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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要经颅磁刺激（TMS）表明双相情感障碍（BD）需要新的治疗方法。 BD 的前景广阔，但躁狂、抑郁和情绪稳定的最佳治疗目标尚不清楚。研究导致双相情感障碍症状的脑部病变可以为神经解剖学提供因果见解。洞察力对于利用人类的目标识别至关重要。连接组将大脑病变映射到大脑网络而不是单个大脑区域，从而增强病变 LNM 由 Fox 实验室 (Mentor) 首创，显示出优化 TMS 的前景。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。涉及躁狂症（n=56，两个数据集）和抑郁症（n=461，五个数据集）。首先，将躁狂症和抑郁症作为独立的状态进行分析，而不是进行分析。 BD 中价谱的对立极点将通过单一模型分析来解决。其次，这些研究没有验证 BD 患者的目标。通过使用功能神经影像验证 BD 患者的病变衍生靶标，可以解决局限性目标 1 是导出并验证这些特定效价的 TMS 目标。目标将通过先验前额皮质中躁狂症与抑郁症（反之亦然）的 LNM 对比得出面具，并且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 患者的效价偏差目标 2 是推导出并验证情绪稳定的 TMS 目标。效价非特异性目标将通过先验的躁狂加抑郁与对照的 LNM 对比得出腹外侧前额叶皮层掩模，所得目标将通过关联其全脑进行验证与 BD 患者基于任务的情绪调节测量的联系。这项研究符合 NIMH 2020 年战略计划的目标，即开发新颖的工具来描述与情感过程有因果关系的大脑网络后续 R01 或 R61/33 资助。检查 TMS 是否改变患者的行为指标、功能连接和临床结果 BD 与 NIMH 的实验治疗方法相一致，这笔拨款旨在提供逐步的治疗方法。完成该计划所需的科学培训，从 LNM 和生物统计学到涉及的转化研究 BD 患者的表型和影像学也非常符合成为 BD 患者的长期目标。独立资助的医师科学家，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，以此为目标，没有比这更好的了。比哈佛医学院附属的布莱根妇女医院提供世界一流的培训导师，Harvard Catalyst 脑回路治疗中心提供的强大 TMS 服务临床/转化科学中心和 Athinoula A. Martinos 生物医学成像中心。