Effect of virtual reality PTSD treatment on mood and neurocognitive outcomes.

Virtual reality (VR) is an emerging tool to help treat posttraumatic stress disorder (PTSD). Previously published studies have shown that VR graded exposure therapy (VR-GET) treatment can result in improvements in PTSD symptoms. Less is known about the impact on depression, general anxiety, and neuropsychological functioning in patients with PTSD. This study examined changes in self-reports of PTSD, depression, and anxiety before and after treatment, and also examined neuropsychological functioning as assessed by a computerized test of simple reaction time, procedural reaction time, and performance on the congruent, incongruent, emotional, and neutral (match the color of the "nonsense word") Stroop tests. Results showed that subjects treated with VR-GET showed significant reductions in PTSD and anxiety severity and significant improvements on the emotional Stroop test. Changes in depression and other measures of neuropsychological function were not significant. Change scores on the emotional Stroop test did not correlate with changes in self-report measures of PTSD. Overall, these findings support the use of VR-GET as a treatment for PTSD but indicate that benefits may be narrowly focused. Additional treatments may be needed after or alongside VR-GET for service members with neuropsychological impairments.

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.

Neuropsychological test performance in soldiers with blast-related mild TBI.

This exploratory study was conducted to increase understanding of neuropsychological test performance in those with blast-related mild traumatic brain injury (mTBI). The two variables of interest for their impact on test performance were presence of mTBI symptoms and history of posttraumatic stress disorder (PTSD). Forty-five soldiers postblast mTBI, 27 with enduring mTBI symptoms and 18 without, completed a series of neuropsychological tests. Seventeen of the 45 met criteria for PTSD. The Paced Auditory Serial Addition Test (Frencham, Fox, & Mayberry, 2005; Spreen & Strauss, 1998) was the primary outcome measure. Two-sided, 2-sample t tests were used to compare scores between groups of interest. Presence of mTBI symptoms did not impact test performance. In addition, no significant differences between soldiers with and without PTSD were identified. Standard neuropsychological assessment may not increase understanding about impairment associated with mTBI symptoms. Further research in this area is indicated.

Use of computerized neuropsychological testing to help determine fitness to return to combat operations when taking medication that can influence cognitive function.

Nowhere is it more important to maintain peek mental functioning than in a combat zone. Conditions ranging from pain to head injury to post-traumatic stress disorder can cause impairments in neuropsychological function and place service members at risk. Medications can sometimes help alleviate these problems, but also have the risk of further slowing cognitive function or impairing reaction time. Standard methods of neuropsychological testing are often not available in a combat environment. New technologies are being advanced that can allow portable, computerized neuropsychological testing to be performed at almost any location. We present a case that demonstrates how the use of such handheld technology can assist a military physician in assessing the influence of medication on reaction time and in determining if and when a service member is ready to return to combat.

A randomized placebo-controlled clinical trial of the effectiveness of thyroxine and triiodothyronine and short-term exposure to bright light in prevention of decrements in cognitive performance and mood during prolonged Antarctic residence.

OBJECTIVE: We examined the effects of a combined levothyroxine/liothyronine supplement and exposure to bright (10,000 lux) light in euthyroid men and women who spent the austral summer (n = 43) and/or winter (n = 42) in Antarctica. METHODS: Subjects were randomized to receive 64 nmol of levothyroxine and 16 nmol of liothyronine supplement or a placebo capsule for 93.2 +/- 3.0 days in summer and/or 149.5 +/- 2.2 days in winter. Subjects were further randomized to receive 10,000 lux bright white light or 50 lux dim red light for 14 days at the end of summer and/or winter. Cognitive performance and mood were assessed using the Automatic Neuropsychological Assessment Metric - Isolated and Confined Environments. RESULTS: In winter, bright light exposure was associated with a significantly greater reduction in TSH and anger (P < 0.05), a significantly greater increase in fT(3) (P < 0.05), and a significantly smaller increase in depressive symptoms (P < 0.001), when compared with dim light. The T4/T3 supplement also led to a significantly greater reduction in TSH (P < 0.05), but a greater reduction in cognitive task efficiency (P < 0.05) as well, when compared with placebo. CONCLUSION: Administration of bright light leads to a significant reduction in serum TSH and prevents increases in anger and depressive symptoms in winter. However, these associations were not observed in summer, suggesting a seasonal influence of photoperiod over temperature upon this intervention in the polar environment.

