PI: Kalo Tanev MD MPH

Sponsor: National Institute of Mental Health (NIMH)

This research study will test the effect of a novel intervention based on memory reconsolidation blockade on the participants’ physiological reactivity during script-driven imagery of the traumatic event. The project will test two interventions, MisMatch (“MM”) memory recall vs. standard (“STD”) memory reactivation, under the influence of an FDA-approved anti-adrenaline drug called propranolol (a pharmacological agent that blocks memory reconsolidation). This project will serve as a proof-of-concept study for further clinical propranolol mismatch studies in the future.

PI: Kalo Tanev MD MPH

Sponsor: Rush University Medical Center (Originating sponsor: Wounded Warrior Project)

The MGH Home Base team will collect treatment data and will provide de-identified datasets to the Rush University Medical Center (RUMC) team for this Machine Learning Project.  Additionally, clinical leadership at Home Base will provide feedback on the model output and other aspects of the project. This is a joint effort with all 4 members of the Warrior Care Network (RUMC Road Home, MGH Home Base, UCLA Operation Mend, and Emory Healthcare Veterans Program). The implementation of machine learning facilitates decision making in medicine. This study will attempt to predict the treatment course of patients in our Intensive Clinical Program. Being able to predict the outcome at the end of treatment while the patient is undergoing treatment may lead to improved quality of treatment planning.

PI: Scott Sorg PhD

Sponsor: Home Base (internal Catalyst grant)

This project seeks to leverage a large set of existing data collected within the scope of special operators’ clinical care to evaluate potential associations between blast exposure and white matter microstructure and neurocognitive functions. We will analyze diffusion-weighted imaging (DWI) data from over 200 special operators who participated in the Home Base Comprehensive Brain Health and Trauma (ComBHaT) program and who meet inclusion criteria. We will use a measure of blast exposure (GBEV) to estimate aggregate lifetime blast exposure. We will integrate results of clinical neuropsychological assessments as measures of cognition, in addition to measures of psychiatric symptoms.

This project involves integrating and analyzing data from multiple sources:

1) IRB Protocol # 2022P002143 “Advanced Assessments in Special Operations Forces Members” (aka Home Base Imaging Repository), PI: Rajiv Gupta – diffusion imaging, T1 structural imaging, and other imaging data.

2) IRB Protocol # 2011P001197 “Home Base Data Repository”, PI: Kalo Tanev: symptom data, blast survey interview data.

3) Medical record reviews related to neuropsychological data or other relevant clinical data that is not yet incorporated into the either of the above data repositories.

PI: Kalo Tanev MD

Specific Aim 1: Assess the changes in depressive symptoms following Buspirone + Melatonin combination (B+MEL) in post-TBI depression. Hypothesis 1: The B+MEL treatment combination will be associated with improvements in depressive symptoms (changes in HAM-D scores pre- to post-treatment).

Specific Aim 2: Assess the changes in cognitive symptoms following Buspirone + Melatonin combination (B+MEL) in post-TBI depression.

Hypothesis 2: The B+MEL treatment combination will be associated with improvements in measures of verbal memory, executive functioning, and speed of information processing pre- to post-treatment.

Specific Aim 3 (exploratory aim): To assess neuroimaging changes in fMRI resting state functional connectivity in outpatients with post-TBI depression treated with the B+MEL combination. Hypothesis 3: The B+MEL treatment combination will show pre- to post-treatment resting state functional connectivity increases within the frontoparietal control network (implicated in cognitive control of attention), decreases within the default network (implicated in internally oriented and self-referential thought), and decreases between the frontoparietal control network and the default network.

PI: Kalo Tanev MD

This study investigates the usefulness of a simple electrophysiological test in predicting the likelihood of a favorable response to a selective serotonin reuptake inhibitor (SSRI). SSRIs are typically prescribed as antidepressants and can be used to treat posttraumatic stress disorder (PTSD); however, we know that many patients are not responsive to SSRIs. Accordingly, finding ways to predict treatment outcomes before prescribing is of the utmost importance in successfully treating PTSD.  This study will use electroencephalography (EEG), a test that measures electrical activity in the brain, to better understand a certain indicator of the neurotransmitter serotonin. Better understanding this indicator, termed the loudness dependence of auditory evoked potentials (LDAEP), and its relationship with SSRIs, will allow researchers to draw conclusions about the effectiveness of such EEG technology in predicting an individual’s response to SSRI treatments.

