Open research questions in Traumatic Brain Injury Research

What the literature leaves open

• While the psychosocial consequences of TBI for patients and caregivers have been extensively studied, the emotional burden borne by treating clinicians—particularly experiences of grief, moral distress, and moral injury—remains comparatively underexplored.

  Clinician grief, moral distress, and moral injury in traumatic brain injury care: an integrative narrative · 2026 · DOI

• ABSTRACT Background Emotional disturbances are common after traumatic brain injury (TBI), yet the neuroanatomic basis of these sequalae remains unclear.

  Structural Injuries Are Associated with Better Emotional Well-being after Traumatic Brain Injury · 2026 · DOI

• This review highlights gaps that could be addressed by future studies. Future reviews should expand their focus beyond RCTs to include non-randomised studies. This broader evidence-base may provide valuable insights into the envi- ronmental approaches currently recommended in expert guidelines and used in clinical practice, but not yet captured in systematic syntheses. Such approaches are, by nature, often individualised and may therefore be captured in non-RCT designs. For instance, single-case experimental designs are well suited to evaluating environmental approaches, as they allow for the examination of intervention effects at the indi- vidual level, aligning with the tailored and context-dependent nature of these interventions. They can also have a high level of experimental control when well designed (Tate & Perdices, 2019). Notably, 20 studies were excluded from this review due to non-RCT study designs, despite investigating relevant 1 3Neuropsychology Review environmental strategies, such as prompting (Baldwin & Powell, 2015; Ledbetter et al., 2019), feedback (Zencius et al., 1990), and setting modifications (Chan et al., 2002). Future efforts to synthesise evidence from non-RCT designs would therefore be valuable to comprehensively capture the current evidence base. Clinicians also require clearer, evidence-based guidelines specifying which environmental approaches are effective, including their components as defined by the RTSS. This should further extend to practical implementation con- siderations, guiding the selection of targets and administra- tion of ingredients (Hamilton et al., 2024). Given the limited empirical evidence available in the context of common clini- cal use, involving end-users (people with TBI, their families, and clinicians) in the co-design of environmental interven- tion approaches is an important next step. This participatory approach may assist in ensuring that environmental inter- ventions are feasible, acceptable, and aligned with the needs and preferences of end-users (Bird et al., 2021; Silvola et al., 2023). Critically, future studies should also prioritise method- ological rigour, clearly define intervention components (e.g., using the RTSS), adopt standardised outcomes measures (e.g., aligned with the framework provided by the ICF), and include follow-up assessment to evaluate longer-term effectiveness. This will support broader evaluation and future statistical syn- theses, enabling more substantiated and meaningful conclu- sions about the effectiveness of environmental approaches. reflect the typical use of these interventions in clinical practice. Future studies must employ greater methodologi- cal rigour, clearer description of intervention components, consistent use of outcome measures, and follow-up assess- ments. This will help to further clarify the effectiveness of environmental approaches and the mechanisms through which they may improve outcomes for adults with TBI. Supplementary Information The online version contains supplementary material available at h t t p s : / / d o i . o r g / 1 0 . 1 0 0 7 / s 1 1 0 6 5 - 0 2 6 - 0 9 7 1 1 - y . Acknowledgements The authors would like to acknowledge Farhad Shokraneh, information specialist, for input in the design of search strategies and support in conducting the literature search. This review will partially fulfill degree requirements in the Doctor of Clinical Neu- ropsychology for Ella Waldman. Author Contributions All authors contributed to the study conception and design. Ella Waldman conducted the literature search (aided by an information specialist) and data analysis, with assistance from Michal Boneh and Jessica Trevena-Peters as the second reviewers and Jennie Ponsford as the third reviewer. The first draft of the manuscript was writ- ten by Ella Waldman and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Funding Open Access funding enabled and organized by CAUL and its Member Institutions. Ella Waldman is the recipient of an Australian Government Research Training Program Scholarship. Data Availability The full systematic review search strategy used is provided in Online Resource 2.

  Description and Effectiveness of Environmental Approaches to Cognitive Rehabilitation for Traumatic Brain Injury: A Systematic Review of Randomised Controlled Trials · 2026 · DOI

• Given that concussion is oftentimes poorly understood, with few specialist concussion clinics available, CE’s widespread use and guideline- aligned engagement patterns support its utility as an accessible and practical tool to assist individuals throughout their recovery.

