Deriving TMS Targets for Mood Valence and Mood Stabilization in Bipolar Disorder

导出双相情感障碍情绪效价和情绪稳定的 TMS 目标

• 批准号: 10590940
• 负责人: Joseph Jeffrey Taylor
• 金额: $ 19.55万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-19 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10590940
• 关键词: Address; Adult; Affective; Behavioral; Biometry; Bipolar Disorder; Brain; Brain region; Case Study; Center for Translational Science Activities; Cessation of life; Chronic; Clinical; Clinical Research; Clinical Trials; Data; Data Science; Data Set; Disease Management; Effectiveness; Emotional; Enhancing Lesion; Foxes; Functional disorder; Funding; Future; Goals; Grant; Hospitals; Human; Intervention; Investigational Therapies; Learning; Left; Lesion; Localized Lesion; Location; Manic; Maps; Masks; Measures; Medical; Mental Depression; Mentors; Modeling; Mood Disorders; Moods; Morbidity - disease rate; National Institute of Mental Health; Network-based; Neuroanatomy; Outcome; Patient imaging; Patients; Phenotype; Physicians; Prefrontal Cortex; Process; Psychiatry; Research; Research Methodology; Scientist; Services; Strategic Planning; Symptoms; Techniques; Testing; Therapeutic; Training; Transcranial magnetic stimulation; Translational Research; Unipolar Depression; United States; Woman; Work; affective disturbance; base; behavior test; behavioral phenotyping; biomedical imaging; brain circuitry; career; catalyst; cohort; connectome; design; disability; emotion regulation; follow-up; insight; medical schools; mortality; neuroimaging; novel; older patient; optimal treatments; premature; programs; psychiatric symptom; side effect; therapeutic evaluation; tool

Project Summary New treatments are needed for bipolar disorder (BD). Transcranial magnetic stimulation (TMS) shows promise for BD, but the optimal treatment targets for mania, depression, and mood stabilization are unknown. Studying brain lesions that cause BD symptoms provides causal insights into neuroanatomy. These causal insights are critically important for target identification. Lesion network mapping (LNM) leverages the human connectome to map brain lesions onto brain networks rather than single brain regions, enhancing lesion localization and target identification. Pioneered by the Fox lab (Mentor), LNM shows promise for optimizing TMS targets for unipolar depression. Two recent Fox lab studies used LNM to examine the brain circuitry causally implicated in mania (n=56, two datasets) and depression (n=461, five datasets). However, there are two critical limitations of this prior work. First, mania and depression were analyzed as independent states rather than opposing poles of a valence spectrum in BD. This limitation will be addressed with a single model analysis of mania, depression, and control lesions. Second, these studies did not validate targets in patients with BD. This limitation will be addressed by validating lesion-derived targets in patients with BD using functional neuroimaging and behavioral testing. Aim 1 is to derive and validate TMS targets for mood valence. These valence-specific targets will be derived with LNM contrasts of mania vs. depression (and vice versa) in an a priori prefrontal cortex mask, and the results will be validated by correlating their whole-brain connectivity to task-based measures of valence bias in patients with BD. Aim 2 is to derive and validate a TMS target for mood stabilization. This valence-nonspecific target will be derived with LNM contrasts of mania plus depression vs. controls in an a priori ventrolateral prefrontal cortex mask, and the resulting target will be validated by correlating its whole-brain connectivity to a task-based measure of emotion regulation in patients with BD. This study aligns with the NIMH 2020 Strategic Plan objective of developing novel tools with which to characterize brain networks causally implicated in affective processes. A follow-up R01 or R61/33 grant examining whether TMS alters behavioral metrics, functional connectivity, and clinical outcomes in patients with BD aligns with NIMH’s experimental therapeutics approach. This grant was designed to provide the stepwise scientific training necessary to fulfill this plan, from LNM and biostatistics to translational research involving phenotyping and imaging of patients with BD. It also fits well with the long-term goal of becoming an independently funded physician-scientist who leads an Interventional Psychiatry research program primarily focused on deriving, validating, and testing circuit-based TMS targets. With this goal in focus, there is no better place to train than Brigham and Women’s Hospital, a Harvard Medical School affiliate offering world-class mentors, a robust TMS service in the Center for Brain Circuit Therapeutics, Harvard Catalyst Clinical/Translational Science Center, and Athinoula A. Martinos Center for Biomedical Imaging.

项目摘要 双相情感障碍（BD）需要新的治疗方法。经颅磁刺激（TMS）显示 但是对于躁狂症、抑郁症和情绪稳定的最佳治疗靶点尚不清楚。 研究导致BD症状的脑病变提供了对神经解剖学的因果见解。这些因果 洞察力对于目标识别至关重要。病变网络映射（LNM）利用人类 连接体将脑损伤映射到脑网络而不是单个脑区域， 定位和目标识别。由Fox实验室（Mentor）开创的LNM显示出优化TMS的前景 单相抑郁症的治疗目标福克斯实验室最近的两项研究使用LNM来检查大脑回路的因果关系 与躁狂症（n=56，两个数据集）和抑郁症（n=461，五个数据集）有关。然而，有两个关键 这是先前工作的局限性。首先，躁狂症和抑郁症被作为独立的状态进行分析，而不是 BD中价谱的相反极性。这一限制将通过以下单一模型分析来解决： 躁狂症、抑郁症和控制病变。其次，这些研究没有验证BD患者的靶点。这 将通过使用功能性神经成像验证BD患者的病变衍生靶点来解决局限性 和行为测试目的1是推导和验证情绪效价的TMS目标。这些化合价特异性 目标将通过先验前额叶皮层中躁狂与抑郁（反之亦然）的LNM对比来推导 面具，结果将通过将他们的全脑连接与基于任务的测量相关联来验证。 BD患者的效价偏倚。目的2是推导和验证情绪稳定的TMS目标。这 价非特异性靶点将通过躁狂加抑郁与对照组的LNM对比推导出， 腹外侧前额叶皮层掩模，并且由此产生的目标将通过将其全脑 BD患者的情绪调节的任务为基础的措施连接。 这项研究符合NIMH 2020战略计划的目标，即开发新的工具， 描述与情感过程有因果关系的大脑网络。后续R 01或R61/33补助金 检查TMS是否改变了患者的行为指标，功能连接和临床结果， BD与NIMH的实验治疗方法保持一致。该补助金旨在提供逐步 完成该计划所需的科学培训，从LNM和生物统计学到涉及 BD患者的表型和成像。它也非常符合成为一个 独立资助的医生兼科学家，主要领导介入精神病学研究项目 专注于推导、验证和测试基于电路的TMS目标。有了这个目标的关注，没有比这更好的了。 布里格姆妇女医院是哈佛医学院的附属医院，提供世界一流的 导师，一个强大的TMS服务中心脑回路治疗，哈佛催化剂 临床/转化科学中心和Athinoula A. Martinos生物医学成像中心。