Defining the Neural Circuitry of Agency Deficits in Psychotic Disorders

定义精神障碍中代理缺陷的神经回路

基本信息

批准号：
10240526
负责人：
Wilsaan M Joiner
金额：
$ 50.31万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10240526
关键词：
Area Basic Science Behavior Behavior Therapy Behavior assessment Behavioral Behavioral Paradigm Bipolar Disorder Brain Brain imaging Clinical Clinical assessments Data Defect Delusions Diagnostic Disease Environment Esthesia Evaluation Eye Movements Form Perception Functional Magnetic Resonance Imaging Future Goals Hallucinations Human Impairment Knowledge Link Location Mental disorders Methods Modeling Monkeys Motion Motor Movement Neural Pathways Outcome Outcomes Research Pathway interactions Patients Perception Persons Pharmacological Treatment Physiological Primates Psychophysics Psychoses Psychotic Disorders Research Research Domain Criteria Rest Role Saccades Sampling Schizophrenia Sensory Signal Transduction Statistical Data Interpretation Symptoms Testing Thalamic structure Thinking Translational Research Update Variant Visual Visual Perception Work base behavior measurement clinical application clinical translation experience frontal lobe innovation meetings neural circuit neurobehavioral nonhuman primate novel patient population prevent psychotic symptoms reduce symptoms research clinical testing theories transmission process treatment strategy

项目摘要

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.

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感觉的能力下降来自外部引起的行动或思想。在区分和分类的行动和分类方面的困难作为自我启动或外部的思想被共同称为代理意识中的一种干扰（SOA）。一种理论是推论放电的中断（CD，发行的内部生成的副本运动命令）是精神病中证明的SOA缺陷的基础。但是，由于固有量化自我体验的主观性很难客观地评估异常经验跨患者人群的代理。此困难随后阻止了CD在代理，并确定传达这些信号的神经回路的破坏。研究该应用的目的是开发对CD利用的敏感，定量的感知评估为了定义精神病患者SOA异常的连续性，并隔离校长与行为异常相关的神经回路破坏。中心假设应用是（1）CD传播的缺陷导致患者的视觉感知障碍经历精神病的人群和（2）以前在灵长类动物中表征的神经回路传达扫视CD是人类精神病中观察到的视觉感知障碍的基础疾病。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观察到的范围相关的神经回路破坏的连续体行为异常。该应用的假设是根据强大的（1）证明视觉感知行为范式可以隔离和定量评估CD利用率，（2）确定猴子中相关的CD神经回路，（3）探针当该电路可逆破坏并且（4）确认类似感知时，感知后果会产生精神分裂症患者的缺陷。该研究的长期目标是了解CD在 SOA，以及这些信号的破坏如何导致精神病的临床症状。这研究的预期结果是提供从行为到神经的详细信息途径，基于CD中断对SOA疾病的贡献。这项贡献很重要，因为它将提供一个精确的神经行为模型，以制定分析诊断和治疗策略对于异常的自我经验。