The Effects of Stanford Accelerated Intelligent Neuromodulation Therapy on Explicit and Implicit Suicidal Cognition

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ABSTRACT The overarching aim of this proposal is to test the efficacy and safety of a highly efficient and personalized repetitive transcranial magnetic stimulation (rTMS) method, termed Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT). In this proposal, we will utilize SAINT as a rapid-acting intervention for the reduction of explicit and implicit suicidal cognition within the context of an emergency psychiatric admission for suicidal thoughts and behaviors. Although rTMS is FDA approved for treatment-resistant depression (TRD), the average required treatment application is 6 weeks before signs of symptomatic improvement, which is not an optimal strategy for symptomatic treatment of an acute suicidal crisis. This application is motivated by three recent findings in the neuromodulation field. First is a sham-controlled pilot study evaluating an accelerated conventional rTMS protocol, where multiple stimulation sessions were safely delivered to the left dorsolateral prefrontal cortex (L-DLPFC) across three days in patients with suicidal ideation. This study demonstrated that conventional rTMS can be ‘accelerated’ as well as demonstrated a signal of reductions in explicit suicidal cognition. Second, there are two notable randomized trials of intermittent theta-burst stimulation applied to the L-DLPFC that demonstrated the efficacy of intermittent theta burst stimulation (iTBS) as a treatment for TRD, a condition commonly associated with suicidal cognition. iTBS has been demonstrated to have 5X the pulse potency of conventional rTMS, which allows for a much-reduced stimulation session time in comparison to traditional rTMS and therefore makes multiple treatments per day a feasible intervention. The final innovation is that rTMS targeting utilizing resting state functional connectivity improves antidepressant outcomes of rTMS. We designed an approach, which we termed SAINT, which utilizes numerous applications of iTBS per day, as per principles of spaced learning theory (optimized intersession-intervals), within a functional connectivity derived target (L-DLPFC-sgACC). In TRD, we have observed dramatic changes in mood and associated explicit suicidal cognition using SAINT. We propose utilizing SAINT to modulate the neural circuitry that underlies explicit and implicit suicidal cognition along with moderators/mediators (hopelessness, anhedonia, and depression). We will conduct a randomized, controlled trial of SAINT applied to the L-DLPFC-sgACC to assess efficacy of the approach in reducing suicidal cognition in hospitalized psychiatric inpatients.