Blast-related Traumatic Brain Injury Research Articles

Closed-Globe Injuries of the Ocular Surface Associated with Combat Blast Exposure

To describe closed-globe conjunctival and corneal injuries and endothelial cell abnormalities associated with blast exposure and their relationships to other closed-globe injuries and blast-event characteristics. Observational cross-sectional study. Veterans with a history of blast-related traumatic brain injury (TBI). History and ocular examination, including slit-lamp biomicroscopy, gonioscopy, specular microscopy. Type and location of blast injuries to the conjunctiva and cornea. Ocular surface injuries were present in 25% (16 of 65) of blast-exposed veterans with TBI. Injuries included partial-thickness anterior stromal corneal scars (15 eyes), Descemet membrane ruptures (6 eyes), and conjunctival or corneal foreign bodies (7 eyes). Based on normative information from an age-matched comparison group, endothelial cell abnormalities were identified in 37% of participants. Eyes with ocular surface injury were more likely to have lower endothelial cell density, higher coefficient of variation of cell area, and lower percentage of hexagonal cells compared with eyes without injury. Presence of ocular surface injury or endothelial cell abnormalities was associated with elevated rates of other anterior and posterior segment injuries, as well as impairment of visual acuity. We found no relationship between ballistic eyewear use or severity level of TBI and presence of ocular surface injuries from blast. Independent of TBI severity or use of protective eyewear, ocular surface injuries and endothelial cell abnormalities were found in significant numbers of veterans with blast-related brain injury. Descemet membrane ruptures from blast exposure were described. Ocular surface trauma was associated with other ocular injuries throughout the globe. Potential mechanisms for the types and locations of ocular injuries seen were discussed. Any corneal or conjunctival injury in a blast survivor should prompt a thorough ocular trauma examination, including gonioscopy and specular microscopy, with appropriate follow-up for associated injuries. Longitudinal studies are required to determine long-term visual outcomes after blast exposure.

Selective vulnerability of the cerebral vasculature to blast injury in a rat model of mild traumatic brain injury.

BackgroundBlast-related traumatic brain injury (TBI) is a common cause of injury in the military operations in Iraq and Afghanistan. How the primary blast wave affects the brain is not well understood. The aim of the present study was to examine whether blast exposure affects the cerebral vasculature in a rodent model. We analyzed the brains of rats exposed to single or multiple (three) 74.5 kPa blast exposures, conditions that mimic a mild TBI. Rats were sacrificed 24 hours or between 6 and 10 months after exposure. Blast-induced cerebral vascular pathology was examined by a combination of light microscopy, immunohistochemistry, and electron microscopy.ResultsWe describe a selective vascular pathology that is present acutely at 24 hours after injury. The vascular pathology is found at the margins of focal shear-related injuries that, as we previously showed, typically follow the patterns of penetrating cortical vessels. However, changes in the microvasculature extend beyond the margins of such lesions. Electron microscopy revealed that microvascular pathology is found in regions of the brain with an otherwise normal neuropil. This initial injury leads to chronic changes in the microvasculature that are still evident many months after the initial blast exposure.ConclusionsThese studies suggest that vascular pathology may be a central mechanism in the induction of chronic blast-related injury.

Abstracts fromThe 32nd AnnualNational Neurotrauma SymposiumJune 29–July 2, 2014San Francisco, California

Abstracts fromThe 32^nd AnnualNational Neurotrauma SymposiumJune 29–July 2, 2014San Francisco, California

Response to goal management training in veterans with blast-related mild traumatic brain injury.

Veterans with blast-related mild traumatic brain injury (TBI) experience cognitive deficits that interfere with functional activities. Goal Management Training (GMT), which is a metacognitive intervention, offers an executive function rehabilitation approach that draws upon theories concerning goal processing and sustained attention. GMT has received empirical support in studies of patients with TBI but has not been tested in Veterans with blast-related mild TBI. GMT was modified from 7 weekly to 10 biweekly sessions. Participants included six combat Veterans that reported multiple blast exposures resulting in symptoms consistent with mild TBI. Group analysis showed a significant improvement in measures of executive function derived from performance on the computerized Tower of London. There were no significant changes on self/informant questionnaires of executive function, indicating a lack of generalization of improvement from the clinic to everyday activities. Overall, while the data indicate efficacy of GMT in the rehabilitation of combat Veterans with executive function deficits because of blast-related mild TBI, enhancement of generalization is needed.

