Dissecting Causal Reasoning Abnormalities in Obsessive-Compulsive Disorder (OCD)

项目总结/摘要 耶鲁大学临床心理学家帕特里夏·格鲁纳博士提出的K23建议考察了因果推理。 强迫症（OCD）患者的异常-朝着长期目标迈出的关键一步， 开发精确针对认知和神经系统功能障碍患者的临床治疗补救措施 严重的强迫症和强迫症。与此同时，配套的培训和指导计划将支持 PI向独立发展，重点是基于神经科学的治疗开发。 强迫症患者的适应不良重复行为反映了他们对疾病的错误因果信念。 环境关于强迫症的因果推理缺陷以及这一核心的神经生物学， 临床异常仍不清楚。因果推理是一个复杂的结构，依赖于几个不同的基础 计算，包括学习偶然性和表示抽象结果的能力。这些计算 使用现有的神经认知评估难以在现实世界中分离。为了缩小这一知识差距，我们 已经开发出一种神经生物学知情的行为范式，旨在消除这些特定元素的歧义 因果推理该范例结合最先进的神经成像技术进行优化，以检验以下假设： 特定权变学习与结果表征的行为和神经信号在强迫症中不同， 匹配的对照。反过来，我们将量化症状之间的关系（通过一组 经过充分验证的临床测量）、神经信号和特定应急学习和结果的行为测量 表示.因此，该项目推进了我们对强迫症神经生物学的理解，并为 围绕精确的神经生物学基础计算的治疗开发- Pi.反过来，概述的培训支助促进了PI向独立过渡。 Gruner博士拥有广泛的临床和认知评估专业知识，与强迫症患者一起工作。她收到 在耶鲁大学接受神经成像和认知矫正的博士后培训。该提案旨在深入发展 在神经成像采集和分析技术方面的专业知识，重点是由 人类连接组项目，增加强迫症神经生物学的知识，并使用基于任务的成像的高级技能 基于模型的分析。PI已经组建了一支出色的指导团队。主要导师克里斯托弗博士 Pittenger是耶鲁大学强迫症研究诊所的主任，他在强迫症及相关疾病的转化研究方面享誉世界。 紊乱布鲁斯韦克斯勒博士，在神经可塑性和神经认知干预发展的专家，将提供 关于强迫症神经认知功能的共同指导。PI将接受Alan Anticevic博士的培训， Daeyeol Lee博士是复杂行为数据的数学建模专家。拉吉塔医生 Sinha是耶鲁大学精神病学系心理学科科长，他将提供更多的专业知识， 导师制该提案支持PI通过补充神经影像学和理论研究向独立性过渡。 技能，促进追求R 01资金集中在神经科学为基础的治疗强迫症。

PROJECT SUMMARY/ ABSTRACT This K23 proposal from Dr. Patricia Gruner, a clinical psychologist at Yale University, examines causal reasoning abnormalities in individuals with obsessive-compulsive disorder (OCD) – a critical step towards the long-term goal of developing therapeutic remediation precisely targeting cognitive and neural system dysfunction in patients with clinically significant obsessions and compulsions. Concurrently, the accompanying training and mentorship plan will support the PI’s progression towards independence, with a focus on neuroscience-based therapeutic development. Individuals with OCD engage in maladaptive repetitive behaviors reflecting erroneous causal beliefs about the environment. Large knowledge gaps remain regarding causal reasoning deficits in OCD, and the neurobiology of this core clinical abnormality remains unclear. Causal reasoning is a complex construct relying on several distinct underlying computations, including the ability to learn contingencies and to represent abstract outcomes. These computations are difficult to dissociate in real-world situations using existing neurocognitive assessments. To close this knowledge gap, we have developed a neurobiologically-informed behavioral paradigm designed to disambiguate these specific elements of causal reasoning. The paradigm is optimized in conjunction with state-of-the-art neuroimaging to test the hypothesis that behavioral and neural signals of specific contingency learning versus outcome representation differ in OCD relative to matched controls. In turn, we will quantify relationships between symptoms (dimensionally assessed through a battery of well-validated clinical measures), neural signals, and behavioral measure of specific contingency learning and outcome representation. Thus, this project advances our understanding of OCD neurobiology and provides the foundation for treatment development around precise neurobiologically-grounded computations – a longer-term career objective of the PI. In turn, the outlined training support facilitates the PI’s transition towards independence. Dr. Gruner has extensive clinical and cognitive assessment expertise working with OCD patients. She received postdoctoral training in neuroimaging and cognitive remediation at Yale. This proposal is designed to develop deep expertise in neuroimaging acquisition and analysis techniques with a focus on state-of-the-art protocols developed by the Human Connectome Project, increase knowledge of OCD neurobiology, and advanced skills in task-based imaging using model-based analyses. The PI has assembled an exceptional mentoring team. The primary mentor, Dr. Christopher Pittenger, Director of the Yale OCD Research Clinic, is world-renowned for translational research on OCD and related disorders. Dr. Bruce Wexler, an expert in neuroplasticity and development of neurocognitive interventions, will provide co-mentorship regarding neurocognitive function in OCD. The PI will receive training from Dr. Alan Anticevic, a leading clinical neuroimager, and Dr. Daeyeol Lee, an expert in the mathematical modeling of complex behavioral data. Dr. Rajita Sinha, Chief of the Psychology Section in the Department of Psychiatry at Yale, will provide additional professional mentorship. This proposal supports the PI’s transition to independence via complementary neuroimaging and theoretical skills, facilitating pursuit of R01 funding focused on neuroscience-based therapeutics in OCD.