White matter abnormalities are associated with chronic postconcussion symptoms in blast‐related mild traumatic brain injury

Blast‐related mild traumatic brain injury (mTBI) is a common injury among Iraq and Afghanistan military veterans due to the frequent use of improvised explosive devices. A significant minority of individuals with mTBI report chronic postconcussion symptoms (PCS), which include physical, emotional, and cognitive complaints. However, chronic PCS are nonspecific and are also associated with mental health disorders such as posttraumatic stress disorder (PTSD). Identifying the mechanisms that contribute to chronic PCS is particularly challenging in blast‐related mTBI, where the incidence of comorbid PTSD is high. In this study, we examined whether blast‐related mTBI is associated with diffuse white matter changes, and whether these neural changes are associated with chronic PCS. Ninety Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans were assigned to one of three groups including a blast‐exposed no ? TBI group, a blast‐related mTBI without loss of consciousness (LOC) group (mTBI ? LOC), and a blast‐related mTBI with LOC group (mTBI + LOC). PCS were measured with the Rivermead Postconcussion Questionnaire. Results showed that participants in the mTBI + LOC group had more spatially heterogeneous white matter abnormalities than those in the no ? TBI group. These white matter abnormalities were significantly associated with physical PCS severity even after accounting for PTSD symptoms, but not with cognitive or emotional PCS severity. A mediation analysis revealed that mTBI + LOC significantly influenced physical PCS severity through its effect on white matter integrity. These results suggest that white matter abnormalities are associated with chronic PCS independent of PTSD symptom severity and that these abnormalities are an important mechanism explaining the relationship between mTBI and chronic physical PCS. Hum Brain Mapp 37:220–229, 2016. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.     

The contributions of self-reported injury characteristics and psychiatric symptoms to cognitive functioning in OEF/OIF veterans with mild traumatic brain injury

Mild traumatic brain injury (mTBI) affects a significant number of combat veterans returning from Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF). Although resolution of mTBI symptoms is expected over time, some individuals continue to report lingering cognitive difficulties. This study examined the contributions of self-reported mTBI injury characteristics (e.g., loss of consciousness, post-traumatic amnesia) and psychiatric symptoms to both subjective and objective cognitive functioning in a sample of 167 OEF/OIF veterans seen in a TBI clinic. Injury characteristics were not associated with performance on neuropsychological tests but were variably related to subjective ratings of cognitive functioning. Psychiatric symptoms were highly prevalent and fully mediated most of the relationships between injury characteristics and cognitive ratings. This indicates that mTBI characteristics such as longer time since injury and loss of consciousness or post-traumatic amnesia can lead to increased perceived cognitive deficits despite having no objective effects on cognitive performance. Psychiatric symptoms were associated with both cognitive ratings and neuropsychological performance, illustrating the important role that psychiatric treatment can potentially play in optimizing functioning. Finally, subjective cognitive ratings were not predictive of neuropsychological performance once psychiatric functioning was statistically controlled, suggesting that neuropsychological assessment provides valuable information that cannot be gleaned from self-report alone.     

Neuropsychological Effects of Self-Reported Deployment-Related Mild TBI and Current PTSD in OIF/OEF Veterans

