Track-Weighted Dynamic Functional Connectivity Profiles and Topographic Organization of the Human Pulvinar

The human pulvinar is considered a prototypical associative thalamic nucleus as it represents a key node in several cortico-subcortical networks. Through this extensive connectivity to widespread brain areas, it has been suggested that the pulvinar may play a central role in modulating cortical oscillatory dynamics of complex cognitive and executive functions. Additionally, derangements of pulvinar activity are involved in different neuropsychiatric conditions including Lewy-body disease, Alzheimer's disease, and schizophrenia. Anatomical investigations in nonhuman primates have demonstrated a topographical organization of cortico-pulvinar connectivity along its dorsoventral and rostrocaudal axes; this specific organization shows only partial overlap with the traditional subdivision into subnuclei (anterior, lateral, medial, and inferior) and is thought to coordinate information processing within specific brain networks. However, despite its relevance in mediating higher-order cognitive functions, such a structural and functional organization of the pulvinar in the human brain remains poorly understood. Track-weighted dynamic functional connectivity (tw-dFC) is a recently developed technique that combines structural and dynamic functional connectivity, allowing the identification of white matter pathways underlying the fluctuations observed in functional connectivity between brain regions over time. Herein, we applied a data-driven parcellation approach to reveal topographically organized connectivity clusters within the human pulvinar complex, in two large cohorts of healthy human subjects. Unsupervised clustering of tw-dFC time series within the pulvinar complex revealed dorsomedial, dorsolateral, ventral anterior, and ventral posterior connectivity clusters. Each of these clusters shows functional coupling to specific, widespread cortico-subcortical white matter brain networks. Altogether, our findings represent a relevant step towards a better understanding of pulvinar anatomy and function, and a detailed characterization of his role in healthy and pathological conditions.