Faculty Bibliography

The Center for Rehabilitation Sciences Research (CRSR) was established to advance the rehabilitative care for service members with combat-related injuries, particularly those with orthopedic, cognitive, and neurological complications. The center supports comprehensive research projects to optimize treatment strategies and promote the successful return to duty and community reintegration of injured service members. The center also provides a unique platform for fostering innovative research and incorporating clinical/technical advances in the rehabilitative care for service members. CRSR is composed of four research focus areas: (1) identifying barriers to successful rehabilitation and reintegration, (2) improving pain management strategies to promote full participation in rehabilitation programs, (3) applying novel technologies to advance rehabilitation methods and enhance outcome assessments, and (4) transferring new technology to improve functional capacity, independence, and quality of life. Each of these research focus areas works synergistically to influence the quality of life for injured service members. The purpose of this overview is to highlight the clinical research efforts of CRSR, namely how this organization engages a broad group of interdisciplinary investigators from medicine, biology, engineering, anthropology, and physiology to help solve clinically relevant problems for our service members, veterans, and their families.

This study describes the psychometric investigation of an 11-item symptom checklist, the Abbreviated Concussion Symptom Inventory (ACSI). The ACSI is a dichotomously scored list of postconcussive symptoms associated with mild traumatic brain injury. The ACSI was administered to Marines (N = 1,435) within the 1st month of their return from combat deployments to Afghanistan. Psychometric analyses based upon nonparametric item response theory supported scoring the ACSI via simple summation of symptom endorsements; doing so produced a total score with good reliability (α = .802). Total scores were also found to significantly differentiate between different levels of head injury complexity during deployment, F(3, 1,431) = 100.75, p < .001. The findings support the use of the ASCI in research settings requiring a psychometrically reliable measure of postconcussion symptoms.

The authors describe the mechanisms of traumatic brain injury (TBI), examining in depth the characteristics of closed head, penetrating, and blast-related TBI. Events on a structural as well as cellular level are reviewed. Blast-related brain injury, in particular, affects military service members preferentially, but is also relevant in cases of industrial accidents as well as terrorist events.

Although the experience of vicarious sensations when observing another in pain have been described postamputation, the underlying mechanisms are unknown. We investigated whether vicarious sensations are related to posttraumatic stress disorder (PTSD) symptoms and chronic pain. In Study 1, 236 amputees completed questionnaires about phantom limb phenomena and vicarious sensations to both innocuous and painful sensory experiences of others. There was a 10.2% incidence of vicarious sensations, which was significantly more prevalent in amputees reporting PTSD-like experiences, particularly increased arousal and reexperiencing the event that led to amputation (φ = .16). In Study 2, 63 amputees completed the Empathy for Pain Scale and PTSD Checklist-Civilian Version. Cluster analyses revealed 3 groups: 1 group did not experience vicarious pain or PTSD symptoms, and 2 groups were vicarious pain responders, but only 1 had increased PTSD symptoms. Only the latter group showed increased chronic pain severity compared with the nonresponder group (p = .025) with a moderate effect size (r = .35). The findings from both studies implicated an overlap, but also divergence, between PTSD symptoms and vicarious pain reactivity postamputation. Maladaptive mechanisms implicated in severe chronic pain and physical reactivity posttrauma may increase the incidence of vicarious reactivity to the pain of others.

Brain-derived neurotrophic factor (BDNF) plays a key role in energy balance. In population studies, SNPs of the BDNF locus have been linked to obesity, but the mechanism by which these variants cause weight gain is unknown. Here, we examined human hypothalamic BDNF expression in association with 44 BDNF SNPs. We observed that the minor C allele of rs12291063 is associated with lower human ventromedial hypothalamic BDNF expression (p < 0.001) and greater adiposity in both adult and pediatric cohorts (p values < 0.05). We further demonstrated that the major T allele for rs12291063 possesses a binding capacity for the transcriptional regulator, heterogeneous nuclear ribonucleoprotein D0B, knockdown of which disrupts transactivation by the T allele. Binding and transactivation functions are both disrupted by substituting C for T. These findings provide a rationale for BDNF augmentation as a targeted treatment for obesity in individuals who have the rs12291063 CC genotype.

Worldwide prevalence of amputation has created an increasing demand for improved upper and lower extremity prostheses. Current prosthetics are often uncomfortable and difficult to control and provide limited functional restoration. Moreover, the inability to normalize anthropomorphic biomechanics with a prosthesis increases one's risk of developing long-term health risks such as arthritis, skin breakdown, and pain. Recent advances in bionic prosthetic development hold great promise for rehabilitation and improving quality of life with limb loss. This brief review discusses the current state of advanced prostheses, the integration of robotics in the care of individuals with major limb amputation, and some innovative surgical techniques that are being explored for clinical feasibility.

An understanding of human responses to hypoxia is important for the health of millions of people worldwide who visit, live, or work in the hypoxic environment encountered at high altitudes. In spite of dozens of studies over the last 100 years, the basic mechanisms controlling acclimatization to hypoxia remain largely unknown. The AltitudeOmics project aimed to bridge this gap. Our goals were 1) to describe a phenotype for successful acclimatization and assess its retention and 2) use these findings as a foundation for companion mechanistic studies. Our approach was to characterize acclimatization by measuring changes in arterial oxygenation and hemoglobin concentration [Hb], acute mountain sickness (AMS), cognitive function, and exercise performance in 21 subjects as they acclimatized to 5260 m over 16 days. We then focused on the retention of acclimatization by having subjects reascend to 5260 m after either 7 (n = 14) or 21 (n = 7) days at 1525 m. At 16 days at 5260 m we observed: 1) increases in arterial oxygenation and [Hb] (compared to acute hypoxia: PaO2 rose 9±4 mmHg to 45±4 while PaCO2 dropped a further 6±3 mmHg to 21±3, and [Hb] rose 1.8±0.7 g/dL to 16±2 g/dL; 2) no AMS; 3) improved cognitive function; and 4) improved exercise performance by 8±8% (all changes p<0.01). Upon reascent, we observed retention of arterial oxygenation but not [Hb], protection from AMS, retention of exercise performance, less retention of cognitive function; and noted that some of these effects lasted for 21 days. Taken together, these findings reveal new information about retention of acclimatization, and can be used as a physiological foundation to explore the molecular mechanisms of acclimatization and its retention.

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.