Using human brain connectivity to identify the causal neuroanatomical substrate of depression symptoms

利用人脑连接来识别抑郁症状的因果神经解剖学基础

• 批准号: 10646488
• 负责人: MICHAEL D FOX
• 金额: $ 74.72万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-19 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10646488
• 关键词: 3-Dimensional; Admission activity; Age; Antidepressive Agents; Behavior; Brain; Brain hemorrhage; Brain region; Clinical; Clinical Trials; Computer software; Data; Data Set; Deep Brain Stimulation; Diagnosis; Diagnostic; Enrollment; Epilepsy; Functional Magnetic Resonance Imaging; Future; Goals; Human; Human Characteristics; Ischemic Stroke; Lead; Lesion; Link; Location; Magnetic Resonance Imaging; Major Depressive Disorder; Maps; Mediating; Mental Depression; Modality; Motor; National Institute of Mental Health; Neuroanatomy; Neuronavigation; Obsession; Obsessive-Compulsive Disorder; Outcome; Parkinson Disease; Patients; Pattern; Pharmaceutical Preparations; Postoperative Period; Prospective Studies; Publishing; Recording of previous events; Rest; Seizures; Site; Source; Symptoms; Techniques; Testing; Therapeutic; Time; Transcranial magnetic stimulation; Translating; United States National Institutes of Health; Validation; Work; X-Ray Computed Tomography; clinical practice; cohort; compulsion; connectome; depressive symptoms; diagnostic value; disability; improved; individual patient; large datasets; neuroimaging; neuroregulation; noninvasive brain stimulation; physically handicapped; post stroke; post stroke depression; predictive marker; prospective; prospective test; response; sex; stroke outcome; stroke trials; therapeutic target

PROJECT SUMMARY: Using human brain connectivity to identify the causal neuroanatomical substrate of depression symptoms Depression is the leading cause of disability worldwide. Identifying the brain regions causing depression symptoms can lead to better treatment targets and therapies. Most neuroimaging studies identify brain regions where activity correlates with depression symptoms but cannot determine whether these regions actually cause symptoms. The goal of this project is to causally link depression symptoms to human neuroanatomy. Lesions and brain stimulation can provide causal links to human neuroanatomy. Because symptoms can come from regions connected to the lesion or stimulation site, we study the connectivity of these sites (not just their location) using brain connectivity data from a large cohort of normal subjects (functional connectivity MRI, n=1000). This allows us to map symptoms caused by lesions or stimulation to brain circuits without connectivity data from the patients themselves. With NIMH support, we found that lesions, transcranial magnetic stimulation (TMS) sites, and deep brain stimulation (DBS) sites that cause a change in depression symptoms are all connected to a common brain circuit across 14 independent datasets (Siddiqi et. al 2021 Nature Human Behaviour). Connectivity to this circuit was a better predictor of antidepressant response to TMS or DBS than connectivity to other candidate regions (e.g., subgenual cingulate). However, this circuit requires validation before it can be translated into a target for clinical trials. Here, we will validate our brain circuit for depression using three independent causal sources of information: lesions (Aim 1), DBS (Aim 2), and TMS (Aim 3). For all aims, we will use our published a priori depression circuit to predict overall depression outcomes. We will also perform exploratory data-driven analyses to test whether different circuits are responsible for different symptoms of depression. In Aim 1, we will prospectively test whether our depression circuit can predict depression scores after stroke. In Aim 2, we will test whether our depression circuit can predict change in depression score after DBS across a wide range of DBS patients with different diagnoses. In Aim 3, we will test whether individualized connectivity to our circuit prospectively predicts change in depression symptoms with TMS. Completion of these Aims will validate our depression circuit across different diagnoses and across three independent causal sources of information, providing much stronger validation than could be achieved with one modality alone. If successful, this study will facilitate future trials directly targeting our brain circuit with therapeutic neuromodulation for depression.

项目概述：利用人脑连通性识别因果神经解剖学

项目成果

Reply: Heterogeneous neuroimaging findings, damage propagation and connectivity: an integrative view.

答复：异质神经影像学发现、损伤传播和连接：综合观点。

• DOI: 10.1093/brain/awz081
• 发表时间: 2019
• 期刊: Brain : a journal of neurology
• 作者: Darby,RRyan;Fox,MichaelD
• 通讯作者: Fox,MichaelD

Network Effects of Brain Lesions Causing Central Poststroke Pain.

• DOI: 10.1002/ana.26468
• 发表时间: 2022-11
• 期刊: ANNALS OF NEUROLOGY
• 影响因子: 11.2
• 作者: Kim, Na Young;Taylor, Joseph J.;Kim, Yong Wook;Borsook, David;Joutsa, Juho;Li, Jing;Quesada, Charles;Peyron, Roland;Fox, Michael D.
• 通讯作者: Fox, Michael D.

Mapping Lesion-Related Epilepsy to a Human Brain Network.

• DOI: 10.1001/jamaneurol.2023.1988
• 发表时间: 2023-09-01
• 期刊: JAMA neurology
• 影响因子: 29

Lead-OR: A multimodal platform for deep brain stimulation surgery.

• DOI: 10.7554/elife.72929
• 发表时间: 2022-05-20
• 期刊: ELIFE
• 影响因子: 7.7
• 作者: Oxenford, Simon;Roediger, Jan;Neudorfer, Clemens;Milosevic, Luka;Guttler, Christopher;Spindler, Philipp;Vajkoczy, Peter;Neumann, Wolf-Julian;Kuehn, Andrea;Horn, Andreas
• 通讯作者: Horn, Andreas

A Human Depression Circuit Derived From Focal Brain Lesions.

• DOI: 10.1016/j.biopsych.2019.07.023
• 发表时间: 2019-11-15
• 期刊: Biological psychiatry
• 影响因子: 10.6
• 作者: Padmanabhan JL;Cooke D;Joutsa J;Siddiqi SH;Ferguson M;Darby RR;Soussand L;Horn A;Kim NY;Voss JL;Naidech AM;Brodtmann A;Egorova N;Gozzi S;Phan TG;Corbetta M;Grafman J;Fox MD
• 通讯作者: Fox MD