Current combat veterans are exposed to many incidents that may result in mild traumatic brain injury (mTBI) and/or posttraumatic stress disorder (PTSD). While there is literature on the neuropsychological consequences of PTSD only (PTSD-o) and mTBI alone (mTBI-o), less has been done to explore their combined (mTBI+PTSD) effect. The goal of this study was to determine whether Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) veterans with mTBI+PTSD have poorer cognitive and psychological outcomes than veterans with PTSD-o, mTBI-o, or combat exposure-only. The final sample included 20 OIF/OEF veterans with histories of self-reported deployment mTBI (mTBI-o), 19 with current PTSD (PTSD-o), 21 with PTSD and self-reported mTBI (mTBI+PTSD), and 21 combat controls (CC) (no PTSD and no reported mTBI). Groups were formed using structured interviews for mTBI and PTSD. All participants underwent comprehensive neuropsychological testing, including neurocognitive and psychiatric feigning tests. Results of cognitive tests revealed significant differences in performance in the mTBI+PTSD and PTSD-o groups relative to mTBI-o and CC. Consistent with previous PTSD literature, significant differences were found on executive (switching) tasks, verbal fluency, and verbal memory. Effect sizes tended to be large in both groups with PTSD. Thus, PTSD seems to be an important variable affecting neuropsychological profiles in the post-deployment time period. Consistent with literature on civilian mTBI, the current study did not find evidence that combat-related mTBI in and of itself contributes to objective cognitive impairment in the late stage of injury.     

Variables associated with subjective cognitive change among Iraq and Afghanistan war Veterans with blast-related mild traumatic brain injury

Introduction: This study investigated variables associated with subjective decline in executive function among Veterans of Operations Enduring Freedom, Iraqi Freedom, and New Dawn (OEF/OIF/OND) following a history of blast-related mild traumatic brain injury (mTBI).

Method: Fifty-six male U.S. Veterans (M_Age = 35.3 ± 8.8 years) with a history of blast-related mTBI (6.6 ± 3.2 years post injury) completed a battery of self-report questionnaires and neuropsychological measures. Participants rated current and retrospectively estimated pre-mTBI executive function difficulties on the Frontal Systems Behavior Scale (FrSBe). A difference score (post- minus pre-mTBI ratings) was the dependent variable (?FrSBe). Linear regression models examined variables predicting ?FrSBe, including: pre-injury characteristics (education, premorbid intelligence), injury-related characteristics (number of blast exposures, losses of consciousness), post-injury clinical symptoms (PTSD Checklist–Military version; Pittsburgh Sleep Quality Index), and post-injury neuropsychological performances on executive function measures (Trail Making Test Part B; Controlled Oral Word Association Test; Auditory Consonant Trigrams; Wisconsin Card Sorting Test).

Results: While 11% of participants had a clinically elevated pre-injury FrSBe total score, 82% had a clinically elevated post-injury FrSBe total score. Only self-reported PTSD symptom severity independently predicted perceived change in executive function.

Conclusions: Many OEF/OIF/OND Veterans with a history of blast-related mTBI experience subjective decline in executive function following injury. Perceived executive function decline was associated with higher PTSD symptom severity, aligning with previous research associating PTSD with cognitive complaints. Results did not support a correspondence between perceived cognitive change and neuropsychological performances.     

Postconcussion symptoms reported by Operation Enduring Freedom/Operation Iraqi Freedom veterans with and without blast exposure,mild traumatic brain injury,and posttraumatic stress disorder

Objective: This study examined symptom reporting related to the 10th Edition of the International Statistical Classification of Diseases and Related Health Problems (ICD–10) criteria for postconcussional syndrome (PCS) in Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) Veterans. Our aims were to: (a) examine relationships among PCS symptoms by identifying potential subscales of the British Columbia Postconcussion Symptom Inventory (BC-PSI); and (b) examine group differences in BC-PSI items and subscales in Veterans with and without blast exposure, mild traumatic brain injury (mTBI), and posttraumatic stress disorder (PTSD). Method: Our sample included Veterans with blast-related mTBI history (n = 47), with blast exposure but no mTBI history (n = 20), and without blast exposure (n = 23). Overall, 37 Veterans had PTSD, and 53 did not. We conducted an exploratory factor analysis (EFA) of the BC-PSI followed by multivariate analysis of variance to examine differences in BC-PSI subscale scores by blast exposure, mTBI history, and PTSD. Results: BC-PSI factors were interpreted as cognitive, vestibular, affective, anger, and somatic. Items and factor scores were highest for Veterans with blast exposure plus mTBI, and lowest for controls. Vestibular, affective, and somatic factors were significantly higher for Veterans with blast exposure plus mTBI than for controls, but not significantly different for those with blast exposure but no mTBI. These results remained significant when PTSD symptom severity was included as a covariate. Cognitive, anger, and somatic subscales were significantly higher for Veterans with PTSD, though there was no interaction effect of PTSD and mTBI or blast history. Conclusions: EFA-derived subscales of the BC-PSI differentiated Veterans based on blast exposure, mTBI history, and PTSD.     

