Human thalamocortical structural connectivity develops in line with a hierarchical axis of cortical plasticity
Human cortical development follows a hierarchical, sensorimotor-to-association sequence. The brain's capacity to enact this sequence indicates that it relies on unknown mechanisms to regulate regional differences in the timing of cortical maturation. Given evidence from animal systems that thalamic axons mechanistically regulate periods of cortical plasticity, here we evaluate in humans whether the development of structural connections between the thalamus and cortex aligns with cortical maturational heterochronicity. By deriving a new tractography atlas of human thalamic connections and applying it to diffusion data from three youth samples (8-23 years; total n = 2,676), we demonstrate that thalamocortical connectivity matures in a generalizable manner along the cortex's sensorimotor-association axis. Associative cortical regions with thalamic connections that take the longest to mature exhibit neurochemical, structural and functional signatures of protracted developmental plasticity as well as heightened sensitivity to the socioeconomic environment. This work highlights the role of the thalamus in the expression of hierarchical periods of cortical developmental plasticity and environmental receptivity.
Authors
- Steven L. Meisler (ORCID: https://orcid.org/0000-0002-8888-1572)
- Danielle S. Bassett (ORCID: https://orcid.org/0000-0002-6183-4493)
- Alexandre R. Franco (ORCID: https://orcid.org/0000-0002-1552-1090)
- Philip A. Cook (ORCID: https://orcid.org/0000-0002-1985-8475)
- James M. Shine (ORCID: https://orcid.org/0000-0003-1762-5499)
- Raquel E. Gur (ORCID: https://orcid.org/0000-0002-4082-8502)
- Eli J. Müller (ORCID: https://orcid.org/0000-0003-2497-0194)
- Aaron Alexander‐Bloch (ORCID: https://orcid.org/0000-0001-6554-1893)
- Tyler M. Moore (ORCID: https://orcid.org/0000-0002-1384-0151)
- Deanna M. Barch (ORCID: https://orcid.org/0000-0003-1693-8506)
- Joëlle Bagautdinova (ORCID: https://orcid.org/0000-0001-7201-467X)
- Theodore Daniel Satterthwaite (ORCID: https://orcid.org/0000-0001-7072-9399)
- David R. Roalf (ORCID: https://orcid.org/0000-0002-1728-9782)
- Michael Peter Milham (ORCID: https://orcid.org/0000-0003-3532-1210)
- Michael J. Arcaro (ORCID: https://orcid.org/0000-0002-4612-9921)
- Sydney Covitz (ORCID: https://orcid.org/0000-0002-7430-4125)
- Jakob Seidlitz (ORCID: https://orcid.org/0000-0002-8164-7476)
- Matthew Cieslak (ORCID: https://orcid.org/0000-0002-1931-4734)
- Bart Larsen (ORCID: https://orcid.org/0000-0001-7896-4342)
- Kahini Mehta (ORCID: https://orcid.org/0000-0001-9466-100X)
- Valerie J. Sydnor (ORCID: https://orcid.org/0000-0002-8640-668X)
- Fang‐Cheng Yeh (ORCID: https://orcid.org/0000-0002-7946-2173)
- Taylor Salo (ORCID: https://orcid.org/0000-0001-9813-3167)
- Gabriel Schubiner
- Russell T. Shinohara
- Allyson P. Mackey (ORCID: https://orcid.org/0000-0003-2969-0028)
Institutions
- Nathan Kline Institute for Psychiatric Research (US)
- The University of Sydney (AU)
- University of Minnesota (US)
- Santa Fe Institute (US)
- Children's Hospital of Philadelphia (US)
- Harvard University (US)
- University of Pittsburgh (US)
- Washington University in St. Louis (US)
- Child Mind Institute (US)
- Translational Therapeutics (United States) (US)
- Penn Center for AIDS Research (US)
- University of Pittsburgh Medical Center (US)
- Lifespan (US)
- Neurological Surgery (US)
- New York University (US)
- University of Pennsylvania (US)
- Stanford University (US)
Publication Details
- Journal
- Nature Neuroscience
- Published
- 2025-07-04
- DOI
- https://doi.org/10.1038/s41593-025-01991-6
- Citations
- 18
- Primary Topic
- Advanced Neuroimaging Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 24.48
Funders
- National Science Foundation
- National Institute of Mental Health
- NIH Office of the Director
- National Institute of Neurological Disorders and Stroke