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bioRxiv · 10.64898/2026.09.09.750447

Postnatal maturation of putamen microstructure accompanies topographic white matter connectivity and altered circuits in autism

Natu, V. S.·Tyagi, C.·Yan, X.·Tung, S. S.·Kubota, E.·Karakose-Akbiyik, S.·Wu, H.·Mezer, A.·Drori, E.·Wang, N.·Liao, C.·Cao, X.·Setsompop, K.·Grill-spector, K.
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Abstract

The putamen is a major hub of the basal ganglia that emerges early in gestation. However, whether its mature organization is established before birth or emerges postnatally remains unknown. Using cross-sectional and longitudinal quantitative MRI (R1 and R2*, related to tissue density and iron, respectively) and diffusion MRI, we characterized the development of putamen's microstructure and its white matter connectivity with cortex from birth to 12 months and compared their trajectories with those in adults. Despite its prenatal emergence, the putamen undergoes substantial postnatal development. R1 increases from birth to 12 months, producing a prominent anterior-posterior gradient, whereas R2* increases primarily between age one and adulthood, producing a medial-lateral gradient. Cortico-putamen white matter connectivity is diffuse in infants but becomes topographic in adults, with anterior putamen linked to frontal cortex and posterior putamen to sensorimotor cortex. In autism spectrum disorder, this organization is largely preserved and accompanied by increased anterior putamen-prefrontal connectivity. Our findings reveal distinct spatial developmental trajectories of putamen microstructure and cortical connectivity providing a developmental framework for understanding the organization of the putamen in infancy, which has implications for assessing neurodevelopmental disorders of the basal ganglia.

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Natu, V. S., Tyagi, C., Yan, X., Tung, S. S., Kubota, E., Karakose-Akbiyik, S., Wu, H., Mezer, A., Drori, E., Wang, N., Liao, C., Cao, X., Setsompop, K., Grill-spector, K.. 2026-09-11. Postnatal maturation of putamen microstructure accompanies topographic white matter connectivity and altered circuits in autism. https://doi.org/10.64898/2026.09.09.750447

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