White Matter Microstructural Lateralization and Links to Language Function in Perinatal Stroke

Abstract Perinatal strokes occur more commonly in the left hemisphere and often impact language areas, yet language disability only occurs in 20–25% of cases. Functional imaging studies investigating language processing have shown that perinatal stroke in the left hemisphere may result in contralesional shifts of activity, but none have investigated the structure of white matter connections in such altered language network conditions. Diffusion tensor imaging and neurite orientation dispersion and density imaging offer robust, microstructurally-sensitive metrics which can probe links between language-related tracts and function. In a sample of 73 participants with perinatal stroke and 32 typically-developing controls, we applied these methods to evaluate microstructure and lateralization of the arcuate fasciculus and uncinate fasciculus, two tracts classically associated with language. Furthermore, we examined associations between the microstructure of the contralesional arcuate and uncinate and language-based measures (i.e., verbal learning and verbal fluency) in children with unilateral perinatal stroke. We observed greater lateralization of white matter microstructure in the arcuate and uncinate for stroke participants than typically developing controls driven largely by differences in the ipsilesional hemisphere. Microstructure of the contralesional arcuate fasciculus was associated with both verbal learning and verbal fluency, while the contralesional uncinate fasciculus structure was associated with verbal fluency only. Overall, we demonstrate that white matter microstructure of bilateral language networks is impacted by unilateral perinatal stroke, and microstructural development of the arcuate and uncinate appear to be associated with language-based tests. Enhanced understanding of such functionally-relevant neuroplasticity may inform future rehabilitation strategies and intervention trials.