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A systematic review of brain structural and functional alterations in pediatric mild traumatic brain injury
Open accessAbstract
Introduction: Pediatric mild traumatic brain injury (pmTBI) constitutes 70–90% of childhood traumatic brain injury cases. While magnetic resonance imaging (MRI) reveals subtle brain alterations, fragmented evidence across modalities limits understanding of long-term neurobiological consequences. Methods: This systematic review synthesized 42 studies from MEDLINE/PubMed, Web of Science, Cochrane Library, and Scopus (inception to December 2025) employing structural MRI and functional MRI (fMRI). Methodological quality was assessed using a modified GRADE framework. Results: White matter investigations ( n = 18) suggested widespread microstructural alterations in limbic and commissural pathways-alongside reduced global network efficiency and disrupted hub connectivity in executive and salience networks. Gray matter studies ( n = 9) identified regional cortical thinning in prefrontal and parietal regions, hippocampal atrophy persisting up to 1 year. Resting-state fMRI studies ( n = 5) revealed diminished default mode network (DMN) integrity and elevated striatal spontaneous activity. Task-based fMRI studies ( n = 10) demonstrated compensatory hyperactivation during working memory and inhibitory tasks-manifesting as enhanced preparatory activation but resource depletion during execution-alongside lower DMN deactivation and persistent cerebrovascular reactivity abnormalities extending to chronic phases. Discussion: In sum, multimodal MRI provides evidence suggesting systematic structural and functional alterations in pmTBI encompassing white matter disruption, gray matter vulnerability, and network reorganization.
Overview
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TL;DR
This systematic review synthesizes 42 MRI studies and reports that pediatric mild traumatic brain injury is associated with multimodal structural and functional brain alterations, including white matter microstructural changes, gray matter cortical/thickness and hippocampal changes, and functional network reorganization. The authors conclude that pmTBI disrupts ongoing neurodevelopmental trajectories rather than producing static focal injury, but heterogeneity prevents quantitative meta-analysis.
Key findings
- Across 42 included studies, white matter investigations (n = 18) most commonly reported increased fractional anisotropy and/or decreased diffusivity metrics; 6 conventional DTI studies found increased FA and/or decreased ADC, MD, or RD, with limbic pathways (fornix, cingulum) and commissural/projection tracts affected. Four graph-theory studies showed altered topology, including reduced global efficiency and disrupted hub connectivity in executive control and salience networks.
- Gray matter studies (n = 9) identified regional cortical thinning in prefrontal and parietal regions and hippocampal atrophy persisting up to 1 year; 5 studies examined clinical associations, while 2 found no significant associations between structural abnormalities and post-concussive symptom burden.
- Resting-state fMRI studies (n = 5) reported diminished default mode network integrity, altered dynamic connectivity, lower gray matter fractal dimension in regions including the right amygdala and left hippocampus, and increased fALFF in the left striatum; ReHo showed no group differences.
- Task-based fMRI studies (n = 10) demonstrated compensatory hyperactivation during working memory and inhibitory tasks, lower DMN deactivation during cognitive control, and persistent cerebrovascular reactivity abnormalities extending to chronic phases. Quality assessment rated all 42 studies good on directness, 31 good and 11 fair on precision, and 41 good and 1 fair on absence of bias.
Methods
- Systematic review of MEDLINE/PubMed, Web of Science, Cochrane Library, and Scopus from inception to December 2025; 4,627 records were identified, 1,843 duplicates removed, 2,784 titles/abstracts screened, 120 full texts assessed, and 42 studies included.
- Eligible studies were English-language, peer-reviewed original human MRI studies of pmTBI with a pmTBI-control comparison or continuous analysis of injury/clinical measures; pediatric age was defined as 0–18 years, with final included participant age range approximately 6–18 years.
- Data were extracted by two independent reviewers and synthesized qualitatively by MRI modality and outcome domain; methodological quality was assessed with a modified GRADE framework across risk of bias, directness, and precision. Because of substantial heterogeneity, no quantitative meta-analysis was performed.
