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Regional and global changes in brain structure 1-year post pediatric “mild” traumatic brain injury
Abstract
Objective: Despite the high prevalence of pediatric “mild” traumatic brain injury (pmTBI), very little is known about the long‐term effects of injury on brain structure and how injuries manifest in the context of dynamic and regionally specific neurodevelopmental changes. Methods: Prospective study design characterizing long‐term effects of pmTBI on both global (brain age) and regional (hippocampal volume, hippocampal subfields, and cortical thickness) brain structure at approximately 7 days, 4 months, and 1‐year post‐injury. A large sample of age‐ and sex‐matched healthy controls was imaged at identical temporal intervals to account for typical neurodevelopmental changes, and to assess how trauma potentially affects developmental trajectories. Results: A total of 269 pmTBI (age = 14.4 ± 2.9; 41.6% female) and 232 healthy controls (age = 14.1 ± 2.9; 44.8% female) were included in the final analyses (>70% 1‐year retention). Results demonstrated that the presence of loss of consciousness and/or post‐traumatic amnesia was associated with increased brain age up to 1‐year post‐injury, increased frontal cortical thickness at 4 months, as well as hippocampal atrophy across all time points relative to controls. “Mild” head trauma also interfered with hippocampal neurodevelopment in a dose‐dependent fashion, including within the CA1 subfield. In contrast, post‐concussive symptom burden was not associated with any structural abnormalities or alterations to neurodevelopment. Interpretation: Current findings suggest a dose‐dependent relationship between injury severity and alterations in both global and regional brain structure within the spectrum of pmTBI. Our results emphasize the importance of using objective biomarkers rather than subjective self‐reported symptoms to better understand the long‐term effects of injury. ANN NEUROL 2025;98:341–353
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“It has found that frontal cortical thickening was associated with loss of consciousness or post-traumatic amnesia (Nathaniel et al., 2025).”
From A systematic review of brain structural and functional alterations in pediatric mild traumatic brain injury (2026) · cites this paper as Nathaniel et al., 2025
In the citing paper
“However, two studies found no significant associations between structural abnormalities and PCS burden (Nathaniel et al., 2025; Dégeilh et al., 2023).”
From A systematic review of brain structural and functional alterations in pediatric mild traumatic brain injury (2026) · cites this paper as Nathaniel et al., 2025
In the citing paper
“Hippocampal atrophy persisting up to 1 year post-injury was identified (Nathaniel et al., 2025)”
From A systematic review of brain structural and functional alterations in pediatric mild traumatic brain injury (2026) · cites this paper as Nathaniel et al., 2025
In the citing paper
“Additionally, dose-dependent interference with hippocampal neurodevelopment, specifically within the CA1 subfield, was further demonstrated (Nathaniel et al., 2025).”
From A systematic review of brain structural and functional alterations in pediatric mild traumatic brain injury (2026) · cites this paper as Nathaniel et al., 2025
In the citing paper
“(1) Presence of LOC/PTA is associated with increased brain age, frontal cortical thickening, and hippocampal atrophy up to 1 year after injury.”
From A systematic review of brain structural and functional alterations in pediatric mild traumatic brain injury (2026) · cites this paper as Nathaniel et al. (2025)
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Cites
Initial Reliability and Validity of the Ohio State University TBI Identification Method
Corrigan, J. D., & Bogner, J. (2007) · Journal of Head Trauma Rehabilitation · doi:10.1097/01.htr.0000300227.67748.77 · Cited by 816
The American Congress of Rehabilitation Medicine Diagnostic Criteria for Mild Traumatic Brain Injury
Silverberg, N. D., Iverson, G. L., Cogan, A., Dams-O-Connor, K., Delmonico, R., Graf, M. J. P., Iaccarino, M. A., Kajankova, M., Kamins, J., McCulloch, K. L., et al. (2023) · Archives of Physical Medicine and Rehabilitation · doi:10.1016/j.apmr.2023.03.036 · Cited by 480 · cited 2×
“27 It was hypothesized that regional, but not global changes in brain structure would persist to at least 4 months post-injury, with full recovery at 1-year.”
A Multidimensional Approach to Post-concussion Symptoms in Mild Traumatic Brain Injury
Polinder, S., Cnossen, M. C., Real, R. G. L., Covic, A., Gorbunova, A., Voormolen, D. C., Master, C. L., Haagsma, J. A., Diaz-Arrastia, R., & von Steinbuechel, N. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.01113 · Cited by 376
Giedd, J. N., Raznahan, A., Alexander-Bloch, A., Schmitt, E., Gogtay, N., & Rapoport, J. L. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2014.236 · Cited by 297
Harris, N. G., Mironova, Y. A., Hovda, D. A., & Sutton, R. L. (2010) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181cb5bee · Cited by 70
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Cited by
Xu, H., Wu, S., Zhan, H., Xu, G., Zhao, J., & Yin, B. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1879109
Metadata
- Authors
- Nathaniel, U., Wick, T. V., Ling, J. L., McQuaid, J. R., Sasi Kumar, D., Miller, S. D., Wu, J., Zotev, V., Meier, T. B., van der Horn, H. J., Phillips, J. P., Campbell, R. A., Sapien, R. E., Keskin, R., Vakhtin, A. A., & Mayer, A. R.
- Affiliations
- The Mind Research Network/Lovelace Biomedical Research Institute Albuquerque NM USA
- Department of Neurosurgery Medical College of Wisconsin Milwaukee WI USA
- Department of Psychiatry and Behavioral Sciences University of New Mexico Albuquerque NM USA
- Department of Emergency Medicine University of New Mexico Albuquerque NM USA
- Department of Physical Medicine and Rehabilitation University of New Mexico Albuquerque NM USA
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2025-06-06
- Volume
- 98
- Issue
- 2
- Pages
- 341-353
- ISSN
- 0364-5134
- 1531-8249
- Cited by
- 6
- References
- 5
- Language
- en
- Funders
- National Institutes of Health (P30 GM122734, R01 NS098494‐01A1, R01 NS098494‐03S1A1, 2R01NS098494‐06A1, S10OD025313)
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- Nathaniel, U., Wick, T. V., Ling, J. L., McQuaid, J. R., Sasi Kumar, D., Miller, S. D., Wu, J., Zotev, V., Meier, T. B., van der Horn, H. J., Phillips, J. P., Campbell, R. A., Sapien, R. E., Keskin, R., Vakhtin, A. A., & Mayer, A. R. (2025). Regional and global changes in brain structure 1-year post pediatric “mild” traumatic brain injury. Annals of Neurology. https://doi.org/10.1002/ana.27259
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