Does white matter structure relate to hemispheric language lateralization? A systematic review

The relationship between functional language lateralization and diffusion MRI-based white matter metrics remains a subject of considerable interest and complexity. This systematic review aims to synthesize existing diffusion MRI studies examining white matter correlates of functional language dominance. Twenty-five studies were identified through searches of Web of Science, Scopus and Ovid MEDLINE (search period: inception to 16th May 2023), involving adults with epilepsy, tumours or healthy controls. The results suggest that while the arcuate fasciculus and corpus callosum are commonly associated with language lateralization in clinical populations, the findings in healthy individuals are more variable, often influenced by factors such as handedness. Other white matter tracts, such as uncinate fasciculus, showed less consistent associations with language dominance across studies. Interestingly, temporal lobe regions, especially those involved in semantic processing, exhibited stronger correlations with diffusion measures compared to frontal areas associated with phonological tasks. Methodological inconsistencies, such as variability in sample selection, task design and analytical techniques, were identified as significant challenges in comparing findings across studies. Future research should aim for larger, more diverse sample sizes, whole-brain approaches and a wider range of functional MRI tasks to better elucidate the role of white matter in language lateralization. If regions of interest-based studies are utilized, a more standardized approach to tract segmentation should be adopted to ensure consistency and improve comparability across studies.