疾病和 疾病）。