Efficacy of an Interdisciplinary Intensive Outpatient Program in Treating Combat-Related Traumatic Brain Injury and Psychological Health Conditions.

Background: Since 2000, over 413,000 US service members (SM) experienced at least one traumatic brain injury (TBI), and 40% of those with in-theater TBIs later screened positive for comorbid psychological health (PH) conditions, including post-traumatic stress disorder (PTSD), depression, and anxiety. Many SMs with these persistent symptoms fail to achieve a recovery that results in a desirable quality of life or return to full duty. Limited information exists though to guide treatment for SMs with a history of mild TBI (mTBI) and comorbid PH conditions. This report presents the methods and outcomes of an interdisciplinary intensive outpatient program (IOP) in the treatment of SMs with combat-related mTBI and PH comorbidities. The IOP combines conventional rehabilitation therapies and integrative medicine techniques with the goal of reducing morbidity in multiple neurological and behavioral health domains and enhancing military readiness. Methods: SMs (n = 1,456) with residual symptoms from mTBI and comorbid PH conditions were treated in a 4-week IOP at the National Intrepid Center of Excellence (NICoE) at Walter Reed National Military Medical Center (WRNMMC). The IOP uses an interdisciplinary, holistic, and patient-centric rehabilitative care model. Interdisciplinary teams provide a diagnostic workup of neurological, psychiatric, and existential injuries, and from these assessments, individualized care plans are developed. Treatment response was assessed using the Neurobehavioral Symptom Inventory (NSI), PTSD Checklist-Military Version (PCL-M), Satisfaction With Life Scale (SWLS), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Epworth Sleepiness Scale (ESS), and Headache Impact Test-6 (HIT-6) and administered at admission, discharge, and at 1, 3, and 6 months post-discharge. Findings: Following treatment in the IOP, the symptomatic patients had statistically significant and clinically meaningful improvements across all outcome measures. The largest effect size was seen with GAD-7 (r = 0.59), followed by PHQ-8 (r = 0.56), NSI (r = 0.55), PCL-M (r = 0.52), ESS (r = 0.50), SWLS (r = 0.49), and HIT-6 (r = 0.42). In cross-sectional follow ups, the significant improvements were sustained at 1, 3, and 6 months post-discharge. Interpretation: This report demonstrates that an interdisciplinary IOP achieves significant and sustainable symptom recovery in SMs with combat-related mTBI and comorbid PH conditions and supports the further study of this model of care in complex medical conditions.

Feasibility of using normobaric hypoxic stress in mTBI research.

Studies of mild traumatic brain injury (mTBI) recovery generally assess patients in unstressed conditions that permit compensation for impairments through increased effort expenditure. This possibility may explain why a subgroup of individuals report persistent mTBI symptoms yet perform normally on objective assessment. Accordingly, the development and utilization of stress paradigms may be effective for enhancing the sensitivity of mTBI assessment. Previous studies, discussed here, indirectly but plausibly support the use of normobaric hypoxia as a stressor in uncovering latent mTBI symptoms due to the overlapping symptomatology induced by both normobaric hypoxia and mTBI. Limited studies by our group and others further support this plausibility through proof-of-concept demonstrations that hypoxia reversibly induces disproportionately severe impairments of oculomotor, pupillometric, cognitive and autonomic function in mTBI individuals.

Evaluating the clinical utility of the Validity-10 for detecting amplified symptom reporting for patients with mild traumatic brain injury and comorbid psychological health conditions.

The objective of this study was to compare the Validity-10 scale with the PAI Negative Impression Management Scale (PAI-NIM) for detecting exaggerated symptom reporting in active-duty military service members (SMs) admitted with unremitting mild TBI symptoms and comorbid psychological health conditions (mTBI/PH). Data were analyzed from 254 SMs who completed the Neurobehavioral Symptom Inventory (NSI) and Personality Assessment Inventory (PAI) as a part of a larger battery of self-report symptom scales upon admission to the intensive-outpatient TBI treatment program at a military medical center. Symptom exaggeration was operationalized using the PAI Negative Impression Management Scale (PAI-NIM). A PAI-NIM score of ≥73 was categorized as positive for symptom exaggeration (SVTpos), while a lower score was categorized as negative for symptom exaggeration (SVTneg). SMs in the SVTpos group (n = 34) had significantly higher scores (p ≤ .004) on the PAI clinical scales as well as on the NSI total score (range: d = 0.59-1.91) compared to those who were SVTneg (n = 220). The optimal cut-score for the NSI Val-10 scale to identify possible symptom exaggeration was ≥26 (sensitivity = .29, specificity = .95, PPP = .74, NPP = .71). In patients suffering from mTBI/PH, the Validity-10 requires a higher cut-score than previously reported to be useful as a metric of exaggerated symptom reporting.