Accelerated longitudinal cortical atrophy in OEF/OIF/OND veterans with severe PTSD and the impact of comorbid TBI

Veterans who deployed in support of Operation Enduring Freedom (OEF), Iraqi Freedom (OIF), and New Dawn (OND) commonly experience severe psychological trauma, often accompanied by physical brain trauma resulting in mild traumatic brain injury (mTBI). Prior studies of individuals with posttraumatic stress disorder (PTSD) have revealed alterations in brain structure, accelerated cellular aging, and impacts on cognition following exposure to severe psychological trauma and potential interactive effects of military‐related mTBI. To date, however, little is known how such deployment‐related trauma changes with time and age of injury of the affected veteran. In this study, we explored changes in cortical thickness, volume, and surface area after an average interval of approximately 2 years in a cohort of 254 OEF/OIF/OND Veterans ranging in age from 19 to 67 years. Whole‐brain vertex‐wise analyses revealed that veterans who met criteria for severe PTSD (Clinician‐Administered PTSD Scale ≥60) at baseline showed greater negative longitudinal changes in cortical thickness, volume, and area over time. Analyses also revealed a significant severe‐PTSD by age interaction on cortical measures with severe‐PTSD individuals exhibiting accelerated cortical degeneration with increasing age. Interaction effects of comorbid military‐related mTBI within the severe‐PTSD group were also observed in several cortical regions. These results suggest that those exhibiting severe PTSD symptomatology have accelerated atrophy that is exacerbated with increasing age and history of mTBI.     

Development of a Practice Tool for Primary Care Providers: Medication Management of Posttraumatic Stress Disorder in Veterans with Mild Traumatic Brain Injury

Psychiatric Quarterly - Posttraumatic stress disorder (PTSD) and comorbid mild traumatic brain injury (mTBI) are highly prevalent in veterans who served in Iraq [Operation Iraqi Freedom/Operation...     

Apolipoprotein E (APOE) ε4 genotype is associated with reduced neuropsychological performance in military veterans with a history of mild traumatic brain injury

Introduction: The purpose of this study was to investigate the effect of the apolipoprotein E (APOE) ε4 allele on neuropsychological functioning in military Veterans with a remote history of mild traumatic brain injury (mTBI).

Method: This cross-sectional study included 99 Veterans (mTBI = 53; military controls, MC = 46) who underwent neuropsychological assessment and APOE genotyping. Three neurocognitive composite scores—memory (α = .84), speed (α = .85), and executive functioning (α = .76)—were computed from 24 norm-referenced variables, and the total number of impaired scores (>1.5 SDs below mean) for each participant was calculated.

Results: Analyses of covariance adjusting for ethnicity and posttraumatic stress disorder (PTSD) symptoms revealed that although no significant differences were observed between mTBI ε4 allele groups on the executive functioning composite (p > .05), mTBI ε4+ Veterans performed more poorly than ε4? Veterans on the memory (p = .045, η_p² = .083) and speed (p = .023, η_p² = .106) composites. Furthermore, Mann–Whitney U tests showed that ε4+ mTBI Veterans displayed a significantly greater number of impaired scores than did ε4? mTBI Veterans (p = .010, r = .355). In contrast, there were no significant differences across any of the cognitive variables between ε4+ and ε4? MCs (all p > .05).

