Shared functional organization between pulvinar-cortical and cortico-cortical connectivity and its structural and molecular imaging correlates

Basile, Gianpaolo Antonio;Ielo, Augusto;Bonanno, Lilla;Cerasa, Antonio;Santoro, Giuseppe;Milardi, Demetrio;Anastasi, Giuseppe Pio;Torre, Ambra;Baldari, Sergio;Laudicella, Riccardo;Gaeta, Michele;Quartu, Marina;Serra, Maria Pina;Trucas, Marcello;Quartarone, Angelo;Saranathan, Manojkumar;Cacciola, Alberto

2025-01-01

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Abstract

The pulvinar, the largest thalamic nucleus, is a highly interconnected structure supporting perception, visuospatial attention, and emotional processing. Such a central role relies on a precise topographical organization reflected in anatomical connectivity and neurochemical markers. Traditionally subdivided into distinct subnuclei, recent work shows that these divisions only partially explain its organization, which is better captured by continuous gradients of cortical connections along dorso-ventral and medio-lateral axes. While well studied in primates, this gradient-based architecture remains less explored in humans. The present work combines high-quality, multimodal structural and functional imaging with a whole-brain, large-scale, PET atlas mapping 19 neurotransmitter systems. By applying diffusion embedding to tractography, functional connectivity, and receptor coexpression, we identify multiple gradients of structural connections, functional coactivation, and molecular binding patterns. These converge on a shared representation along the dorso-ventral and medio-lateral axes of the human pulvinar, aligning with connectivity transitions from lower-level to higher-order cortical regions. Moreover, this is paralleled by gradual changes in the expression of molecular markers associated with key neuromodulator systems, including serotoninergic, noradrenergic, dopaminergic, and opioid systems. Our findings advance the understanding of pulvinar anatomy and function, offering an exploratory framework to investigate the role of this structure in both health and disease.