Michael N. Dretsch

Evaluation of the Military Acute Concussion Evaluation for Use in Combat Operations More Than 12 Hours After Injury

The diagnosis and management of concussion can be difficult in a combat environment, especially in the absence of loss of consciousness or post-traumatic amnesia. As no validated test exists to diagnose or grade neurocognitive impairment from a concussion, the military currently employs the Military Acute Concussion Evaluation (MACE) in Iraq. This is a two-part test, which incorporates the standardized assessment of concussion (SAC) as its objective score, although it has not been shown to be valid unless administered shortly after injury. A research team deployed to Iraq between January and April 2009 to examine the validity of several tests of neurocognitive function following a concussion, including the MACE. When administered more than 12 hours after the concussive injury, the MACE lacked sufficient sensitivity and specificity to be clinically useful.

The ANAM Lacks Utility as a Diagnostic or Screening Tool for Concussion More Than 10 Days Following Injury

Congress has mandated that the Department of Defense perform screening for concussion, or mild traumatic brain injury, on all service members redeploying from Iraq and Afghanistan. However, the retrospective diagnosis of concussion is complicated by the subjective nature of the complaints, overlap of symptoms with other conditions, and the normally rapid recovery of neurocognitive function following a concussive event. One diagnostic and screening test in current use by the Department of Defense is the Automated Neuropsychological Assessment Metrics (ANAM). A team of researchers deployed to Iraq between January and April 2009 to test the validity of the ANAM for the diagnosis of concussion in the combat environment. Performance by concussed participants on all six ANAM subtests was compared with that of controls. The ANAM appears to have no utility as an individual diagnostic or population screening tool for the detection of neurocognitive dysfunction from a single, uncomplicated concussion when administered 10 or more days following injury. Further studies are required to determine the modalities providing optimal sensitivity and specificity for use as diagnostic or screening tests beyond the first 72-hour acute postinjury period.

Red blood cell omega-3 fatty acid levels and neurocognitive performance in deployed U.S. Servicemembers

Abstract Objective To explore the cross-sectional relationships between blood eicosapentaenoic acid + docosahexaenoic acid (HSOmega-3 Index®) and sleep disorders, depression, anxiety, and neurocognitive performance in Servicemembers deployed to Iraq. Methods Servicemembers with mild-to-moderate depression by the Patient Health Questionnarie-9 from two US military camps were invited to participate in this study. A battery of validated psychosocial (Pittsburgh Sleep Quality Index, and Zung Depression, Zung Anxiety, Epworth Sleepiness, and Combat Experiences scales) and computerized neurocognitive tests were completed by each participant. Five neurocognitive domain scores were calculated – Processing Speed, Complex Attention, Reaction Time, Cognitive Flexibility (CF), and Executive Function (EF). A drop of blood was also collected on an anti-oxidant-treated filter paper card and sent for HS-Omega-3 Index® analysis. An analysis of variance contrast was used to test for linear trends between quartiles of the HS-Omega-3 Index® for both EF and CF. Results The mean HS-Omega-3 Index® was 3.5 ± 0.7% (n = 78). The HS-Omega-3 Index® was not significantly associated with scores for anxiety, depression, or sleep, whether assessed as continuous or dichotomous variables, but was directly associated with CF and EF (P < 0.02 and 0.01, respectively), especially in the 81% who reported poor sleep quality. In those with poor sleep quality (n = 63), EF and CF were higher (P = 0.005) in subjects with Omega-3 levels above versus below the mean. Conclusion Optimal neurocognitive performance is essential during deployment. Our finding that EF and CF were positively related to HS-Omega-3 Index® suggests that improving omega-3 status through an increase in omega-3 intake may improve neurocognitive performance and confer an element of resilience to poor sleep.

Brain‐derived neurotropic factor polymorphisms, traumatic stress, mild traumatic brain injury, and combat exposure contribute to postdeployment traumatic stress

In addition to experiencing traumatic events while deployed in a combat environment, there are other factors that contribute to the development of posttraumatic stress disorder (PTSD) in military service members. This study explored the contribution of genetics, childhood environment, prior trauma, psychological, cognitive, and deployment factors to the development of traumatic stress following deployment.