A History of Mild Traumatic Brain Injury Affects Peripheral Pulse Oximetry during Normobaric Hypoxia.

INTRODUCTION: Physiological and emotional stressors increase symptoms of concussion in recently injured individuals and both forms of stress-induced symptoms in people recovering from mild traumatic brain injury (mTBI), but who are asymptomatic when not stressed or are at rest. METHODS: Healthy asymptomatic adults (25.0 ± 5.1 years) with a history of mTBI (n = 36) and matched healthy controls (HC) (n = 36) with no mTBI history were exposed to three levels of normobaric hypoxic stress generated with the Reduced Oxygen Breathing Device (ROBD) (Environics, Inc., Tollande, CT, USA), which reduced the percent O2 by mixing sea level air with nitrogen. The ROBD reduced the percent O2 in the breathable air from the normal 21% to 15.5% O2, 14% O2, and 13% O2. Under these conditions: (a) a standard pulse oximeter recorded peripheral oxygen saturation (SpO2) and pulse rate (beats per minute) and (b) the Functional Impairment Tester (FIT) (PMI, Inc., Rockville, MD, USA) recorded saccadic velocity and pupillary response dynamics to a brief light flash. RESULTS: For all three hypoxic stress conditions, the mTBI group had significantly higher SpO2 during the final minute of exposure than did the controls [F(2.17,151.8) = 5.29, p < 0.001, η2 = 0.852] and the rate of SpO2 change over time was significantly shallower for the mTBI than for the controls [F(2.3,161.3) = 2.863, p < 0.001, η2 = 0.569], Greenhouse-Geisser corrected. Overall, mTBI had lower pulse rate but the difference was only significant for the 14% O2 condition. FIT oculomotor measures were not sensitive to group differences. When exposed to mild or moderate normobaric hypoxic stress (15% O2): (1) SpO2 differences emerged between the mTBI and matched HC groups, (2) heart rate trended lower in the mTBI group, and (3) FIT measures were not sensitive to group differences. CONCLUSION: A relatively minor hypoxic challenge can reveal measurable differences in SpO2 and heart rate in otherwise asymptomatic individuals with a history of mTBI.

Performance on the Defense Automated Neurobehavioral Assessment across controlled environmental conditions.

Neurocognitive assessment tools (NCAT) are commonly used to screen for changes in cognitive functioning following a mild traumatic brain injury and to assist with a return to duty decision. As such, it is critical to determine if performance on the Defense Automated Neurobehavioral Assessment (DANA) is adversely affected by operationally-relevant field environments. Differences in DANA performance between a thermoneutral environment and three simulated operationally-relevant field environments across the thermal stress continuum were calculated for 16 healthy U.S. Navy service members. Practice effects associated with brief test-retest intervals were calculated within each environmental condition. There were no significant differences between the simulated environmental conditions suggesting that performance on the DANA Brief is not impacted by thermal stress. Additionally, there were no significant differences in performance within each simulated environmental condition associated with repeated administrations.

Three Scoring Approaches to the Neurobehavioral Symptom Inventory for Measuring Clinical Change in Service Members Receiving Intensive Treatment for Combat-Related mTBI.

OBJECTIVE: To examine the use of the Neurobehavioral Symptom Inventory to measure clinical changes over time in a population of US service members undergoing treatment of mild traumatic brain injury and comorbid psychological health conditions. SETTING: A 4-week, 8-hour per day, intensive, outpatient, interdisciplinary, comprehensive treatment program at the National Intrepid Center of Excellence in Bethesda, Maryland. PARTICIPANTS: Three hundred fourteen active-duty service members being treated for combat-related comorbid mild traumatic brain injury and psychological health conditions. DESIGN: Repeated-measures, retrospective analysis of a single-group using a pretest-posttest treatment design. MAIN MEASURES: Three Neurobehavioral Symptom Inventory scoring methods: (1) a total summated score, (2) the 3-factor method, and (3) the 4-factor method (with and without orphan items). RESULTS: All 3 scoring methods yielded statistically significant within-subject changes between admission and discharge. The evaluation of effect sizes indicated that the 3 different Neurobehavioral Symptom Inventory scoring methods were comparable. CONCLUSION: Findings indicate that the different scoring methods all have potential for assessing clinical changes in symptoms for groups of patients undergoing treatment, with no clear advantage with any one method.