Neural Activation during Response Inhibition Differentiates Blast from Mechanical Causes of Mild to Moderate Traumatic Brain Injury

Military personnel involved in Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) commonly experience blast-induced mild to moderate traumatic brain injury (TBI). In this study, we used task-activated functional MRI (fMRI) to determine if blast-related TBI has a differential impact on brain activation in comparison with TBI caused primarily by mechanical forces in civilian settings. Four groups participated: (1) blast-related military TBI (milTBI; n=21); (2) military controls (milCON; n=22); (3) non-blast civilian TBI (civTBI; n=21); and (4) civilian controls (civCON; n=23) with orthopedic injuries. Mild to moderate TBI (MTBI) occurred 1 to 6 years before enrollment. Participants completed the Stop Signal Task (SST), a measure of inhibitory control, while undergoing fMRI. Brain activation was evaluated with 2 (mil, civ)×2 (TBI, CON) analyses of variance, corrected for multiple comparisons. During correct inhibitions, fMRI activation was lower in the TBI than CON subjects in regions commonly associated with inhibitory control and the default mode network. In contrast, inhibitory failures showed significant interaction effects in the bilateral inferior temporal, left superior temporal, caudate, and cerebellar regions. Specifically, the milTBI group demonstrated more activation than the milCON group when failing to inhibit; in contrast, the civTBI group exhibited less activation than the civCON group. Covariance analyses controlling for the effects of education and self-reported psychological symptoms did not alter the brain activation findings. These results indicate that the chronic effects of TBI are associated with abnormal brain activation during successful response inhibition. During failed inhibition, the pattern of activation distinguished military from civilian TBI, suggesting that blast-related TBI has a unique effect on brain function that can be distinguished from TBI resulting from mechanical forces associated with sports or motor vehicle accidents. The implications of these findings for diagnosis and treatment of TBI are discussed.

Effects of interactive metronome therapy on cognitive functioning after blast-related brain injury: A randomized controlled pilot trial.

We report preliminary findings on the efficacy of interactive metronome (IM) therapy for the remediation of cognitive difficulties in soldiers with persisting cognitive complaints following blast-related mild-to-moderate traumatic brain injury (TBI). Forty-six of a planned sample of 50 active duty soldiers with persistent cognitive complaints following a documented history of blast-related TBI of mild-to-moderate severity were randomly assigned to receive either standard rehabilitation care (SRC) or SRC plus a 15-session standardized course of IM therapy. Primary outcome measures were Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Index Scores. Secondary outcome measures included selected subtests from the Delis-Kaplan Executive Functioning System (Trail Making Test and Color-Word Interference) and the Wechsler Adult Intelligence Scale-Fourth Edition (Symbol Search, Digit-Symbol Coding, Digit Span, and Letter-Number Sequencing) as well as the Integrated Visual and Auditory Continuous Performance Test. Significant group differences (SRC vs. IM) were observed for RBANS Attention (p = .044), Immediate Memory (p = .019), and Delayed Memory (p = .031) indices in unadjusted analyses, with the IM group showing significantly greater improvement at Time 2 than the SRC group, with effect sizes in the medium-to-large range in the adjusted analyses for each outcome (Cohen's d = 0.511, 0.768, and 0.527, respectively). Though not all were statistically significant, effects in 21 of 26 cognitive outcome measures were consistently in favor of the IM treatment group (binomial probability = .00098). The addition of IM therapy to SRC appears to have a positive effect on neuropsychological outcomes for soldiers who have sustained mild-to-moderate TBI and have persistent cognitive complaints after the period for expected recovery has passed.

Disrupted modular organization of resting-state cortical functional connectivity in U.S. military personnel following concussive ‘mild’ blast-related traumatic brain injury