Compromised hippocampus-striatum pathway as a potential imaging biomarker of mild-traumatic brain injury and posttraumatic stress disorder

Military service members risk acquiring posttraumatic stress disorder (PTSD) and mild‐traumatic brain injury (mTBI), with high comorbidity. Owing to overlapping symptomatology in chronic mTBI or postconcussion syndrome (PCS) and PTSD, it is difficult to assess the etiology of a patients condition without objective measures. Using resting‐state functional MRI in a novel framework, we tested the hypothesis that their neural signatures are characterized by functionally hyperconnected brain regions which are less variable over time. Additionally, we predicted that such connectivities possessed the highest ability in predicting the diagnostic membership of a novel subject (top‐predictors) in addition to being statistically significant.

Multiple Past Concussions Are Associated with Ongoing Post-Concussive Symptoms but Not Cognitive Impairment in Active-Duty Army Soldiers.

The extent to which multiple past concussions are associated with lingering symptoms or mental health problems in military service members is not well understood. The purpose of this study was to examine the association between lifetime concussion history, cognitive functioning, general health, and psychological health in a large sample of fit-for-duty U.S. Army soldiers preparing for deployment. Data on 458 active-duty soldiers were collected and analyzed. A computerized cognitive screening battery (CNS-Vital Signs(®)) was used to assess complex attention (CA), reaction time (RT), processing speed (PS), cognitive flexibility (CF), and memory. Health questionnaires included the Neurobehavioral Symptom Inventory (NSI), PTSD Checklist-Military Version (PCL-M), Zung Depression and Anxiety Scales (ZDS; ZAS), Perceived Stress Scale (PSS), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and the Alcohol Use and Dependency Identification Test (AUDIT). Soldiers with a history of multiple concussions (i.e., three or more concussions) had significantly greater post-concussive symptom scores compared with those with zero (d=1.83, large effect), one (d=0.64, medium effect), and two (d=0.64, medium effect) prior concussions. Although the group with three or more concussions also reported more traumatic stress symptoms, the results revealed that traumatic stress was a mediator between concussions and post-concussive symptom severity. There were no significant differences on neurocognitive testing between the number of concussions. These results add to the accumulating evidence suggesting that most individuals recover from one or two prior concussions, but there is a greater risk for ongoing symptoms if one exceeds this number of injuries.

Mood symptoms contribute to working memory decrement in active‐duty soldiers being treated for posttraumatic stress disorder

A significant proportion of military veterans of operations in Afghanistan and Iraq have been diagnosed with posttraumatic stress disorder (PTSD). Growing evidence suggests that neuropsychological deficits are a symptom of PTSD. The current study investigated neurocognitive functioning among soldiers diagnosed with PTSD. Specifically, active‐duty soldiers with and without a diagnosis of PTSD were assessed for performance on tests of attention and working memory. In addition, factors such as combat experience, depression, anxiety, PTSD symptom severity, and alcohol consumption were explored as possible mediators of group differences in neurocognitive functioning. Twenty‐three active‐duty soldiers diagnosed with PTSD were matched with 23 healthy Soldier controls; all were administered the Attention Network Task (ANT), Backward Digit Span (BDS) task, Beck Depression Inventory, Beck Anxiety Inventory, PTSD Checklist—Military Version, Combat Exposure Scale, and Modified Drinking Behavior Questionnaire. Soldiers diagnosed with PTSD performed significantly worse on the working memory task (BDS) than healthy controls, and reported greater levels of PTSD symptoms, combat exposure, depression, and anxiety. However, after controlling for depression and anxiety symptoms, the relationship between PTSD and working memory was no longer present. The results indicate that PTSD is accompanied by deficits in working memory, which appear to be partially attributed to anxiety and depression symptoms.

Systematic Review of Genetic Risk Factors for Sustaining a Mild Traumatic Brain Injury.

