Personalized circuit-based neuromodulation targets for depression

针对抑郁症的个性化基于电路的神经调节目标

基本信息

批准号：
10683261
负责人：
Shan Siddiqi
金额：
$ 19.57万
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：
2020
资助国家：
美国
起止时间：
2020-09-04 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10683261
关键词：
Address Anatomy Antidepressive Agents Anxiety Beck depression inventory Behavior Behavioral Behavioral Assay Biometry Brain Clinical Clinical Trials Clinical Trials Design Cluster Analysis Complement Conflict (Psychology)Data Data Science Data Set Databases Development Plans Diagnostic Dimensions Elements Emotional Equipment and supply inventories FDA approved Foundations Goals Human Individual Israel Link Location Magnetic Resonance Imaging Major Depressive Disorder Maps Medical center Mental Depression Mental disorders Mentorship Methods Modeling Monitor Nature Outcome Participant Patient Self-Report Patients Phenotype Procedures Prospective Studies Psychiatry Randomized Request for Proposals Research Research Domain Criteria Research Methodology Research Personnel Scalp structure Site Symptoms Task Performances Taxonomy Testing Therapeutic Training Training Programs Transcranial magnetic stimulation Translational Research Work behavioral phenotyping brain based career development conflict resolution connectome data-driven model depressive symptoms effective therapy electric field experience heuristics improved individual patient inter-individual variation multidisciplinary neuropsychiatry neuroregulation personalized approach prospective randomized trial skills symptom cluster therapeutic target treatment-resistant depression trial comparing

项目摘要

PROJECT SUMMARY/ABSTRACT This proposal requests support for a five-year program of training and research to better understand how distinct brain circuits can be mapped and selectively stimulated with transcranial magnetic stimulation (TMS) to treat different symptoms of major depression. In the proposed training plan, I will build upon my previous psychiatric and computational experience to perform a multidisciplinary project at Beth Israel Deaconess Medical Center. My career development plan includes training in brain circuit mapping, neuromodulation, biostatistics/data science, psychiatric phenotyping, clinical trials, and general translational research. TMS is an effective treatment for major depression which is capable of modulating specific brain circuits. However, efficacy varies greatly across patients and the mechanisms are not well-understood. Recent work from our lab shows that the efficacy of TMS can be improved by stimulating specific targets based on their connectivity profile. Additionally, different TMS targets can modulate different brain networks which may be involved in different symptoms of depression. The brain circuit connected to each stimulation site can be mapped by using functional connectivity MRI (fcMRI), either at the group level or the individual level. A general estimated map of stimulation site connectivity can be generated from the human connectome, a normative wiring diagram of the human brain based on fcMRI of a thousand healthy controls. A more precise map of connectivity can be generated based on subject-specific fcMRI data. This proposal aims to personalize TMS targets based on symptoms, emotional task performance, and brain connectivity. In my preliminary data, this approach yielded distinct circuits responsible for improvement in “dysphoric” versus “anxiosomatic” symptom clusters. However, these results are limited by retrospective nature, reliance on subjective symptom scales, and reliance on group-based connectivity. In this proposal, I will address these limitations by confirming our results in a prospective randomized trial, incorporating task-based behavioral metrics, and incorporating subject-specific connectivity. More broadly, this research aims to develop a model for mapping specific circuits associated with distinct symptom clusters that can be modulated with therapeutic brain stimulation. This will lay the foundation for personalized approaches to transdiagnostic neuromodulation in clinical psychiatry.

项目摘要/摘要该建议要求支持为期五年的培训和研究计划，以更好地了解可以通过经颅磁刺激（TMS）映射不同的脑电路并选择性地刺激治疗重度抑郁症的不同症状。在拟议的培训计划中，我将基于以前的精神病和计算经验在贝丝以色列执事医疗中心执行多学科项目。我的职业发展计划包括脑电路映射，神经调节，生物统计学/数据科学，精神病表型的培训，临床试验和一般翻译研究。 TMS是对重度抑郁症的有效治疗方法，能够调节特定的脑电路。但是，效率在患者之间的范围很大，而且机制并不理解。最近的工作从我们的实验室表明，可以通过根据其刺激特定目标来提高TMS的效率连接配置文件。此外，不同的TMS目标可以调节不同的大脑网络参与抑郁症的不同症状。连接到每个刺激部位的大脑电路可以是通过使用功能连接性MRI（FCMRI）映射，无论是在组级别还是个体级别。将军估计的刺激位点连接图可以从人类连接组中产生，这是正常的基于一千个健康对照的FCMRI，人脑的接线图。更精确的地图连接性可以基于特定于主题的FCMRI数据生成。该建议旨在根据符号，情感任务表现和大脑连通性。在我的初步数据中，这种方法产生了不同的电路来改进在“烦躁不安”与“抗焦虑”症状簇中。但是，这些结果受到回顾性的限制自然，对主观症状量表的缓解以及基于组的连通性的缓解。在这个建议中，我将通过证实我们的结果，在一项前瞻性随机试验中确认我们的结果，并编码基于任务的结果行为指标和编码特定于主题的连接性。更广泛地，该研究旨在开发一个模型，用于绘制与不同的电路相关的特定电路可以通过治疗性脑刺激调节的症状簇。这将为临床精神病学中转诊神经调节的个性化方法。