NICoE's Research Department currently supports more than 30 active research protocols/studies. The goal of each of these studies is to add to our collective understanding of TBI and brain health and can be classified into one of three main categories:
- Treatment
- Observational
- Retrospective
If you're interested in participating in research, please contact the following email address: [email protected]
Treatment Studies
Treatment studies are those in which researchers introduce participants to an intervention and study the effects. Generally the participants are randomized, meaning they are grouped by chance.
View Treatment Studies:
- Treating mild TBI (mTBI) and post-traumatic stress disorder (PTSD) with Bilateral Prefrontal Transcranial Magnetic Stimulation (TMS) - In collaboration with the Uniformed Services University of the Health Services (USUHS) and the Center for Rehabilitation Sciences Research (CRSR), NICoE researchers are assessing whether TMS can help to lessen symptoms that can be associated with mTBI and posttraumatic stress disorder (PTSD). Results from this study may additionally shed light on whether there are positive effects on quality of life, and cognitive abilities, while also improving ongoing PTSD and mTBI symptoms.
- Study Impact: This study may shed light on the ability of rTMS to reduce the symptoms associated with PTSD and mTBI to improve the overall quality of life for injured service members.
- Biopsychosocial Effect of Service Dog Training on Post-Traumatic Stress (PTS) and Post Concussive Symptoms - Preliminary anecdotal evidence suggests that service members with symptoms of PTS report improved physical, social, and psychological symptoms after participation in the NICoE's Service Dog Training Program (SDTP). The SDTP teaches service members how to train dogs to become service dogs, to provide support to veterans with mobility impairments and mood disorders. The program's purpose is to help service members develop skills such as effective communication and emotion regulation that are translatable to other social settings. This research assesses various biological, psychological, and sociological outcomes to evaluate the effectiveness of the SDTP.
- Study Impact: Findings from this study will inform the efficacy of implementing the SDTP as a complementary program for service members undergoing treatment for symptoms of PTS and TBI. If this study's results are positive, it could lead to more service members and veterans being offered access to the SDTP to augment their ongoing care.
- A Randomized, Sham-Controlled, Blinded Study of Bilateral Prefrontal Individual Connectome – Targeted Repetitive Transcranial Magnetic Stimulation (ICT-rTMS) to Treat the Symptoms of Depression Associated with Concussive TBI - In collaboration with USUHS, this CNRM sponsored study investigates the efficacy and tolerability of ICT-rTMS treatment to improve symptoms of depression that are often associated with concussive TBI. This study aims to develop a novel, effective treatment for depressive symptoms associated with concussive TBI by using a coordinate-based computer system to deliver a more precise and individualized intervention.
- Study Impact: If successful, findings from this study will speed the development of a novel, non-pharmacologic treatment for depression for service members with a history of concussion.
- CAREN versus Augmented Reality: Expanding 3MDR Therapy for PTSD: A Randomized Controlled Trial - PTSD and mTBI are persistent and frequently comorbid complications of combat. There is no proven treatment for mTBI, and standard treatments for PTSD often achieve only transient, modest impact. Motion-assisted, Multi-modular Memory Desensitization and Reconsolidation (3MDR) is a novel treatment for PTSD combining aspects of virtual reality exposure therapy and eye movement desensitization and reprocessing treatment currently conducted within the Computer Assisted Rehabilitation Environment (CAREN). The CAREN facilitates the multi-modal approach of 3MDR by enabling physical activity (walking), and simultaneous verbal engagement with a therapist, to occur within a fully immersive VR experience that can be individualized to enable confrontation, and in doing so to overcome avoidance, of reminders of one's traumatic experience and associated feared stimuli. The purpose of this study is to determine whether 3MDR delivered via an augmented reality head-mounted display (AR-HMD) has similar benefits to 3MDR delivered in the CAREN.
- Study Impact: The proposed research has the potential to have a significant positive impact on the care of individuals with PTSD. This treatment may be particularly useful or of interest to veterans and service members, who are accustomed to being physically active, may be less inclined to turn to pharmacotherapy than others with PTSD, and also have had resistance to established, more traditional therapies. This relatively short treatment approach could have tremendous implications for improvement in symptoms as well as quality of life.
