Spatiotemporal Developmental Gradient of Thalamic Morphology, Microstructure, and Connectivity fromthe Third Trimester to Early Infancy

Abstract

Thalamus is a critical component of the limbic system that is extensively involved in both basic and high-order brain functions. However, how the thalamic structure and function develops at macroscopic and microscopic scales during the perinatal period development is not yet well characterized. Here, we used multishell high-angular resolution diffusion MRI of 144 preterm-born and full-term infants in both sexes scanned at 32–44 postmenstrual weeks (PMWs) from the Developing Human Connectome Project database to investigate the thalamic development in morphology, microstructure, associated connectivity, and subnucleus division. We found evident anatomic expansion and linear increases of fiber integrity in the lateral side of thalamus compared with the medial part. The tractography results indicated that thalamic connection to the frontal cortex developed later than the other thalamocortical connections (parieto-occipital, motor, somatosensory, and temporal). Using a connectivity-based segmentation strategy, we revealed that functional partitions of thalamic subdivisions were formed at 32 PMWs or earlier, and the partition developed toward the adult pattern in a lateral-to-medial pattern. Collectively, these findings revealed faster development of the lateral thalamus than the central part as well as a posterior-to-anterior developmental gradient of thalamocortical connectivity from the third trimester to early infancy.SIGNIFICANCE STATEMENTThis is the first study that characterizes the spatiotemporal developmental pattern of thalamus during the third trimester to early infancy. We found that thalamus develops in a lateral-to-medial pattern for both thalamic microstructures and subdivisions; and thalamocortical connectivity develops in a posterior-to-anterior gradient that thalamofrontal connectivity appears later than the other thalamocortical connections. These findings may enrich our understanding of the developmental principles of thalamus and provide references for the atypical brain growth in neurodevelopmental disorders.

Perinatal development of structural thalamocortical connectivity

“…We observe a primary axis of variation orientated along an anterior/medial-to-posterior/lateral direction in the thalamus. This is consistent with previous findings in neonates (Wilson et al, 2023; Zheng et al, 2023), and adults (Oldham & Ball, 2023). The primary thalamic axis is associated a pattern of preferential connectivity to cortical areas that varies along a rostral-caudal direction, as observed in adults (Oldham & Ball, 2023).…”

“…We used data processing with optimised pipelines to migrate these issues (Bastiani et al, 2019) and employed strict quality control to minimise any impact to our results. Our thalamocortical findings are consistent with histological and animal studies (Brysch et al, 1990;Höhl-Abrahão & Creutzfeldt, 1991), and are in agreement with thalamocortical connectivity observed in adult imaging data (Howell et al, 2024;Oldham & Ball, 2023), and other early life studies (Wilson et al, 2023;Zheng et al, 2023), adding further confidence our results are not adversely affected by motion induced distortions. Finally, it should be noted that applying PCA or any dimensionality reduction technique is intrinsically more likely to bring out these wide-spread patterns of connectivity, as by definition these patterns extend across most thalamic seeds/cortical vertices and so are likely to explain more variance in the data.…”

“…The second half of gestation is a critical period for the formation of thalamocortical connections (Kostović et al, 2019(Kostović et al, , 2021Kostović & Judaš, 2010). By birth, the overall patterning of structural thalamocortical connections is established (Kostović et al, 2019), with ongoing maturation progressing from early-maturing primary sensory areas to later-maturing association cortex in the frontal lobe (Zheng et al, 2023).…”

“…Despite its central importance in brain organisation and function, only a relatively limited number of neuroimaging studies have addressed the development of thalamocortical connectivity in the human brain during the perinatal period (Ball et al, 2012, 2013, 2015; Batalle et al, 2017; Jakab et al, 2020; Sa De Almeida et al, 2021; Toulmin et al, 2021; Wilson et al, 2023; Zheng et al, 2023). The second half of gestation is a critical period for the formation of thalamocortical connections (Kostović et al, 2019, 2021; Kostović & Judaš, 2010).…”

A Multimodal Characterization of Low-Dimensional Thalamocortical Structural Connectivity Patterns

“…The distribution of myelin could again touch on the spatiotemporal brain development during the perinatal phase. Zheng et al (2023) reported a lateral-to-medial development of thalamic microstructure, where fiber integrity (measured by fractional anisotropy, fiber density, and diffusivity) in the lateral thalamus seemed to develop faster compared to medial thalamic portion. Further, our finding of higher myelination in lateral thalamic portions, which captured unimodal nuclei, resonated with observations of higher myelination of unimodal regions in the cerebral cortex (Glasser and Van Essen, 2011) and may be related to a higher conduction velocity in sensorimotor regions compared to transmodal regions (Demirtaş et al, 2019; Burt et al, 2018a).…”