Impact of repeated blast exposure on active-duty United States Special Operations Forces.

United States (US) Special Operations Forces (SOF) are frequently exposed to explosive blasts in training and combat, but the effects of repeated blast exposure (RBE) on SOF brain health are incompletely understood. Furthermore, there is no diagnostic test to detect brain injury from RBE. As a result, SOF personnel may experience cognitive, physical, and psychological symptoms for which the cause is never identified, and they may return to training or combat during a period of brain vulnerability. In 30 active-duty US SOF, we assessed the relationship between cumulative blast exposure and cognitive performance, psychological health, physical symptoms, blood proteomics, and neuroimaging measures (Connectome structural and diffusion MRI, 7 Tesla functional MRI, [11C]PBR28 translocator protein [TSPO] positron emission tomography [PET]-MRI, and [18F]MK6240 tau PET-MRI), adjusting for age, combat exposure, and blunt head trauma. Higher blast exposure was associated with increased cortical thickness in the left rostral anterior cingulate cortex (rACC), a finding that remained significant after multiple comparison correction. In uncorrected analyses, higher blast exposure was associated with worse health-related quality of life, decreased functional connectivity in the executive control network, decreased TSPO signal in the right rACC, and increased cortical thickness in the right rACC, right insula, and right medial orbitofrontal cortex-nodes of the executive control, salience, and default mode networks. These observations suggest that the rACC may be susceptible to blast overpressure and that a multimodal, network-based diagnostic approach has the potential to detect brain injury associated with RBE in active-duty SOF.

Predictive modeling of initiation and delayed mental health contact for depression.

BACKGROUND: Depression is prevalent among Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) Veterans, yet rates of Veteran mental health care utilization remain modest. The current study examined: factors in electronic health records (EHR) associated with lack of treatment initiation and treatment delay; the accuracy of regression and machine learning models to predict initiation of treatment. METHODS: We obtained data from the VA Corporate Data Warehouse (CDW). EHR data were extracted for 127,423 Veterans who deployed to Iraq/Afghanistan after 9/11 with a positive depression screen and a first depression diagnosis between 2001 and 2021. We also obtained 12-month pre-diagnosis and post-diagnosis patient data. Retrospective cohort analysis was employed to test if predictors can reliably differentiate patients who initiated, delayed, or received no mental health treatment associated with their depression diagnosis. RESULTS: 108,457 Veterans with depression, initiated depression-related care (55,492 Veterans delayed treatment beyond one month). Those who were male, without VA disability benefits, with a mild depression diagnosis, and had a history of psychotherapy were less likely to initiate treatment. Among those who initiated care, those with single and mild depression episodes at baseline, with either PTSD or who lacked comorbidities were more likely to delay treatment for depression. A history of mental health treatment, of an anxiety disorder, and a positive depression screen were each related to faster treatment initiation. Classification of patients was modest (ROC AUC = 0.59 95%CI = 0.586-0.602; machine learning F-measure = 0.46). CONCLUSIONS: Having VA disability benefits was the strongest predictor of treatment initiation after a depression diagnosis and a history of mental health treatment was the strongest predictor of delayed initiation of treatment. The complexity of the relationship between VA benefits and history of mental health care with treatment initiation after a depression diagnosis is further discussed. Modest classification accuracy with currently known predictors suggests the need to identify additional predictors of successful depression management.

The utility of completing adjuvant video lessons based on the unified protocol during psychotherapy: A retrospective study using a telehealth platform in routine clinical care.

Digital supplements to tele-psychotherapy are increasingly needed. The purpose of this retrospective study was to investigate the association between outcomes and the use of supplemental video lessons based on the Unified Protocol (UP), an empirically supported transdiagnostic treatment.Participants included 7,326 adults in psychotherapy for depression and/or anxiety. Partial correlations were calculated between number of UP video lessons completed and change in outcomes after 10 weeks, controlling for number of therapy sessions and baseline scores. Then, participants were divided into those who did not complete any UP video lessons (n = 2355) and those who completed at least 7/10 video lessons (n = 549), and propensity-matched on 14 covariates. Repeated measures analysis of variance compared these groups (n = 401 in each group) on outcomes.Among the entire sample, symptom severity decreased as the number of UP video lessons completed increased, with the exception of lessons on avoidance and exposure. Those watching at least 7 lessons showed significantly greater reduction in both depression and anxiety symptoms than those who did not watch any.Viewing supplemental UP video lessons in addition to tele-psychotherapy had a positive and significant association with symptom improvement and may provide an additional tool for clinicians to implement UP components virtually.

