Concussive or mild Traumatic Brain Injury (MTBI) related to blast injury is the most common form of combat-related injury in the Iraq and Afghanistan Wars. Along with post traumatic stress disorder (PTSD), cognitive and mood dysfunction, headache (HA) is the most debilitating clinical symptom in Veteran with MTBI. Unfortunately, conventional pharmacological treatments for MTBI related headache (MTBI-HA) has not shown to be effective and contain many long term untoward psychosomatic and abusive side effects. Recently, the use of non- invasive brain stimulation such as repetitive transcranial magnetic stimulation (rTMS) at the dorsal lateral prefrontal cortex(LDLPFC) has yielded favorable clinical outcomes in a few chronic central pain conditions including post-stroke central pain and headaches. In the past three years, the PI's clinical service has treated over 45 MTBI-HA Veteran with rTMS and observed favorable outcomes in headache relief and prevention. These benefits appear to be sustaujinable for a majority of patients with monthly repeated treatment. To further validate these observed favorable clinical outcomes, the investigators propose an initial randomized controlled project with the following main objectives:
Aim #1 : To compare the effect of active rTMS at LDLFC with sham rTMS in reducing the intensity and the duration of MTBI-HA;
Aim #2 : To compare the effect of active rTMS at LDLPFC with sham rTMS in improving cognitive and depressive symptoms associated with MTBI; In addition, to facilitate future studies in assessing the effect of repeat rTMS treatment at one month as an applicable clinical protocol and its effect on PTSD, and to further establishing the disease and therapeutic mechanisms related to MTBI-HA and rTMS respectively, the proposal also contains three exploratory aims: Exploratory Aim 1: In correlation with the headache and neurophysiological outcomes, this study will explore the effect of rTMS on supraspinal resting and evoked pain states in MTBI- HA patients with fMRI; Exploratory Aim 2: To explore the effect of maintenance rTMS for headache relief at the one-month interval after the initial treatments; Exploratory Aim 3: Since Headache, MTBI and Post-traumatic Stress Disorder (PTSD) are highly co-morbid conditions in Veterans, this study will explore the treatment effect of rTMS on alleviating functionally impairing conditions associated with PTSD(as identified with Clinician Administered PTSD Scale) in MTBI-HA Veterans. The proposed aims are closely interconnected and can be achieved without over- burdening both the Veteran and the investigators . Though these studies, the investigators aim to further develop rTMS as a non-invasive treatment tool for MTBI-HA and related neuropsychological dysfunctions, and enhance the understanding in MTBI related neurological mechanisms.

Public Health Relevance

Due to recent wars in Afghanistan and Iraq, the number of Veteran suffering from Mild traumatic brain (MTBI) injury and PTSD increases rapidly. Headache is one of the most debilitating clinical symptoms in Veteran with MTBI and the cause of it is still not entirely clear. Recently, the use of non-invasive brain stimulation such as repetitive transcranial magnetic stimulation (rTMS) has yielded favorable clinical outcome in a few intractable chronic central pain conditions including headaches. The PI's VA rTMS clinic has recently successfully treated over 45 MTBI Veteran with encouraging headache improvement, and other functional and mood enhancing rehabilitative benefits. This study aims to 1) assess the effect of rTMS in relieving headache and improving neurophysiological functions;and 2) explore the neuronal mechanisms associated with MTBI related headache and the analgesic effect of rTMS with fMRI.

National Institute of Health (NIH)
Veterans Affairs (VA)
Veterans Administration (I21)
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Special Emphasis Panel (RRDS)
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VA San Diego Healthcare System
San Diego
United States
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