Conclusions: Results suggest that APOE ε4 genotype is related to reduced memory and processingspeed performance, as well as overall cognitive impairment, in those with a history of mTBI, but does not appear to have the same negative effects on cognition in the absence of neurotrauma. Although results are preliminary, the present study advances understanding of genetic influences on cognitive functioning in Veterans with remote mTBIs. Future longitudinal work is needed to elucidate the underlying brain-based mechanisms of ε4 allelic effects on cognitive and clinical outcomes following TBI.     

White matter abnormalities associated with military PTSD in the context of blast TBI

Mild traumatic brain injury (mTBI) and post‐traumatic stress disorder (PTSD) are common among recent military veterans and involve substantial symptom overlap, making clinical distinction and effective intervention difficult. Emerging evidence of cerebral white matter abnormalities associated with mTBI may provide a biological measure to inform diagnosis and treatment, but the potentially confounding effects between PTSD and mTBI have largely gone unexamined. We collected diffusion imaging data from 133 recently‐deployed American service members who developed PTSD and/or sustained mTBI, or had neither condition. Effects of PTSD and mTBI on traditional tensor‐based measures of cerebral white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD]) were compared in anatomical regions of interest and individual voxels throughout the brain. Generalized FA (GFA), which allows for multiple fiber orientations per voxel, was also included to improve sensitivity in white matter areas containing crossing or diverging axon bundles. PTSD was consistently associated with high GFA in select brain regions, greater likelihood of regions and voxels with abnormally low MD, and a greater number of voxels with abnormally high FA, while mTBI was associated with fewer high MD regions. Overall, PTSD was associated with more restricted diffusion (low MD) and greater anisotropy (high GFA) in regions of crossing/diverging fibers poorly characterized by a single tensor (FA), suggesting that interstitial fibers may be involved. Contrary to earlier results in a sample without PTSD, mTBI was not associated with anisotropy abnormalities, perhaps indicating the cooccurrence of PTSD and mTBI requires special consideration with regard to structural brain connectivity. Hum Brain Mapp 36:1053–1064, 2015. © 2014 Wiley Periodicals, Inc.     

White matter network damage mediates association between cerebrovascular disease and cognition

To determine whether white matter network disruption mediates the association between MRI markers of cerebrovascular disease (CeVD) and cognitive impairment. Participants (n = 253, aged ≥60 years) from the Epidemiology of Dementia in Singapore study underwent neuropsychological assessments and MRI. CeVD markers were defined as lacunes, white matter hyperintensities (WMH), microbleeds, cortical microinfarcts, cortical infarcts and intracranial stenosis (ICS). White matter microstructure damage was measured as fractional anisotropy and mean diffusivity by tract based spatial statistics from diffusion tensor imaging. Cognitive function was summarized as domain-specific Z-scores.Lacunar counts, WMH volume and ICS were associated with worse performance in executive function, attention, language, verbal and visual memory. These three CeVD markers were also associated with white matter microstructural damage in the projection, commissural, association, and limbic fibers. Path analyses showed that lacunar counts, higher WMH volume and ICS were associated with executive and verbal memory impairment via white matter disruption in commissural fibers whereas impairment in the attention, visual memory and language were mediated through projection fibers.Our study shows that the abnormalities in white matter connectivity may underlie the relationship between CeVD and cognition. Further longitudinal studies are needed to understand the cause-effect relationship between CeVD, white matter damage and cognition.     

