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：
10706627
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/10706627
关键词：
Address Adult Affective Behavioral Biometry Bipolar Disorder Brain Brain Mapping 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 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 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.

项目摘要躁郁症（BD）需要新的治疗方法。对BD的承诺，但是躁狂，抑郁和情绪稳定的最佳治疗目标尚不清楚。研究引起BD症状的大脑病变为神经解剖学提供了因果关系洞察力对目标识别至关重要。连接组以将脑病变映射到大脑网络而不是单个大脑区域，从而增强病变福克斯实验室（Mentor）的定位和目标识别。单极抑郁症的靶标。与躁狂症有关（n = 56，两个数据集）和抑郁症（n = 461，五个数据集）。首先的局限性。 BD中的价频谱的相对极。躁狂症，抑郁症和对照病变，这些研究未验证BD患者限制将是在按值添加之前。行为测试1是为情绪价验证和验证TMS目标在先验前额叶皮层中，具有LNM对比的LNM对比（反之亦然）的靶标面具，结果将通过将基于WHEIR的整个基于任务的措施关闭来验证 BD患者的价偏差是衍生并验证情绪站的TMS目标价值非特异性目标将以MANIA的LNM对比加上抑郁症与对照组的对比腹外侧前额叶皮层面膜，由此产生的目标将通过相关性验证是整个脑与BD患者的基于任务的情绪调节的连通性。这项研究符合NIMH 2020战略计划的目标，即开发新颖的工具。表征与情感过程有关的大脑网络。检查TMS是否改变了患者患者的行为指标，功能连接和临床结果是否会改变 BD与NIMH的实验治疗方法保持一致。从LNM和生物统计学到转化研究所必需的科学培训，涉及 BD患者的表型和成像也适合成为一种长期目标不称职的医师科学家，主要领导干预精神病学专注于衍生，验证和测试基于电路的TMS目标。训练的地方比杨百翰和妇女医院是哈佛医学院的分支机构，提供世界一流导师，在哈佛大学催化剂的脑电路治疗中心的强大TMS服务临床/翻译科学中心和Athinoula A。