Does Bupropion Increase Anxiety?: A Naturalistic Study Over 12 Weeks.

PURPOSE/BACKGROUND: There has long been a clinical belief that bupropion exacerbates anxiety. The purpose of the current retrospective study is to compare anxiety severity over time in those prescribed selective serotonin reuptake inhibitors (SSRIs) versus bupropion. METHODS/PROCEDURES: Archival data (N = 8457) from patients receiving psychiatric care from a national tele-mental health company were used. Propensity matching was used to create SSRI and bupropion groups using 17 covariates. These samples were then compared using repeated measures analysis of variance on Generalized Anxiety Disorder Scale 7 scores at start of treatment, 6 weeks, and 12 weeks. FINDINGS/RESULTS: The SSRI and bupropion groups were significantly different across a number of variables. In the entire sample, the bupropion group had significantly greater anxiety levels. However, for propensity-matched comparisons, there were no significant interactions between group and time (ie, groups did not differ and improved comparably over time). IMPLICATIONS/CONCLUSIONS: Using propensity matching, there were no differences in anxiety outcome between those prescribed selective serotonin reuptake inhibitor versus bupropion across 12 weeks of treatment.

Early Response to Antidepressant Medications in Adults With Major Depressive Disorder: A Naturalistic Study and Odds of Remission at 14 Weeks.

PURPOSE/BACKGROUND: Early response after 2 to 4 weeks of antidepressant therapy has been shown to predict remission by 8 to 12 weeks. Most of the work to date on early response has been done using data from randomized controlled trials. METHODS/PROCEDURES: This naturalistic study uses archival data from a national tele-mental health company. The positive and negative predictive values as well as sensitivity and specificity were calculated using different drops in baseline Patient Health Questionnaire 9 scores at various periods. Demographic and clinical characteristics were compared between early responders versus those lacking early response. Binary logistic regression analyses determined if early response was predictive of remission, response, and greater than minimal improvement at 14 weeks. For those who do not show early improvement, treatments were investigated using binary logistic regression to see if changes predicted later outcomes. FINDINGS/RESULTS: Positive predictive values for all endpoints improved with the strength of early response but did not improve much with the time allowed for that response to occur. In contrast, negative predictive values increased substantially with time. Using a definition of 30% drop in Patient Health Questionnaire 9 score at week 4, 56.5% of patients were early responders. Early responders were ~3.2 times more likely to achieve remission than those lacking early response. Of nonresponders by week 4, those prescribed atypical antipsychotics (+SSRI) had significantly reduced odds of response at week 14, whereas those prescribed a norepinephrine and dopamine reuptake inhibitor had increased odds. IMPLICATIONS/CONCLUSIONS: Early response may be associated with better outcomes at 14 weeks. In those with lack of response by week 4, patients prescribed a norepinephrine and dopamine reuptake inhibitor may achieve superior outcomes.

Feasibility and acceptability of a novel telepsychiatry-delivered precision prescribing intervention for anxiety and depression.

BACKGROUND: Major Depressive Disorder and Generalized Anxiety Disorder are pervasive and debilitating conditions, though treatment is often inaccessible and based on trial-and-error prescribing methods. The present observational study seeks to describe the use of a proprietary precision prescribing algorithm piloted during routine clinical practice as part of Brightside's telepsychiatry services. The primary aim is to determine the feasibility and acceptability of implementing this intervention. Secondary aims include exploring remission and symptom improvement rates. METHODS: Participants were adult patients enrolled in Brightside who completed at least 12 weeks of treatment for depression and/or anxiety and received a prescription for at least one psychiatric medication. A prescription recommendation was made by Brightside's algorithm at treatment onset and was utilized for clinical decision support. Participants received baseline screening surveys of the PHQ-9 and GAD-7, and at weeks 2,4,6,8,10 and 12. Intent-to-treat (ITT) sensitivity analyses were conducted. Feasibility of the implementation was measured by the platform's ability to enroll and engage participants in timely psychiatric care, as well as offer high touch-point treatment options. Acceptability was measured by patient responses to a 5-star satisfaction rating. RESULTS: Brightside accessed and treated 6248 patients from October 2018 to April 2021, treating a majority of patients within 4-days of enrollment. The average plan cost was $115/month. 89% of participants utilized Brightside's core medication plan at a cost of $95/month. 13.4% of patients in the study rated Brightside's services as highly satisfactory, averaging a 4.6-star rating. Furthermore, 90% of 6248 patients experienced a MCID in PHQ-9 or GAD-7 score. Remission rates were 75% (final PHQ-9 or GAD-7 score < 10) for the study sample and 59% for the ITT sample. 69.3% of Brightside patients were treated with the medication initially prescribed at intake. CONCLUSIONS: Results suggest that the present intervention may be feasible and acceptable within the assessed population. Exploratory analyses suggest that Brightside's course of treatment, guided by precision recommendations, improved patients' symptoms of anxiety and depression.

