Cerebellar repetitive transcranial magnetic stimulation (rTMS) for reduction of negative affect and treatment of alcohol use disorder

Abstract Alcohol use disorder (AUD) is a major cause of morbidity and mortality. More treatments are needed. Repetitive transcranial magnetic stimulation (rTMS) alters neuroplasticity and connectivity within the brain, is an FDA-approved treatment for major depressive disorder, and is being explored for the treatment of AUD. To date, however, an efficacious rTMS protocol for reduction of drinking and other important clinical outcomes in AUD have yet to be identified. Preliminary data indicates that the cerebellum may be an important treatment target for reduction of negative affect and downstream alcohol use in individuals with AUD. In particular, greater activation in cerebellum during a multisensory Stroop task is strongly correlated with both self-reported negative affect and alcohol use disorder severity. The overall aim of this study is to investigate the efficacy of inhibitory rTMS on self-reported negative affect and on activation in cerebellum during a multisensory Stroop task. Thirty-four treatment-seeking individuals with AUD will be recruited from local intensive outpatient treatment programs (IOPs), enrolled, randomized to active treatment or sham (blinded), and treated in 10 sessions over 2 weeks. To assess changes in brain function that result from treatment with rTMS, fMRI scans will be obtained at baseline and 2 weeks (baseline and 1 day following treatment completion). Our primary outcome measures will include self-reported negative affect, cerebellar activation during the Stroop task, and alcohol use outcomes. We hypothesize that reductions in negative affect and in BOLD signal will be greater in individuals on active compared to sham inhibitory rTMS. We also hypothesize that these reductions and active treatment will be related to better alcohol use outcomes (greater percent days abstinent, longer time to relapse). Findings will provide critical information about whether or not a larger clinical-trial investigating the efficacy of rTMS to the cerebellum for individuals with AUD is warranted.