Frontal iTBS for Impulsivity and Suicidal Ideation in Veterans With Mild Traumatic Brain Injury

Individuals with mild traumatic brain injury (mTBI) are at increased risk of dying by suicide compared to those without - both among Veteran and civilian populations. 22% of Veterans with mTBI report struggling with suicidal ideation (SI). Despite this, there are no effective evidence-based treatments for co-occurring mTBI and SI. Deficits in social and occupational functioning, which often follow mTBI, are strongly related to suicidal ideation (SI) and improvements in these areas are known to lessen SI. Thus, improving function for those with mTBI and SI is of great potential significance. The impulsivity that Veterans with mTBI exhibit is referred to as "negative urgency impulsivity". It often involves aggressive and self-harming behaviors, which impede societal re-integration and rehabilitation. Prior studies indicate negative urgency impulsivity is: (1) a common TBI sequela and (2) a risk factor for SI. Previous studies have also indicated individuals with TBI, SI and negative urgency impulsivity had reduced right-sided ventromedial prefrontal cortex (VMPFC) volume compared to Veterans without these conditions. The VMPFC plays a key role in controlling impulsive limbic responses. These findings are consistent with published reports suggesting individuals with reduced VMPFC volume are more likely to (a) have SI and (b) behave impulsively.

Transcranial magnetic stimulation (TMS) holds significant therapeutic promise for post-mTBI SI, impulsivity and functional deficits. TMS induces neuroplasticity, leading to changes that have the potential to improve neurorehabilitation outcomes. TMS is effective for treating post-TBI depression when administered to the dorsolateral prefrontal cortex. Intermittent theta burst stimulation (iTBS) is a "second generation" form of TMS that is delivered more rapidly. It has been proposed that frontal pole TMS could directly strengthen connections throughout the prefrontal cortex, including the VMPFC, thereby dampening limbic system activity. Such a TMS treatment strategy could be used to treat post-mTBI impulsivity and SI, ultimately allowing Veterans to regain functioning. It is not know which Veterans would benefit most from this treatment; examining neural connectivity changes before and after iTBS could determine who would respond to frontal pole iTBS and why.

The investigators will conduct a randomized, double-blinded frontal iTBS pilot clinical trial for Veterans with mTBI, impulsivity and SI. As this is a novel treatment approach for this population, this project will focus on testing the safety, feasibility and tolerability of frontal pole iTBS. To inform future research, this project will determine the preliminary effects of iTBS on functioning, negative urgency impulsivity and SI among the pilot sample. This project will also inform future research by examining the relationships between the functional neural connectivity of the VMPFC to the limbic system and how this is affected by iTBS using resting state functional connectivity (rsFC) neuroimaging data, pre- and post-iTBS.

Inclusion criteria

• 22-65 years of age
• can read and speak English
• meets criteria for mTBI according to the symptom attribution and classification (SACA) scale
• Has a C-SSRS (suicidal ideation rating) of >1 within the past month
• Has a history of impulsivity documented in the medical chart and/or a score of >20 on the UPPS-P negative urgency impulsivity subscale

Exclusion criteria

• Has contraindications to iTBS (i.e., epilepsy)
• Has contraindications to MRI (i.e., claustrophobia, ferromagnetic metal implants)
• Has an active substance use disorder per the DSM-V criteria
• Has a history of moderate to severe TBI
• Has a history of non-traumatic neuroinjury (i.e., stroke, neurosurgery, hemorrhage)
• Has a history of, or current psychosis not due to an external cause
• Is pregnant
• Has an active, unstable medical condition
• Is within 12 weeks of a major surgery or operation
• Is within 1 year of TBI