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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.

项目总结