  Digital Tools for Concussion Management in Community Sport: Evaluation of the Updated HeadCheck (Concussion Essentials) App · 2026 · DOI

• Both TBI and neurological disease independently increase vulnerability to psychiatric disorders, yet the long-term impact of lifetime TBI exposure on mental health outcomes within these neurological populations remains poorly understood.

  Traumatic Brain Injury Increases Risk of Psychiatric Disorders Following Neurological Disease: Evidence from the UK Biobank Cohort · 2026 · DOI

• Future research should explore the utility of more sensitive biomechanical mea- sures and evaluate the impact of fear-reduction strategies on long-term outcomes. Second, whereas the TSK-11 has demonstrated reliability in musculoskeletal popula- tions, its psychometric properties in concussion cohorts re- main underexplored.

  Psychological and Neuromechanical Recovery After Concussion: Dual-Task Stability and Kinesiophobia from Return to Play to Six Months · 2026 · DOI

• MeaningThese findings suggest that the cumulative physiological burden of chronic stress may be an underrecognized modifier of TBI recovery and outcomes that could inform brain trauma risk stratification and prognostication.

  Allostatic load modifies neuropsychiatric risk following traumatic brain injury · 2026 · DOI

• To address this gap in knowledge, we present a unique combination of pre-clinical models of TBI and UTI to define the biological effects of bladder infection after brain injury.

  Urinary Tract Infection Exaggerates Cognitive Deficits and Region-Specific Neuroinflammation Following Traumatic Brain Injury · 2026 · DOI

• UTIs are most often caused by uropathogenic Escherichia coli (UPEC) and can cause delirium-like symptoms in vulnerable patients, but the specific neuroimmune and cognitive effects of post-injury UTI remain underexplored.

  Urinary Tract Infection Exaggerates Cognitive Deficits and Region-Specific Neuroinflammation Following Traumatic Brain Injury · 2026 · DOI

• Together, these data offer novel insight into the effects of UTI after TBI, showing that UTI after TBI is detrimental to overall outcome and warrant further investigation into the signaling mechanisms between bladder infection and neuroinflammation.

  Urinary Tract Infection Exaggerates Cognitive Deficits and Region-Specific Neuroinflammation Following Traumatic Brain Injury · 2026 · DOI

• Future research is warranted to further examine the effects of BET under different conditions, assess its resistance to mental fatigue across various states, and incorporate neuroimaging techniques to better elucidate the underlying mechanisms.

  The effects of brain endurance training on mental fatigue, endurance, and cognitive function: a systematic review and meta-analysis · 2026 · DOI

• Conclusions: Safe return to athletics and academics after SRC follows protocols, but processes by which medical retirement takes place remain in development and without consensus.

  Medical Retirement From Sport After Concussion: A Survey of Perspectives and Experiences of Collegiate Physicians and Athletic Trainers · 2026 · DOI

• Background/Objectives: Traumatic brain injury (TBI) is increasingly understood as a chronic condition, but the role of early post-injury lifestyle behaviors in later cardiometabolic risk remains unclear.

  The First Year Matters: Lifestyle Behaviors and Five-Year Cardiometabolic Risk Factor Accumulation After Traumatic Brain Injury · 2026 · DOI

• However, the influence of TBI on the sequential progression from a healthy state to CMD, subsequent to cardiometabolic multimorbidity (CMM), and ultimately to mortality remains unclear.

  Traumatic Brain Injury and Risk of Cardiometabolic Multimorbidity: a Prospective Cohort Study · 2026 · DOI

• This study has its limitations. First, although the generalized linear ARTICLE IN PRESS ARTICLE IN PRESS ACCEPTED MANUSCRIPT model with GEE is well-suited to handle missing data, the relatively small sample size constrained the statistical power and limited the generalizability of the findings. While consistent trends were observed, a larger sample would increase confidence in the robustness of observed group differences. Second, participants with a concussion history varied in terms of the time elapsed since their most recent concussion. The heterogeneity in injury recency likely introduced variability in the extent of motor control impairment, potentially masking time-dependent recovery patterns. Third, the bodyweight squat was performed at a fixed pace synchronized to a 40 BPM metronome. Although this moderate speed was selected based on a pilot study and logistical constraints related to athlete availability, using a single preset tempo may not have accurately captured each athlete’s natural movement rhythm or their maximal motor control capacity. Future research should continue exploring GEM's utility across diverse athletic populations and tasks, including assessments at varying movement speeds to better reflect individual control capacities. Investigations should also compare acute versus chronic stages post- concussion and examine how motor control deficits evolve over time and relate to subsequent injury risk. Longitudinal research employing advanced biomechanical and electrophysiological methods could provide deeper insight into the mechanisms underlying persistent motor impairments post-concussion. Further studies should also investigate the effectiveness of neuromuscular training interventions specifically designed to improve motor coordination deficits identified through 3D GEM analysis, thus offering direct, evidence-based recommendations for clinical rehabilitation practices.

