Neuromotor dysfunction after a concussion is common, but balance tests used to assess neuromotor dysfunction are typically subjective. Current objective balance tests are either cost- or ...space-prohibitive, or utilize a static balance protocol, which may mask neuromotor dysfunction due to the simplicity of the task. To address this gap, our team developed an Android-based smartphone app (portable and cost-effective) that uses the sensors in the device (objective) to record movement profiles during a stepping-in-place task (dynamic movement). The purpose of this study was to examine the extent to which our custom smartphone app and protocol could discriminate neuromotor behavior between concussed and non-concussed participants. Data were collected at two university laboratories and two military sites. Participants included civilians and Service Members (N = 216) with and without a clinically diagnosed concussion. Kinematic and variability metrics were derived from a thigh angle time series while the participants completed a series of stepping-in-place tasks in three conditions: eyes open, eyes closed, and head shake. We observed that the standard deviation of the mean maximum angular velocity of the thigh was higher in the participants with a concussion history in the eyes closed and head shake conditions of the stepping-in-place task. Consistent with the optimal movement variability hypothesis, we showed that increased movement variability occurs in participants with a concussion history, for which our smartphone app and protocol were sensitive enough to capture.
The Department of Defense (DOD) has recently prioritized the investigation of the acute and chronic adverse brain health and performance effects of low-level blast (LLB) generated by the use of ...weapons systems. While acute exposure can be quantified by sensor technology, career exposure has no widely accepted and validated measure for characterization. Currently, distinct research groups are developing and validating four promising measures to estimate career blast exposure history: the Salisbury Blast Interview, Blast Exposure Threshold Survey, Blast Ordnance and Occupational Exposure Measure, and the Blast Frequency and Symptom Severity. Each measure offers an assessment of blast history that is uniquely beneficial to addressing specific research questions. However, use of divergent strategies is not efficient to accelerate the field's understanding of the impact of career exposure and Service-connected health outcomes. As a DOD-wide solution, collaboration across these groups is required to develop a tool(s) that can be standardized across research studies and, ultimately, pared down to be implemented in clinical settings. Here, we overview the current four measures and provide a perspective on the way forward for optimization and/or combination in support of this solution.
This study examines the impact of lifetime blast exposure on white matter integrity in service members and veterans (SMVs). Participants were 227 SMVs, including those with a history of mild ...traumatic brain injury (mTBI;
= 124), orthopedic injury controls (
= 58), and non-injured controls (
= 45), prospectively enrolled in a Defense and Veterans Brain Injury Center (DVBIC)/Traumatic Brain Injury Center of Excellence (TBICoE) study. Participants were divided into three groups based on number of self-reported lifetime blast exposures: none (
= 53); low (i.e., 1-9 blasts;
= 81); and high (i.e., ≥10 blasts;
= 93). All participants underwent diffusion tensor imaging (DTI) at least 11 months post-injury. Tract-of-interest (TOI) analysis was applied to investigate fractional anisotropy and mean, radial, and axial diffusivity (AD) in left and right total cerebral white matter as well as 24 tracts. Benjamini-Hochberg false discovery rate (FDR) correction was used. Regressions investigating blast exposure and mTBI on white matter integrity, controlling for age, revealed that the presence of mTBI history was associated with lower AD in the bilateral superior longitudinal fasciculus and arcuate fasciculus and left cingulum (βs = -0.255 to -0.174;
s < 0.01); however, when non-injured controls were removed from the sample (but orthopedic injury controls remained), these relationships were attenuated and did not survive FDR correction. Regression models were rerun with modified post-traumatic stress disorder (PTSD) diagnosis added as a predictor. After FDR correction, PTSD was not significantly associated with white matter integrity in any of the models. Overall, there was no relationship between white matter integrity and self-reported lifetime blast exposure or PTSD.