Blast-related traumatic brain injury (TBI) has been one of the “signature injuries” of the wars in Iraq and Afghanistan. However, neuroimaging studies in concussive ‘mild’ blast-related TBI have been challenging due to the absence of abnormalities in computed tomography or conventional magnetic resonance imaging (MRI) and the heterogeneity of the blast-related injury mechanisms. The goal of this study was to address these challenges utilizing single-subject, module-based graph theoretic analysis of resting-state functional MRI (fMRI) data. We acquired 20min of resting-state fMRI in 63 U.S. military personnel clinically diagnosed with concussive blast-related TBI and 21 U.S. military controls who had blast exposures but no diagnosis of TBI. All subjects underwent an initial scan within 90days post-injury and 65 subjects underwent a follow-up scan 6 to 12months later. A second independent cohort of 40 U.S. military personnel with concussive blast-related TBI served as a validation dataset. The second independent cohort underwent an initial scan within 30days post-injury. 75% of the scans were of good quality, with exclusions primarily due to excessive subject motion. Network analysis of the subset of these subjects in the first cohort with good quality scans revealed spatially localized reductions in the participation coefficient, a measure of between-module connectivity, in the TBI patients relative to the controls at the time of the initial scan. These group differences were less prominent on the follow-up scans. The 15 brain areas with the most prominent reductions in the participation coefficient were next used as regions of interest (ROIs) for single-subject analyses. In the first TBI cohort, more subjects than would be expected by chance (27/47 versus 2/47 expected, p<0.0001) had 3 or more brain regions with abnormally low between-module connectivity relative to the controls on the initial scans. On the follow-up scans, more subjects than expected by chance (5/37, p=0.044) but fewer subjects than on the initial scans had 3 or more brain regions with abnormally low between-module connectivity. Analysis of the second TBI cohort validation dataset with no free parameters provided a partial replication; again more subjects than expected by chance (8/31, p=0.006) had 3 or more brain regions with abnormally low between-module connectivity on the initial scans, but the numbers were not significant (2/27, p=0.276) on the follow-up scans. A single-subject, multivariate analysis by probabilistic principal component analysis of the between-module connectivity in the 15 identified ROIs, showed that 31/47 subjects in the first TBI cohort were found to be abnormal relative to the controls on the initial scans. In the second TBI cohort, 9/31 patients were found to be abnormal in identical multivariate analysis with no free parameters. Again, there were not substantial differences on the follow-up scans. Taken together, these results indicate that single-subject, module-based graph theoretic analysis of resting-state fMRI provides potentially useful information for concussive blast-related TBI if high quality scans can be obtained. The underlying biological mechanisms and consequences of disrupted between-module connectivity are unknown, thus further studies are required.

Blast overpressure induces shear-related injuries in the brain of rats exposed to a mild traumatic brain injury

BackgroundBlast-related traumatic brain injury (TBI) has been a significant cause of injury in the military operations of Iraq and Afghanistan, affecting as many as 10-20% of returning veterans. However, how blast waves affect the brain is poorly understood. To understand their effects, we analyzed the brains of rats exposed to single or multiple (three) 74.5 kPa blast exposures, conditions that mimic a mild TBI.ResultsRats were sacrificed 24 hours or between 4 and 10 months after exposure. Intraventricular hemorrhages were commonly observed after 24 hrs. A screen for neuropathology did not reveal any generalized histopathology. However, focal lesions resembling rips or tears in the tissue were found in many brains. These lesions disrupted cortical organization resulting in some cases in unusual tissue realignments. The lesions frequently appeared to follow the lines of penetrating cortical vessels and microhemorrhages were found within some but not most acute lesions.ConclusionsThese lesions likely represent a type of shear injury that is unique to blast trauma. The observation that lesions often appeared to follow penetrating cortical vessels suggests a vascular mechanism of injury and that blood vessels may represent the fault lines along which the most damaging effect of the blast pressure is transmitted.

Cerebellar White Matter Abnormalities following Primary Blast Injury in US Military Personnel

Little is known about the effects of blast exposure on the human brain in the absence of head impact. Clinical reports, experimental animal studies, and computational modeling of blast exposure have suggested effects on the cerebellum and brainstem. In US military personnel with isolated, primary blast-related ‘mild’ traumatic brain injury and no other known insult, we found diffusion tensor MRI abnormalities consistent with cerebellar white matter injury in 3 of 4 subjects. No abnormalities in other brain regions were detected. These findings add to the evidence supporting the hypothesis that primary blast exposure contributes to brain injury in the absence of head impact and that the cerebellum may be particularly vulnerable. However, the clinical effects of these abnormalities cannot be determined with certainty; none of the subjects had ataxia or other detected evidence of cerebellar dysfunction. The details of the blast events themselves cannot be disclosed at this time, thus additional animal and computational modeling will be required to dissect the mechanisms underlying primary blast-related traumatic brain injury. Furthermore, the effects of possible subconcussive impacts and other military-related exposures cannot be determined from the data presented. Thus many aspects of topic will require further investigation.