PI: Ron Hirschberg MD

The goal of this study is to determine the feasibility and effectiveness of listening to Lydian-based music as a therapeutic, mindfulness, and wellness intervention for veterans and service members with PTSD. Hypothesis 1: Listening to Lydian-based music will elicit a greater parasympathetic and relaxation response, compared to Major-based music.  Hypothesis 2: Listening to Lydian-based music will facilitate a greater sense of focus on the present moment, compared to Major-based music.  Hypothesis 3: Listening to Lydian-based music will facilitate a greater reduction in PTSD symptoms, compared to Major-based music.

PI: Edward Pace-Schott

Sponsor: Home Base (internal Catalyst grant)

This project seeks to advance scientific knowledge about sleep problems, and their relationships with PTSD symptoms, before and after treatment for PTSD in veterans and active-duty military service members.  We will investigate sleep quality and physiology before, during, and after trauma-focused cognitive behavioral therapy (tf-CBT) for PTSD, and the relationship between sleep and PTSD symptoms, using sleep diaries, wrist actigraphy, and polysomnography (PSG). We will compare our subjects before tf-CBT with sleep data from age-matched healthy controls in an existing database, and will also examine the relationship between pre- to post-treatment improvements in PTSD symptoms and sleep quality.   We expect our study to identify treatment targets that will become the focus of future studies, and spur sleep medicine advocacy initiatives directed at veterans and service members. We expect our results to lead to broader use of this technology by the medical community that would result in higher quality care for this vulnerable population.

PI: Antonia Seligowski PhD

Sponsor: MGH Home Base Catalyst grant

In this study, we are evaluating the impact of exercise on the link between symptoms of post-traumatic stress disorder (PTSD) and cardiovascular disease via advanced imaging techniques in 10 individuals. We hypothesize that exercise will lead to beneficial changes in the brain that lead to reductions in the “fight-or-flight” response and inflammation, which will subsequently lead to reduced inflammation in the arteries.

PI: Clas Linnman PhD

Sponsor: MGH Home Base Catalyst grant

The aim of the project is to evaluate the sensitivity of [18F]3F4AP to detect active demyelination processes in mild to moderate primary blast-induced human TBI. Results will be compared to state-of-the art ultra-high resolution diffusion-, T1/T2-, and resting state functional-MRI.

PI: Kalo Tanev MD

This is a study of a smartphone pain app (MobileNetrix MasterMyPain) used by veterans participating in the Home Base Pain Program. The app provides daily Ecological Momentary Assessment (EMA) of the participants’ pain intensity, activity interference, mood, medication use, side effects, and coping. We are seeking to learn if the pain app demonstrates good tolerability, adequate retention, adherence, and positive feedback over the 3-month study period. In addition, we are seeking to learn if the pain app demonstrates a high degree of convergent validity compared to traditional pain scales, providing information on the degree to which participants experience a reduction in pain, emotional distress, or pain interference.

PIs: Shan Siddiqi MD, Joseph Taylor MD

Sponsor: Home Base Innovation Award to Catalyze Military-Connected Research

Aim 1: Assess the safety, feasibility, tolerability, and acceptability of brain-circuit-targeted aTMS for PTSD. We hypothesize that aTMS for PTSD will be safe, feasible, tolerable, and acceptable to veterans with PTSD.
Aim 2: Estimate the effect size of active versus sham circuit-targeted aTMS for PTSD. We hypothesize that, relative to sham aTMS, active aTMS will show a moderate-to-large effect size that will power a subsequent confirmatory efficacy trial.

PI: Sahand Babapoor-Farrokhran MD

Sponsor: Home Base Innovation Award to Catalyze Military-Connected Research

Aim 1: Determine the impact of closed-loop centro-parietal alpha-band stimulation on alpha band entrainment of the centro-parietal areas. We hypothesize that anti-phase closed-loop alpha band tACS will lead to a greater decrease in alpha power in these areas following ketamine treatment.
Aim 2: Determine the impact of closed-loop centro-parietal alpha-band stimulation on improvement in depressive symptoms. We hypothesize that anti-phase closed-loop alpha band tACS will lead to a greater improvement in depressive symptoms.
Aim 3: Determine the impact of closed-loop centro-parietal alpha-band stimulation on improvement in PTSD symptoms. We hypothesize that anti-phase closed-loop alpha band tACS will lead to a greater improvement in PTSD symptoms.

PI: Kalo Tanev

Using clinical data covered by existing Data Repository IRB Protocols, we will try to predict treatment outcomes for PTSD from baseline imaging (fMRI) and cognitive predictors among Home Base ICP patients. Previous published research (Tanev et al., 2024) has reported that patients with PTSD and cognitive impairment had a higher level within-ventral attention network (VAN) as compared to controls. In this study, we hypothesize that the combination of pre-treatment impaired memory and executive functioning plus altered within-VAN connectivity will predict treatment outcomes.

