Head wounds, blast effects, neurotoxin exposure and psychological trauma all affect the brain in distinct and overlapping ways. Building our understanding of what's happening in the brain may reveal strategies to prevent, diagnose and treat neurological as well as mental injury.

Mental disorders are the second most common reason for medical encounters in the military, and the DoD has reported more than 150,000 cases of concussion among returning service members from 2000 to 2010. While promising research is ongoing in several scientific fields, injuries rarely occur in isolation. It is critical to take a wider view of what technologies and practices could improve the care of our soldiers and veterans.

In a unique, interdisciplinary workshop on the biological assessment of brain dysfunction, leading researchers and clinicians from several fields shared information to see how current tools and knowledge could converge to arrive more quickly at real solutions for those injured in combat.

One consensus was that in assessing trauma-related injuries, it is crucial to determine whether the brain is functioning properly; it may be more important to identify dysfunction(s) correctly than it is to determine whether it stems from physical or psychological trauma. Both events can cause changes in the brain that may advance to debilitating conditions and increase the risk of, for example, Parkinson's and Alzheimer's.

The national workshop was held in Washington, D.C., in May with funding from the U.S. Army Medical Research and Materiel Command's Telemedicine and Advanced Technology Research Center. Co-chairing the meeting were TATRC director Col. Karl Friedl; Dr. Victoria Tepe, a program manager for the Survivability and Vulnerability Information Analysis Center; Dr. Robert Kane, project manager for the Neurocognitive Assessment Tool Program at the Defense and Veterans Brain Injury Center; and Dr. Jay Shore, TATRC Psychological Health Portfolio manager.

Said Friedl, "We gathered the top people in the nation'not just the researchers, but the ones running the laboratories'to share different perspectives on brain dysfunction. These individuals probably wouldn't get together without an interdisciplinary meeting like this. It's exciting to think of the new syntheses that may come from this experience."

A Gathering of National Experts

The two-day workshop included nearly 30 presentations broken into several key topics for discussion among the participants. These included:

• Overviews of the issues in both psychological trauma and concussion
• The use of advanced structural imaging in neurological trauma, including current and potential MRI methods
• The use of functional imaging techniques such as fMRI, PET and molecular imaging to assess brain function and dysfunction
• Physiological measures of concussion and psychological trauma such as EEG, heart rate variability, neurogenesis and brain volume change, and sleep monitoring
• Cell physiology and biomarkers of physical trauma
• Clinical evaluation, including neurocognitive and balance assessments
• Novel therapies, including virtual reality, exercise and cognitive retraining

Presenters brought extensive civilian and military experience. For instance, Dr. Kevin Guskiewicz's research at the University of North Carolina Chapel Hill on sport-related concussion in high school and college athletes and retired professional football players has made national headlines. Neurologist and psychiatrist Col. Michael Jaffee has served as the national director of the Defense and Veterans Brain Injury Center and the inaugural senior TBI executive at the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury. Harvard psychiatry professor Dr. Roger Pitman has been conducting a large-scale psychobiologic twin study for the past 15 years to compare Vietnam veterans with their non-deployed siblings. Dr. Robert Ursano of the Uniformed Services University of the Health Sciences specializes in disaster psychiatry and was recently awarded the largest NIMH grant ever given for the study of suicide in the U.S. Army.

Increasing Biological Understanding

Meeting co-chair Dr. Jay Shore noted that our biological understanding of mental health has grown in the last 20 years, along with an incredible revolution in technology within the last decade. Shore described the search for "psychiatric vital signs" and said, "There are several promising evidence-based parameters to identify potential problems, and this workshop will help us determine where to focus our efforts for the best results."

Cellular changes and nerve injury lead to a damaging metabolic cascade after concussion. Proteins and other biomarkers in serum and cerebrospinal fluid have illuminated this process. Advanced imaging techniques such as diffusion tensor imaging and functional magnetic resonance imaging have enabled scientists to visualize the effects and see areas of decreased brain activity. Biological changes also occur due to grief or other stress.

