Total Brain Diagnostics (TBD): Analyzing the Impact of Functional Symptom and Clinical Measures on Co-Morbid Mental Health Conditions after TBI

Mild traumatic brain injuries (mTBI) were commonly sustained among those who served in Operation
Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) and are
associated with increased rates of mental health disorders, including posttraumatic stress disorder
(PTSD). Indeed, among a cohort of those who served in the conflicts and sought Veterans Health
Administration care, 89% of Veterans with a mTBI had a comorbid psychiatric disorder, with PTSD
being the most common (73%). Unfortunately, symptom overlap between mTBI and mental health
conditions can impact diagnostic clarity and prognosis. This can hamper implementation of
personalized approaches (i.e., precision medicine) focused on enhancing assessment and treatment
to ensure brain health and associated optimal psychosocial functioning. Moreover, such personalized
care strategies would also be expected to decrease risk for negative outcomes like suicide. Based on
increased risk for suicide among both younger and older cohorts of Veterans, suicide prevention
remains the highest clinical priority within the VHA. One solution to overcoming existing data and
clinical challenges is the integration of existing data sets focused on both clinical outcomes (e.g.,
PTSD symptom severity) and physiologic biosignals/functional measures (e.g., electroencephalogram
[EEG] activity, computerized posturography, computerized eye tracking). Such an approach would
allow the application of advanced analytic techniques to develop algorithms (e.g., diagnostic,
prognostic) that can be used to promote brain health among Veterans with co-occurring mTBI and
mental health sequelae (e.g., PTSD). To carry this out, members of this team with significant
expertise in mental health and suicide prevention will collaborate with other teams engaged in the
Total Brain Diagnostics (TBD) Proof of Concept linked submissions. As a first step, we will create a
unified/harmonized dataset of measures collected as part of the Long-Term Impact of Military Brain
Injury (LIMBIC) and Translational Research Center for TBI and Stress Disorders (TRACTS) protocols.
Based on LIMBIC and TRACTS longitudinal data collection, clinical and physiologic
biosignals/functional measures will be available. The goal of this mental-health focused TBD
submission will be to explore associations between physiologic measures and mental health
outcomes, including depression, anxiety, substance/alcohol use, PTSD, and suicidal thoughts and
behaviors. Specific efforts will focus on identifying key objective, functional physiologic measures
within the harmonized longitudinal dataset which predict: 1) the presence of mental health
outcomes/conditions (e.g., symptoms, suicidal thoughts and behaviors) after combat-related mTBI;
and 2) distinct trajectories of mental health outcomes/conditions (e.g., symptoms, suicidal thoughts
and behaviors) post-combat-related mTBI. Study Aims are as follows: Aim 1. Work with the LIMBC-
TRACTS harmonization team to construct and become familiarized with the unified dataset. Aim 2.
Identify one or more uniform analytic approaches (e.g., machine learning) to facilitate analysis of this
unified dataset. Aim 3. Analyze the impact of physiological biosignals/functional indicators on the
longitudinal trajectory of mental health symptoms and conditions. Aim 4. Collaborate with behavioral
and biomarker measure experts to conduct multimodal factor analyses. A key project deliverable is
the development of the LIMBC-TRACTS combined data set. Initial findings from this proposed effort
will be foundational for subsequent inquiry focused on enhancing diagnostic and prognostic efforts to
improve brain health and psychosocial functioning among Veterans living with mTBI and mental
health conditions.

Grant Number: 5I01RX004911-02
NIH Institute/Center: VA
Principal Investigator: Lisa Brenner