Predictors of adherence to triptans: factors of sustained vs lapsed users.

OBJECTIVE: The present study was conducted to identify factors that predict adherence to triptans by migraine patients. BACKGROUND: Triptans have demonstrated efficacy for acute migraine yet many migraine sufferers discontinue their use. DESIGN AND METHODS: A survey study was conducted using 785 subjects (390 health maintenance organizations [HMO] and 395 non-HMO). Of those, 586 were sustained users of triptans (defined by at least 1 refill within the past year), and 199 were classified as lapsed users (ie, individuals who had 0 refills in the past year). Groups were compared on a variety of measures including a comprehensive Migraine Survey that included items related to efficacy and adverse events associated with the patient's current medication, as well as the Headache Impact Test (HIT)-6 and Migraine Disability Assessment Score (MIDAS) questionnaires. Data were analyzed with multivariate analysis of variance and stepwise multiple regression. RESULTS: Sustained users of triptans were significantly more satisfied with their medication, confident in the medication's ability to control headache, and reported control of migraine with fewer doses of medication. Sustained users also switched triptans products significantly less often than lapsed users, and reported greater benefit from triptan intervention in restoring normal daily functions, including improved cognitive ability, compared with lapsed users' ratings of their nontriptan medication. More lapsed users than sustained users reported adverse events associated with past triptan use. Results from multiple and logistic regression analyses correctly classified 95% of sustained users and identified the most significant predictors for sustained use as: satisfaction and belief in medication, reliability of response, effectiveness in rapidly restoring normal levels of productivity, and fewer doses of medication for resolving an attack. The HIT-6 and MIDAS distinguished between sustained and lapsed triptan users on days unable to do household work and missed family and social events. CONCLUSIONS: Predictors of adherence to triptans included satisfaction and confidence in triptans' ability to stop the migraine and associated symptoms and to return the individual to normal functioning. The findings suggest that lapsed users may not be receiving optimal treatment, and that if their past response to triptans was a consequence of inadequate education, they may benefit from additional education on proper use of triptans.

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.

Combat related post traumatic stress disorder: a multiple case report using virtual reality graded exposure therapy with physiological monitoring.

The current report summarizes case studies from an Office of Naval Research (ONR) funded project to compare the effects of Virtual Reality Graded Exposure Therapy (VRGET) with a treatment as usual control condition in active-duty Navy Corpsmen, Navy SeaBees and Navy and Marine Corps Support Personnel. Details of the collaborative program between the Virtual Reality Medical Center (VRMC) and Naval Medical Center San Diego (NMCSD) will be discussed.

Environmental influences on hypothalamic-pituitary-thyroid function and behavior in Antarctica.

We examined the physiological and psychological status of men and women who spent the summer (n=100) and/or winter (n=85) seasons in Antarctica at McMurdo (latitude 78.48 S, elevation 12 m) and South Pole (latitude 90 S, elevation 3880 m) stations to determine whether there were any significant differences by severity of the stations' physical environment. Physiological measures (body mass index, blood pressure, heart rate, tympanic temperature), serum measures of thyroid hormones, cortisol, and lipids and plasma catecholamines were obtained at predeployment (Sep-Oct) and the beginning of the summer (November) and winter (Mar-Apr) seasons. Cognitive performance and mood were assessed using the Automatic Neuropsychological Assessment Metric - Isolated and Confined Environments (ANAM-ICE), a computerized test battery. South Pole residents had a lower body mass index (p<0.05) and body temperature (p<0.01) and higher levels of plasma norepinephrine (p<0.05) in summer and winter than McMurdo residents. Upon deployment from the United States and during the summer, South Pole residents experienced significantly higher thyroid hormone values (free and total T(3) and T(4)) (p<0.01) than McMurdo residents; in summer they also experienced lower levels of triglycerides (p<0.01) cortisol (p<0.05) and LDL (p<0.05). In winter, South Pole residents also experienced a 39% decrease in serum TSH compared with a 31.9% increase in McMurdo (p<0.05). South Pole residents also were significantly more accurate (p<0.05) and efficient (p<0.01) in performance of complex cognitive tasks in summer and winter. Higher thyroid hormone levels, combined with lower BMI and body temperature, may reflect increased metabolic and physiological responses to colder temperatures and/or higher altitude at South Pole with no apparent adverse effect on mood and cognition.

