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).

项目总结/摘要 神经层面的语言习得需要言语理解的成熟和投入 以及位于额叶和颞叶的语言产生中心。结构连接（白色物质，WM） 因此，这些中心之间的联系在儿童快速学习语言的能力中起着重要作用。 熟练，没有明确的指示。然而，一个重要的问题是：WM束的成熟 （通过增加髓鞘形成或连接效率）先于获得越来越复杂的 语言的组成部分，建立发育中的大脑来获得语言？还是语言习得 简单地以活动依赖的方式加强正在进行的WM发展？人们对典型的 在工作记忆成熟的发展趋势方面的已知阶段的语言习得，尽管 这些连接在成熟语言功能中的重要性。该提案的目的首先是澄清 在典型发育的婴儿中， 工作记忆的时间随着语言功能的出现而改变。我们的假设是WM束的快速成熟 使婴儿能够通过额叶和额叶之间的反复反馈来学习越来越复杂的语言 和时间语言中心 当考虑到在病理学中观察到的语言缺陷时，WM的重要性得到进一步加强， 损害WM连接以及皮层语言中心。成年人的WM损伤可导致以下缺陷： 从命名和言语流畅性问题到失语症，但婴儿拥有非凡的语言习得能力 正常情况下，当WM束受到类似的影响，提出了关于WM可塑性在发育中的大脑的问题。 本研究的第二个目的是检查早发性局灶性癫痫（L-EPI）和围产期癫痫发作后的WM束。 中风（L-PSP）在左半球，并表征其微结构的差异如何影响整体 语言处理我们的假设是，由于急性脑缺血或急性脑梗死， 中风或慢性癫痫不同地损害神经束组织，使得慢性癫痫发作活动破坏典型的神经束组织， L-EPIs中语言网络中WM束的髓鞘形成，损害皮层语言之间的交流 而不会导致半球重组。相比之下，L-PSP中WM的早期消融可抑制 右半球束发育，允许语言习得和功能正常进行。 该建议旨在描述语言中关键WM通路的脑-行为关系 网络在典型的发展中的婴儿和幼儿正在获得语言（目标1）（NIDCD语音， 演讲和语言程序：语言，理解正常功能）;并旨在了解如何 由于L-EPI或L-PSP对这些关键的WM束的破坏影响了长期的WM组织和语言 功能（目标2）（NIDCD语音，言语和语言程序：语言，理解疾病和 疾病）。