The impact of multiple concussions on emotional distress, post-concussive symptoms, and neurocognitive functioning in active duty United States marines independent of combat exposure or emotional distress.

Controversy exists as to whether the lingering effects of concussion on emotional, physical, and cognitive symptoms is because of the effects of brain trauma or purely to emotional factors such as post-traumatic stress disorder or depression. This study examines the independent effects of concussion on persistent symptoms. The Defense Automated Neurobehavioral Assessment, a clinical decision support tool, was used to assess neurobehavioral functioning in 646 United States Marines, all of whom were fit for duty. Marines were assessed for concussion history, post-concussive symptoms, emotional distress, neurocognitive functioning, and deployment history. Results showed that a recent concussion or ever having experienced a concussion was associated with an increase in emotional distress, but not with persistent post-concussive symptoms (PPCS) or neurocognitive functioning. Having had multiple lifetime concussions, however, was associated with greater emotional distress, PPCS, and reduced neurocognitive functioning that needs attention and rapid discrimination, but not for memory-based tasks. These results are independent of deployment history, combat exposure, and symptoms of post-traumatic stress disorder and depression. Results supported earlier findings that a previous concussion is not generally associated with post-concussive symptoms independent of covariates. In contrast with other studies that failed to find a unique contribution for concussion to PPCS, however, evidence of recent and multiple concussion was seen across a range of emotional distress, post-concussive symptoms, and neurocognitive functioning in this study population. Results are discussed in terms of implications for assessing concussion on return from combat.

AltitudeOmics: Decreased reaction time after high altitude cognitive testing is a sensitive metric of hypoxic impairment.

Humans experiencing hypoxic conditions exhibit multiple signs of cognitive impairment, and high altitude expeditions may be undermined by abrupt degradation in mental performance. Therefore, the development of psychometric tools to quickly and accurately assess cognitive impairment is of great importance in aiding medical decision-making in the field, particularly in situations where symptoms may not be readily recognized. The present study used the Defense Automated Neurobehavioral Assessment (DANA), a ruggedized and portable neurocognitive assessment tool, to examine cognitive function in healthy human volunteers at sea level, immediately after ascending to an elevation over 5000 m, and following 16 days of acclimatization to this high altitude. The DANA battery begins with a simple reaction time test (SRT1) which is followed by a 20-min series of complex cognitive tests and ends with a second test of simple reaction time (SRT2). Tabulating the performance scores from these two tests allows the calculation of an SRT change score (dSRT=SRT1-SRT2) that reflects the potential effect of mental effort spent during the 20-min testing session. We found that dSRT, but not direct SRT in comparison to sea-level baseline performance, is highly sensitive to acute altitude-related performance deficits and the remission of impairment following successful acclimatization. Our results suggest that dSRT is a potentially useful analytical method to enhance the sensitivity of neurocognitive assessment.

Defense Automated Neurobehavioral Assessment (DANA)-psychometric properties of a new field-deployable neurocognitive assessment tool.

The Defense Automated Neurobehavioral Assessment (DANA) is a new neurocognitive assessment tool that includes a library of standardized cognitive and psychological assessments, with three versions that range from a brief 5-minute screen to a 45-minute complete assessment. DANA is written using the Android open-source operating system and is suitable for multiple mobile platforms. This article presents testing of DANA by 224 active duty U.S. service members in five operationally relevant environments (desert, jungle, mountain, arctic, and shipboard). DANA was found to be a reliable instrument and compared favorably to other computer-based neurocognitive assessments. Implications for using DANA in far-forward military settings are discussed.

Uncovering latent deficits due to mild traumatic brain injury by using normobaric hypoxia stress.

Memory deficits and other cognitive symptoms frequently associated with mTBI are commonly thought to resolve within 7-10 days. This generalization is based principally on observations made in individuals who are in the unstressed environmental conditions typical of a clinic and so does not consider the impact of physiologic, environmental, or psychological stress. Normobaric hypoxic stress can be generated with normal mean sea level (MSL) air, which is about 21% oxygen (O2) and 78% nitrogen (N), by reducing the percentage of O2 and increasing the percentage of N so that the resultant mixed-gas has a partial pressure of O2 approximating that of specified altitudes. This technique was used to generate normobaric hypoxic equivalents of 8,000, 12,000, and 14,000 feet above MSL in a group of 36 volunteers with a mTBI history and an equal number of controls matched on the basis of age, gender, tobacco smoking consumption, weight, height, and body mass index. Short-term visual memory was tested using the Matching to Sample (M2S) subtest of the BrainCheckers analog of the Automated Neuropsychological Assessment Metrics. Although there were no significant differences in M2S performance between the two groups of subjects at MSL, with increased altitude, the mTBI group performance was significantly worse than that of the control group. When the subjects were returned to MSL, the difference disappeared. This finding suggests that the "hypoxic challenge" paradigm developed here has potential clinical utility for assessing the effects of mTBI in individuals who appear asymptomatic under normal conditions.

