Neuroanatomically informed biomarker discovery and neurofeedback intervention for OCD

基于神经解剖学的生物标志物发现和强迫症的神经反馈干预

基本信息

批准号：
10739000
负责人：
Lucas R Trambaiolli
金额：
$ 10.14万
依托单位：
MCLEAN HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-05 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10739000
关键词：
Affect Algorithms Anatomy Anterior Area Attention Award Biological Markers Brain Clinical Clinical Trials Cooperative Group Clinical assessments Complementary therapies Complex Corpus striatum structure Data Data Analyses Dedications Development Devices Diagnosis Disease Education Emotions Environment Feedback Foundations Functional Magnetic Resonance Imaging General Hospitals Goals Hospitals Human Intervention Learning Location Macaca Machine Learning Magnetic Resonance Imaging Maps Massachusetts Mental Health Services Mental disorders Mentors Methods Modality Modeling Neuroanatomy Normalcy Obsessive-Compulsive Disorder Participant Pathway interactions Patients Pattern Pharmacological Treatment Pharmacology Phase Physician Executives Physiology Population Postdoctoral Fellow Prefrontal Cortex Protocols documentation Psychiatry Psychopathology Publications Regional Anatomy Research Rest Role Scientist Signal Transduction Solid Specificity Stimulus Symptoms Technology Testing Therapeutic Time Tracer Training Translating Translations Universities Visit anatomical tracing anxiety symptoms attentional bias biomarker discovery blood oxygen level dependent career cingulate cortex clinical training data acquisition emotion regulation experience frontal lobe functional near infrared spectroscopy hemodynamics improved insight interest machine learning algorithm medical schools multimodal neuroimaging multimodality neural neural circuit neurofeedback neuroimaging neuroregulation nonhuman primate potential biomarker preservation professor reduce symptoms signal processing symptomatic improvement symptomatology targeted biomarker translational model

项目摘要

Project Summary Obsessive-Compulsive Disorder (OCD) is a debilitating psychiatric illness affecting 1-3% of the world population. Although current therapeutic and pharmacological treatments provide some level of symptom relief, 40-60% of OCD patients do not respond adequately to these approaches. Thus, a better understanding of the OCD neural circuitry is much needed to develop new treatments. Recent studies show that combining non-human primate (NHP) neuroanatomy with human neuroimaging allows for a precise anatomic-functional description of specific brain circuits and pathways. In this application, Dr. Trambaiolli will use NHP neuroanatomy to evaluate specific cortico-striatal connections relevant to avoidance symptoms in OCD. He will map precise connections between these areas using NHP tract-tracing methods and translate these circuits to NHP and human functional magnetic resonance imaging (fMRI) (Aim 1-K99). He will combine the connections mapped in Aim 1 with normative modeling algorithms to identify connections within this circuit that deviate from normality and correlate with OCD symptomatology (Aim 2-R00). This translational circuit will be targeted during a real-time fMRI neurofeedback protocol, in which the participant will be trained to achieve voluntary control over specific functional connections. First, this protocol will be optimized in healthy participants (K99). Later, the effects of neurofeedback control on OCD symptoms will be evaluated in a single-group clinical trial (R00). Dr. Trambaiolli's prior training and publication record indicate his expertise in real-time signal processing, machine learning, and quantitative methods in neuroanatomy. To fully attain his research goals, however, he needs additional training in translational models in psychopathologies (Core A), neuroimaging in clinical settings (Core B), and clinical assessments and interventions (Core C). During the mentored phase, he will receive guidance from a mentoring team led by Dr. Suzanne Haber, a translational neuroanatomist with experience in OCD circuitry (Core A and B), and a Professor of Pharmacology and Physiology at the University of Rochester and a permanent Visiting Professor at McLean Hospital – Harvard Medical School (HMS), Dr. Justin Baker, a clinical neuroscientist experienced in NHP data analysis and biomarker discovery (Cores A and B), and the Scientific Director of the McLean Institute for Technology in Psychiatry (ITP), Dr. Brian Brennan, a clinical scientist with expertise in OCD biomarkers and interventions (Cores B and C), and the Medical Director of the OCD Institute (OCDI) at McLean, and Dr. Darin Dougherty, a clinical scientist experienced in OCD biomarkers and the development of new device- based therapies (Cores B and C), and the Director of the Division of Neurotherapeutics at the Massachusetts General Hospital (MGH). The training and associated research will occur at McLean Hospital and HMS, a unique environment dedicated to providing mental health care, research, and education. Dr. Trambaiolli will engage in formal coursework, continue his training in translational neuroanatomy, perform fMRI data acquisition and participate in clinical training. This award will give him a solid foundation for his independent research career.

项目摘要强迫症（OCD）是一种令人衰弱的精神病，影响了世界人口的1-3％。尽管目前的治疗和药物治疗可缓解一定程度的症状，但有40-60％强迫症患者对这些方法没有适当的反应。这是对OCD中立的更好理解开发新的治疗迫切需要电路。最近的研究表明，将非人类灵长类动物结合在一起（NHP）与人类神经影像学的神经解剖学可以对特定的精确解剖功能描述脑电路和路径。在此应用中，Trambaiolli博士将使用NHP神经解剖学来评估特定与强迫症中的回避症状相关的皮质 - 纹状体连接。他将绘制在之间的精确连接这些区域使用NHP轨道追踪方法，并将这些电路转换为NHP和人类功能磁性共振成像（fMRI）（AIM 1-K99）。他将将映射在AIM 1中的连接组合到正常建模算法以识别该电路中偏离正态性并与OCD相关的连接症状学（AIM 2-R00）。该翻译电路将在实时fMRI神经反馈期间成为目标协议，将对参与者进行培训以实现对特定功能连接的自愿控制。首先，该方案将在健康参与者中进行优化（K99）。后来，神经反馈控制对 OCD符号将在单组临床试验（R00）中进行评估。 Trambaiolli博士的先前培训和出版记录表明他在实时信号处理，机器学习和定量方面的专业知识神经解剖学的方法。为了完全实现他的研究目标，他需要额外的培训心理病理学（核心A）的转化模型，临床环境中的神经影像学（核心B）和临床评估和干预措施（核心C）。在修补阶段，他将获得修补的指导由Suzanne Haber博士领导的团队，他是一位经验丰富的神经解剖学家（核心A和 b），罗切斯特大学的药理学与生理学教授和永久访问麦克莱恩医院 - 哈佛医学院（HMS）教授，临床神经科学家贾斯汀·贝克博士在NHP数据分析和生物标志物发现（核A和B）方面经验丰富，以及麦克莱恩技术技术研究所（ITP），Brian Brennan博士，OCD专业知识的临床科学家生物标志物和干预措施（核心B和C），以及麦克莱恩（OCDI）的医学主任，麦克莱恩（OCDI），以及Darin Dougherty博士，OCD生物标志物的临床科学家经验以及新设备的开发 - 基于疗法（核B和C），以及马萨诸塞州神经疗法的主任综合医院（MGH）。培训和相关的研究将在麦克莱恩医院和HMS进行，这是一个独特的致力于提供心理保健，研究和教育的环境。 Trambaiolli博士将参与正式的课程，继续他在翻译神经解剖学方面的培训，进行fMRI数据获取和参加临床培训。该奖项将为他为他的独立研究生涯奠定坚实的基础。