Nucleus-level thalamic organization anchors multimodal signatures of thalamocortical maturation

Abstract

The human thalamus is composed of multiple nuclei that differ in structure and function. From early development onwards, these nuclei form reciprocal, nucleus-specific connections with the cerebral cortex, contributing to sensory and cognitive processing. In childhood and adolescence, a key period of neurocognitive development, these connections undergo widespread refinement, yet how developmental trajectories of thalamocortical connections vary across nuclei remains unknown. Here, we leveraged the Human Connectome Project in Development dataset (HCP-D, N = 604, age range 8-21) and segmented 10 thalamic nuclei using a segmentation approach optimized for intrathalamic contrast. Applying probabilistic tractography, we reconstructed nucleus-specific thalamocortical connections and charted their maturational profiles based on changes in fractional anisotropy (FA) using generalized additive models. We found FA to increase in thalamocortical connections, with nucleus-specific variation in temporal profiles and magnitude of age effects. Connections of core-cell-rich, sensory-projecting nuclei, such as the lateral geniculate nucleus, showed earlier maturational plateaus, whereas matrix-cell-rich, association-projecting nuclei, such as ventral anterior nucleus, showed more sustained maturation. This links maturational heterochronicity to thalamic organization of cell distribution and connectivity embedding. In parallel, functional thalamocortical connectivity decreased with age, with FA and functional connectivity age effects coupled in nucleus-connections showing prolonged maturation. Finally, concordant age effects in connectivity and nucleus volumes suggest that intra-nucleus remodeling may support refinement of structural connections while reducing thalamocortical functional synchrony. Together, our work reveals that thalamocortical maturation is anchored in the developmental and organizational heterogeneity of thalamic nuclei, offering a framework for understanding how diverse thalamic nuclei contribute to neurocognitive development.