A review of magnetic resonance imaging and diffusion tensor imaging findings in mild traumatic brain injury

Mild traumatic brain injury (mTBI), also referred to as concussion, remains a controversial diagnosis because the brain often appears quite normal on conventional computed tomography (CT) and magnetic resonance imaging (MRI) scans. Such conventional tools, however, do not adequately depict brain injury in mTBI because they are not sensitive to detecting diffuse axonal injuries (DAI), also described as traumatic axonal injuries (TAI), the major brain injuries in mTBI. Furthermore, for the 15 to 30 % of those diagnosed with mTBI on the basis of cognitive and clinical symptoms, i.e., the "miserable minority," the cognitive and physical symptoms do not resolve following the first 3 months post-injury. Instead, they persist, and in some cases lead to long-term disability. The explanation given for these chronic symptoms, i.e., postconcussive syndrome, particularly in cases where there is no discernible radiological evidence for brain injury, has led some to posit a psychogenic origin. Such attributions are made all the easier since both posttraumatic stress disorder (PTSD) and depression are frequently co-morbid with mTBI. The challenge is thus to use neuroimaging tools that are sensitive to DAI/TAI, such as diffusion tensor imaging (DTI), in order to detect brain injuries in mTBI. Of note here, recent advances in neuroimaging techniques, such as DTI, make it possible to characterize better extant brain abnormalities in mTBI. These advances may lead to the development of biomarkers of injury, as well as to staging of reorganization and reversal of white matter changes following injury, and to the ability to track and to characterize changes in brain injury over time. Such tools will likely be used in future research to evaluate treatment efficacy, given their enhanced sensitivity to alterations in the brain. In this article we review the incidence of mTBI and the importance of characterizing this patient population using objective radiological measures. Evidence is presented for detecting brain abnormalities in mTBI based on studies that use advanced neuroimaging techniques. Taken together, these findings suggest that more sensitive neuroimaging tools improve the detection of brain abnormalities (i.e., diagnosis) in mTBI. These tools will likely also provide important information relevant to outcome (prognosis), as well as play an important role in longitudinal studies that are needed to understand the dynamic nature of brain injury in mTBI. Additionally, summary tables of MRI and DTI findings are included. We believe that the enhanced sensitivity of newer and more advanced neuroimaging techniques for identifying areas of brain damage in mTBI will be important for documenting the biological basis of postconcussive symptoms, which are likely associated with subtle brain alterations, alterations that have heretofore gone undetected due to the lack of sensitivity of earlier neuroimaging techniques. Nonetheless, it is noteworthy to point out that detecting brain abnormalities in mTBI does not mean that other disorders of a more psychogenic origin are not co-morbid with mTBI and equally important to treat. They arguably are. The controversy of psychogenic versus physiogenic, however, is not productive because the psychogenic view does not carefully consider the limitations of conventional neuroimaging techniques in detecting subtle brain injuries in mTBI, and the physiogenic view does not carefully consider the fact that PTSD and depression, and other co-morbid conditions, may be present in those suffering from mTBI. Finally, we end with a discussion of future directions in research that will lead to the improved care of patients diagnosed with mTBI.     

Fatigue – but not mTBI history,PTSD, or sleep quality – directly contributes to reduced prospective memory performance in Iraq and Afghanistan era Veterans

Abstract

Objective: Memory problems that affect daily functioning are a frequent complaint among Veterans reporting a history of repetitive mild traumatic brain injury (mTBI), especially in cohorts with comorbid PTSD. Here, we test the degree to which subjective sleep impairment and daytime fatigue account for the association of PTSD and self-reported mTBI history with prospective memory. Method: 82 Veterans with and without personal history of repeated blast-related mTBI during deployment were administered the Clinician Administered PTSD Scale (CAPS), Memory for Intentions Test (MIST), Patient Health Questionnaire-9 (PHQ-9), Neurobehavioral Symptom Inventory (NSI), and the Pittsburgh Sleep Quality Index (PSQI). Relationships between self-reported mTBI, PTSD, self-reported poor sleep and daytime fatigue, and MIST performance were modeled using partial least squares structural equation modeling (PLS-SEM). Results: Reported daytime fatigue was strongly associated with poorer prospective memory performance. Poor subjective sleep quality was strongly and positively associated with reported daytime fatigue, but had no significant direct effect on prospective memory performance. PTSD diagnosis and self-reported mTBI history were only associated with prospective memory via their impact on subjective sleep quality and daytime fatigue. Conclusions: Results suggest that daytime fatigue may be a mediating factor by which both mTBI and PTSD can interfere with prospective memory. Additional attention should be given to complaints of daytime fatigue, independent of subjective sleep quality, in the clinical care of those with a self-reported history of mTBI, and/or PTSD. Further research into whether interventions that decrease daytime fatigue lead to improvement in prospective memory and subjective cognitive functioning is warranted.     