Combat-related post-traumatic stress disorder: a case report using virtual reality exposure therapy with physiological monitoring.

The current report summarizes a case study from an Office of Naval Research (ONR) funded project to compare the effects of virtual reality graded exposure therapy (VRGET) with cognitive behavioral group therapy in active-duty corpsmen. Details of the collaborative program between the Virtual Reality Medical Center (VRMC) and Naval Medical Center San Diego (NMCSD) will be discussed.

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.

Neuropsychological assessment in extreme environments.

In this paper, we summarize studies that used ANAM tests to assess the effects of environmental stressors. The findings document performance changes resulting from conditions relevant to military operational medicine. These conditions included radiation exposure, toxins, high altitude, undersea conditions, Marine basic training, advanced military training, and fatigue. The results of these studies demonstrate that ANAM detects cognitive changes in extreme environments.

The ARES test system for palm OS handheld computers.

The ARES (ANAM Readiness Evaluation System) is a cognitive testing system designed for operation on palm OS handheld computers i.e., Personal Digital Assistants (PDA). It provides an inexpensive and portable testing platform for field and clinical applications. ARES test batteries can be configured from a library of tests derived from the ANAM test system. ARES features include support of multiple users on a single PDA, a Microsoft Windows test battery authoring program, and a program for downloading, viewing, graphing, and archiving data. In validity tests, the same subjects were tested on identical ARES and conventional ANAM NeuroCog test batteries. Scores from the two platforms correlated highly, but absolute scores differed slightly. In reliability testing with the ARES Warrior battery, ARES scores were highly correlated in daily tests.

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.

Psychoneuroendocrine effects of combined thyroxine and triiodothyronine versus tyrosine during prolonged Antarctic residence.

OBJECTIVES: We previously reported that cognitive function improves with thyroxine and that there is a circannual pattern to mood and human TSH during Antarctic residence. To extend these findings, we examined the effects of tyrosine and a combined levothyroxine/liothyronine supplement in euthyroid men and women who spent the austral summer (n = 43) and/or winter (n = 42) in Antarctica. STUDY DESIGN: Randomized, placebo-controlled, clinical trial. METHODS: Subjects were randomized to receive the following each day for 91.6 +/- 3.2 days in summer and/or 138.0 +/- 3.2 days in winter: (1) 12g tyrosine mixed in 113g applesauce; (2) 50 microg of levothyroxine and 12.5 microg of liothyronine (T4-T3 Supplement); or (3) placebo. Cognitive performance and mood were assessed using the Automatic Neuropsychological Assessment Metric - Isolated and Confined Environments. RESULTS: With placebo in summer, mood did not change while TSH decreased by 28%; in winter, there was a 136% degradation in mood (p < 0.01) and TSH increased by 18%. With combined T4-T3 supplement, there was a 51% degradation in mood in summer compared with placebo (p < 0.05) and TSH decreased by 57%; in winter there was a 135% degradation in mood while TSH was reduced by 26% (p < 0.05). Tyrosine use in summer was associated with no change in mood and a 30% decline in TSH, while in winter there was a 47% improvement in mood and TSH decreased by 28% along with a 6% increase in fT3 (p < 0.05). CONCLUSIONS: Administration of tyrosine leads to a significant reduction in serum TSH and improvement in mood in winter compared with placebo, while the combined T4-T3 supplement leads to a worsening of mood in summer and no improvement in winter. There appears to be a seasonal influence on the psychological response to interventions and the relationship to changes in TSH reductions.

Reference values for performance on the Automated Neuropsychological Assessment Metrics V3.0 in an active duty military sample.