The purpose of this study was to identify factors that are predictive of, or associated with, high endorsement of postconcussion and posttraumatic stress symptoms following military-related traumatic ...brain injury (TBI). Participants were 1,600 U.S. service members (age: M = 27.1, SD = 7.1; 95.4% male) who had sustained a mild-to-moderate TBI and who had been evaluated by the Defense and Veterans Brain Injury Center at one of six military medical centers. Twenty-two factors were examined that included demographic, injury circumstances/severity, treatment/evaluation, and psychological/physical variables. Four factors were statistically and meaningfully associated with clinically elevated postconcussion symptoms: (i) low bodily injury severity, (ii) posttraumatic stress, (iii) depression, and (iv) military operation where wounded (p < .001, 43.2% variance). The combination of depression and posttraumatic stress symptoms accounted for the vast majority of unique variance (41.5%) and were strongly associated with, and predictive of, clinically elevated postconcussion symptoms range: odds ratios (OR) = 4.24-7.75; relative risk (RR) = 2.28-2.51. Five factors were statistically and meaningfully associated with clinically elevated posttraumatic stress symptoms: (i) low bodily injury severity, (ii) depression, (iii) a longer time from injury to evaluation, (iv) military operation where wounded, and (v) current auditory deficits (p < .001; 65.6% variance accounted for). Depression alone accounted for the vast majority of unique variance (60.0%) and was strongly associated with, and predictive of, clinically elevated posttraumatic stress symptoms (OR = 38.78; RR = 4.63). There was a very clear, strong, and clinically meaningful association between depression, posttraumatic stress, and postconcussion symptoms in this sample. Brain injury severity, however, was not associated with symptom reporting following TBI.
Comorbid mental illness may negatively impact recovery from concussion. This study evaluated whether the level of symptom clusters at clinic intake contribute to poor mental health recovery in ...concussed patients during treatment, which may in turn serve as a target intervention.
The objective of this study is to examine the association between the level of initial symptoms and mental health symptoms among service members with concussion.
Data were obtained from 483 active duty service members treated in interdisciplinary treatment programs for traumatic brain injury, all of which were concussions. Pre-treatment symptom clusters included self-reported hyperarousal, dissociation/depression, cognitive dysfunction/headache and neurological symptoms. The outcomes, clinically-relevant decreases in depressive symptoms (assessed by the 8-item Patient Health Questionnaire, PHQ-8) and PTSD symptoms (assessed by the PTSD Checklist for DSM-5, PCL-5), were defined as a decrease in PHQ-8 > 5 and PCL-5 > 7, respectively. Poisson regression with robust error variance was used to evaluate the relationship between the level of each symptom cluster and clinically-relevant decrease in outcomes.
Participants with higher (vs. lower) levels of pre-treatment hyperarousal and dissociation/depression symptom cluster were less likely to improve in depressive and PTSD symptoms during treatment. The level of cognitive/headache and neurological symptom clusters were not significantly associated with any symptom changes.
These findings support the need for individualized treatment for symptoms identified and treated after determining concussion history, with particular attention to high levels of hyperarousal and dissociation/depression prior to treatment.
Concurrent posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) is common in military populations. The purpose of this study was to examine long‐term neurobehavioral outcomes in ...service members and veterans (SMVs) with versus without PTSD symptoms following TBI of all severities. Participants were 536 SMVs prospectively enrolled from three military medical treatment facilities who were recruited into three experimental groups: TBI, injured controls (IC), and noninjured controls (NIC). Participants completed the PTSD Checklist, Neurobehavioral Symptom Inventory, and the TBI–Quality of Life (TBI‐QOL) and were divided into six subgroups based on the three experimental categories, two PTSD categories (i.e., present vs. absent), and two broad TBI severity categories (unMTBI, which included uncomplicated mild TBI; and smcTBI, which included severe TBI, moderate TBI, and complicated mild TBI): (a) NIC/PTSD‐absent, (b) IC/PTSD‐absent, (c) unMTBI/PTSD‐absent, (d) unMTBI/PTSD‐present, (e) smcTBI/PTSD‐absent, and (f) smcTBI/PTSD‐present. There were significant main effects across the six groups for all TBI‐QOL measures, ps < .001. Select pairwise comparisons revealed significantly lower scores, p < .001, on all TBI‐QOL measures in the PTSD‐present groups when compared to the PTSD‐absent groups within the same TBI severity classification, ds = 0.90–2.11. In contrast, when controlling for PTSD, there were no significant differences among the TBI severity groups for any TBI‐QOL measures. These results provide support for the strong influence of PTSD but not TBI severity on neurobehavioral outcomes following TBI. Concurrent PTSD and TBI of all severities should be considered a risk factor for poor long‐term neurobehavioral outcomes that require ongoing monitoring.
The majority of patients with autosomal dominant optic atrophy (DOA) harbour pathogenic OPA1 mutations. Although DOA is characterised by the preferential loss of retinal ganglion cells (RGCs), about ...20% of patients with OPA1 mutations will develop a more severe disease variant (DOA+), with additional neuromuscular features. In this prospective, observational case series, optical coherence tomography (OCT) was used to define the pattern of retinal nerve fibre layer (RNFL) loss in patients with both the pure and syndromal forms of DOA.
