Neural Disconnection and Errant Visual Perception in Psychotic Psychopathology

 描述(由申请人提供)：错误的感知是严重精神病病理学的一个定义特征，并有助于精神病患者经历的现实扭曲。越来越多的证据表明，精神障碍患者的神经连通性受损，这与幻觉体验有关--这是现实扭曲的一种突出形式。尽管导致知觉错误和幻觉的精确神经回路尚不清楚，但低级感觉和高级认知过程的异常相互作用似乎是造成这些现实扭曲的原因之一。这个项目将使用心理物理任务和磁共振成像(MRI)数据来定量模拟精神错乱中低水平和高水平对视觉感知异常的影响的作用。通过整合与视觉感知相关的结构和功能神经连接的新知识，该模型将受到限制。这项拟议工作的目标是开发和测试局部和远程神经机制的量化模型，这些机制通过使用人类连接组项目(HCP)获取协议和心理物理任务来解释精神病中的视觉错误感知。该项目涉及两个具体目标。第一个目标是通过提供来自150名精神病患者、100名精神病参与者的一级亲生亲属和50名健康的非精神病对照的MRI数据来扩大HCP数据库。成像数据将在西门子Prisma扫描仪上使用2小时HCP华盛顿大学(WU)寿命协议收集。这些数据将使健康对照、精神病患者和具有精神病遗传易感性的个人与现有的HCP寿命数据进行直接比较。访问现有的HCP寿命数据将可能表征视觉皮质连接的正常变异性，并促进神经网络的标准化评估。第二个目标是使用7特斯拉磁铁和用于UMinn 7T寿命协议的相同序列和扫描仪在视觉任务期间获取功能MRI数据，以便定量建模局部和远程功能连接在视觉错觉中的作用，并将模型参数与与精神病相关的知觉异常的维度变化联系起来。结合使用7T HCP数据和视觉异常的可测试神经生理学定量模型，将在描绘导致精神病症状的机制回路方面产生前所未有的特异性。纳入更广泛的HCP寿命数据集和经过测试的通用定量模型将为其他研究人员提供直接检查的手段，并促进与精神病的发展和表现有关的功能连接异常的标准化和个性化评估。

 DESCRIPTION (provided by applicant): Errant perception is a defining feature of severe psychopathology and contributes to distortions of reality experienced by individuals with psychosis. Growing evidence indicates that individuals with psychotic disorders have compromised neural connectivity which is associated with hallucinatory experiences - a prominent form of reality distortion. Although the precise neural circuitry that gives rise to perceptual errors and hallucinations is unknown, anomalous interactions of low-level sensory and high-level cognitive processes appear to contribute to these distortions of reality. This project will use psychophysical tasks and magnetic resonance imaging (MRI) data to quantitatively model the role of low-level and high-level influences on visual perceptual abnormalities in psychosis. The model will be constrained through incorporating new knowledge of structural and functional neural connections relevant to visual perception. The goal of the proposed work is to develop and test quantitative models of local and long-range neural mechanisms that account for visual misperception in psychosis through the use of Human Connectome Project (HCP) acquisition protocols and psychophysical tasks. The project involves two specific aims. The first aim is to expand the HCP data repository by contributing MRI data from 150 people with psychotic psychopathology, 100 first-degree biological relatives of psychotic participants, and 50 healthy non-psychiatric controls. Imaging data will be collected using the 2-hour HCP Washington University (WU) Lifespan protocol on a Siemens Prisma scanner. These data will enable direct comparison between healthy controls, individuals with psychosis, and individuals with genetic liability for psychosis with existing HCP Lifespan data. Access to existing HCP Lifespan data will make possible characterization of normal variability in visual cortical connectivity and facilitate standardized assessment of neural networks. The second goal is to acquire functional MRI data during visual tasks using a 7 Tesla magnet and the same sequences and scanner used for the UMinn 7T Lifespan protocol in order to quantitatively model the role of local and long-range functional connectivity in visual misperception, as well as relate model parameters to dimensional variation in perceptual anomalies associated with psychosis. Combined use of 7T HCP data and a testable neurophysiological quantitative model of visual anomalies will yield unprecedented specificity in delineating mechanistic circuitry giving rise to psychotic symptomatology. Inclusion of the broader HCP Lifespan data set and a tested generalized quantitative model will provide a means for direct examination by other investigators as well as facilitate standardized and individualized assessment of functional connectivity anomalies pertinent to the development and expression of psychosis.