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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：
10001007
负责人：
Wilsaan M Joiner
金额：
$ 49.68万
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 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10001007
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 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.

项目总结