Neuroanatomically informed biomarker discovery and neurofeedback intervention for OCD

项目摘要 强迫症（OCD）是一种使人衰弱的精神疾病，影响世界人口的1-3%。 尽管目前的治疗和药物治疗提供了一定程度的症状缓解，但40-60%的患者仍需要药物治疗。 强迫症患者对这些方法没有充分的反应。因此，更好地了解强迫症神经 开发新的治疗方法非常需要电路。最近的研究表明，结合非人类灵长类动物 (NHP)神经解剖学与人类神经成像允许精确的解剖功能描述的具体 大脑回路和路径。在本申请中，Trambaiolli博士将使用NHP神经解剖学来评估特定的 与强迫症回避症状相关的皮质-纹状体联系他将绘制出 这些地区使用NHP的tract-tracing方法和翻译这些电路NHP和人类功能磁 磁共振成像（fMRI）（目标1-K99）。他将联合收割机结合目标1中映射的连接与规范 建模算法来识别该电路中偏离正常状态并与强迫症相关的连接 泌尿学（目标2-R 00）。在实时功能磁共振成像神经反馈期间， 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，将在健康受试者中优化该方案（K99）。后来，神经反馈控制对 将在单组临床试验（R 00）中评价OCD症状。Trambaiolli博士之前的训练和 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 神经解剖学方法。然而，为了完全实现他的研究目标，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， 由Suzanne Haber博士领导的团队，他是一位具有强迫症电路经验的翻译神经解剖学家（核心A和核心B）。 B），以及罗切斯特大学药理学和生理学教授， 姆克林医院-哈佛医学院（HMS）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， 姆克林精神病学技术研究所（ITP），布莱恩·布伦南博士，一位专门研究强迫症的临床科学家 生物标志物和干预措施（核心B和C），以及姆克林强迫症研究所（OCDI）的医学主任， 和Darin Doughnut博士，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- 基于治疗（核心B和C），以及马萨诸塞州神经治疗部主任 综合医院。培训和相关的研究将发生在姆克林医院和HMS，一个独特的 致力于提供心理健康护理，研究和教育的环境。Trambaiolli博士将参与 正式的课程，继续他的翻译神经解剖学的培训，进行功能磁共振成像数据采集， 参加临床培训。这个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.