This Career Development Award Level 2 (CDA2) represents the candidate’s effort to execute a pilot study of a novel neuromodulatory treatment for Veteran [social and occupational functioning], impulsivity and [suicidal ideation] following mild traumatic brain injury (mTBI). The candidate’s first aim will examine the tolerability, safety and feasibility of frontal pole intermittent theta burst stimulation (iTBS) for Veterans with mild traumatic brain injury (mTBI), negative urgency impulsivity, [and suicidal ideation]. This is important because impulsivity, which is exhibited in up to 40% of individuals with TBI, is an independent risk factor for dying by suicide and is associated with poorer functional outcomes following TBI. Presently, there are no widely accepted treatment strategies for impulsivity, [suicidal ideation and social and occupational functional deficits] following TBI. The candidate’s second aim is to determine the effects of frontal pole iTBS on social and community functioning, negative urgency impulsivity and [suicidal ideation]. This will allow the scientific community to better understand how frontal pole iTBS treatment impacts [social and community] functioning and mental health outcomes. Finally, the candidate aims to evaluate whether iTBS improves connectivity between the VMPFC and limbic system, using resting state functional connectivity MRI. Completing this aim will allow us to better understand how iTBS affects neural connectivity and whether these changes are related to functional and mental health outcomes. This research is critical as suicide is a major issue among Veterans within the VA system. Veterans are 22% more likely to die by suicide than civilians. Veterans with TBI are even more likely to die by suicide than those without TBI. It is important to create a treatment to prevent unnecessary Veteran deaths while helping Veterans feel empowered and functional within their communities. [Suicide and TBI are not unique to Veterans, however. Civilians with TBI are also more likely to die by suicide than those without. Thus, findings from this research could serve to improve neuropsychiatric care in the civilian sector, as well.] This project serves as a critical first step in allowing the candidate and her team to develop a biologically-informed treatment strategy for the many individuals who struggle with mTBI, [social and occupational functional deficits], impulsivity and [suicidal ideation]. Ultimately, the candidate’s long-term career goal is to become an independent clinical researcher in the VA system with expertise in TBI, suicidality, neurostimulation and neuroimaging. As such, she will complete a careful training plan under the mentorship of a strong, multidisciplinary training team involving opportunities for networking with experts in fields relating to the above research, hands-on training in necessary research skills and coursework complementary to the research project. The planned research is significant, innovative, and impactful, as it will be the first pilot study of a new iTBS treatment paradigm, designed to improve Veteran lives and functional outcomes after mTBI. It will also strengthen the candidate’s knowledge base and research skills, preparing her for an independent career in post-TBI rehabilitation research, with expertise in impulsivity, suicidality and neuromodulation.

This proposal is relevant to Veterans because it is the first study of a new treatment to help Veterans struggling with mild traumatic brain injury (mTBI), impulsivity and [suicidal ideation]. These three conditions have been shown to be linked [and all are associated with problems functioning]. First, this study will make sure the new treatment, intermittent theta burst stimulation (iTBS), which involves a high-powered magnet placed directly on the forehead, is safe and easy for Veterans to tolerate. Second, this project will also test to see if the treatment improves Veteran community functioning, [lessens suicidal ideation] and lessens impulsivity. Finally, Veterans enrolled in the study will get brain magnetic resonance imaging (MRI) before and after the treatment to determine how iTBS changes Veterans’ brain connectivity to make them function better. Completing this research will improve Veterans’ health through the development of a new treatment for impulsivity and suicidality following mTBI.