Reference data from the automated Neuropsychological Assessment Metrics for use in traumatic brain injury in an active duty military sample.

The current study examined the performance of active duty soldiers on the Automated Neuropsychological Assessment Metrics (ANAM) traumatic brain injury test battery, to expand the reference data for use in military settings. The effects of age and gender on cognitive performance also were explored. The ANAM traumatic brain injury battery, consisting of six performance tests and two subjective scales, was administered to a sample of healthy active duty soldiers (N = 5,247) as part of a concussion surveillance program. Performance means and SDs, stratified according to age and gender, are reported as reference data. In addition, the impact of age and gender on performance measures was analyzed. Because ANAM is rapidly being adopted for use in many military medical and research applications, the establishment of these reference values is invaluable, particularly for assisting with rapid accurate evaluation and treatment in clinical settings.

Automated neuropsychiatric measurements of information processing in fibromyalgia.

Aberrant central neurological functioning is believed to contribute to the abnormal sensations of fibromyalgia (FM). Most patients with FM complain of diminished cognitive function. This study sought to compare objective cognitive function between FM and healthy controls at baseline and to determine if symptomatic improvement was related to objective cognitive improvement. Automated neuropsychological assessment metrics (ANAM) was used to quantify neurocognitive function. Performance on ANAM was compared between subjects with FM, musculoskeletal pain, and pain-free controls. Ten separate FM subjects completed an 8-week comprehensive treatment program. Serial testing with ANAM and the Fibromyalgia Impact Questionnaire was conducted. Statistical analysis was performed using repeated Wilcoxon signed rank tests. No differences were noted on ANAM between controls and subjects with pain disorders. A clinical improvement (FIQ median change 33.9, P = 0.002) was noted with treatment without concomitant change in ANAM scores. No cognitive impairment in FM was demonstrated using ANAM.

Review of sports-related concussion: Potential for application in military settings.

This article reviews current issues and practices in the assessment and clinical management of sports-related concussion. An estimated 300,000 sports-related concussions occur annually in the United States. Much of what has been learned about concussion in the sports arena can be applied to the diagnosis and management of concussion in military settings. Current military guidelines for assessing and managing concussion in war zones incorporate information and methods developed through sports-concussion research. We discuss the incidence, definition, and diagnosis of concussion; concussion grading scales; sideline evaluation tools; neuropsychological assessment; return-to-action criteria; and complications of concussion.

Hemodynamic and cognitive effects of lofexidine and methadone coadministration: a pilot study.

STUDY OBJECTIVE: To determine the hemodynamic and cognitive effects of lofexidine and methadone coadministration. DESIGN: Prospective, double-blind study. SETTING: Outpatient drug treatment research clinic. SUBJECTS: Fourteen participants (aged 18-45 yrs) with physical dependence on opioids. INTERVENTION: Subjects were stabilized on methadone maintenance therapy, starting with 30 mg/day and increasing by 10-mg/day increments, based on each subject's tolerability to achieve a target dose of 80 mg/day. After 3 weeks of methadone stabilization, lofexidine 0.4 mg/day or matching placebo were coadministered with methadone, in doses escalating by 0.2-mg/week increments, to achieve a target dose of 1.6 mg/day over the next 8 weeks. MEASUREMENTS AND MAIN RESULTS: Acute orthostatic vital signs and neuropsychological effects of lofexidine and methadone coadministration were monitored for 5 hours after the dose on the first day of each new lofexidine dose. Orthostatic vital signs and adverse events were assessed daily thereafter to determine the effects of repeated doses. Lofexidine significantly decreased sitting systolic and diastolic blood pressure (p=0.045 and p=0.033, respectively) compared with placebo (i.e., methadone alone). With lofexidine 0.4 mg/day, mean decreases in systolic and diastolic blood pressure were 27 +/- 17 and 15 +/- 16 mm Hg, respectively. No significant association was noted between changes in orthostatic vital signs and lofexidine dose. Decreased cognitive efficiency was associated with lofexidine administration, and higher lofexidine doses adversely affected performance on a mathematical task compared with placebo (p=0.0035). The rate of adverse events was no higher with lofexidine than with placebo; the majority (54.3%) were common adverse effects of lofexidine. CONCLUSION: Significant changes in hemodynamic and cognitive efficiency were observed with coadministration of lofexidine and methadone compared with methadone alone. When patients receiving methadone are prescribed lofexidine, they should be closely monitored for cardiovascular and cognitive changes.