Neuropsychological outcomes of u.s. Veterans with report of remote blast-related concussion and current psychopathology

This study explored whether remote blast-related MTBI and/or current Axis I psychopathology contribute to neuropsychological outcomes among OEF/OIF veterans with varied combat histories. OEF/OIF veterans underwent structured interviews to evaluate history of blast-related MTBI and psychopathology and were assigned to MTBI (n = 18), Axis I (n = 24), Co-morbid MTBI/Axis I (n = 34), or post-deployment control (n = 28) groups. A main effect for Axis I diagnosis on overall neuropsychological performance was identified (F(3,100) = 4.81; p = .004), with large effect sizes noted for the Axis I only (d = .98) and Co-morbid MTBI/Axis I (d = .95) groups relative to the control group. The latter groups demonstrated primary limitations on measures of learning/memory and processing speed. The MTBI only group demonstrated performances that were not significantly different from the remaining three groups. These findings suggest that a remote history of blast-related MTBI does not contribute to objective cognitive impairment in the late stage of injury. Impairments, when present, are subtle and most likely attributable to PTSD and other psychological conditions. Implications for clinical neuropsychologists and future research are discussed. (JINS, 2012, 18, 1-11).     

Robust detection of traumatic axonal injury in individual mild traumatic brain injury patients: Intersubject variation, change over time and bidirectional changes in anisotropy

To identify and characterize otherwise occult inter-individual spatial variation of white matter abnormalities across mild traumatic brain injury (mTBI) patients. After informed consent and in compliance with Health Insurance Portability and Accountability Act (HIPAA), Diffusion tensor imaging (DTI) was performed on a 3.0 T MR scanner in 34 mTBI patients (19 women; 19-64 years old) and 30 healthy control subjects. The patients were imaged within 2 weeks of injury, 3 months after injury, and 6 months after injury. Fractional anisotropy (FA) images were analyzed in each patient. To examine white matter diffusion abnormalities across the entire brain of individual patients, we applied Enhanced Z-score Microstructural Assessment for Pathology (EZ-MAP), a voxelwise analysis optimized for the assessment of individual subjects. Our analysis revealed areas of abnormally low or high FA (voxel-wise P-value < 0.05, cluster-wise P-value < 0.01(corrected for multiple comparisons)). The spatial pattern of white matter FA abnormalities varied among patients. Areas of low FA were consistent with known patterns of traumatic axonal injury. Areas of high FA were most frequently detected in the deep and subcortical white matter of the frontal, parietal, and temporal lobes, and in the anterior portions of the corpus callosum. The number of both abnormally low and high FA voxels changed during follow up. Individual subject assessments reveal unique spatial patterns of white matter abnormalities in each patient, attributable to inter-individual differences in anatomy, vulnerability to injury and mechanism of injury. Implications of high FA remain unclear, but may evidence a compensatory mechanism or plasticity in response to injury, rather than a direct manifestation of brain injury.     

