Neuromodulation for Enhancement of Emotion Regulation in Bipolar Mood Disorders

项目摘要/摘要 双相情感障碍(BD)患者经历严重的间歇性情绪失调。我们的 现有的药物和心理社会治疗未能使许多双相情感障碍正常化 病人。我们需要新的和创新的方法来帮助改善这些患者的情绪失调。 这项建议的长期目标是了解BD情绪失调的病理生理学，以及 制定直接针对和提高情绪调节能力的策略。为此，候选人 建议：(1)培训目标是获取基于网络的高级神经成像数据分析方面的专门知识 以及使用经颅磁刺激(TMS)作为转化性临床和研究工具的培训； (2)研究目的：确定BD患者特有的情绪调节障碍的生物标志物 使用TMS试验性地吸引这些目标；(3)一组导师和顾问，以确保候选人的 成功，具有双相情感障碍病理和治疗方面的专业知识(安德鲁·尼伦伯格博士)，高级 神经影像数据的网络分析(兰迪·巴克纳博士)，TMS的临床和研究应用(Dr。 Mark George和Joan Camprodon博士)，情绪障碍的神经调节(Darin Dougherty博士)，情绪 法规(James Gross博士)，BD基于任务的神经成像(Thilo Deckersbach博士)，以及高级 统计学方法(马克·范赫尔博士)。该研究提案的中心假设是神经调节 使用TMS的情绪调节相关神经回路的患者特定靶点将增强 BD中的情绪调节。这项提议的理由是，现有的治疗方法不能充分解决 BD严重的情绪失调，因此需要新的创新方法。这个项目有潜力 为TMS作为一种创新的治疗策略的未来发展提供初步证据 可用于现有治疗方法的辅助，以改善BD患者的情绪调节。建议的具体目标包括： 1)明确BD内隐和外显情绪失调的患者特异性病理生理标志物； 2)确定TMS对BD情绪调节回路动力学的影响；3)确定其影响 TMS对BD情绪调节行为反应的影响这种方法是创新的，因为它使用了一个患者- 结合TMS-fMRI的特定、精确的医学方法，靶向和探测情绪障碍 神经回路的水平。这项拟议的研究意义重大，因为它有可能推动我们的 了解BD情绪失调的病理生理学机制，将提供重要的先导数据 目的探讨TMS改善BD患者情绪调节障碍的疗效。总体而言，候选人 我将利用这个项目及其相关的培训来将这项工作转变并扩展为一个独立的计划 为双相情感障碍开发神经科学知情干预的研究。

PROJECT SUMMARY/ABSTRACT Individuals with bipolar mood disorders (BD) experience severe and episodic emotion dysregulation. Our existing pharmacological and psychosocial treatments fail to normalize emotion dysregulation for many bipolar patients. We need new and innovative approaches to help improve emotion dysregulation for these patients. The long-term goal of this proposal is to understand the pathophysiology of emotion dysregulation in BD, and to develop strategies to directly target and improve emotion regulation capacity. To this end, the candidate proposes: (1) training objectives to acquire expertise in advanced network-based analysis of neuroimaging data and training in the use of transcranial magnetic stimulation (TMS) as a translational clinical and research tool; (2) a research objective to identify patient-specific biomarkers of emotion dysregulation in BD and to experimentally engage these targets using TMS; (3) a team of mentors and advisors to ensure the candidate’s success, with expertise in bipolar disorder pathology and treatment (Dr. Andrew Nierenberg), advanced network analysis of neuroimaging data (Dr. Randy Buckner), clinical and research applications of TMS (Dr. Mark George and Dr. Joan Camprodon), neuromodulation of mood disorders (Dr. Darin Dougherty), emotion regulation (Dr. James Gross), task-based neuroimaging in BD (Dr. Thilo Deckersbach), and advanced statistical methods (Dr. Mark Vangel). The central hypothesis of the research proposal is that neuromodulation of patient-specific targets of emotion regulation-related neurocircuitry using TMS will enhance the capacity for emotion regulation in BD. The rationale for this proposal is that existing treatments don’t adequately address severe emotion dysregulation in BD, thus new innovative approaches are needed. This project has the potential to provide preliminary evidence for the future development of TMS as an innovative treatment strategy that can be used adjunctive to existing treatments to improve emotion regulation in BD. Specific aims proposed are: 1) to identify patient-specific pathophysiological markers of implicit and explicit emotion dysregulation in BD; 2) to determine the effect of TMS on emotion regulation circuit dynamics in BD; and 3) to determine the effect of TMS on emotion regulation behavioral responses in BD. The approach is innovative in that it uses a patient- specific, precision medicine approach with combined TMS-fMRI to target and probe emotion dysregulation at the level of neurocircuitry. The proposed research is significant, because it is has the potential to advance our understanding of the pathophysiology of emotion dysregulation in BD and will provide crucial pilot data towards testing the efficacy of TMS for improving emotion dysregulation in BD patients. Overall, the candidate will use this project and its associated training to transition and expand this work into an independent program of research developing neuroscience-informed interventions for bipolar mood disorders.