- Rehabilitation of Acquired Auditory Processing Deficits – Mobile Application-Based Computerized Auditory Training - The specific aim of this study is to provide evidence regarding the effectiveness of computerized auditory training as a treatment option for adults with normal to-near-normal hearing thresholds and auditory processing deficits, who have a history of blast exposure and/or TBI.
- Study Impact: Analysis from this data may influence the standard of care that service members impacted by TBI receive, in order to improve our ability to treat functional hearing problems, which directly correlate to their quality of life.
- The Investigation of Cranial Electrical Stimulation (CES) to Reduce Anxiety in Service Members with a History of Mild TBI - Service members with a history of mild TBI are at an increased risk for developing anxiety, which has secondarily been implicated in extended recovery timelines and poorer outcomes. This study's primary purpose is to determine the efficacy of non-invasive CES in conjunction with an integrative treatment program for improving symptoms of anxiety associated with TBI.
- Study Impact: Findings of this study may support the use of CES as an adjunctive therapy to reduce persistent post-concussive and psychological health symptoms.
- Art Therapy and Emotional Wellbeing in Military Populations with Post-traumatic Stress Symptoms - In collaboration with the Penn Center for Neuroaesthetics, this National Endowment of the Arts (NEA) Creative Forces funded feasibility study will assess the impact of an art therapy protocol developed at the NICoE on emotional wellbeing in service members and veterans with post-traumatic stress symptoms as well as investigate potential neural biomarkers of this therapy through the use of advanced functional neuroimaging techniques. The study will recruit up to 25 service members and veterans who will participate in self-report assessments, advanced functional MRI, and an eight week individual art therapy protocol.
- Study Impact: Results from this study will provide preliminary evidence of the efficacy of art therapy as well as the neurobiological underpinnings of its effects that will be used to develop future randomized controlled trials.
- Evaluation of quantitative electroencephalography (qEEG) During Art Therapy in Service Members with Comorbid TBI and Post-traumatic Stress Symptoms - Although there is great anecdotal evidence of the benefits of art therapy at the NICoE, there is a gap in knowledge regarding the underlying neurobiological mechanisms of this therapy. This pilot project funded by NEA Creative Forces will conduct a longitudinal study collecting mobile, qEEG directly before, during, and after art therapy sessions. The goal of this study is to investigate brain signals associated with the art therapy process as well as generate preliminary data for the efficacy of art therapy in a population of service members with comorbid mTBI and post-traumatic stress symptoms.
- Study Impact: Findings from this study will provide novel evidence of neurobiological changes associated with the treatment benefits of art therapy. These may be used to guide future research in the creative art therapies and offer creative art therapists greater insight into the mechanisms of action of this therapy, allowing them to further refine their therapeutic techniques and continue to personalize treatment.
- Randomized Controlled Trials of Closed-Loop Allostatic Neurotechnology to Improve Sensory Function and Pain Management After Traumatic Brain Injury - This clinical trial, conducted in Walter Reed's America Building, involves translating one's brainwaves to musical notes as well as electrical impulses that stimulate the scalp at a level so low that you do not feel it, to try to reduce symptoms of mTBI. In this study, everyone rests in a zero-gravity chair and listens to musical notes that represent their brainwaves. Half of them also receive stimulation of their scalp, at a level less than the electromagnetic field created by a cell phone, to see if that addition decreases symptoms more than just the musical notes alone.
- Study Impact: This study may help to prove the benefit of a completely new treatment for post-concussive symptoms, for which it has been very hard to find effective treatment.
- RECONsolidation of Traumatic memories to ResOLve Posttraumatic Stress Disorder (RECONTROL) - This clinical trial compares the gold standard therapy for PTSD, known as prolonged exposure therapy (PE), with a new therapy called reconsolidation of traumatic memories (RTM), which is generally easier to do. As part of this study everyone receives one of these therapies, to see which does better in reducing symptoms of PTSD (e.g., nightmares, sleep difficulties, irritability) and improve the quality of mental healthcare for active duty service members and veterans.
