Defining the Neural Circuitry of Agency Deficits in Psychotic Disorders

项目摘要 精神病是一种精神障碍，表现为一系列症状，包括幻觉和 妄想这些症状反映了准确识别自我产生的感觉的能力下降 从外部引起的行动或想法。这种区分和分类行动的困难， 自我引发的或外部的想法被统称为能动性意义上的干扰 （SoA）。一种理论认为，在必然的排放（CD，内部产生的副本已发出）中断， 运动指令）是精神病中所表现的SoA缺陷的基础。然而，由于固有的 量化自我体验的主观性客观评价异常体验是困难的 在患者群体中的作用。这一困难随后妨碍了确定裁谈会在以下方面的作用： 代理，以及识别传达这些信号的中断的神经回路。研究 本申请的目的是开发一种灵敏的、定量的CD利用感知评估 为了确定精神障碍中SoA异常的连续性，并分离出主要的 与行为异常相关的神经回路中断的中心假设 应用是（1）CD传输的缺陷导致患者的视觉感知障碍 群体经历精神病和（2）神经回路，以前在灵长类动物的特点， 传达了扫视CD是在人类精神病患者中观察到的视觉感知障碍的基础 紊乱该研究使用人类心理物理学，临床评估，统计分析和大脑 成像以分离与所观察到的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有力的 初步数据，（1）表明视觉感知行为范式可以隔离， 定量评估CD利用率，（2）鉴定猴中相关的CD神经回路，（3）探测 当这个回路被可逆地破坏时的感知结果，以及（4）确认类似的感知结果。 精神分裂症患者的缺陷。这项研究的长期目标是了解CD在 SoA，以及这些信号的中断如何导致精神病的临床症状。的 研究的预期结果是提供详细的信息，从行为到神经 途径，CD破坏对SoA疾病的贡献。这一贡献意义重大，因为 它将提供一个精确的神经行为模型，以开发分析诊断和治疗策略， 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.