Elevated rates of memory impairment in military service-members and veterans with posttraumatic stress disorder

Introduction: Studies investigating the neurocognitive effects of posttraumatic stress disorder (PTSD) routinely find “deficits” in various cognitive domains. However, the rate of cognitive impairment in individuals with PTSD remains unclear, as studies have focused on null hypothesis testing (NHT) and inferring patterns of impairment rather than empirically determining the rate of cognitive impairment in this sample. Method: This study examined rates of cognitive impairment using a domain-specific approach in non-treatment-seeking Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn service members and veterans with (n = 92) and without (n = 79) PTSD and without substance abuse/dependence who passed a performance validity measure and were matched on age, education, estimated IQ, and ethnicity. Chi-square analyses were used to compare the rate of cognitive impairment across groups based on normative scores using three cutoffs (?1, ?1.5, and ?2 SDs). NHT was also used to compare performances across groups. Results: Individuals with PTSD showed higher rates of impairment in memory (?1-SD cutoff) than controls, but equivalent rates of impairment in attention, processing speed, and executive functioning; no significant differences were found on NHT. Impairment in any domain was also more prevalent in PTSD (?1-, ?1.5-, and ?2-SD cutoffs). No differences were found on NHT or rates of impairment in individuals with PTSD with (n = 34) and without (n = 58) depression. Conclusions: Patients with PTSD were more likely to meet criteria for memory impairment and to show impairment in any domain than controls. Patients with PTSD and comorbid depression were no more likely to be impaired in any cognitive domain or to have lower scores on individual cognitive tasks than patients with PTSD alone. Clinicians noting cognitive impairment in individuals with PTSD should exercise caution before ascribing that impairment to another etiology if deficits are limited to memory.     

White matter tract injury and cognitive impairment in human immunodeficiency virusinfected individuals

Approximately half of those infected with the human immunodeficiency virus (HIV) exhibit cognitive impairment, which has been related to cerebral white matter damage. Despite the effectiveness of antiretroviral treatment, cognitive impairment remains common even in individuals with undetectable viral loads. One explanation for this may be subtherapeutic concentrations of some antiretrovirals in the central nervous system (CNS). We utilized diffusion tensor imaging and a comprehensive neuropsychological evaluation to investigate the relationship of white matter integrity to cognitive impairment and antiretroviral treatment variables. Participants included 39 HIV-infected individuals (49% with acquired immunodeficiency syndrome [AIDS]; mean CD4=529) and 25 seronegative subjects. Diffusion tensor imaging indices were mapped onto a common whole-brain white matter tract skeleton, allowing between-subject voxelwise comparisons. The total HIV-infected group exhibited abnormal white matter in the internal capsule, inferior longitudinal fasciculus, and optic radiation; whereas those with AIDS exhibited more widespread damage, including in the internal capsule and the corpus callosum. Cognitive impairment in the HIV-infected group was related to white matter injury in the internal capsule, corpus callosum, and superior longitudinal fasciculus. White matter injury was not found to be associated with HIV viral load or estimated CNS penetration of antiretrovirals. Diffusion tensor imaging was useful in identifying changes in white matter tracts associated with more advanced HIV infection. Relationships between diffusion alterations in specific white matter tracts and cognitive impairment support the potential utility of diffusion tensor imaging in examining the anatomical underpinnings of HIV-related cognitive impairment. The study also confirms that CNS injury is evident in persons infected with HIV despite effective antiretroviral treatment.     

Neuropathology of Explosive Blast Traumatic Brain Injury

During the conflicts of the Global War on Terror, which are Operation Enduring Freedom (OEF) in Afghanistan and Operation Iraqi Freedom (OIF), there have been over a quarter of a million diagnosed cases of traumatic brain injury (TBI). The vast majority are due to explosive blast. Although explosive blast TBI (bTBI) shares many clinical features with closed head TBI (cTBI) and penetrating TBI (pTBI), it has unique features, such as early cerebral edema and prolonged cerebral vasospasm. Evolving work suggests that diffuse axonal injury (DAI) seen following explosive blast exposure is different than DAI from focal impact injury. These unique features support the notion that bTBI is a separate and distinct form of TBI. This review summarizes the current state of knowledge pertaining to bTBI. Areas of discussion are: the physics of explosive blast generation, blast wave interaction with the bony calvarium and brain tissue, gross tissue pathophysiology, regional brain injury, and cellular and molecular mechanisms of explosive blast neurotrauma.     

