Brain Targets for Alcohol Craving in Veterans with mTBI.

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DESCRIPTION : Mild traumatic brain injury (mTBI) is the signature injury of the current military conflicts: Operation Iraqi Freedom, Operation Enduring Freedom, and Operation New Dawn (OEF/OIF/OND). In Veterans of these conflicts, mTBI commonly co-occurs with mental health disorders such as post-traumatic stress disorder (PTSD). Hazardous alcohol use or probable alcohol use disorder (AUD) is also extremely prevalent in Veterans. The presence of an AUD has further negative impact on rehabilitation effectiveness for our Veterans with TBI. Craving, or the urge to consume a substance, is a critical characteristic of AUD. Alcohol craving negatively impacts rehabilitation and is associated with relapse in the alcohol-withdrawn addict. No studies to date have examined the role of alcohol craving in Veterans with co-occurring mTBI, PTSD and AUD (mTBI+PTSD+AUD). Therefore, the objectives of the current CDA II application are to characterize alcohol craving, develop a better understanding of the mechanism underlying alcohol craving, and develop a novel treatment intervention for alcohol craving reduction. In order to do so, OEF/OIF/OND Veterans will be recruited and classified into one of two groups based on self-report and neuropsychological assessments: 1) asymptomatic combat control Veterans with probable AUD (AUD alone) and 2) Veterans with mTBI+PTSD+AUD. First, alcohol craving and excessive alcohol use in these two groups will be compared. This will be done by conducting objective measures of alcohol use (e.g., urine and breath alcohol concentration tests), self-reports of alcohol use, and alcohol craving. Second, the neurophysiological mechanisms of alcohol craving will be examined in order to develop a novel treatment intervention for craving reduction. To do so, Veterans will participate in a functional magnetic resonance imaging (fMRI) protocol where brain activation will be measured in response to viewing images relating to alcohol compared to neutral images. Advanced neuroimaging procedures to determine the structural integrity of white matter fibers in the brain and to determine spontaneous activity in neuronal networks, a process called functional connectivity analysis, will also take place. The neuroimaging data will be evaluated collectively to elucidate the mechanism underlying alcohol craving and, along with the literature, these data will be used to develop a protocol for the neurotherapeutic intervention repetitive transcranial magnetic stimulation (rTMS). Third, the safety, feasibility, and the immediate effect of a single rTMS session on alcohol cravings along with neural activity and connectivity in Veterans with mTBI+PTSD+AUD will be examined. Veterans will complete neuroimaging, alcohol craving, and alcohol use measures as described above pre- and post-rTMS. Self-report alcohol craving will also be assessed at one day, one week, and one month post-rTMS via phone interview. It is expected that this innovative project will contribute a missing, fundamental element to our base knowledge, without which alcohol craving in Veterans with mTBI+PTSD+AUD cannot be understood. The acquisition of such knowledge is critical to the development of improved therapeutic strategies for alcohol addiction in Veterans with co-occurring mTBI and PTSD.