Mechanisms of TBI and Visual Consequences in Military and Veteran Populations

Blast-related (BR) traumatic brain injuries (TBIs) occur secondary to explosive blasts. Blast-related TBIs can be caused by the blast wave itself or by direct head trauma caused by events surrounding the blast. Non-blast-related (NBR) TBIs are caused by direct head trauma. Recent evidence shows that TBIs are associated with vision problems, particularly binocular system problems. The purpose of this study was to determine if similar types and amounts of vision problems are present in patients with BR TBIs and NBR TBIs. A retrospective analysis of eye examination records of 50 NBR TBI and 50 BR TBI patients was conducted. Frequencies of visual symptoms and abnormal vision function measurements were computed and compared for the two patient groups. More than 65% of NRB TBI and BR TBI patients reported vision problems. Reading complaints were found in approximately 50% of the patients. Light sensitivity was reported significantly more often in BR TBI patients (67%) than in NBR TBI patients (33%) (p < 0.01). Saccadic dysfunction was measured more often in NBR TBI patients (85%) than in BR TBI patients (58%) (p < 0.01). High rates of accommodative dysfunction and convergence insufficiency were also found, but the group differences were not significant. Strabismus, pursuit abnormalities, fixation defects, and visual field defects were also common in both groups. For most findings, the mechanism of injury (NBR vs. BR) did not result in different frequencies or types of visual dysfunction. The reasons for finding higher frequencies of light sensitivity in the BR TBI group and saccadic dysfunction in the NBR TBI group are unknown, and further research is needed. Overall, the rates of vision complaints and oculomotor defects were high in both groups, indicating a need for a thorough eye examination for any patient with a history of TBI.

Functional MRI in the Investigation of Blast-Related Traumatic Brain Injury

This review focuses on the application of functional magnetic resonance imaging (fMRI) to the investigation of blast-related traumatic brain injury (bTBI). Relatively little is known about the exact mechanisms of neurophysiological injury and pathological and functional sequelae of bTBI. Furthermore, in mild bTBI, standard anatomical imaging techniques (MRI and computed tomography) generally fail to show focal lesions and most of the symptoms present as subjective clinical functional deficits. Therefore, an objective test of brain functionality has great potential to aid in patient diagnosis and provide a sensitive measurement to monitor disease progression and treatment. The goal of this review is to highlight the relevant body of blast-related TBI literature and present suggestions and considerations in the development of fMRI studies for the investigation of bTBI. The review begins with a summary of recent bTBI publications followed by discussions of various elements of blast-related injury. Brief reviews of some fMRI techniques that focus on mental processes commonly disrupted by bTBI, including working memory, selective attention, and emotional processing, are presented in addition to a short review of resting state fMRI. Potential strengths and weaknesses of these approaches as regards bTBI are discussed. Finally, this review presents considerations that must be made when designing fMRI studies for bTBI populations, given the heterogeneous nature of bTBI and its high rate of comorbidity with other physical and psychological injuries.

Do Sleep Problems Mediate the Relationship between Traumatic Brain Injury and Development of Mental Health Symptoms after Deployment?

Military members screening positive for blast-related traumatic brain injury (TBI) may subsequently screen positive for posttraumatic stress disorder (PTSD) or depression. The role of sleep as a mediating factor in the development of mental health symptoms was explored. Prospective study with symptoms evaluated at two time points. Postdeployment service in Iraq, Afghanistan, or Kuwait during 2008 and 2009. There were 29,640 US Navy and Marine Corps men (29,019 who did not screen positive for PTSD at baseline, 27,702 who did not screen positive for depression at baseline, and 27,320 who did not screen positive at baseline for either condition). After controlling for sleep problems, the adjusted odds of receiving a positive PTSD screening at follow-up decreased from 1.61 (95% confidence interval [CI] 1.21-2.14) to 1.32 (95% CI 0.99-1.77) for a subject screening positive for TBI relative to a subject screening negative, suggesting that sleep problems mediated 26% of TBI's effect on development of PTSD. Likewise, after controlling for sleep problems, the adjusted odds of receiving a positive depression screening decreased from 1.41 (95% CI 1.11-1.80) to 1.15 (95% CI 0.90-1.47), suggesting that sleep problems mediated 41% of TBI's effect on development of depression. Results were similar for those with either PTSD or depression (37% mediated). These results suggest that sleep problems mediate the effect of a positive TBI screening on the development of mental health disorders, and sleep problems may be an early indicator of risk for PTSD or depression.