Limitations
- The paper states substantial clinical heterogeneity, including a wide age range (6–18 years) that entwines injury effects with normal developmental variance, and variation in mTBI diagnostic criteria and assessment timelines.
- The paper states substantial methodological heterogeneity across structural analysis strategies, fMRI task paradigms, and functional metrics, which prevented direct quantitative integration and meta-analysis.
- Evident from the text: inclusion was restricted to English-language, peer-reviewed original research, and the review extracted study-level reported findings rather than raw participant-level or quantitative effect-size data for meta-analysis; these choices may limit generalizability and quantitative precision.
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0 Valid · 1 Not valid · 164 Not checked · 72 Own results and interpretations
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In the paper
“alongside reduced global network efficiency”
- Also stated in: § Investigations of white matter microstructure · plain
“reduced global efficiency”
§ A systematic review of brain structural and functional alterations in pediatric mild traumatic brain injury > Abstract > Results
What the sources say
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption not shown here.
- Also stated in: § Investigations of white matter microstructure · plain
In the paper
“(3) Greater right frontal cortical thickness was associated with higher parent-reported post-acute somatic post-concussive symptoms (PCS) across both groups.”
§ A systematic review of brain structural and functional alterations in pediatric mild traumatic brain injury > Results > Investigations of gray matter morphology
What the sources say
- Not checked yetcites Ware et al. (2020) source
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Specifically, lower cortical thickness in the left dorsolateral prefrontal cortex (DLPFC) and right inferior parietal lobule, regions associated with executive control and attention networks, was observed (Urban et al., 2017).”
§ A systematic review of brain structural and functional alterations in pediatric mild traumatic brain injury > Results > Investigations of gray matter morphology
What the sources say
- Not checked yetcites Urban et al., 2017 source
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption not shown here.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and persistent cerebrovascular reactivity abnormalities extending to chronic phases”
§ A systematic review of brain structural and functional alterations in pediatric mild traumatic brain injury > Abstract > Results
plainstates an associationn = 10- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption not shown here.
In the paper
“It was demonstrated that mTBI alters typical cortical thinning courses, resulting in chronic cortical thinning up to 6 months post-injury, moderated by time, age, sex, and symptom status (Ware et al., 2023b).”
§ A systematic review of brain structural and functional alterations in pediatric mild traumatic brain injury > Results > Investigations of gray matter morphology
What the sources say
- Not matchedcites Ware et al., 2023b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boostedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ A systematic review of brain structural and functional alterations in pediatric mild traumatic brain injury > Results > Investigations of white matter microstructure
“Ware et al. (2023b) | Pediatric mTBI, 137F/223M”
§ A systematic review of brain structural and functional alterations in pediatric mild traumatic brain injury > References
“Ware A. L. Onicas A. I. Abdeen N. Beauchamp M. H. Beaulieu C. Bjornson B. H.. (2023a). Altered longitudinal structural connectome in paediatric mild traumatic brain injury: an advancing concussion assessment in Paediatrics study.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ A systematic review of brain structural and functional alterations in pediatric mild traumatic brain injury > Results > Investigations of gray matter morphology
“Ware et al. (2023a) | pmTBI, 160F/247M”
§ A systematic review of brain structural and functional alterations in pediatric mild traumatic brain injury > References
“Ware A. L. Lebel C. Onicas A. Abdeen N. Beauchamp M. H. Beaulieu C.. (2023b). Longitudinal gray matter trajectories in pediatric mild traumatic brain injury.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ A systematic review of brain structural and functional alterations in pediatric mild traumatic brain injury > Results > Investigations of white matter microstructure
“Ware et al. (2022) | Pediatric mTBI, 30F/53M”
§ A systematic review of brain structural and functional alterations in pediatric mild traumatic brain injury > References
“Ware A. L. Yeates K. O. Geeraert B. Long X. Beauchamp M. H. Craig W.. (2021). Structural connectome differences in pediatric mild traumatic brain and orthopedic injury.”