Poor Performance Validity Predicts Clinical Characteristics and Cognitive Test Performance of OEF/OIF/OND Veterans in a Research Setting

This study examined the performance of 198 Veteran research participants deployed during Operation Enduring Freedom, Operation Iraqi Freedom, and/or Operation New Dawn (OEF/OIF/OND) on four measures of performance validity: the Medical Symptom Validity Test (MSVT), California Verbal Learning Test: Forced Choice Recognition (FCR), Reliable Digit Span (RDS), and TOVA Symptom Exaggeration Index (SEI). Failure on these performance validity tests (PVTs) ranged from 4% to 9%. The overall base rate of poor performance validity, as measured by failure of the MSVT in conjunction with an embedded PVT (FCR, RDS, SEI), was 5.6%. Regression analyses revealed that poor performance validity predicted cognitive test performance and self-reported psychological symptom severity. Furthermore, a greater prevalence of traumatic brain injury (TBI), Post-Traumatic Stress Disorder (PTSD), co-morbid TBI/PTSD, and other Axis I diagnoses, was observed among participants with poor effort. Although poor performance validity is relatively uncommon in a research setting, these findings demonstrate that clinicians should be cautious when interpreting psychological symptoms and neuropsychological test performance of Veteran participants who fail effort measures.     

Cognitive impairment and associated loss in brain white microstructure in aircrew members exposed to engine oil fumes

Cabin air in airplanes can be contaminated with engine oil contaminants. These contaminations may contain organophosphates (OPs) which are known neurotoxins to brain white matter. However, it is currently unknown if brain white matter in aircrew is affected. We investigated whether we could objectify cognitive complaints in aircrew and whether we could find a neurobiological substrate for their complaints. After medical ethical approval from the local institutional review board, informed consent was obtained from 12 aircrew (2 females, on average aged 44.4 years, 8,130 flying hours) with cognitive complaints and 11 well matched control subjects (2 females, 43.4 years, 233 flying hours). Depressive symptoms and self-reported cognitive symptoms were assessed, in addition to a neuropsychological test battery. State of the art Magnetic Resonance Imaging (MRI) techniques were administered that assess structural and functional changes, with a focus on white matter integrity. In aircrew we found significantly more self-reported cognitive complaints and depressive symptoms, and a higher number of tests scored in the impaired range compared to the control group. We observed small clusters in the brain in which white matter microstructure was affected. Also, we observed higher cerebral perfusion values in the left occipital cortex, and reduced brain activation on a functional MRI executive function task. The extent of cognitive impairment was strongly associated with white matter integrity, but extent of estimated number of flight hours was not associated with cognitive impairment nor with reductions in white matter microstructure. Defects in brain white matter microstructure and cerebral perfusion are potential neurobiological substrates for cognitive impairments and mood deficits reported in aircrew.     

Diffusion tensor imaging in mild traumatic brain injury litigation

A growing body of literature addresses the application of diffusion tensor imaging (DTI) to traumatic brain injury (TBI). Most TBIs are of mild severity, and their diagnosis and prognosis are often challenging. These challenges may be exacerbated in medicolegal contexts, where plaintiffs seek to present objective evidence that supports a clinical diagnosis of mild (m)TBI. Because DTI permits quantification of white matter integrity and because TBI frequently involves white matter injury, DTI represents a conceptually appealing method of demonstrating white matter pathology attributable to mTBI. However, alterations in white matter integrity are not specific to TBI, and their presence does not necessarily confirm a diagnosis of mTBI. Guided by rules of evidence shaped by Daubert v. Merrell Dow Pharmaceuticals, Inc., we reviewed and analyzed the literature describing DTI findings in mTBI and related neuropsychiatric disorders. Based on this review, we suggest that expert testimony regarding DTI findings will seldom be appropriate in legal proceedings focused on mTBI.