Forty patients with a molecular diagnosis of DOA due to OPA1 mutations were prospectively recruited from our neuro-ophthalmology clinic: 26 patients with isolated optic atrophy and 14 patients manifesting DOA+ features. Peripapillary RNFL thickness was measured with the Fast RNFL (3.4) acquisition protocol on a Stratus OCT.
There was a statistically significant reduction in average RNFL thickness in the OPA1 group compared with normal controls (P<0.0001). The percentage decrease was greatest in the temporal quadrant (59.0%), followed by the inferior (49.6%), superior (41.8%), and nasal (25.9%) quadrants. Patients with DOA+ features had worse visual outcomes compared with patients with pure DOA. Except in the temporal quadrant, RNFL measurements were significantly thinner for the DOA+ group. There was an inverse correlation between average RNFL thickness and logarithm of the minimum angle of resolution (LogMAR) visual acuity (P<0.0001).
RGC loss in DOA is characterised by severe involvement of the temporal papillomacular bundle, with relative sparing of the nasal fibres. RNFL thinning is more pronounced in patients with DOA+ phenotypes.
These studies examined the ability of the dopamine D1-like agonist SKF 81297 and D1-like antagonist SCH 23390 in the medial prefrontal cortex to alter the reinstatement of cocaine-induced conditioned ...place preference behavior. Male Sprague–Dawley rats were fitted with bilateral cannulae over the medial prefrontal cortex and subsequently trained in a conditioned place preference task. Animals were trained in this task using four pairings of cocaine (12 mg/kg, i.p.). Conditioned place preference was demonstrated in all animals, and this behavior was then extinguished over a 5–10-day period before testing for reinstatement. Just prior to reinstatement by immobilization stress or a cocaine priming injection (5 mg/kg, i.p.), a microinjection of the D1-like receptor antagonist SCH 23390 (0.01, 0.1 or 1.0 μg/side), or the D1-like receptor agonist SKF 81297 (0.1, 0.3 or 1.0 μg/side) was given into the medial prefrontal cortex. SCH 23390 blocked both stress- and cocaine-induced reinstatement of conditioned place preference after the two higher doses were administered into the medial prefrontal cortex. The highest dose of SKF 81297 (1.0 μg/side) prevented immobilization stress- but not cocaine-induced reinstatement. The highest dose of these drugs given in the absence of stress or cocaine did not produce reinstatement. The results indicate that immobilization stress given within the place-preference chamber is capable of producing reinstatement of cocaine-seeking behavior. The microinjection studies suggest that D1-like receptor antagonism within the prefrontal cortex is sufficient to block reinstatement by stress and cocaine. Furthermore, the results from D1-like receptor activation in the medial prefrontal cortex point to utilization of different neural pathways for stress- and cocaine-induced reinstatement.
The purpose of this study was to investigate the relationship between race/ethnicity and post-concussive mental health (i.e., depressive, post-traumatic stress disorder PTSD) and neurobehavioral ...symptoms among service members, and whether this association differed by education level.
The study sample consisted of 524 patients from a multidisciplinary US military outpatient treatment facility for post-concussive symptoms. Poisson regression with robust error variance was utilized to investigate outcome (i.e., clinically-elevated depressive Patient Health Questionnaire-8 ≥15, PTSD PTSD Checklist, DSM 5 ≥38 and neurobehavioral Neurobehavioral Symptom Inventory >75th percentile symptoms at admission and last follow-up in this cohort study. Modification by education level (low no college degree vs. high associate's degree or higher) was additionally evaluated.
The relationship between race/ethnicity and mental health/neurobehavioral symptoms varied by education level (p-interaction: depressive symptoms = 0.002, PTSD symptoms = 0.035, neurobehavioral symptoms = 0.040). Specifically, non-Whites were at a significantly higher prevalence for clinically-elevated depressive symptoms post-treatment than Whites, but only among those with higher education level (PR = 2.22, CI = 1.37–3.59). A similar trend was demonstrated for PTSD and neurobehavioral symptoms.
Military healthcare may need to increase depression-focused treatment options that are acceptable for racial/ethnic minority patients, particularly those with higher education, while they are recovering from comorbid traumatic brain injury.
•Race differences in mental health recovery post-TBI are found among service members•The relationship between race and mental health symptoms varied by education level•Highly-educated minorities had higher levels of depressive symptoms posttreatment•Neurobehavioral symptoms posttreatment increased more in highly-educated minorities•Among neurobehavioral symptoms, affective symptoms were most affected by race
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