  Detection of season-long post-concussion motor deficits in female soccer players using a 3D goal equivalent manifold framework · 2026 · DOI

• The current scoping review was limited to the English language and, as a result, may have excluded relevant research published in other languages. This may have potentially led to important findings and perspectives being omitted. Future reviews should consider including studies published in different languages to capture a broader, more diverse range of evidence and reduce the risk of language bias. Several studies examined retired athletic populations that presented with substantial time gaps between initial injury and symptom assessment. These prolonged periods introduce additional confounding factors such as the influence of lifestyle, accumulative health risk exposure, and ageing, which have the potential to complicate associations between PSaC and symptoms of depression and/or anxiety. It is therefore recommended that the findings of this review be interpreted with caution, and that future research aim to address confounding variables, such as time since concussion and match groups by athletic/activity status. Most studies that used group-based designs treated PSaC as individual a homogeneous condition. By doing so, characteristic differences, pre-injury psychological status, number of previous concussions, and individual prognostic timelines on recovery, to name a few, were not taken into consideration, limiting the interpretability of results and furthermore the application of the findings in a clinical setting. Future research can benefit from defining injury characteristics prior to analysis and conducting subgroup analyses to better capture the heterogeneity in SRC and PSaC presentations. Future researchers are encouraged to build upon the foundations established by this scoping review and conduct a systematic review with meta-analysis, which will allow for more detailed quantitative analysis on the associations between PSaC and symptoms of depression and anxiety. Furthermore, early and graded exercise prescription is recommended for concussion treatment as per the latest consensus statement. However, guidance on exercise’s role as a prescriptive modality for PSaC is limited, particularly when considering it in relation to symptoms of depression and anxiety. The literature identified in this review was consistent with this, with a lack of exploration on exercise prescription as a modifier for symptoms of depression and anxiety in PSaC. Stakeholder engagement is a recommended optional step in scoping reviews following the JBI and the Arksey and O’Malley methodology for scoping reviews; however, it was not implemented in this scoping review, as the aim of this review was to map the extent and nature of existing literature rather than attempt to develop guidelines around PSaC and symptoms of depression and/or anxiety.[18,19,22] We, as the reviewers, acknowledge the benefit and value stakeholders can provide in the review process and recommend that this process be implemented in future and may aim to include engagement at a later stage to integrate their viewpoints with the current literature.[18,19,22] Finally, the primary discipline underpinning this scoping review is sports concussion science and sports medicine and as such, a detailed grounding in psychiatric terminology falls outside of the defined scope of this work. A further limitation identified is the heterogeneity in mental health terminology used across the included studies; this review attempts to rectify this by operationalising outcomes as symptoms of depression and/or anxiety measured by validated tools in each study. Future research should collaborate with psychiatrists and psychologists to more thoroughly explore the psychiatric domains of PSaC, including the development of specific clinical guidelines through methods such as expert consensus or Delphi surveys.

  The Association Between Persisting Symptoms after Concussion (PSaC) and Symptoms of Depression and/or Anxiety in the Athletic Population: A Scoping Review · 2026 · DOI