- Study Impact: RTM, if shown to achieve a greater or more rapid response than PE in the treatment of service member and veterans with PTSD, would provide another treatment option for those struggling with PTSD, which may be easier for many to do.
- Rehabilitation of Acquired Auditory Processing Disorders (APD) – Low-Gain Hearing Aids (LGHA) - This work aims to examine the efficacy of LGHAs in an active duty military population with a history of mild TBI and blast exposure who have been diagnosed with APD in the presence of normal-to-near-normal hearing thresholds. This research addresses the limited evidence to support fitting LGHAs in this population by comparing aided and unaided outcomes using both subjective and objective measures. In addition, the potential "hidden" peripheral damage associated with the functional presentation of these deficits, despite NHTs, will be examined as it relates to subjective and objective outcomes.
- Study Impact: Results from this study will influence the standard of care received by adult TBI patients diagnosed with APD in the presence of NHT, thus improving the ability to treat and limit associated functional impairments.
- Use of Virtual and Augmented Reality Devices in Vestibular Physical Therapy for mTBI - Following mTBI, symptoms can include physical, cognitive, vestibular, oculomotor and psychological impairments. Vestibular physical therapy (VPT) is often recommended and has been shown to improve functional dynamic visual acuity, standing balance, and gait in service members with mTBI. At the NICoE and Naval Health Research Center, the Computer Assisted Rehabilitation Environment (CAREN) is used as a clinical modality and includes virtual environments (VEs) that have been specifically created to address vestibular symptoms. Given the positive outcomes observed, there has been a desire to replicate CAREN-based therapies with a more portable system that can be used in conventional therapy settings. In recent years, augmented reality head-mounted display (AR-HMD) technologies have become more affordable and accessible. For this study, battery of VPT VEs, which can be used on both the CAREN and mobile systems, has been developed. The purpose is to determine whether advanced VR (CAREN) and AR-HMD based therapies, improve functional status and vestibular symptoms in service members with vestibular dysfunction and mTBI.
- Study Impact: Results from this study should help determine whether the treatment of vestibular dysfunction, could become more accessible with the mobile system and possibly result in greater patient compliance and overall satisfaction.
Observational Studies
Comprise study designs in which researchers observe the effect of a risk factor, diagnostic test, treatment, or other intervention without attempting to impact who is exposed to it.
View Observational Studies:
- Expanding Our Understanding of Computer-Based Cognitive Rehabilitation in the Military Population – A Longitudinal Brain Fitness Center (BFC) Database - Computer-based cognitive programs, biofeedback tools, and educational classes offered through the Brain Fitness Center at NICoE may help individuals enhance cognitive performance. Researchers at the NICoE use these data to study potential changes in cognitive performance and assess the feasibility of computer-based rehabilitation services to enhance standard clinical practices.
- Study Impact: This study will improve the understanding of the population, the utilization, and the efficacy of the BFC through retrospectively analyzing data from a pre-existing and preapproved data collection protocol.
- NICoE TBI Magnetoencephalography (MEG) Core Project - The NICoE's MEG study allows researchers to map brain activity by non-invasively recording the magnetic fields produced when brain cells communicate with one another. By understanding the functional changes in brain activity seen in different patient populations, NICoE researchers aim to further identify strategies to improve cognitive and emotional functioning in those affected by TBI and associated health conditions.
- Study Impact: This study hopes to advance the understanding of the relationship between specific symptoms that affect those with TBI and the brain activity changes that underlie them. The physiologic changes associated with these symptoms may provide increased insight to tailor specific therapies and treatments for TBI and psychological health concerns.
- NICoE Traumatic Brain Injury Neuroimaging Core Project - NICoE investigators are using advanced imaging techniques along with sophisticated processing methods to develop imaging biomarkers for TBI. These biomarkers would serve both as objective evidence of TBI in clinical practice and as measures useful for validating TBI therapies. The data acquired under this study is compiled into a database that can be shared with investigators at other institutions to promote collaboration and share knowledge.
