A shifting role of thalamocortical connectivity in the emergence of cortical functional organization

The cortical patterning principle has been a long-standing question in neuroscience, yet how this translates to macroscale functional specialization in the human brain remains largely unknown. Here we examine age-dependent differences in resting-state thalamocortical connectivity to investigate its role in the emergence of large-scale functional networks during early life, using a primarily cross-sectional but also longitudinal approach. We show that thalamocortical connectivity during infancy reflects an early differentiation of sensorimotor networks and genetically influenced axonal projection. This pattern changes in childhood, when connectivity is established with the salience network, while decoupling externally and internally oriented functional systems. A developmental simulation using generative network models corroborated these findings, demonstrating that thalamic connectivity contributes to developing key features of the mature brain, such as functional segregation and the sensory-association axis, especially across 12–18 years of age. Our study suggests that the thalamus plays an important role in functional specialization during development, with potential implications for studying conditions with compromised internal and external processing. The thalamus is important for neocortical functional specialization. Here the authors show its shifting role in shaping large-scale functional organization during early life in humans, particularly in developing the internal–external cortical hierarchy.