Cognitive mechanisms of delusion severity throughout recovery from an acute psychotic episode: a computational approach

项目总结 妄想症是一种精神病症状，会导致严重的情绪困扰，生活质量下降，功能性 损伤、住院和暴力。在许多患者中，妄想症是无法治疗的。机械性理解 妄想的严重程度仍然难以捉摸，限制了治疗进展。异常信念更新是一种提出的机制 不断积累证据支持的妄想症框架。先前的横断面研究表明 认知任务中精神病患者的信念更新能力及相关神经生物学异常。 然而，尚不清楚信念更新异常是否是妄想症思维转变的状态标志 时间，或者代表导致妄想倾向的稳定的认知特征。回答这个问题不仅可以 告知妄想症的机械模型，但将指导靶向治疗的发展。这位K23指导的病人- 定向职业发展奖建议对妄想的严重性和信念更新进行纵向检查 精神病患者从精神疾病的急性发作中恢复过来。该项目将使用计算和 功能神经成像(FMRI)方法用于1)确定信念更新参数在以下六个方面的变化 从急性妄想状态中恢复数月，以及2)表征信念更新的神经生物学相关性 参数随症状严重程度的变化而变化。申请人是一名有执照的临床心理学家，有使用 神经心理学任务和神经成像技术，以了解整个精神病谱系的认知缺陷。 她的长期职业目标是建立一个独立的研究项目，利用复杂的认知神经科学 测试精神病的机械模型的技术，然后利用这些知识开发和测试新的干预措施。 为了实现这些短期和长期目标，申请人需要额外的培训，如本文件所述 求婚。培训领域包括：1)妄想症的计算和认知神经科学，2)纵向研究 设计和统计，以及3)干预性研究，为申请人的翻译研究生涯做好准备。培训将会 包括正式的课程、教学和现场培训，在纵向专家指导团队的指导下 精神病的认知神经成像，精神病症状的计算机模拟，以及治疗 妄想症。有指导的培训和完成拟议的项目将为申请人提供技能和经验 这是启动成功的独立研究事业所必需的。

PROJECT SUMMARY Delusions are psychotic symptoms that contribute to significant emotional distress, poorer quality of life, functional impairment, hospitalization and violence. Delusions are treatment-resistant in many patients. Mechanistic understanding of delusion severity remains elusive, limiting treatment advancement. Abnormal belief updating is a proposed mechanistic framework of delusions with accumulating evidentiary support. Prior cross-sectional work has demonstrated altered belief updating ability and associated neurobiological abnormalities in psychotic disorder patients during cognitive tasks. However, it is unknown whether belief updating abnormalities are state-markers of delusional thinking that change over time, or represent stable cognitive traits that contribute to delusion-proneness. Answering this question can not only inform mechanistic models of delusions, but will guide targeted treatment development. This K23 mentored patient- oriented career development award proposes a longitudinal examination of delusion severity and belief updating in psychotic disorder patients recovering from an acute episode of psychosis. This project will use computational and functional neuroimaging (fMRI) approaches to 1) determine how belief updating parameters change throughout six months of recovery from an acute delusional state, and 2) characterize neurobiological correlates of belief updating parameters as symptom severity changes. The applicant is a licensed clinical psychologist with a background in using neuropsychological tasks and neuroimaging techniques to understand cognitive deficits across the psychosis spectrum. Her long-term career goal is to build an independent research program that employs sophisticated cognitive neuroscience techniques to test mechanistic models of psychosis, and then use that knowledge to develop and test novel interventions. In order to accomplish these short and long-term goals, the applicant requires additional training, as outlined in this proposal. Training areas include: 1) the computational and cognitive neuroscience of delusions, 2) longitudinal research design and statistics, and 3) intervention research to prepare the applicant for a translational research career. Training will include formal coursework, didactics, and on-site trainings, guided under a mentorship team of experts in the longitudinal cognitive neuroimaging of psychotic disorders, computational modeling of psychotic symptoms, and treatment of delusions. Mentored training and completion of the proposed project will provide the applicant the skills and experience necessary to launch a successful independent research career.