• Strengths of this study include the use of clinically confirmed TBI diagnoses and the recruitment of a non-injured control group from the same geographic region, screened to exclude neurological or ocular conditions aecting vision. The emphasis on standardized eect sizes and domain-specific symptom patterns enhances the clinical interpretability of the findings. Several limitations should be acknowledged. First, the sample size is modest (43 TBI, 54 controls) and was recruited by convenience from a single region, so the findings should be regarded as exploratory and may not generalize to other populations. In particular, the TBI cases were clinic-recruited from neurology, rehabilitation, and general optometry settings, whereas the control group was drawn from the Qassim University student body; these groups may not be fully comparable in age structure, healthcare-seeking behavior, or baseline symptom reporting, and this mismatch may inflate the apparent between-group dierences (eect sizes, AUC, sensitivity, and specificity) reported here. Second, the TBI cohort is highly heterogeneous: time since injury ranged from 1 to 9490 days (median 730 days), formal severity classification was unavailable for 10 of 43 participants, and the acute subgroup (n = 9) was small and unbalanced for gender. This heterogeneity limits the interpretability of the pooled TBI mean, of the exploratory acute– chronic comparison, and of the candidate score cut-os, and should be considered alongside the descriptive findings. Third, this analysis adds local Arabic case–control data but does not establish Arabic-specific measurement behavior: cross-language measurement invariance, dierential item functioning, factor structure, and clinically validated screening thresholds were not assessed and are not claimed for the Arabic BIVSS on the basis of these data; full psychometric work is reported in the companion paper. Fourth, because of the case–control sampling design, the AUC, sensitivity, specificity, and especially the positive and negative predictive values reported here are sample-specific estimates and require external validation in independent prospective samples before any cut-o can be recommended for clinical use. Fifth, the cross-sectional design precludes causal inference and prevents any inference about within-person recovery from the acute– chronic comparison, and symptom reports were not paired with objective visual performance measures, so links between specific BIVSS domains and underlying accommodative, binocular, or oculomotor dysfunction remain inferential. Future studies integrating symptom surveys with detailed neuro-optometric testing, well-characterized severity strata, and longitudinal follow- up will be essential to further elucidate the mechanisms underlying these symptom patterns, to confirm or refute the apparent acute– chronic dierences, and to externally validate any candidate Arabic BIVSS screening cut-os in clinically representative populations.

  Visual symptom burden after traumatic brain injury: a case-control evaluation of the Arabic BIVSS · 2026 · DOI

• 6 Implications for future research Based on the findings of this study and the characteristics of the included studies, future research should focus on the following aspects. 5 Limitations This study has some limitations. Interactive music therapy and passive music listening should be evaluated separately, and the optimal parameters for each, such as minimum effective duration, frequency, music type, and degree of personalization, should be explored.

  Exploratory meta-analysis of the effect of music intervention on arousal promotion in patients with disorders of consciousness: evidence from controlled studies · 2026 · DOI

• As an in-depth exploratory study, this research has allowed us to both examine the potential for the LTA to be a thera- peutic intervention, while also honouring the priorities of participants by highlighting the unique vulnerabilities and com- plex needs of families after TBI, which were central to their experiences and perspectives. As such, the answers to the research objectives were not as clear-cut as those typically yielded by pre-feasibility studies and reflects a more contex- tually bounded qualitative insight. However, this leaves opportunity for further analysis and closer scrutiny of our under- standing of the complex lives of families after TBI and specifically, validation of the narrative dimensions as a framework in which to view these. Furthermore, despite the unique characteristics of study participants, the final demographics of this sample mean that the findings reflect experiences constructed through a predominantly White English, female, heteronormative lens. While Table 9. Summary of understanding reached regarding feasibility and acceptability of the LTA as a therapeutic tool.

  Supported storytelling through the ‘Life Threads’ approach for family members after traumatic brain injury: “We’ve been through all of this trauma, and you’re giving me some string?” · 2026 · DOI

• Comment critically on the study, reflecting on the things that went well and those that did not, so others can learn from this experience https://doi.org/10.1371/journal.pone.0349304.t002 Two family members were co-investigators, with four additional members forming an advisory group. Families were consulted prior to funding and involved throughout the research process. PPIE input significantly improved the LTA, particularly in presentation, support materials, and recruitment (including a co-produced recruitment video: https://tinyurl. com/4stfbn5c). Members also contributed to data interpre- tation, drawing on lived experience. PPIE members felt heard and valued, highlighting a sense of inclusion and mutual respect. The group evolved into a supportive, collaborative team. Challenges included tem- porary withdrawals from the advisory group due to caring responsibilities and other critical life events, reflecting the real-life complexity of life after TBI for family members. Involving carers brought both deep insight and logistical challenges. PPIE training and onboarding requirements (including the need for references) also created a barrier to effective engagement. the findings with their lived experience. The PPIE evaluation showed group members felt that the experience of working together provided them with a sense of purpose and identity outside of their roles as carers for their loved ones.

  Supported storytelling through the ‘Life Threads’ approach for family members after traumatic brain injury: “We’ve been through all of this trauma, and you’re giving me some string?” · 2026 · DOI

• These results suggest that measuring the recovery of athletes with SRC warrant further investigation using physiological testing to accompany clinical measures in the determination of a player’s readiness to return to play.

