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

摘要 该提案的总体目标是测试高效和个性化的 重复经颅磁刺激（rTMS）方法，称为斯坦福大学加速智能 神经调节治疗（SAINT）。在本提案中，我们将利用SAINT作为快速干预措施， 在急诊精神科入院的背景下，减少外显和内隐自杀认知， 自杀的想法和行为。虽然rTMS被FDA批准用于治疗难治性抑郁症（TRD）， 平均需要的治疗应用是在症状改善迹象之前6周，这不是一个有效的治疗方法。 急性自杀危机对症治疗的最佳策略。本申请的动机有三个 神经调节领域的最新发现。首先是一个假对照的试点研究，评估加速 传统的rTMS方案，其中多个刺激会话安全地输送到左背外侧 前额叶皮层（L-DLPFC）在三天内与自杀意念的患者。本研究证明 传统的rTMS可以被“加速”，并显示出减少显性自杀的信号。 认知.其次，有两项值得注意的间歇性θ-爆发刺激的随机试验， L-DLPFC证明了间歇性θ波爆发刺激（iTBS）作为TRD治疗的有效性， 通常与自杀认知有关的病症。iTBS已被证明具有5倍的脉冲 传统rTMS的效能，与传统rTMS相比， 传统的rTMS，因此使每天多次治疗成为可行的干预措施。最后的创新是 利用静息状态功能连接的rTMS靶向改善了rTMS的抗抑郁效果。我们 设计了一种方法，我们称之为SAINT，它每天利用大量的iTBS应用程序， 间隔学习理论的原则（优化的闭会期间间隔），在一个功能性连接推导 靶标（L-DLPFC-sgACC）。在TRD中，我们观察到情绪的戏剧性变化和相关的外显自杀 使用SAINT的认知。我们建议利用SAINT来调节神经回路， 内隐自杀认知沿着调节因子/中介因子（绝望、快感缺乏和抑郁）。我们将 进行SAINT应用于L-DLPFC-sgACC的随机对照试验，以评估 降低住院精神病患者自杀认知的方法

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.