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bioRxiv · 10.64898/2026.05.01.722231

Thalamic Nuclei Functional Controllability Explains Cognition Over and Above Grey and White Matter Structure

Yang, Y.·Woollams, A.·Litwinczuk, M. C.·Trujillo-Barreto, N. J.·Muhlert, N.
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Abstract

IntroductionThe thalamic nuclei play a crucial role in regulating information flow to the cortex and supports diverse cognitive functions. Although previous studies have linked thalamic structural and functional characteristics to cognition, these measures do not fully capture the thalamuss role in dynamic control, which is essential for complex cognitive processes. Moreover, it remains unclear how these different metrics relate to each other in the way they account for cognition. MethodsT1-weighted MRI, diffusion MRI, resting-state fMRI, and neuropsychological data were obtained from 419 unrelated participants in the Human Connectome Project. We measured grey matter volume, white matter integrity, and functional controllability of each thalamic nucleus to examine their associations with cognitive performance across domains identified through clustering analysis of the neuropsychological data. We also assessed the relationships among these structural and functional metrics and evaluated their individual and combined contributions in capturing covariance with performance in various cognitive domains. ResultsSignificant correlations were observed between thalamic grey matter volume and white matter integrity; however, thalamic functional controllability showed no significant association with either structural metric. White matter integrity demonstrated the strongest association with sequence working memory and language processing. In contrast, thalamic controllability metrics accounted more for performance in executive function, reasoning and encoding, visuospatial processing, and impulse control, outperforming the combination of grey and white matter structural metrics. ConclusionThis study highlights the critical role of the thalamus from a dynamic control perspective, demonstrating that thalamic structural and functional metrics provide complementary rather than redundant information related to cognitive performance. These findings underscore a promising new direction for understanding the complex and dynamic contributions of the thalamus to human cognition.

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Yang, Y., Woollams, A., Litwinczuk, M. C., Trujillo-Barreto, N. J., Muhlert, N.. 2026-05-01. Thalamic Nuclei Functional Controllability Explains Cognition Over and Above Grey and White Matter Structure. https://doi.org/10.64898/2026.05.01.722231

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