Defining the Neural Circuitry of Agency Deficits in Psychotic Disorders

项目总结 精神病是一种精神障碍，表现为一系列症状，包括幻觉和 妄想症。这些症状反映了准确识别自我产生的感觉的能力减弱。 来自外部引起的行为或思想。这种区分和分类行为的困难以及 自我启蒙或外在的思想被统称为代理意义上的干扰 (SOA)。一种理论认为，推论放电的中断(CD，内部生成的已发布的副本 运动指令)是精神病表现出的SOA缺陷的基础。然而，由于固有的 自我体验量化的主观性对异常体验的客观评价存在困难 跨患者群体的机构。这一困难随后妨碍了界定裁谈会在#年的作用。 以及识别传递这些信号的中断的神经回路。这项研究 此应用程序的目标是开发对Cd使用情况的敏感的、定量的感知评估 为了确定精神障碍患者SOA异常的连续体，并分离出主要 与行为异常相关的神经回路中断。的核心假说 应用是(1)CD传输缺陷导致患者的视觉损害 经历精神病的种群和(2)神经回路，以前在灵长类动物中具有特征， 传达眼跳CD是在人类精神病患者中观察到的视觉感知障碍的基础 精神错乱。这项研究使用了人类心理物理学、临床评估、统计分析和大脑 成像以隔离与观察范围相关的神经回路中断的连续体 行为异常。应用的假设是在强势的基础上提出的 初步数据表明，(1)视觉感知行为范式可以隔离和 定量评估镉的利用，(2)确定猴子相关的镉神经回路，(3)探针 此回路可逆性中断时的知觉后果和(4)确认类似的知觉 精神分裂症患者的缺陷。这项研究的长期目标是了解镉在 以及这些信号的中断如何导致精神病的临床症状。这个 研究的预期结果是提供从行为到神经的详细信息 途径，关于镉干扰对SOA障碍的贡献。这一贡献意义重大，因为 它将提供精确的神经行为模型，以开发分析性诊断和治疗策略 不正常的自我体验。

PROJECT SUMMARY Psychosis is a mental disorder that manifests as a range of symptoms, including hallucinations and delusions. These symptoms reflect a diminished ability to accurately recognize self-generated sensations from externally caused actions or thoughts. This difficulty in differentiating and classifying actions and thoughts as self-initiated or external has been collectively referred to as a disturbance in sense of agency (SoA). One theory is that disruptions in corollary discharge (CD, the internally generated copy of issued motor commands) underlie the SoA defects demonstrated in psychosis. However, due to the inherent subjectivity of quantifying self-experience there is difficulty in objectively evaluating abnormal experiences of agency across patient populations. This difficulty subsequently prevents defining the role of CD in agency, as well as identifying the disrupted neural circuits that convey these signals. The research objective of this application is to develop a sensitive, quantitative perceptual assessment of CD utilization in order to define the continuum of abnormalities in SoA in psychotic disorders, and isolate the principal neural circuit disruptions associated with the behavioral abnormalities. The central hypothesis of the application is that (1) deficits in CD transmission contribute to visual perception impairments in patient populations that experience psychosis and (2) a neural circuit, previously characterized in primates, that conveys the saccade CD underlies the visual perception impairments observed in human psychotic disorders. The research uses human psychophysics, clinical evaluations, statistical analysis and brain imaging to isolate the continuum of neural circuit disruptions associated with the range of observed behavioral abnormalities. The hypothesis of the application has been formulated on the basis of strong preliminary data that (1) demonstrate that a visual perception behavioral paradigm can isolate and quantitatively assess CD utilization, (2) identify the associated CD neural circuitry in monkeys, (3) probe the perceptual consequences when this circuit is reversibly disrupted and (4) confirm similar perceptual deficits in schizophrenia patients. The long-term goal of the research is to understand the role of CD in SoA, and how the disruption of these signals contribute to the clinical symptoms of psychosis. The expected outcome of the research is to provide detailed information, from behavior to the neural pathways, on the contribution of CD disruption to SoA disorders. This contribution is significant because it will provide a precise neurobehavioral model to develop analytical diagnostics and treatment strategies for abnormal self-experience.