  Time-course responses following sports-related concussion: a multi-modality study · 2025 · DOI

• Then, we investigate the question of whether genomics research focusing on racial categories and race-specific genes of sport performance and of risk of health outcomes due to repetitive head impacts (RHI) is justified from an epistemological point of view, arguing that it is not; we show that the evidence supporting the existence of genetic variants determining an elite athlete status or a predisposition to health outcomes after SRC is scarce, and the use of racial categories (e.

  Uses and abuses of the concept of race in genomics of sport performance and sport-related traumatic brain injury: epistemological and ethical considerations · 2024 · DOI

• Prior research highlights family functioning as an important predictor of psychosocial outcomes in the ABI population; however, there remains limited research aimed at understanding the role of family functioning in predicting rehabilitation progress and community participation.

  Family Functioning, Community Participation, and Rehabilitation Barriers in the Acquired Brain Injury Community: An Exploratory Analysis · 2024 · DOI

• BACKGROUND: Limited information about school outcomes among children (especially early childhood) with lifetime history of head injury, including traumatic brain injury (TBI), may inhibit efforts to support their academics and physical and mental health.

  Lifetime History of Head or Traumatic Brain Injury Before Age 9 and School Outcomes: Results From the Adolescent Brain Cognitive Development Study · 2024 · DOI

• Discussion: The findings from this integrative review will inform healthcare professionals working in post-concussion rehabilitation settings regarding relationships between FAM psychological factors and PSaC-an area that until recently has not been thoroughly explored.

  PROTOCOL: Fear avoidance model psychological factors as predictors for persistent post‐concussion clinical outcomes: An integrative review · 2023 · DOI

Most-cited papers in Traumatic Brain Injury Research

• Mild Traumatic Brain Injury in U.S. Soldiers Returning from Iraq · New England Journal of Medicine · 2008 · 2,191 citations
• Major Depression Following Traumatic Brain Injury · Archives of General Psychiatry · 2004 · 582 citations
• Sport-Related Concussion in Children and Adolescents · PEDIATRICS · 2010 · 505 citations
• The Role of Age and Sex in Symptoms, Neurocognitive Performance, and Postural Stability in Athletes After Concussion · The American Journal of Sports Medicine · 2012 · 396 citations
• Which On-field Signs/Symptoms Predict Protracted Recovery From Sport-Related Concussion Among High School Football Players? · The American Journal of Sports Medicine · 2011 · 308 citations
• Rate of Psychiatric Illness 1 Year After Traumatic Brain Injury · American Journal of Psychiatry · 1999 · 286 citations
• Impact of Early Intervention on Outcome After Mild Traumatic Brain Injury in Children · PEDIATRICS · 2001 · 279 citations
• “Playing Through It”: Delayed Reporting and Removal From Athletic Activity After Concussion Predicts Prolonged Recovery · Journal of Athletic Training · 2016 · 249 citations
• National High School Athlete Concussion Rates From 2005-2006 to 2011-2012 · The American Journal of Sports Medicine · 2014 · 212 citations
• Relationship between Postconcussion Headache and Neuropsychological Test Performance in High School Athletes · The American Journal of Sports Medicine · 2003 · 209 citations

Most recent work

• Performance and durability of Taekwondo headgear · Sports Engineering · 2026
• Dimensions of participation as predictors of satisfaction with roles and abilities after traumatic brain injury. · Rehabilitation Psychology · 2026
• Non-concussive head impacts sustained during American football correlate with changes in gut microbiome diversity and composition · PLoS ONE · 2026
• Medical Retirement From Sport After Concussion: A Survey of Perspectives and Experiences of Collegiate Physicians and Athletic Trainers · Clinical Journal of Sport Medicine · 2026
• The Effect of an Exertion Protocol on Cognitive and Functional Performance in Adolescents After Concussion · Clinical Journal of Sport Medicine · 2026
• Effects of traumatic brain injury on interhemispheric and intrahemispheric EEG coherence in adolescents · The European Physical Journal Special Topics · 2026
• The performance ceiling: why clinical data is insufficient for precision prognosis in concussion · Frontiers in Neurology · 2026
• What are the effects of pharmacological treatment compared with placebo or no treatment for managing fatigue in people who have experienced a traumatic brain injury (TBI)? · Cochrane Clinical Answers · 2026
• 393. Altered Salience Network Connectivity in Veterans With Mild Traumatic Brain Injury and Alcohol Use Disorder · Biological Psychiatry · 2026
• Interdisciplinary Process Improvement for Behavior Management of Acute Brain Injury. · PubMed · 2026

Related topics in Medicine