Neuroanatomically informed biomarker discovery and neurofeedback intervention for OCD

项目摘要 强迫症(OCD)是一种影响1-3%世界人口的衰弱精神疾病。 尽管目前的治疗和药物治疗在一定程度上缓解了症状，但40%-60%的 强迫症患者对这些方法没有足够的反应。因此，对强迫症神经有了更好的了解 开发新的治疗方法非常需要电路。最近的研究表明，将非人类灵长类动物 (NHP)神经解剖学和人类神经成像技术允许精确的解剖功能描述特定的 大脑回路和通路。在这项申请中，Trambai olli博士将使用NHP神经解剖学来评估特定的 皮质-纹状体连接与强迫症的回避症状相关。他将绘制出两者之间的精确联系 这些区域使用NHP轨迹追踪法，并将这些电路转换为NHP和人类功能磁 磁共振成像(FMRI)(AIM 1-K99)。他将把目标1中描绘的联系与规范结合起来 建模算法，以识别此电路中偏离常态并与OCD相关的连接 症状学(目标2-R00)。在实时的fMRI神经反馈期间，这个翻译电路将成为目标 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，该方案将在健康参与者(K99)中进行优化。后来，神经反馈控制对 强迫症症状将在单组临床试验(R00)中进行评估。Trambai olli博士之前的培训和 发表记录表明他在实时信号处理、机器学习和量化方面的专业知识 方法神经解剖学。然而，为了充分实现他的研究目标，他需要在以下方面进行额外的培训 精神病理学中的翻译模型(核心A)、临床环境中的神经成像(核心B)和临床 评估和干预(核心C)。在指导阶段，他将接受指导人员的指导 由Suzanne Haber博士领导的团队，她是一名翻译神经解剖学家，在强迫症电路(核心A和 B)，罗切斯特大学药理学和生理学教授，长期访问 麦克莱恩医院-哈佛医学院(HMS)教授，临床神经学家贾斯汀·贝克博士 在NHP数据分析和生物标志物发现(A和B岩芯)方面经验丰富， 麦克莱恩精神病学技术研究所(ITP)，布莱恩·布伦南博士，一位在强迫症方面有专长的临床科学家 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， 达林·多尔蒂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(B和C核心)，以及马萨诸塞州神经治疗学部主任 综合医院(MGH)。培训和相关研究将在麦克莱恩医院和HMS进行，这是一个独特的 致力于提供精神卫生保健、研究和教育的环境。Trambai olli博士将致力于 正规课程，继续他在翻译神经解剖学方面的培训，执行fMRI数据采集和 参加临床培训。这一奖项将为他的独立研究生涯奠定坚实的基础。

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.