PI: Dan Daneshvar

The degree to which specific life exposures accelerate aging, precipitate the premature onset of disease, and reduce healthspan (the period of life without chronic disease) remains incompletely understood. The impact of chronic military exposures on later life healthspan remains incompletely characterized, and data examining chronic disease burden among special operators is lacking. The purpose of this study is to: (a) compare the incidence of comorbidities among a sample of special operators to a large, general population sample from open-source, national databases (i.e., National Health and Nutrition Examination Survey [NHANES], National Health Interview Survey [NHIS]), and (b) calculate and compare the intact healthspan between special operators and the general population. Comorbidity data will derive from available clinical data corresponding to the incidence (yes, no, or missing) of arthritis, hypertension, diabetes, cancers, posttraumatic stress disorder, anxiety, and depression. Comorbidity incidence and intact healthspan (incidence of individuals without chronic disease) will be computed as across age-specific, race-specific, BMI-specific, and service length exposure-specific bins. Military exposures will be reflected by service length, number of combat deployments, extent of blast exposure during service, and if applicable, sleep behavior and injuries accrued during service. This project will utilize existing data collected through the Home Base Comprehensive Brain Health and Trauma (ComBHaT) Program for special operators. This data consists of demographic and service-related information, as well as the incidence of medical/psychiatric condition, and will be derived from self-report survey questions and clinician-administered assessments. In addition, this secondary use protocol will compile additional data through medical record review.

PI: Jane Tseng

Sponsor: Department of Defense

Repeated blast exposure (RBE) is being increasingly recognized as an “invisible wound” of military service members as it may not result in a diagnosis of mild traumatic brain injury or concussion but can still lead to memory difficulties and changes in mental health. The impact of RBE on the brain is not well characterized, making it difficult to identify and manage these wounds. This study aims to better understand the neurobiological changes associated with RBE and how it relates to cognitive and behavioral symptoms. We hope that the knowledge gained from this study will contribute to the advancement of care for military brain health. This study investigates how epigenetics (the process through which environment influences how genes are read) in the brain is associated with repeated blast exposure in combat veterans and how epigenetics may contribute to changes in memory and mental health. We are interested in measuring the expression of histone deacetylases (HDACs), which are epigenetic proteins that are important for turning genes on/off. We will ask participants to undergo a PET-MRI brain scan, answer questionnaires, and complete memory tests.

PI: Hannah Steere MD                                                                                                                                                                         Sponsor: Wounded Warrior Project

One of the most frequent and persistent types of chronic pain after mTBI is post traumatic headache (PTH). Understanding the mechanisms within PTH is necessary for identifying optimum treatment. However, these mechanisms are poorly understood. This project seeks to better understand the pathophysiology of PTH by performing quantitative sensory testing (QST), a range of psychophysical, non-invasive tests that offer insight into pain processing. The project also aims to collect pilot data on the responsiveness to treatment with sphenopalatine ganglion nerve block and whether the response correlates with QST phenotype.

Goal 1: To identify pain thresholds, tolerance, and conditioned pain modulation in patients with PTH and history of TBI and in headache-free TBI participants.

Goal 2: To collect pilot data on the effect of SGB versus placebo on PTH pain scores in an outpatient cohort with history of mTBI.

Goal 3: Examine whether SGB is associated with changes in pain processing, and determine whether the effect from SGB correlates with PTH phenotype in this pilot study.

PI: Grant Iverson PhD

Sponsor: Wounded Warrior Project

The NIH sponsored investigators at Boston University to lead a consensus effort to develop new and more refined criteria for traumatic encephalopathy syndrome (TES) and chronic traumatic encephalopathy (CTE). Those criteria were published in March 2021.  Our project will involve conducting four studies that will be foundational to, and essential for, examining the reliability, validity, and accuracy of the new criteria for diagnosing CTE and TES in a living service member, veteran, or civilian.

Study #1: Systematic review of the course and clinical features of CTE as understood from all known cases in the 20th Century.

Study #2: Examine the new diagnostic criteria for TES by carefully applying it to all presumed cases of CTE from the 20th century.

Study #3: Examine the specificity of the new research criteria for the clinical diagnosis of traumatic encephalopathy syndrome in men and women from the general population.

Study #4: Examine the new clinical diagnostic criteria for CTE in post 9/11 veterans with PTSD.

