The superficial white matter in language processing: Broca's area connections are bilaterally associated with individual performance in children and adults

Hassanzadeh-Behbahani, S.; Lan, Z.; Zekelman, L.; Rushmore, R. J.; Chen, Y.; Xue, T.; Cetin Karayumak, S.; Pieper, S.; Tie, Y.; Yeterian, E.; Golby, A. J.; Makris, N.; Zhang, F.; Rathi, Y.; O'Donnell, L. J.

doi:10.1101/2025.07.31.666959

bioRxiv · 10.1101/2025.07.31.666959

The superficial white matter in language processing: Broca's area connections are bilaterally associated with individual performance in children and adults

Hassanzadeh-Behbahani, S.·Lan, Z.·Zekelman, L.·Rushmore, R. J.·Chen, Y.·Xue, T.·Cetin Karayumak, S.·Pieper, S.·Tie, Y.·Yeterian, E.·Golby, A. J.·Makris, N.·Zhang, F.·Rathi, Y.·O'Donnell, L. J.

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Abstract

While deeper white matter connections, such as the arcuate fasciculus and frontal aslant tract, are well known for their role in language and show leftward asymmetries in adults, the contribution of the short-range cortico-cortical superficial white matter (SWM) connections remains less understood. In this preregistered study, we examined white matter connections of Brocas area and its right hemisphere homolog in early adolescents and young adults using two large, publicly available datasets: the Adolescent Brain Cognitive Development Study and the Human Connectome Project Young Adult Study, totaling over 10,000 participants. We anatomically curated the ODonnell Research Group (ORG) tractography atlas to identify SWM fiber clusters intersecting Brocas area (pars opercularis and pars triangularis), confirmed through expert visual inspection. We investigated the microstructure, structural connectivity, and lateralization of Brocas area SWM and its relationship with language performance (Picture Vocabulary and Oral Reading Recognition assessments), in comparison to the deeper white matter connections of the frontal aslant tract and arcuate fasciculus. The arcuate fasciculus demonstrated the strongest and most consistent leftward lateralization of both microstructure (fractional anisotropy, FA) and structural connectivity (number of streamlines, NoS), with structure-function associations that were bilateral in adolescents and left-dominant in adults. Interestingly, despite weaker lateralization than the arcuate fasciculus, both the SWM and the frontal aslant tract demonstrated comparable associations with language performance. The frontal aslant tract showed greater leftward lateralization (FA and NoS) with age and was bilaterally associated with language performance, particularly in adolescents. Compared to these deeper tracts, Brocas area SWM demonstrated left-lateralized FA and right-lateralized NoS in both adolescents and adults, with stronger FA lateralization in adults. Bilateral SWM FA and NoS were significantly associated with language performance in both hemispheres and age groups. Overall, these results suggest that Brocas area SWM may support language in a more bilaterally distributed manner and highlight the importance of considering SWM connections in studies of language development and neurosurgical planning.

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Hassanzadeh-Behbahani, S., Lan, Z., Zekelman, L., Rushmore, R. J., Chen, Y., Xue, T., Cetin Karayumak, S., Pieper, S., Tie, Y., Yeterian, E., Golby, A. J., Makris, N., Zhang, F., Rathi, Y., O'Donnell, L. J.. 2025-08-01. The superficial white matter in language processing: Broca's area connections are bilaterally associated with individual performance in children and adults. https://doi.org/10.1101/2025.07.31.666959

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