This systematic review examined the association between genetics and risk for sustaining a traumatic brain injury. We retrieved articles published in English from 1980 to July 2016 obtained from the online databases PubMed, PsycINFO®, MEDLINE®, Embase, and Web of Science. In total 5903 articles were identified, 77 underwent full-text screening, and 6 were included in this review. Five studies examined the risk of concussion associated with apolipoprotein E alleles (APOE-ɛ2, ɛ3,ɛ4), and polymorphisms of the APOE promoter (rs405509), brain derived neurotrophic factor (BDNF, rs6265), and dopamine receptor D2 (DRD2, rs1800497) were each considered in two studies. Microtubule associated protein tau (TAU exon 6 polymorphisms His47Tyr [rs2258689] and Ser53Pro [rs10445337]), and neurofilament heavy (NEHF, rs165602) genotypic variants, were the focus of single studies. No study showed an increased risk associated solely with the presence of the APOE-ɛ4 allele, nor were there any significant findings for the NEFH, TAU, or DRD2 genotypic variants. Two studies examined the APOE promoter -219G/T polymorphism in athletes, and both found an association with concussion. Both BDNF studies also found a significant association with concussion incidence; United States soldiers with the Met/Met genotype were more likely to report a history of concussion prior to deployment and to sustain a concussion during deployment. We conclude that the APOE promoter -219G/T polymorphism and the BDNF Met/Met genotype might confer risk for sustaining a TBI. Based on research to date, the APOE-ɛ4 allele does not appear to influence risk. More research is needed to determine if these findings replicate.

Imaging chronic traumatic brain injury as a risk factor for neurodegeneration

Population‐based studies have supported the hypothesis that a positive history of traumatic brain injury (TBI) is associated with an increased incidence of neurological disease and psychiatric comorbidities, including chronic traumatic encephalopathy, Alzheimers disease, Parkinsons disease, and amyotrophic lateral sclerosis. These epidemiologic studies, however, do not offer a clear definition of that risk, and leave unanswered the bounding criteria for greater lifetime risk of neurodegeneration. Key factors that likely mediate the degree of risk of neurodegeneration include genetic factors, significant premorbid and comorbid medical history (e.g. depression, multiple head injuries and repetitive subconcussive impact to the brain, occupational risk, age at injury, and severity of brain injury). However, given the often‐described concerns in self‐report accuracy as it relates to history of multiple TBIs, low frequency of patient presentation to a physician in the case of mild brain injuries, and challenges with creating clear distinctions between injury severities, disentangling the true risk for neurodegeneration based solely on population‐based studies will likely remain elusive. Given this reality, multiple modalities and approaches must be combined to characterize who are at risk so that appropriate interventions to alter progression of neurodegeneration can be evaluated. This article presents data from a study that highlights uses of neuroimaging and areas of needed research in the link between TBI and neurodegenerative disease.

Hemodynamic variability in soldiers with trauma: Implications for functional MRI connectivity studies

Functional MRI (fMRI) is an indirect measure of neural activity as a result of the convolution of the hemodynamic response function (HRF) and latent (unmeasured) neural activity. Recent studies have shown variability of HRF across brain regions (intra-subject spatial variability) and between subjects (inter-subject variability). Ignoring this HRF variability during data analysis could impair the reliability of such fMRI results. Using whole-brain resting-state fMRI (rs-fMRI), we employed hemodynamic deconvolution to estimate voxel-wise HRF. Studying the impact of mental disorders on HRF variability, we identified HRF aberrations in soldiers (N = 87) with posttraumatic stress disorder (PTSD) and mild-traumatic brain injury (mTBI) compared to combat controls. Certain subcortical and default-mode regions were found to have significant HRF aberrations in the clinical groups. These brain regions have been previously associated with neurochemical alterations in PTSD, which are known to impact the shape of the HRF. We followed-up these findings with seed-based functional connectivity (FC) analysis using regions-of-interest (ROIs) whose HRFs differed between the groups. We found that part of the connectivity group differences reported from traditional FC analysis (no deconvolution) were attributable to HRF variability. These findings raise the question of the degree of reliability of findings from conventional rs-fMRI studies (especially in psychiatric populations like PTSD and mTBI), which are corrupted by HRF variability. We also report and discus, for the first time, voxel-level HRF alterations in PTSD and mTBI. To the best of our knowledge, this is the first study to report evidence for the impact of HRF variability on connectivity group differences. Our work has implications for rs-fMRI connectivity studies. We encourage researchers to incorporate hemodynamic deconvolution during pre-processing to minimize the impact of HRF variability.