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

• 批准号: 10055178
• 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
• 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/10055178
• 关键词: Address; Anatomy; Antidepressive Agents; Anxiety; Base of the Brain; 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; 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; base; behavioral phenotyping; career development; conflict resolution; connectome; 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

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.

项目总结/摘要 该提案要求支持一项为期五年的培训和研究计划，以更好地了解如何 不同的大脑回路可以被映射，并选择性地用经颅磁刺激（TMS）刺激， 治疗重度抑郁症的不同症状 在拟议的培训计划中，我将建立在我以前的精神病学和计算经验的基础上， 在贝斯以色列女执事医疗中心执行多学科项目。我的职业发展计划 包括脑回路映射，神经调节，生物统计学/数据科学，精神病表型， 临床试验和一般转化研究。 经颅磁刺激是一种有效的治疗抑郁症的方法，它能够调节特定的大脑回路。 然而，不同患者的疗效差异很大，其机制尚不清楚。最近的工作 我们实验室的研究表明，TMS的疗效可以通过刺激特定的靶点来提高， 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， 与抑郁症的不同症状有关连接到每个刺激部位的脑回路可以是 通过使用功能连接MRI（fcMRI）在组水平或个体水平上进行映射。一般 刺激部位连接性的估计图可以从人类连接体生成，这是一个标准的 基于1000名健康对照的fcMRI的人脑接线图。更精确的地图 可以基于受试者特异性fcMRI数据来生成连通性。 该提案旨在根据症状、情绪任务表现和 大脑连接在我的初步数据中，这种方法产生了负责改善的独特电路 “焦虑”和“焦虑”症状群的区别然而，这些结果受到回顾性研究的限制。 自然，依赖主观症状量表，依赖基于组的连接。在这份提案中，我将 通过在一项前瞻性随机试验中证实我们的结果，结合基于任务的 行为指标，并结合特定主题的连接。 更广泛地说，这项研究的目的是开发一个模型，用于映射与不同的神经元相关的特定电路。 可以用治疗性脑刺激来调节的症状群。这将奠定基础， 临床精神病学中跨诊断神经调节的个性化方法。