Yale University, School of Medicine, Department of Psychiatry, New Haven CT, USA.
Medical Scientist Training Program, University of Minnesota, Minneapolis MN, USA.
Pharmacol Biochem Behav. 2021 Oct;209:173240. doi: 10.1016/j.pbb.2021.173240. Epub 2021 Jul 21.
Developing new, effective treatments for substance use disorders (SUDs), especially cocaine and opioid use disorders (CUD and OUD), are of immense importance. These are chronic, relapsing brain diseases characterized by dysregulated circuits manifesting from neuroplastic change brought on by repeated exposure to substances of abuse. A potential treatment is therapeutically inducing neuroplastic change in targeted dysregulated circuits. One such intervention, repetitive transcranial magnetic stimulation (rTMS) has gained traction over the past two decades as a method of noninvasively stimulating cortical structures in order to induce subcortical neuroplastic change. By doing so, rTMS ameliorates symptoms that are consequent of dysregulations in disease-related circuits, such as craving, and reduces drug use. Although rTMS has been successfully applied as a treatment for other clinical disorders, progress toward treatment applications for SUDs has been stymied by what we dub "known unknowns". These are fundamental lines of research within the rTMS-SUD field that have yet to be systematically understood which could help to optimize TMS as an intervention for SUDs. Because progress in treatment for CUD and OUD is imperative given the widespread severity of OUD and the lack of treatment for CUD, it is necessary to critically reflect on the ways in which rTMS research for these disorders can most effectively move forward to help patients. We articulate six "known unknowns" and outline a direction of research to address each. Briefly, the "known unknowns" in the field are: 1) Cortical target selection, 2) subcortical circuit engagement, 3) optimizing rTMS sequences, 4) rTMS as an adjuvant to existing interventions, 5) manipulating brain state, and 6) selecting outcome measures. We also outline research design approaches to address these "known unknowns" in the rTMS-SUDs field. Unification of efforts across research laboratories is necessary to develop empirically validated treatments that will benefit patients in a timely fashion.
开发新的、有效的物质使用障碍（SUD）治疗方法，尤其是可卡因和阿片类物质使用障碍（CUD 和 OUD）的治疗方法，具有重要意义。这些疾病是慢性、复发性的脑部疾病，其特征是受神经可塑性变化影响的调节回路紊乱，而这些变化是由反复接触滥用物质引起的。一种潜在的治疗方法是在靶向调节紊乱的回路中进行治疗性的神经可塑性诱导。一种这样的干预措施是重复经颅磁刺激（rTMS），在过去二十年中，它作为一种非侵入性刺激皮质结构的方法，已获得关注，以诱导皮质下神经可塑性变化。通过这种方式，rTMS 改善了与疾病相关的回路紊乱引起的症状，如渴望，并减少了药物使用。尽管 rTMS 已成功应用于其他临床疾病的治疗，但在将其应用于 SUD 治疗方面的进展受到我们所谓的“已知未知”的阻碍。这些是 rTMS-SUD 领域内尚未得到系统理解的基础研究，这些研究可能有助于优化 TMS 作为 SUD 干预手段。由于阿片类药物使用障碍的广泛严重性和对可卡因使用障碍缺乏治疗，因此迫切需要批判性地反思 rTMS 研究如何最有效地推进以帮助患者。我们阐述了六个“已知未知”，并概述了研究方向以解决每个问题。简而言之，该领域的“已知未知”包括：1）皮质目标选择，2）皮质下回路参与，3）优化 rTMS 序列，4）rTMS 作为现有干预措施的辅助手段，5）操控大脑状态，以及 6）选择结果测量指标。我们还概述了研究设计方法，以解决 rTMS-SUD 领域中的这些“已知未知”。有必要统一研究实验室的努力，以开发及时有益于患者的经验证有效的治疗方法。