- Study Impact: Findings from this study will be used to develop neuroimaging and blood biomarkers that can provide objective evidence of TBI and differentiate them from psychological health issues.
- Imaging [18F]PI-2620 and Florbetaben F18 in Military Service Members with Blast-Related Mild Traumatic Brain Injury - This interdisciplinary study aims to develop an understanding of the molecular imaging features of blast-related mTBI in military personnel while helping to establish assessment tools that may be of use in the diagnosis, determining prognosis, and in future therapeutic clinical trials. The study is one of the first to use positron emission tomography (PET) imaging to investigate tau and amyloid in active duty military service members with a history of blast exposure, to determine whether these individuals are at risk for developing chronic traumatic encephalopathy (CTE).
- Study Impact: This study's results may aid in the delineation of the cognitive and neurobiological profile of blast-related mTBI in the military population and may provide currently unavailable and crucial information with regard to the risk of developing CTE-like dementia. Additionally, findings from this study may be useful in the development of adequate intervention, new treatments, and improved long-term care planning.
- Assessing the Impact of mTBI on Multi-Sensory Integration While Maneuvering on Foot - Service members' success in combat operations is largely dependent on their ability to shoot, move, and communicate on the battlefield. These critical tasks require the execution of numerous complex subtasks that involve processing simultaneous inputs from the auditory, visual, vestibular, tactile, and proprioceptive senses. This project uses an aurally-aided visual search (AAVS) paradigm to examine the impact that unimodal and multi-sensory deficits have on the functional performance of sensory-impaired service members. Experiments are conducted using the CAREN, which makes it possible to measure how well participants perform audio-visual integration tasks while standing still or maneuvering on foot using the system's embedded treadmill. Preliminary results show that the mTBI group responds about 15% slower in the AAVS task and that both groups respond faster while walking without any reduction in accuracy. With further testing, the researchers hope to validate whether the AAVS paradigm is sensitive enough to detect subtle multimodal integration problems that are not apparent in more traditional unimodal sensory tasks.
- Study Impact: Information obtained from this study will have near- and long-term positive impacts, both in defining return-to-duty standards for service members with brain injuries and developing rehabilitation strategies for impaired patients.
- Comparison of Visual and Auditory Technologies in Large Scale and Mobile Virtual Reality Systems - At the NICoE and Naval Health Research Center (NHRC), the CAREN, a VR-based system, is often utilized as an adjunct to traditional therapies. Although there are benefits to using the CAREN, the systems are fixed, large in size, and expensive to install and maintain. These constraints can severely limit the number of patients who have access to them. However, with recent advances in VR and augmented reality head-mounted display (AR-HMD) technology, in conjunction with 3D spatial audio ("virtual audio"), alternatives to larger-scale VR-based systems like the CAREN may finally be possible. The purpose of this study is to replicate virtual environments, used on the CAREN, by leveraging new technologies, combining visual and auditory inputs into a mobile system that can be used in a variety of settings. It is expected that the mobile system will provide similar feedback to participants and that performance outcomes will be comparable between the two systems. This is a multi-site study in collaboration with the Naval Health Research Center and Naval Medical Center San Diego.
- Study Impact: This study seeks to validate a mobile system, which combines visual and audio technologies, and has the potential to improve the current standard of care. This advancement in the field of concussion research may benefit service members who experience persistent sensory systems injury.
- Oculomotor Assessment of Traumatic Brain Injury - To address hearing impairments in NICoE patients who clinically fall within normal hearing thresholds, NICoE researchers are evaluating the impact of low-gain hearing aids to lessen symptoms and improve quality of life. Early results indicate that participants showed significant improvements in auditory processing in noisy environments.
- Study Impact: The military will utilize results from this study for further development of a deployable oculomotor test for use in theater.