Diffusion Tensor Imaging and Mild Traumatic Brain Injury in Soldiers: Abnormal Findings, Uncertain Implications

Diffusion Tensor Imaging and Mild Traumatic Brain Injury in Soldiers: Abnormal Findings, Uncertain Implications

White matter abnormalities in veterans with mild traumatic brain injury.

It has been estimated that 10%-20% of U.S. veterans of the wars in Iraq and Afghanistan experienced mild traumatic brain injury (TBI), mostly secondary to blast exposure. Diffusion tensor imaging (DTI) may detect subtle white matter changes in both the acute and chronic stages of mild TBI and thus has the potential to detect white matter damage in patients with TBI. The authors used DTI to examine white matter integrity in a relatively large group of veterans with a history of mild TBI. DTI images from 72 veterans of the wars in Iraq and Afghanistan who had mild TBI were compared with DTI images from 21 veterans with no exposure to TBI during deployment. Conventional voxel-based analysis as well as a method of identifying spatially heterogeneous areas of decreased fractional anisotropy ("potholes") were used. Veterans also underwent psychiatric and neuropsychological assessments. Voxel-based analysis did not reveal differences in DTI parameters between the veterans with mild TBI and those with no TBI. However, the veterans with mild TBI had a significantly higher number of potholes than those without TBI. The difference in the number of potholes was not influenced by age, time since trauma, a history of mild TBI unrelated to deployment, or coexisting psychopathology. The number of potholes was correlated with the severity of TBI and with performance in executive functioning tasks. Veterans who had blast-related mild TBI showed evidence of multifocal white matter abnormalities that were associated with severity of the injury and with relevant functional measures. Overall, white matter potholes may constitute a sensitive biomarker of axonal injury that can be identified in mild TBI at acute and chronic stages of its clinical course.

Blast Exposure Induces Post-Traumatic Stress Disorder-Related Traits in a Rat Model of Mild Traumatic Brain Injury

Blast related traumatic brain injury (TBI) has been a major cause of injury in the wars in Iraq and Afghanistan. A striking feature of the mild TBI (mTBI) cases has been the prominent association with post-traumatic stress disorder (PTSD). However, because of the overlapping symptoms, distinction between the two disorders has been difficult. We studied a rat model of mTBI in which adult male rats were exposed to repetitive blast injury while under anesthesia. Blast exposure induced a variety of PTSD-related behavioral traits that were present many months after the blast exposure, including increased anxiety, enhanced contextual fear conditioning, and an altered response in a predator scent assay. We also found elevation in the amygdala of the protein stathmin 1, which is known to influence the generation of fear responses. Because the blast overpressure injuries occurred while animals were under general anesthesia, our results suggest that a blast-related mTBI exposure can, in the absence of any psychological stressor, induce PTSD-related traits that are chronic and persistent. These studies have implications for understanding the relationship of PTSD to mTBI in the population of veterans returning from the wars in Iraq and Afghanistan.

Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model.

Blast exposure is associated with traumatic brain injury (TBI), neuropsychiatric symptoms, and long-term cognitive disability. We examined a case series of postmortem brains from U.S. military veterans exposed to blast and/or concussive injury. We found evidence of chronic traumatic encephalopathy (CTE), a tau protein-linked neurodegenerative disease, that was similar to the CTE neuropathology observed in young amateur American football players and a professional wrestler with histories of concussive injuries. We developed a blast neurotrauma mouse model that recapitulated CTE-linked neuropathology in wild-type C57BL/6 mice 2 weeks after exposure to a single blast. Blast-exposed mice demonstrated phosphorylated tauopathy, myelinated axonopathy, microvasculopathy, chronic neuroinflammation, and neurodegeneration in the absence of macroscopic tissue damage or hemorrhage. Blast exposure induced persistent hippocampal-dependent learning and memory deficits that persisted for at least 1 month and correlated with impaired axonal conduction and defective activity-dependent long-term potentiation of synaptic transmission. Intracerebral pressure recordings demonstrated that shock waves traversed the mouse brain with minimal change and without thoracic contributions. Kinematic analysis revealed blast-induced head oscillation at accelerations sufficient to cause brain injury. Head immobilization during blast exposure prevented blast-induced learning and memory deficits. The contribution of blast wind to injurious head acceleration may be a primary injury mechanism leading to blast-related TBI and CTE. These results identify common pathogenic determinants leading to CTE in blast-exposed military veterans and head-injured athletes and additionally provide mechanistic evidence linking blast exposure to persistent impairments in neurophysiological function, learning, and memory.