The Automated Neuropsychological Assessment Metrics (ANAM) is a computerized measure of processing speed, cognitive efficiency, and memory. This study describes performance and psychometric properties of ANAM in an active duty, healthy military sample (N = 2,371) composed primarily of young (18-46 years) adult males. Rarely have neuropsychological reference values for use with individuals in the military been derived from a large, active duty military population, and this is the first computerized neuropsychological test battery with military-specific reference values. Although these results do not provide demographically corrected, formal normative data, they provide reference points for neuropsychologists and other health care providers who are using ANAM data in research or clinical settings, with patients of comparable demographics to the present sample.

Effect of repeated exposures to cold on cognitive performance in humans.

The effects of repeated exposure to cold temperature on cognitive performance were examined in 10 male subjects who were exposed to control (25 degrees C) and cold (10 degrees C) conditions on 10 successive days. A cognitive test battery (ANAM-ICE) was administered each day to assess complex and simple cognitive functioning accuracy, efficiency and response time. Rectal (T(rect)) and skin temperatures, thermal sensations, metabolic rate (M) and cardiovascular reactivity were also recorded. With the used cold exposure, inducing cold sensations and discomfort, superficial skin cooling (6-7 degrees C) and a slightly lowered T(rect) (0.4 degrees C) we observed three distinct patterns of cognitive performance: 1) negative, reflected in increased response times and decreased accuracy and efficiency; 2) positive, reflected in decreased response time and increased efficiency; and 3) mixed, reflected in a pattern of increases in both accuracy and response time and decreases in efficiency, and a pattern of decreases in both accuracy and response time. T(rect), thermal sensations, diastolic blood pressure (DBP) and heart rate (HR) were independent predictors of decreased accuracy, but also decreased response time. Cognitive performance efficiency was significantly improved and response times shorter over the 10-d period both under control and cold exposures suggesting a learning effect. However, the changes in cognitive performance over the 10-d period did not differ markedly between control and cold, indicating that the changes in the thermal responses did not improve performance. The results suggest that cold affects cognitive performance negatively through the mechanisms of distraction and both positively and negatively through the mechanism of arousal.

Longitudinal neurocognitive assessments of Ukrainians exposed to ionizing radiation after the Chernobyl nuclear accident.

A 4-year longitudinal study of the cognitive effects of the Chernobyl nuclear accident was conducted from 1995 to 1998. The controls were healthy Ukrainians residing several hundred kilometers away from Chernobyl. The exposed groups included Eliminators, Forestry workers and Agricultural workers living within 150 km of Chernobyl. Accuracy and efficiency of cognitive performance were assessed using ANAMUKR, a specialized subset of the Automated Neuropsychological Assessment Metrics (ANAM) battery of tests. Analyses of variance, followed by appropriate pairwise comparisons, indicated that the 4-year averaged levels of performance of the exposure groups (especially the Eliminators) were significantly lower than those of the controls on most measures; further, analyses of performance across time revealed significant declines in accuracy and efficiency, as well as psychomotor slowing, for all exposed groups over the 4-year period. These findings strongly indicate impairment of brain function resulting from both acute and chronic exposure to ionizing radiation.

Duration of cognitive impairment after sports concussion.

OBJECTIVE: We sought to determine the duration of cognitive impairment after sports concussion. METHODS: We conducted a study with a prospective design in which 729 athletes underwent preseason baseline testing by being administered a computerized neuropsychological test battery, followed by retesting at regular intervals after they sustained sports-related concussions. A control group consisting of nonconcussed athletes drawn from the same baseline population underwent testing at parallel intervals. RESULTS: Cognitive impairment in this primarily American Academy of Neurology Grade II sample of boxing concussions was apparent on the day of injury and at 1 to 2 days postinjury. Recovery of cognitive performance occurred during the 3- to 7-day interval. Comparison with control subjects showed that absent or attenuated practice effects, in addition to frank deterioration from baseline, were indications of recent concussion. CONCLUSION: The present findings of recovery during the 3- to 7-day interval postinjury are consistent with the American Academy of Neurology Grade II return-to-play practice parameters suggesting a 1-week time-out from participation in contact sports.