The effects of multidisciplinary therapy on positron emission tomography of the brain in fibromyalgia: a pilot study.

Aberrant central neurological functioning is believed to contribute to the abnormal sensations of fibromyalgia (FM). This pilot study sought to determine if alterations in regional brain metabolism from baseline occur in FM after undergoing a multidisciplinary therapeutic regimen. Regional brain metabolic activity was estimated using (18)F-fluorodeoxyglucose positron emission tomography ((18)FDG PET). Nine participants with FM received an 8-week comprehensive treatment program. Serial testing with (18)FDG PET and the Fibromyalgia Impact Questionnaire were performed. Statistical analysis was performed using repeated Wilcoxon signed rank tests. A clinical improvement (FIQ median change 20.68, P = 0.005) was noted with treatment. With treatment, increases in brain metabolism were noted in various components of the limbic system (P = 0.004-0.1). An increase in limbic metabolism was noted with concomitant symptomatic improvement, suggesting that the limbic system attenuates FM symptoms.

ANAM genogram: historical perspectives, description, and current endeavors.

This paper presents a historical overview and current perspective of the Automated Neuropsychological Assessment Metrics (ANAM) test system. We discuss the history of its development along with a synopsis of the evolution of computerized testing that has occurred and led to ANAM over the past 30 years within the Department of Defense (DoD). We include a description of our current system and test library. Finally, we present an overview of advanced development projects that are presently underway. We have intentionally avoided addressing issues of reliability, stability, clinical sensitivity, and construct validity in this paper. These issues are presented in other reports in this special issue.

Assessing change with the Automated Neuropsychological Assessment Metrics (ANAM): issues and challenges.

Accurately documenting cognitive change is important, as neuropsychologists are routinely asked to determine cognitive change following disease progression or medical intervention. Computerized testing batteries, such as the Automated Neuropsychological Assessment Metrics (ANAM), are good tools for assessing change, because they allow for randomization of stimuli, creating near limitless alternate forms and reducing practice effects. The question remains, however, as to how best to determine reliable change in performance using ANAM. The current study compared the use of Reliable Change Index (RCI) and regression based methods (REG) calculated from 28 individuals with migraine. These methods then were applied to an independent sample of 25 individuals with migraine assessed with ANAM at baseline, headache, and following pharmacologic treatment. Traditional repeated measures analyses revealed declines in cognitive efficiency following migraine onset on two of four ANAM tasks and significant improvement on all ANAM tasks following treatment. Rates of deterioration and improvement did not significantly differ between RCI and REG methods, although were slightly different across the ANAM tasks used in this study. A combined ANAM score categorized the most individuals as demonstrating cognitive change, revealing that 60% of subjects declined in performance following headache and 84% improved following migraine treatment.

Automated Neuropsychological Assessment Metrics sports medicine battery.

This paper describes the development and ongoing validation of the ANAM-sports medicine battery (ASMB) for use in concussion surveillance and management. A review of previous research utilizing the ASMB highlights current issues in concussion surveillance including: tracking cognitive recovery, effect of previous concussion history on acute concussion presentation, and clinical decision making using computerized measures. ASMB interpretation using reliable change indices or impairment indices is highlighted. Future development of the ASMB is discussed as it relates to interpretation of ASMB, development of appropriate norms, and defining adequate baseline assessment. This includes the definition of practice effects, the effects of maturation on test performance and definition of adequate baseline assessment that clearly defines a subject's normal cognitive performance level. ASMB is ready for cautious introduction into clinical practice for use by neuropsychologists with experience in both sports concussion and computerized testing.

Sources of error in computerized neuropsychological assessment.

Computerized neuropsychological assessment has integrated slowly into research and practice since the introduction of the personal computer. Though initial integration of technology to the laboratory and clinical setting utilized specialized hardware and software, newer generation assessment tools are integrated with "off-the-shelf" operating systems. Further, neuropsychological assessment is beginning to find Internet-based application for remote assessment. As these applications are more broadly applied, it is essential to understand potential errors that can be created both in test administration and in reaction time measurement due to hardware and software interactions. In this article, user considerations are specifically addressed for resident and Internet-enabled assessment software. Potential hardware and software conflicts are defined and potential remediation is suggested. Computerized assessment is a valuable tool for neuropsychologists as long as it is used responsibly with an understanding of the potential technical complications.