Health Conditions Among Special Operations Forces Versus Conventional Military Service Members: A VA TBI Model Systems Study.

OBJECTIVE: To examine traumatic brain injury (TBI) characteristics and comorbid medical profiles of Special Operations Forces (SOF) Active Duty Service Member/Veterans (ADSM/Vs) and contrast them with conventional military personnel. SETTING: The 5 Veterans Affairs (VA) Polytrauma Rehabilitation Centers. PARTICIPANTS: A subset of participants in the VA TBI Model Systems multicenter longitudinal study with known SOF status. These included 157 participants who identified as SOF personnel (average age = 41.8 years; 96% male, 81% active duty), and 365 who identified as Conventional Forces personnel (average age = 37.4 years; 92% male, 30% active duty). DESIGN: Retrospective analysis of prospective cohort, cross-sectional. MAIN MEASURES: The Health Comorbidities Interview. RESULTS: SOF personnel were more likely to have deployed to a combat zone, had more years of active duty service, and were more likely active duty at time of TBI. SOF personnel were more likely to have had mild TBI (vs moderate/severe) and their TBI caused by violent mechanism. SOF personnel had a higher number of comorbidities, with more diagnoses of chronic pain, osteoarthritis, hyperlipidemia, hip fractures, and obstructive sleep apnea. CONCLUSION: SOF personnel are at a higher risk for multimorbidity after TBI. Current rehabilitation practices should incorporate early screening and treatment of common conditions in this population, while future practices may benefit from a focus on prevention.

Qualitative assessment of the use of a smart phone application to manage post-concussion symptoms in Veterans with traumatic brain injury.

PURPOSE: As part of a larger study to test the efficacy of the Concussion Coach cell phone application for patients with post-concussion symptoms, qualitative data were gathered to assess barriers and facilitators for app use and differences in use of the app among those who declined or improved in symptom severity, or were low-use users. MATERIALS AND METHODS: Using a prospective descriptive study design, 35 semi-structured qualitative interviews were conducted between 2016-2018. Participants had a history of mild traumatic brain injury and were symptomatic. Interview data were analyzed using qualitative content analysis. RESULTS: Primary facilitators were the app's ease of use, privacy, availability/portability, and increased self-efficacy of the user. Primary barriers were a lack of sufficient app training, stigma, overly "basic" content, and symptom severity. While there were not prominent differences among user groups, users whose symptom severity improved described using more modules of the app than users who declined. Low-users attributed not using the app to content that was too basic or to their forgetting. CONCLUSION: Interview data suggest that Concussion Coach can benefit Veterans with post-concussive symptoms through increased agency, perceived benefits to emotional well-being, and the availability of non-stigmatized strategies for symptom management.

Self-efficacy predicts response to cognitive rehabilitation in military service members with post-concussive symptoms.

This study examined whether self-efficacy differentiated treatment responders from non-responders in a trial of cognitive rehabilitation (CR) for postconcussive symptoms. 126 service members with mild TBI seen on average 9.5 months since injury completed one of four cognitive rehabilitation treatments for 6 weeks. The four treatment arms were: (1) Psychoeducation control, (2) Self-administered computerized CR, (3) Interdisciplinary CR, and (4) Interdisciplinary CR integrated with CBT. Outcome was assessed across time (baseline, and 6, 12, and 18 weeks post-treatment) for three domains: psychological (Symptom Checklist-90-Revised; SCL-90-R), cognitive (Paced Auditory Serial Addition Test; PASAT), and functional/behavioural (Key Behaviors Change Inventory; KBCI). Mixed model ANOVAs tested for self-efficacy differences across time in treatment responders versus non-responders, as defined by reliable change indices. A significant interaction was found on the SCL-90 such that responders had increasing self-efficacy with respect to psychological symptoms across four time points, whereas non-responders' self-efficacy did not change. Perceived self-efficacy at the beginning of treatment was associated with treatment engagement within the psychological domain for responders only, suggesting a mediating role in treatment outcome. Overall, results suggest that increasing patients' level of self-efficacy may be important for successful treatment of psychological distress in those with remote concussion.

