A shifting role of thalamocortical connectivity in the emergence of large-scale functional brain organization during early lifespan

Abstract

While cortical patterning has been a perennial research topic in neuroscience, the mechanism for its consequence, namely functional specialization at the macro scale, remains an open question in the human brain. Here, we focused on age-dependent changes of resting-state thalamocortical connectivity to investigate its role in the emergence of large-scale functional networks across infancy, childhood and young adulthood. We found that the thalamocortical connectivity during infancy reflects an early differentiation of sensorimotor networks and genetically-influenced axonal projection. This initial role of the thalamus, however, seems to change during childhood, by establishing connectivity with the salience network and decoupling externally- and internally-oriented functional processes. Developmental simulation and perturbation analyses corroborated these findings, demonstrating the highest contribution of thalamic connectivity, especially in the later age of youth, in the formation of key characteristics of the mature brain, such as functional gradient and cortical hierarchy. Our study highlights a developmentally shifting role of the thalamus in orchestrating complex brain organization and its potential implications for developmental conditions characterized by compromised internal and external processing.

Development of thalamocortical connectivity during the third trimester

“…Recent evidence suggests that, in addition to a well characterised nuclear structure, the thalamus exhibits continuous variations in patterns of connectivity, cytoarchitecture, and molecular identity that extend both within and across specific nuclei (Gao et al, 2020; Howell et al, 2024; John et al, 2024; Jones, 1998; Li et al, 2020; Mai & Majtanik, 2019; McFarland & Haber, 2002; Oldham & Ball, 2023; Park et al, 2024; Phillips et al, 2019; Roy et al, 2022; Saunders et al, 2018). The spatial organisation of the thalamus along continuous axes is reflected by concerted variations in gene transcription, axonal morphology, laminar targeting, and electrophysiological properties, alongside other key principles of cortical organisation (Oldham & Ball, 2023; Phillips et al, 2019).…”