Regional and Global Changes in Brain Structure 1-Year Post Pediatric "Mild" Traumatic Brain Injury

Upasana Nathaniel; Tracey V Wick; Josef L Ling; Jessica R McQuaid; Divyasree Sasi Kumar; Samuel D Miller; Jingshu Wu; Vadim Zotev; Timothy B Meier; Harm J van der Horn; John P Phillips; Richard A Campbell; Robert E Sapien; Rahsan Keskin; Andrei A Vakhtin; Andrew R Mayer

doi:10.1002/ana.27259

Regional and Global Changes in Brain Structure 1-Year Post Pediatric "Mild" Traumatic Brain Injury

Ann Neurol. 2025 Jun 6. doi: 10.1002/ana.27259. Online ahead of print.

Authors

Upasana Nathaniel¹, Tracey V Wick¹, Josef L Ling¹, Jessica R McQuaid¹, Divyasree Sasi Kumar¹, Samuel D Miller¹, Jingshu Wu¹, Vadim Zotev¹, Timothy B Meier^{2

3

4}, Harm J van der Horn^{1

5}, John P Phillips^{1

6}, Richard A Campbell⁷, Robert E Sapien⁸, Rahsan Keskin⁹, Andrei A Vakhtin¹, Andrew R Mayer^{1

6

10}

Affiliations

¹ The Mind Research Network/Lovelace Biomedical Research Institute, Albuquerque, NM, USA.
² Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, USA.
³ Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA.
⁴ Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI, USA.
⁵ University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁶ Department of Neurology, University of New Mexico, Albuquerque, NM, USA.
⁷ Department of Psychiatry and Behavioral Sciences, University of New Mexico, Albuquerque, NM, USA.
⁸ Department of Emergency Medicine, University of New Mexico, Albuquerque, NM, USA.
⁹ Department of Physical Medicine and Rehabilitation, University of New Mexico, Albuquerque, NM, USA.
¹⁰ Department of Psychology, University of New Mexico, Albuquerque, NM, USA.

PMID: 40476699
DOI: 10.1002/ana.27259

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.

Abstract

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