Providing Care for Comorbid Mental Health Conditions in the Polytrauma System of Care.

OBJECTIVE: To summarize challenges and best practices relevant to providing care for mental health comorbidities in veterans and service members (V/SM) treated in the Polytrauma System of Care (PSC) and to review themes that emerged during a May 2017 meeting of rehabilitation professionals on this topic. Management of comorbid mental health conditions remains a critical issue within the PSC, given the high rate of these comorbidities and the impact of mental health conditions on treatment planning and outcomes. DESIGN: To identify the challenges of concomitantly treating TBI-related symptoms and mental health comorbidities in V/SM treated within the PSC, describe specialty programs within the Veterans Health Administration designed to treat these comorbid conditions, and report on the themes and recommendations identified by rehabilitation professionals at the 2017 meeting. CONCLUSION: To further develop mental health treatment within the PSC, the following recommendations were made: (1) continued support for family members as critical members of the rehabilitation team; (2) adding measures and mechanisms to monitor mental health within the PSC; and (3) exploration of modern technologies to enhance care of existing polytrauma clients and to better prepare to serve clients with all types of acquired brain injury.

Neuropsychological Performance and Subjective Symptom Reporting in Military Service Members With a History of Multiple Concussions: Comparison With a Single Concussion, Posttraumatic Stress Disorder, and Orthopedic Trauma.

OBJECTIVE: To examine differences in objective neurocognitive performance and subjective cognitive symptoms in individuals with a history of a single concussion, multiple concussions, orthopedic injuries, and posttraumatic stress disorder (PTSD). METHOD: Participants included 116 military service members who sustained a mild traumatic brain injury (mTBI) during combat deployment. Subjects were subdivided into groups based on concussion frequency: a single concussion (n = 42), 2 concussions (n = 21), and 3 or more concussions (n = 53). Eighty-one subjects sustained an orthopedic injury (n = 60) during deployment or were diagnosed with PTSD (n = 21), but had no history of mTBI. Subjects completed a battery of neuropsychological tests and self-report measures of postconcussive symptoms, PTSD symptoms, and psychopathology. RESULTS: No differences were found among the concussion groups on a composite neuropsychological measure. The PTSD group had the highest number of symptom complaints, with the 2-concussion and 3-plus-concussion groups being most similar to the PTSD group. The concussion groups showed a nonsignificant pattern of increasing distress with increasing number of concussions. CONCLUSIONS: The current findings are consistent with meta-analytic results showing no differential effect on neuropsychological functioning due to multiple concussions. Results also support the burden of adversity hypothesis suggesting increasing symptom levels with increasing psychological or physically traumatic exposures.

Prevalence and predictors of tobacco smoking in veterans and service members following traumatic brain injury rehabilitation: a VA TBIMS study.

OBJECTIVE: To identify prevalence and predictors of tobacco smoking among veterans and military service members (V/SM) with traumatic brain injury (TBI) admitted for rehabilitation. METHODS: Participants were drawn from the VA TBI Model Systems multicentre longitudinal research study. Tobacco smoking was assessed both preinjury and at 1- or 2-year post-TBI follow-up for 336 participants. RESULTS: Smoking prevalence was 32% preinjury and 28% at follow-up. Most participants had a stable smoking pattern but 12% of preinjury non-smokers became smokers at follow-up. Preinjury smoking was the strongest predictor of post-TBI smoking. Higher cognitive function also predicted smoking at follow-up. In univariate analyses, smoking was predicted by lower education, preinjury mental health (MH) history, selected TBI severity metrics, and higher functional status at rehabilitation hospital discharge (Disability Rating Scale [DRS] and motor subscale of the Functional Independence Measure [FIM]). CONCLUSION: Study findings may help clinicians and administrators recognize who is at high risk for smoking following TBI, to plan for in-hospital and postdischarge screening and interventions.

Exploring the factor structure of a battery of neuropsychological assessments among the CENC cohort.