Citations
Cites
Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & the PRISMA Group* (2009) · Annals of Internal Medicine · doi:10.7326/0003-4819-151-4-200908180-00135 · Cited by 37,554
GRADE guidelines: 1. Introduction—GRADE evidence profiles and summary of findings tables
Guyatt, G., Oxman, A. D., Akl, E. A., Kunz, R., Vist, G., Brozek, J., Norris, S., Falck-Ytter, Y., Glasziou, P., & deBeer, H. (2011) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2010.04.026 · Cited by 10,681
The PRISMA 2020 statement: An updated guideline for reporting systematic reviews
Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., Shamseer, L., Tetzlaff, J. M., Akl, E. A., Brennan, S. E., et al. (2021) · PLoS Medicine · doi:10.1371/journal.pmed.1003583 · Cited by 5,148 · cited 1×
“The full screening process is presented in the PRISMA flow diagram (Figure 1) (Page et al., 2021).”
Epidemiology of Global Pediatric Traumatic Brain Injury: Qualitative Review
Dewan, M. C., Mummareddy, N., Wellons, J. C., & Bonfield, C. M. (2016) · World Neurosurgery · doi:10.1016/j.wneu.2016.03.045 · Cited by 650
Schneier, A. J., Shields, B. J., Hostetler, S. G., Xiang, H., & Smith, G. A. (2006) · Pediatrics · doi:10.1542/peds.2005-2588 · Cited by 423
Chronic Aspects of Pediatric Traumatic Brain Injury: Review of the Literature
Babikian, T., Merkley, T., Savage, R. C., Giza, C. C., & Levin, H. (2015) · Journal of Neurotrauma · doi:10.1089/neu.2015.3971 · Cited by 276
Dolcos, F., Katsumi, Y., Moore, M., Berggren, N., de Gelder, B., Derakshan, N., Hamm, A. O., Koster, E. H. W., Ladouceur, C. D., Okon‐Singer, H., et al. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.08.017 · Cited by 250
Iraji, A., Benson, R. R., Welch, R. D., O’Neil, B. J., Woodard, J. L., Ayaz, S. I., Kulek, A. R., Mika, V. H., Medado, P., Hamid Soltanian-zadeh, A., et al. (2014) · Journal of Neurotrauma · doi:10.1089/neu.2014.3610 · Cited by 169
Voxel-based analysis of diffusion tensor imaging in mild traumatic brain injury in adolescents
Chu, Z., Wilde, E. A., Hunter, J. V., McCauley, S. R., Bigler, E. D., Troyanskaya, M., Yallampalli, R., Chia, J. M., & Levin, H. S. (2010) · American Journal of Neuroradiology · doi:10.3174/ajnr.a1806 · Cited by 161
Wu, T. C., Wilde, E. A., Bigler, E. D., Yallampalli, R., McCauley, S. R., Troyanskaya, M., Chu, Z. D., Li, X., Hanten, G. R., Hunter, J. V., et al. (2009) · Journal of Neurotrauma · doi:10.1089/neu.2009.1110 · Cited by 138
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Metadata
- Authors
- Xu, H., Wu, S., Zhan, H., Xu, G., Zhao, J., & Yin, B.
- Affiliations
- Wenzhou Medical University (CN)
- Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University (CN)
- Corresponding author
- Yin, Bo
- Venue
- Frontiers in Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2026-08-25
- Volume
- 20
- Pages
- 1879109-1879109
- ISSN
- 1662-453X (ISSN-L)
- PMC
- PMC13550148
- OpenAlex
- W7204203776
- Semantic Scholar
- c0c37f10a565510f9a8b5c6ab7fbd9e209f263a8
- Cited by
- 0
- References
- 70
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Natural Science Foundation of Zhejiang Province (LQN25H090020)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Physical Sciences › Engineering › Biomedical Engineering › Automotive and Human Injury Biomechanics
- Keywords
- pediatric mild traumatic brain injury, cortical thinning, hippocampal atrophy, default mode network, inhibitory control, cerebrovascular reactivity, brain network reorganization
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