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).

项目概要/摘要 神经层面的语言习得需要言语理解的成熟和参与 额叶和颞叶的言语产生中心（白质，WM）。 因此，这些中心之间的联系必须在儿童快速学习言语的能力中发挥重要作用。 然而，一个重要的问题是：WM 束是否成熟。 （通过增加髓鞘形成或连接效率）先于获得日益复杂的 语言的组成部分，让发育中的大脑习得语言？ 只是以依赖于活动的方式加强正在进行的 WM 发展？ 就语言习得的已知阶段而言，WM 成熟的发展趋势，尽管 这些联系在成熟语言功能中的重要性。该提案首先旨在阐明 通过检查典型发育婴儿的 WM 连接性和语言习得之间的关系 WM 的时间随着语言功能的出现而变化。我们的假设是 WM 区域的快速成熟。 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 和时间语言中心。 当考虑到以下病症中出现的语言缺陷时，WM 的重要性进一步得到加强： 成人 WM 损伤可导致一系列缺陷 从命名和言语流畅性问题到失语症，但婴儿具有非凡的语言习得能力 通常，当 WM 束受到类似影响时，就会引发关于发育中大脑中 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 束。 左半球中风（L-PSP），并描述其微观结构的差异如何影响整体 我们的假设是，由于急性的语言处理，典型的 WM 成熟受到破坏。 中风或慢性癫痫会不同程度地损害神经束组织，因此慢性癫痫发作活动会破坏典型的神经束组织。 L-EPI 语言网络中 WM 束的髓鞘形成，损害皮质语言之间的交流 相比之下，L-PSP 中 WM 的早期消融会抑制。 右半球束发育，使语言习得和功能正常进行。 该提案旨在描述语言中关键 WM 通路的大脑行为关系 网络对正在习得语言的典型婴儿和幼儿的发展（目标 1）（NIDCD 语音、 言语和语言课程：语言、理解正常功能）； L-EPI 或 L-PSP 对这些关键 WM 区域的破坏会影响长期的 WM 组织和语言 功能（目标 2）（NIDCD 语音、言语和语言项目：语言、了解疾病和 障碍）。