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 (Ai...