OBJECTIVE: The goal of the Chronic Effects of Neurotrauma Consortium (CENC) study is to explore the effects of concussions among Service Members and Veterans. A factor model was fit to selected neuropsychological measures to identify potentially useful relationships between assessments collected on CENC-enrolled participants. METHOD: 492 post-9/11 participants with combat exposure were enrolled across four VA study sites. Participants completed assessments including concussion history, neurocognitive functioning, and self-report questionnaires. Exploratory factor analyses (EFA) using four different methods with varimax and promax rotations were used to analyse the cognitive variables. Final model selection was based on factor loadings towards simple structure. RESULTS: The scree plot suggested the number of factors to be extracted was between 4 and 5. EFA produced a 5-factor MINRES model with promax rotation that resulted in a factor loading with variables loading on only one factor with a predefined threshold (0.40). Variables loaded on five cognition domains: list learning, working memory/executive skills, cognitive control, fluency, and memory. CONCLUSION: These results provide reasonable evidence that data collected from the CENC neuropsychological battery can be reduced to five clinically useful factors. This will enable us to use the factors for further study of the impact of concussion on neurodegeneration.

Understanding the impact of mild traumatic brain injury on veteran service-connected disability: results from Chronic Effects of Neurotrauma Consortium.

OBJECTIVES: Disability evaluation is complex. The association between mild traumatic brain injury (mTBI) history and VA service-connected disability (SCD) ratings can have implications for disability processes in the civilian population. We examined the association of VA SCD ratings with lifetime mTBI exposure in three models: any mTBI, total mTBI number, and blast-related mTBI. METHODS: Participants were 492 Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veterans from four US VA Medical Centers enrolled in the Chronic Effects of Neurotrauma Consortium study between January 2015 and August 2016. Analyses entailed standard covariate-adjusted linear regression models, accounting for demographic, military, and health-related confounders and covariates. RESULTS: Unadjusted and adjusted results indicated lifetime mTBI was significantly associated with increased SCD, with the largest effect observed for blast-related mTBI. Every unit increase in mTBI was associated with an increase in 3.6 points of percent SCD. However, hazardous alcohol use was associated with lower SCD. CONCLUSIONS: mTBI, especially blast related, is associated with higher VA SCD ratings, with each additional mTBI increasing percent SCD. The association of hazardous alcohol use with SCD should be investigated as it may impact veteran health services access and health outcomes. These findings have implications for civilian disability processes.

Post-deployment Mental Health Screening: A Systematic Review of Current Evidence and Future Directions.

Population-based post-deployment screening programs within the Departments of Defense and Veterans Affairs have been implemented to assess for mental health conditions and traumatic brain injury. The purpose of this paper is to systematically review the literature on post-deployment screening within this context and evaluate evidence compared to commonly accepted screening implementation criteria. Findings reflected highly variable psychometric properties of the various screens, variable treatment referral rates following screening, low to moderate treatment initiation rates following screening, and no information on treatment completion or long-term outcomes following screening. In sum, the evidence supporting population based post-deployment screening is inconclusive. Implications are discussed.

A Systems Science Approach to Understanding Polytrauma and Blast-Related Injury: Bayesian Network Model of Data From a Survey of the Florida National Guard.

We sought to further define the epidemiology of the complex, multiple injuries collectively known as polytrauma/blast-related injury (PT/BRI). Using a systems science approach, we performed Bayesian network modeling to find the most accurate representation of the complex system of PT/BRI and identify key variables for understanding the subsequent effects of blast exposure in a sample of Florida National Guard members (1,443 deployed to Operation Enduring Freedom/Operation Iraqi Freedom and 1,655 not deployed) who completed an online survey during the period from 2009 to 2010. We found that postdeployment symptoms reported as present at the time of the survey were largely independent of deployment per se. Blast exposure, not mild traumatic brain injury (TBI), acted as the primary military deployment-related driver of PT/BRI symptoms. Blast exposure was indirectly linked to mild TBI via other deployment-related traumas and was a significant risk for a high level of posttraumatic stress disorder (PTSD) arousal symptoms. PTSD arousal symptoms and tinnitus were directly dependent upon blast exposure, with both acting as bridge symptoms to other postdeployment mental health and physical symptoms, respectively. Neurobehavioral or postconcussion-like symptoms had no significant dependence relationship with mild TBI, but they were synergistic with blast exposure in influencing PTSD arousal symptoms. A replication of this analysis using a larger PT/BRI database is warranted.

Utility of the Neurobehavioral Symptom Inventory As an Outcome Measure: A VA TBI Model Systems Study.