Participants agreed there is a need for research to connect the biological changes with clinical signs and symptoms in order to confirm a biological basis for defining concussion and other conditions. A combination of imaging techniques, physiological measures and clinical assessments will be needed to provide the early detection crucial to successful treatment.

Col. Michael Jaffee explained that last year the military increased its screening requirements in theater. In a completely new approach, instead of relying on service members to report symptoms, everyone involved in possible injury-causing events is now screened using cognitive, neurological and symptom-based assessments. "The next step would be to develop measures and techniques that can be employed in the field to further improve determinations on when it is safe to return to duty or who needs more follow-up," said Jaffee.

Promising Directions in Treatment

Participants explored several promising directions in prevention and treatment, from exercise and sleep to exposure therapy. For instance, Dr. Skip Rizzo is conducting a multisite clinical trial to investigate eliminating the startle reaction in post-traumatic stress through virtual reality exposure therapy, with and without the drug D-cycloserine. This medication affects the amygdala, which plays a significant role in processing emotional information.

Dr. Anthony Chen is using fMRI to study the effectiveness of cognitive training to enhance selective attention for real-world goals. This could lead to rehabilitation techniques for the many individuals with brain injuries who have difficulty focusing on tasks or learning. And workshop co-chair Dr. Victoria Tepe noted that research to explore alterations in endocrine response among individuals with brain injuries or traumatic stress may suggest beneficial therapeutic interventions as well.

Treatment breakthroughs could lie in simple measures that have dramatic effects. For instance, after a presentation by University of California San Francisco professor Dr. Thomas Neylan, the panel discussed sleep as a neuroprotectant, a marker and a treatment. Meeting co-chair Friedl said, "Lack of sleep is part of military culture. But from what we've heard today, a logical hypothesis to test is that if you get enough sleep, it'll protect you from some of the damage to the brain after trauma. We could be saving the lives of countless service members simply by respecting and promoting sleep as a healer."

Gaps and the Way Ahead

The group agreed that data sharing and common standards would greatly improve the progress of research toward effective solutions. Separate research efforts, on both the civilian and military side, would benefit from a common data repository that all could use. In addition, huge amounts of information were collected through the military's Automated Neuropsychological Assessment Metrics, which was taken by close to a million deploying service members, as well as through the Millennium Cohort Study that is investigating the long-term effects of service on 140,000 military personnel. Developing means to share access to this data, as well as completing effective transfer of medical information between the active services and the VA, could provide valuable insight into what treatments are working and for whom.

There are currently different systems for defining and noting the severity of concussion, traumatic brain injury and post-traumatic stress, as well as a lack of longitudinal data on development of various neurodegenerative conditions. This makes it difficult to determine common anatomical and biochemical correlations or gather meaningful statistics for comparison of study results. These issues emphasize the need for consensus and standards.

An organized research effort would ideally focus on three outcomes: simple, pragmatic tools for brain "first aid" in the field; ways in the first week of treatment to prevent a vicious cycle of cellular damage; and long-term methods to treat and prevent chronic problems and neurodegenerative diseases such as Parkinson's and Alzheimer's.

Participants expressed hope that this workshop would speed collaboration on pre-deployment, injury and return to duty assessment techniques; resiliency measures; and treatments for a wide range of brain dysfunction.

Said workshop co-chair Kane, "We owe it to those who have sacrificed so much for our country to find better ways to assess brain injury and optimize care, especially for service members whose injuries lead to persistent problems. We particularly need to understand the complexities of brain injury sustained in a combat environment. This interdisciplinary gathering is a model for continuing efforts to address these challenging issues."

TATRC partners with other USAMRMC units such as the Combat Casualty Care Research Program and the Military Operational Medicine Research Program to provide important leadership in military focused research efforts.

For more information on TATRC's research funding and collaborative opportunities, visit www.tatrc.org.