PI: Kalo Tanev MD MPH

Sponsor: Senseye Inc.

Objective: To obtain data on the feasibility of a new smartphone app / software product – the Senseye Diagnostic Tool (DT) – to assess the presence and severity of posttraumatic stress disorder (PTSD) symptoms while individuals undergo intensive treatment for PTSD.  Rationale: PTSD can be difficult to accurately diagnose. Currently, the most accurate means of diagnosis is a clinician-administered PTSD scale (CAPS-5) or a structured clinical interview (SCID), which are time-consuming to administer, and results are influenced by the clinician’s experience and the patient’s responses to questions. Millions of people have experienced trauma and are at-risk for developing PTSD, so it is imperative to find a more accurate and cost-effective means to screen individuals for PTSD. This study will be conducted to inform and train the Senseye DT’s machine learning algorithm, which will then be evaluated for effectiveness in identifying people with PTSD compared to the gold-standard assessments in a subsequent clinical trial.

PI: René Lento PhD

Aim 1: Evaluate the acceptability of a web-based QI provider training on an evidence-based suicide
risk reduction intervention (SPI) and its impact on providers’ general confidence intervening with
patients as-risk for suicide, as well as their willingness and confidence in using the SPI in their
practice. Demographic information, quantitative and qualitative feedback on training content, and overall acceptability and feasibility, will be collected from providers immediately pre- and post-training. Hypothesis: The training will be acceptable and result in increased provider confidence ratings.
Aim 2: Determine the impact of the QI training on provider behavior change. SPI use rates at pre-, post and 3-months following training completion will be measured through provider self-report and EHR enterprise data warehouse reports. Hypothesis: Follow-up data will indicate increased SPI use following the QI training.
Exploratory Aim 3: Explore provider-level differences that moderate training impact on SPI utilization. Potential moderators will include provider discipline, years-in-practice, patient population served, post-training confidence ratings, and seeking out additional SPI training. Hypothesis: provider-level factors will be associated with differential training impact.

PI: Alexis Iaccarino MD

Sponsor: Wounded Warrior Project

Cerebrovascular dysfunction is associated with sub-clinical neural damage, and is a strong predictor of cognitive decline even in the general population.  It is also common even after a mild TBI, and its extent is strongly related to severity of cognitive dysfunction. In addition, autonomic dysfunction can lead to cognitive impairments independent of other factors.  Autonomic dysfunction is common after TBI, persists beyond clinical symptom resolution, and relates to the extent of TBI exposure.  Thus, TBI-related alterations in cerebrovascular and autonomic function may lead to cognitive impairment. However, it remains unclear how these alterations relate to TBI exposure (number, frequency, and severity).  Moreover, a decline in cerebrovascular and autonomic function is also associated with healthy aging. Yet, it is unknown how TBI-related changes differ from those due to advancing age.  The primary aim of this study is to evaluate changes in cerebrovascular function and autonomic function after TBI.

PI: Gabrielle Hoover PhD

Sponsor: Home Base (internal Catalyst grant)

This study utilizes a comprehensive battery of measures of psychopathology as well as clinical diagnoses assigned by a psychologist and leverages advancements in the field of exposure assessment via novel x-ray fluorescence (XRF) technology to measure lead exposure in bone, nails, and hair. Our primary aim is to build the foundation for a biobank or other service utilizing the XRF as a surveillance tool for the Home Base program. Within this aim are two core hypotheses:

1. Among Veterans and active duty servicemembers, determine whether higher lead exposure is related to higher levels of mental health symptoms, including PTSD severity and suicidality.
2. Among Veterans and active duty servicemembers who served in Iraq and Afghanistan or operate lead producing weapons, determine whether there are higher levels of lead exposure and mental health symptoms as compared to those without the mentioned risk factors for lead exposure.

PI: Amanda Baker

Sponsor: Spier Family Foundation

There is evidence that interventions targeting self-compassion improve social functioning and PTSD symptoms among Veterans. This pilot trial will investigate the feasibility, acceptability, and efficacy of Mindful-Self-Compassion (MSC) for Veterans with PTSD. This will lay the groundwork for future studies that will augment the MSC treatment with MDMA to further target symptoms of social disconnection.

PI Amanda Baker

Sponsor: Home Base (internal Catalyst grant)

Many individuals who have completed trauma-focused therapy still experience “less diagnosable” symptoms like a lack of connection or meaning in life, which can interfere with day-to-day functioning. This study seeks to fill this treatment gap by evaluating the feasibility and acceptability of a group-based meaning-centered CBT, with the goal of increasing meaning in life and decreasing loneliness.