The Neural Mechanisms of Motor Dysfunction in Clinical High-Risk Youth.

临床高危青少年运动功能障碍的神经机制。

• 批准号: 10331003
• 负责人: Kenneth Juston Osborne
• 金额: $ 1.8万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2022-07-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10331003
• 关键词: Address; Adolescence; Adolescent and Young Adult; Age; Behavioral; Biological Markers; Career Choice; Chronic; Clinical; Code; Contingent Negative Variation; Development; Disease; Disease Progression; Dopamine; Dyskinetic syndrome; Early Intervention; Educational workshop; Environment; Equipment; Etiology; Event-Related Potentials; Exhibits; Foundations; Functional disorder; Goals; Hand; Impairment; Individual; Institution; Investigation; Knowledge; Left; Measures; Mediating; Mental disorders; Methodology; Methods; Motor; Motor Cortex; Movement; Occupational; Onset of illness; Pathogenesis; Pathogenicity; Pathology; Patients; Performance; Phase; Population; Preparation; Preventive treatment; Probability; Process; Psychoses; Psychotic Disorders; Reaction Time; Research; Research Design; Research Personnel; Resources; Response to stimulus physiology; Risk; Role; Sampling; Schizophrenia; Scientist; Severities; Site; Stimulus; Structural defect; Symptoms; Syndrome; Techniques; Time; Training; Universities; Work; Youth; behavior measurement; clinical high risk for psychosis; clinical predictors; design; disorder risk; emerging adult; first episode psychosis; follow-up; high risk; high risk population; improved; indexing; meetings; motor behavior; motor deficit; motor disorder; multimodality; neuromechanism; novel; programs; psychosis risk; relating to nervous system; response; schizophrenia-spectrum disorder; skills; social; sound; symposium; theories; young adult

Project Summary Motor abnormalities are a core feature of schizophrenia that are present across all phases of the illness from the premorbid stage (i.e., pre-illness) to chronic psychosis. Consistent with a dopamine (DA) etiological conceptualization of psychosis, aberrant motor function across the different phases of the disorder is both associated with abnormal structural and functional dopamine mediated motor circuitry and predicts conversion. However, to date, the majority of research examining motor dysfunction in psychosis has focused on overt motor performance (e.g., video coded movement abnormalities) in patients with schizophrenia. Because of this, little is known about the timing of neural processes underlying abnormal motor behavior in schizophrenia, and there has been no work conducted in youth in the clinical high-risk (CHR) period of the disorder (the stage immediately preceding the first episode of psychosis). Given that both motor planning and motor execution arise from underlying dopamine (DA) mediated motor circuitry implicated in the pathogenesis of the illness, understanding how these mechanisms are impaired before the onset of the disorder (i.e., in CHR populations) stands to inform our understanding of the etiology of psychosis, as well as provide a putative vulnerability marker sensitive to progression. The current proposal will address these questions using a longitudinal investigation of neural abnormalities in motor planning and execution (Aim 1) in CHR youth and healthy controls. The individual processing stages underlying motor planning and execution will be measured using a combination of the lateralized readiness potential ERP component and behavioral reaction time (RT) variability (i.e., standard deviations of RT). The neural measures in Aim 1 will be validated against behavioral motor measures (i.e., dyskinesias) known to reflect abnormal DA mediated motor circuitry (Aim 2). To track clinical progression and risk, associations between the measures from Aim 1 and symptom severity, symptom progression, and psychosis risk will be examined (Aim 3). Training Plan: An extensive training plan has been developed to enable the Applicant to effectively complete the project. Through coursework, colloquia/conference attendance, workshops, and weekly meetings with the sponsors, the Applicant will develop theoretical expertise in motor pathology in psychosis, as well as specialized skills in the ERP technique and longitudinal research design. This training plan was designed to facilitate the Applicant’s career aspirations as a research scientist with the sound theoretical foundation and methodological expertise necessary to conduct his own independent program of research. Training Environment: The project will take place at Northwestern University, an ideal training environment given the accessibility to cutting- edge resources, equipment, and coursework at the site. Further, both the Sponsor and Co-Sponsor are located at the institution and are experts in the theory and methods needed to meet the Applicant’s training aims.

项目摘要 运动异常是精神分裂症的一个核心特征，它存在于从精神分裂症到精神分裂症的所有阶段。 发病前阶段（即，慢性精神病（chronic psychosis）符合多巴胺（DA）病因学 精神病的概念化，在疾病的不同阶段的异常运动功能， 与异常的结构和功能多巴胺介导的运动回路相关，并预测 转换.然而，到目前为止，大多数研究精神病运动功能障碍的研究都集中在 在明显的运动性能上（例如，视频编码的运动异常）。 正因为如此，很少有人知道神经过程的时间基础异常运动行为， 在精神分裂症临床高危期的青年人中， 精神紊乱（第一次精神病发作之前的阶段）。考虑到运动规划和 运动执行是由潜在的多巴胺（DA）介导的运动回路引起的， 疾病的发病机制，了解这些机制是如何受损之前， 紊乱（即，在大多数人群中）代表着我们对精神病病因学的理解， 提供了一个对疾病进展敏感的假定脆弱性标记。目前的建议将解决这些问题 使用运动规划和执行中神经异常的纵向调查的问题（目标1） 青年组和健康对照组。运动规划和运动控制的各个加工阶段 执行情况将使用偏侧准备潜力ERP组件和 行为反应时间（RT）可变性（即，RT的标准偏差）。目标1中的神经测量将是 根据行为运动测量进行验证（即，已知反映异常DA介导的运动 电路（目标2）。为了跟踪临床进展和风险，目的1和目的2的测量之间的关联 将检查症状严重程度、症状进展和精神病风险（目标3）。培训计划： 为了使申请人能够有效地完成项目，已经制定了广泛的培训计划。 通过课程作业、座谈会/会议出席、讲习班和每周与赞助商的会议， 申请人将发展精神病运动病理学的理论知识，以及以下方面的专业技能： ERP技术和纵向研究设计。该培训计划旨在促进 申请人作为研究科学家的职业抱负，具有良好的理论基础和方法论 专业知识进行自己的独立研究计划。培训环境：项目 将在西北大学举行，这是一个理想的培训环境，因为可以进行切割- 边缘资源，设备和现场课程。此外，申办者和联合申办者均位于 在该机构，是专家的理论和方法需要满足申请人的培训目标。

项目成果

Neural mechanisms of motor dysfunction in individuals at clinical high-risk for psychosis: Evidence for impairments in motor activation.

• DOI: 10.1037/abn0000754
• 发表时间: 2022-05
• 期刊: JOURNAL OF PSYCHOPATHOLOGY AND CLINICAL SCIENCE
• 作者: Osborne, K Juston;Zhang, Wendy;Farrens, Jaclyn;Geiger, McKena;Kraus, Brian;Glazer, James;Nusslock, Robin;Kappenman, Emily S;Mittal, Vijay A
• 通讯作者: Mittal, Vijay A

Postural sway and neurocognition in individuals meeting criteria for a clinical high-risk syndrome.

• DOI: 10.1007/s00406-021-01234-2
• 发表时间: 2022-03
• 期刊: European archives of psychiatry and clinical neuroscience
• 影响因子: 4.7
• 作者: Osborne KJ;Mittal VA
• 通讯作者: Mittal VA