OBJECTIVE: To examine the utility of the Neurobehavioral Symptom Inventory (NSI)-a measure of postconcussion symptoms used within the Veterans Health Administration-as an index of rehabilitation outcome. SETTING: Veterans Administration Polytrauma Rehabilitation Centers Traumatic Brain Injury (TBI) Model Systems program. PARTICIPANTS: A total of 159 Veterans (14% with mild TBI; 86% with moderate-severe TBI). MAIN MEASURES: Disability Rating Scale; Functional Independence Measure; Glasgow Outcome Scale-Extended; NSI; Participation Assessment with Recombined Tools-Objective; Posttraumatic Stress Disorder Checklist-Civilian Version; Satisfaction With Life Scale; Supervision Rating Scale. ANALYSES: Correlations and exploratory factor analyses examined the interrelations among outcome measures. Hierarchical regression analyses were utilized to determine if the NSI predicted rehabilitation outcome measures after controlling for demographic variables, TBI severity, and time since injury. NSI reliable changes from pretreatment to 1-year follow-up were examined. Receiver operating characteristics curve analyses were conducted to evaluate the ability of changes in the NSI to predict meaningful change in functioning and employment status. RESULTS: The NSI correlated with psychological distress measures. The NSI administered prior to brain injury rehabilitation had limited predictive utility beyond satisfaction with life. A minority of patients (32%) demonstrated reliable changes on the NSI from baseline to 1-year follow-up. Changes on the NSI were not predictive of meaningful change in employment or functioning. CONCLUSION: The NSI was not useful for assessing meaningful change in a sample of mixed severity TBI patients.

Screening for Remote History of Mild Traumatic Brain Injury in VHA: A Critical Literature Review.

OBJECTIVE: The authors reviewed the existing literature on the Veterans Health Administration's (VHA's) traumatic brain injury (TBI) screening and evaluation program to provide a qualitative synthesis and critical review of results focusing on the psychometric properties of the screen. METHODS: All studies of the VHA's screening and evaluation process were reviewed, both those involving primary data collection and those relying upon VHA data. Diagnostic statistics were summarized and also recalculated on the basis of a positive screening rate of 20%, the observed rate within the VHA, and an estimated population prevalence of TBI of 15% within the Department of Veterans Affairs (VHA). RESULTS: The TBI screen within the VHA is administered to nearly every eligible patient. The majority of clinical presentations are deemed to be due to mental health and/or a combination of mental health and TBI factors. The screen has good internal consistency, variable test-retest reliability, and questionable validity, with poor agreement between the TBI screen and criterion standards overall. Studies based on nonrepresentative samples reported high sensitivity. Assuming the VHA's TBI screening rate of 20% in a hypothetical sample, sensitivity is poor (the screen misses 30%-60% of TBI cases). However, specificity remains adequate. Studies based on samples with high rates of TBI reported much higher positive predictive values (and slightly lower negative predictive values) than those observed when a hypothetical TBI prevalence of 15% was used. CONCLUSION: Questions remain about the validity of the TBI screen. Future research should address the utility of screening for TBI.

Subconcussive Blows to the Head: A Formative Review of Short-term Clinical Outcomes.

BACKGROUND: Given questions about "lower thresholds" for concussion, as well as possible effects of repetitive concussion and chronic traumatic encephalopathy (CTE), and associated controversy, there is increasing interest in "subconcussive" blows and their potential significance. OBJECTIVE: A formative review with critical examination of the developing literature on subconcussive blows in athletes with an emphasis on clinical outcomes. METHODS: Studies of biomechanical, performance and/or symptom-based, and neuroimaging data were identified via PubMed search and critically reviewed. Five studies of symptom reporting/performance and 4 studies of neuroimaging were included. RESULTS: The relation between biomechanical parameters and diagnosed concussion is not straightforward (ie, it is not the case that greater and more force leads to more severe injury or cognitive/behavioral sequelae). Neuropsychological studies of subconcussive blows within a single athletic season have failed to demonstrate any strong and consistent relations between number and severity of subconcussive events and cognitive change. Recent studies using neuroimaging have demonstrated a potential cumulative effect of subconcussive blows, at least in a subset of individuals. CONCLUSION: Human studies of the neurological/neuropsychological impact of subconcussive blows are currently quite limited. Subconcussive blows, in the short-term, have not been shown to cause significant clinical effects. To date, findings suggest that any effect of subconcussive blows is likely to be small or nonexistent, perhaps evident in a subset of individuals on select measures, and maybe even beneficial in some cases. Longer-term prospective studies are needed to determine if there is a cumulative dose effect.