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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.
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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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“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
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- Also stated in: § Investigations of white matter microstructure · plain
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“(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
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- Not checked yetcites Ware et al. (2020) source
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“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
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- Not checked yetcites Urban et al., 2017 source
plainstates an association- Asserted: passes — The authors put it forward as true.
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“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.
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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
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- Not matchedcites Ware et al., 2023b
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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.”
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Mood and anxiety symptoms following pediatric mild traumatic brain injury: a scoping review.
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Regional and global changes in brain structure 1-year post pediatric “mild” traumatic brain injury
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Cited by
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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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-14, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-14 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