- Psychometric Evaluation of the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) and the PTSD Symptom Scale Interview for DSM-5 (PSSI-5) in an Active Duty and Military Veterans Sample - This study aims to evaluate the psychometric properties of the CAPS-5 and PSSI-5 assessment tools in active duty military personnel and veterans. Biomarkers believed to be related to PTSD (e.g., biofluid biomarkers, cognitive and physiological markers, and neural activity as measured by EEG) will be collected to inform targeted interventions in specific groups of patients and other large-scale biomarker discovery efforts in the field. In addition, many PTSD treatment trials have likely failed, at least in part, due to the biological heterogeneity underlying PTSD (i.e., the disruption of many different neurobiological systems can lead to a common set of symptoms consistent with a PTSD diagnosis). Evaluation of biomarkers thought to be related to PTSD will help identify subgroups of patients with common biological abnormalities who may be more likely to respond to certain types of interventions targeted to normalize those specific abnormal systems or circuits.
- Study Impact: The knowledge gained from this study will directly impact the ability of clinicians to reliably diagnose PTSD and assess PTSD symptom severity. It will also directly impact the likelihood of future clinical trials' technical and regulatory success in the development of novel treatments for PTSD.
- The 15-Year Natural History Study - The NICoE and Walter Reed National Military Medical Center (WRNMMC) serve as the core site for this congressionally-mandated, multi-site, longitudinal study into the long-term implications of TBI. Now at its midpoint, this Traumatic Brain Injury Center of Excellence (TBICoE) study employs a host of clinical, behavioral, cognitive, sensory-motor, blood biomarkers, and imaging assessments to identify issues that may make TBI recovery more difficult.
- Study Impact: This study focuses on the long-term physical and mental health outcomes and the effects on service members and their families following TBI with the goal of improving treatments and services for those affected.
- The 15-Year Caregiver Study - The NICoE and WRNMMC serve as the core site for this congressionally-mandated, multi-site, longitudinal study into the impact of TBI on the service member's caregiver and family. Now at its midpoint, this TBICoE study examines caregiver outcomes such as physical and mental health, employment, finances, family functioning, relationship satisfaction, and quality of life, as well as the impact on the health and behavior of the caregiver/service member's children.
- Study Impact: This study focuses on various long-term outcomes and the effects on the families of the service members following TBI with the goal of understanding how families are affected and how to best support them.
Retrospective Studies
A retrospective study is performed using information on past events. Often the data have already been gathered and stored in a registry. Generally, retrospective studies do not follow patients into the future and often requires less time to conduct than a prospective study.
View Retrospective Studies:
- Integration of Image and Clinical Measurements of TBI Patients Using Machine Learning Techniques - This retrospective study uses a large longitudinal clinical dataset of more than 100,000 mTBI patients to create machine learning and artificial intelligence models that can be used to automatically identify clinical trajectories, sub-categories of mTBI, and risk factors associated with the onset of mental health conditions. Through this study, a number of advanced predictive models have been developed, including models to estimate the probability of a patient returning to active duty, forecast models for retention post-injury, machine-learning models to identify the likelihood of developing clinical conditions, and predictors of healthcare utilization post-injury
- Study Impact: The use of machine learning and artificial intelligence with large longitudinal retrospective clinical datasets will allow us to model the progression of mTBI, impacting our understanding of the short- and long-term effects of traumatic brain injuries.
- A Retrospective Study of the Natural History of Traumatic Brain Injury and Psychological Health Outcomes in Military Personnel Through Analysis of the NICoE Clinical Research Database - Utilizing the clinical data collected as part of NICoE's four-week Intensive Outpatient Program (IOP), NICoE researchers look at clinical care outcomes to inform future treatment for TBI and associated health conditions. Observed trends may offer insights into new ways to assess and treat TBI symptoms.
- Study Impact: This systematic approach to collecting information on TBI and other psychological health conditions will advance the ability to evaluate, diagnose, and treat these conditions in both military and civilian populations. Additionally, this study is designed to enhance clinical practice guidelines, leveraging evidence-based analysis to identify best treatment practices for complex patient subpopulations cared for within the military health system.