MECHANISMS OF TBI RECOVERY FOLLOWING MINDFULNESS BASED STRESS REDUCTION FOR PATIENTS WITH SLEEP DYSFUNCTION

Traumatic brain injury (TBI) is a devastating injury, impacting approximately 20% of service members deployed in current military activities. Sleep disorders are a major dysfunction, affecting an estimated 30-70% of those with TBI. It is the most important symptom for post-concussion syndrome (PCS) and has the highest association with co-morbid factors such as post-traumatic stress disorder (PTSD) in service members with TBI. Furthermore, service members with TBI and co-morbid sleep dysfunction reported higher levels of daytime fatigue, lower quality of life scores, increased anxiety, increase depression, and increased chronic pain, and are also prone to suffer from concomitant headache and/or dizziness. Changes in sleep regulation and symptoms of insomnia are attributed in part to interactions among genes and the environment. Deployment exerts unique stressors on military personnel, including adjustment to multiple time zones, chronic sleep deprivation, unsafe sleeping environments, and the use of sedative hypnotics. TBI increases the risk for insomnia, likely through molecular changes in sleep-regulating brain structures. This leads us to question how changes in gene-activity and how biological mechanisms underlining insomnia and TBI increase the risk for PTSD, depression, and PCS. We recently reported gene-expression changes, specifically, we observed a reduction in the activity of urotensin 2, which was significantly lower in participants with insomnia compared to controls. We also observed an up-regulation in genes related to homeostasis, and REM regulation, which is associated with insomnia. Sleep dysfunction and TBI also disproportionately affect major cognitive and limbic structures in the brain. Mild TBI is associated with significantly lower cerebral metabolic rate of glucose (rCMRglc) during wakefulness and REM sleep in the amygdala, hippocampus, thalamus, insula, visual association cortices, and midline medial frontal cortices, along with white matter damage in the parahippocampal gyri. These results suggest that alterations in neurobiological networks during wakefulness and REM sleep subsequent to mTBI exposure may contribute to chronic sleep disturbances. Furthermore, poor sleep increases physiological stress, particularly in patients with TBI. Stress is a significant component of poor recovery and increased symptoms. In this context, we propose studying the effects of Mindfulness Based Stress Reduction (MBSR) for treatment of stress and sleep dysfunction for patients with mTBI. MBSR is a standardized protocol of meditation and yoga that has been studied extensively in other populations, but not well studied in TBI or for sleep. Meditation and yoga have the potential to improve beneficial neuroplasticity to potentially help heal the injury not just symptomatic treatment. Hypotheses: (1) We hypothesize MBSR will improve sleep disturbance and sleep-related impairments as measured by the NIH-sponsored Insomnia Severity Index (ISI) and the Patient Reported Outcomes Measurement Information Systems (PROMIS) in military personnel with chronic symptoms after TBI (2) We hypothesize MBSR will increase sleep quantity as measured by wrist Actigraphy in military personnel with chronic symptoms after TBI (3) We hypothesize that MBSR will improve resiliency factors, health-related quality of life (HRQL), and decrease symptoms of stress, post-concussive syndrome (PCS), PTSD, and depression in military personnel with chronic symptoms after TBI Research: To determine these relationships we will recruit 35 patients from TBI treatment centers at Fort Belvoir Community Hospital, who are currently receiving standard of care treatment (SCT) following a TBI. We will determine changes in neuroplasticity and neuro-inflammatory biomarkers at 8 weeks following MBSR compared to controls, using structural (standard T1/T2 weighted and DTI) methods of advanced neuroimaging and the Single Molecule Array (SIMOA) Technology. Innovation: Insomnia in military personnel is highly comorbid, suggesting that comprehensive interventions such as MBSR, which incorporates psychosocial education, stress management and breathing techniques, offer more promise for a sustained recovery from TBI and sleep disturbance compared to traditional methods [6]. In other patient populations, MBSR improved sleep quality [7] and stress-related outcomes (i.e., anxiety, depression, and pain) [8]. We suggest that molecular mechanisms and neuroplastic changes underlie insomnia recovery, and that a better understanding of the biological changes will help personalize therapies, as well as inform other interventional methods. Impact: This project, if successful, will help identify a low-cost intervention with virtually no adverse events for treating patients with symptoms of insomnia in chronic TBI. This is a patient population that has been difficult to treat and currently requires intensive resources. This intervention has the potential for identifying a treatment that is generalizable, low-cost, and impactful with virtually no adverse events and can work synergetically with other treatments.