On Sources of Error in Finite Element Simulations of Blast Effects in the Human Brain

Recent military conflicts in Iraq and Afghanistan have resulted in an increase in the number of blast related traumatic brain injuries (blast-TBI). It is assumed that the primary mechanism for blast-TBI is the interaction between the blast pressure wave and the central nervous system, but the details of this mechanism are poorly understood. The conditions of such blast injuries are highly variable, and the presence or absence of protective devices such as vehicles or helmets is presumed to have a strong influence on pressure waves. Because of the complexity of this problem and the difficulty of in situ measurement of these effects in actual combat scenarios, one approach is to develop efficient numerical simulations that have the fidelity to reliably model the interaction of the brain and the pressure and shear waves. Here we examine the distribution of pressures and principal strains (stretches) in a brain impinged upon by a blast wave incident from orthogonal directions as simulated by a finite element coupled fluid-solid dynamic interaction framework. We assess the various sources of errors in finite element simulations of wave propagating through tissue, the modeling error, the discretization error, and the error of input parameters (data uncertainty). We conclude that the least important source of error is the assumption of linear kinematics and linear constitutive equation. The discretization error is significant, and controlling it will remain a challenge. The most significant source of error is found to be the input parameter uncertainty (experimental variability) and lack of knowledge of the detailed mechanics of deformation of the brain tissues under conditions of blast loading.

Traumatic Brain Injury and Its Neuropsychiatric Sequelae in War Veterans

The post-September 11, 2001 wars in and around Afghanistan and Iraq have increased awareness of traumatic brain injury (TBI), particularly blast-induced mild TBI. This article provides an overview of TBI and its neuropsychiatric sequelae in U.S. war veterans who participated in the current operations in and around Afghanistan and Iraq, with particular emphasis on blast-related mild TBI. Psychiatric disorders, particularly posttraumatic stress disorder, pain, and sensory impairments are prevalent in war veterans with TBI. Research is needed to more definitively characterize the epidemiology of TBI-related functional difficulties, the effects of blasts compared with other mechanisms of injury, recovery trajectories, and treatment outcomes in this population.

Cognitive sequelae of blast-induced traumatic brain injury: recovery and rehabilitation.

Blast-related traumatic brain injury (bTBI) poses a significant concern for military personnel engaged in Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF). Given the highly stressful context in which such injury occurs, psychiatric comorbidities are common. This paper provides an overview of mild bTBI and discusses the cognitive sequelae and course of recovery typical of mild TBI (mTBI). Complicating factors that arise in the context of co-morbid posttraumatic stress disorder (PTSD) are considered with regard to diagnosis and treatment. Relatively few studies have evaluated the efficacy of cognitive rehabilitation in civilian mTBI, but we discuss cognitive training approaches that hold promise for addressing mild impairments in executive function and memory, akin to those seen in OEF/OIF veterans with bTBI and PTSD. Further research is needed to address the patient and environmental characteristics associated with optimal treatment outcome.

Development of a Finite Element Model for Blast Brain Injury and the Effects of CSF Cavitation

Blast-related traumatic brain injury is the most prevalent injury for combat personnel seen in the current conflicts in Iraq and Afghanistan, yet as a research community,we still do not fully understand the detailed etiology and pathology of this injury. Finite element (FE) modeling is well suited for studying the mechanical response of the head and brain to blast loading. This paper details the development of a FE head and brain model for blast simulation by examining both the dilatational and deviatoric response of the brain as potential injury mechanisms. The levels of blast exposure simulated ranged from 50 to 1000 kPa peak incident overpressure and 1–8 ms in positive-phase duration, and were comparable to real-world blast events. The frontal portion of the brain had the highest pressures corresponding to the location of initial impact, and peak pressure attenuated by 40–60% as the wave propagated from the frontal to the occipital lobe. Predicted brain pressures were primarily dependent on the peak overpressure of the impinging blast wave, and the highest predicted brain pressures were 30%less than the reflected pressure at the surface of blast impact. Predicted shear strain was highest at the interface between the brain and the CSF. Strain magnitude was largely dependent on the impulse of the blast, and primarily caused by the radial coupling between the brain and deforming skull.The largest predicted strains were generally less than 10%,and occurred after the shock wave passed through the head.For blasts with high impulses, CSF cavitation had a large role in increasing strain levels in the cerebral cortex and periventricular tissues by decoupling the brain from the skull. Relating the results of this study with recent experimental blast testing suggest that a rate-dependent strain-based tissue injury mechanism is the source primary blast TBI.