Thalamocortical constraints on areal connectivity in the developing human brain

Overview

1. Developmental Imaging, Murdoch Children’s Research Institute, Melbourne, Australia
2. Turner Institute for Brain and Mental Health, Monash University, Melbourne, Australia
3. Neuroscience Advanced Clinical Imaging Service (NACIS), The Royal Children’s Hospital, Melbourne, Australia
4. Neuroscience Research, Murdoch Children’s Research Institute, Melbourne, Australia
5. Department of Paediatrics, University of Melbourne, Melbourne, Australia
6. Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
7. Research department of Early Life Imaging, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK

Abstract

The thalamus plays a central role in cortical development, organisation and function. Thalamic nuclei acquire distinct molecular identities during gestation, with first-order relays maturing before higher-order nuclei. Thalamic afferents innervate the cortical plate with a precise order, disruptions to which alter cortical function. Recent models propose that thalamic input to primary sensory cortex constrains the development of wider cortical networks, promoting the formation of highly-connected hubs in association cortex. Here, we combine neuroimaging, post mortem gene expression data and network modelling to examine how the timing and spatial distribution of thalamocortical innervation influences the formation of cortical networks during gestation. We find that the maturation rates of thalamic nuclei align with predicted timing and distribution of afferent outgrowth. While higher order nuclei connect widely across the cortex, they do not preferentially target high-degree hubs. Instead, hubs emerge from interdependent spatiotemporal constraints imposed by both wiring distance and thalamocortical maturation.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• biomedia.github.io/dhcp-release-notes, at biomedia.github.io; found in “Data and code availability”
• zenodo:10622337, at Zenodo; found in “Data and code availability”

Data and code availability

Neuroimaging data for the Developing Human Connectome Project are available via the NIMH Data Archive (collection ID: 3955; Access instructions: https://biomedia.github.io/dHCP-release-notes/). The μBrain atlas and associated data is available at: https://zenodo.org/records/10622337. Supporting code for this manuscript is available at: https://github.com/garedaba/prenatal-thalamus. Single-cell RNA-seq data was accessed via the UCSC cell hub: https://cells.ucsc.edu/?ds=dev-thal. BrainSpan RNA-seq data were accessed via: http://development.psychencode.org/.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 30 September 2026: the first record

Recorded: type, journal, dates, 8 authors, 6 keywords, 15 funders, 147 references.

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This paper

Oldham, S., Yang, J., Lautarescu, A., Bonthrone, A., Cruddas, J., Tournier, J., Batalle, D., & Ball, G. (2026). Thalamocortical constraints on areal connectivity in the developing human brain. bioRxiv (preprint). https://doi.org/10.64898/2026.03.24.714079

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