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.

项目概要强迫症 (OCD) 是一种使人衰弱的精神疾病，影响着世界 1-3% 的人口。尽管目前的治疗和药物治疗可以一定程度地缓解症状，但 40-60% 强迫症患者对这些方法反应不充分，因此需要更好地了解强迫症神经。最近的研究表明，结合非人类灵长类动物，非常需要开发新的治疗方法。 (NHP) 神经解剖学与人类神经影像学可以对特定的神经系统进行精确的解剖功能描述在此应用中，Trambaiolli 博士将使用 NHP 神经解剖学来评估特定的神经解剖学。他将绘制与强迫症回避症状相关的皮质纹状体连接。这些区域使用 NHP 束追踪方法，并将这些电路转化为 NHP 和人体功能磁他将目标 1 中映射的联系与规范结合起来。建模算法来识别该电路中偏离常态并与强迫症相关的连接症状学（目标 2-R00）将在实时功能磁共振成像神经反馈过程中作为目标。协议，其中参与者将接受培训以实现对特定功能连接的自愿控制。首先，该协议将在健康参与者（K99）中进行优化，然后，神经反馈控制的效果。强迫症症状将在 Trambaiolli 博士之前的培训和单组临床试验中进行评估。发表记录表明了他在实时信号处理、机器学习和定量方面的专业知识然而，为了完全实现他的研究目标，他需要额外的培训。精神病理学中的转化模型（核心 A）、临床环境中的神经影像学（核心 B）和临床评估和干预（核心 C）。在指导阶段，他将接受指导者的指导。由 Suzanne Haber 博士领导的团队是一位转化神经解剖学家，在 OCD 电路（核心 A 和 B），罗彻斯特大学药理学和生理学教授，并永久访问哈佛医学院 (HMS) 麦克莱恩医院教授、临床神经科学家 Justin Baker 博士在 NHP 数据分析和生物标志物发现（核心 A 和 B）方面经验丰富，并且是该中心的科学总监麦克莱恩精神病学技术研究所 (ITP)，Brian Brennan 博士，一位具有强迫症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），以及麦克莱恩强迫症研究所 (OCDI) 的医学主任， Darin Dougherty 博士是一位在强迫症生物标志物和新设备开发方面经验丰富的临床科学家基础疗法（核心 B 和 C），以及马萨诸塞州神经治疗科主任培训和相关研究将在麦克莱恩医院和 HMS 进行，这是一家独特的医院。 Trambaiolli 博士将致力于提供心理保健、研究和教育。正式课程，继续接受转化神经解剖学培训，执行功能磁共振成像数据采集和参加临床培训将为他的独立研究生涯奠定坚实的基础。