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

项目摘要 运动异常是精神分裂症的核心特征，它存在于疾病的各个阶段，从 病前阶段(即病前)到慢性精神病。与多巴胺(DA)的病因一致 精神病的概念化，在精神障碍的不同阶段运动功能异常 与多巴胺介导的异常的结构和功能有关的运动回路和预测 转换。然而，到目前为止，大多数关于精神病患者运动功能障碍的研究都集中在 关于精神分裂症患者的显性运动表现(例如，视频编码运动异常)。 正因为如此，人们对异常运动行为背后的神经过程的时序知之甚少。 精神分裂症，并且没有在青年中进行过在临床高危时期进行的工作 精神紊乱(紧接在精神病第一次发作之前的阶段)。考虑到汽车规划和 运动执行是由多巴胺(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在发病前受损的 紊乱(即，在慢性阻塞性肺病人群中)将有助于我们理解精神病的病因，以及 提供对进展敏感的假定漏洞标记。目前的提案将解决这些问题 在运动计划和执行中使用神经异常的纵向研究的问题(目标1) 青年CHR组和健康对照组。作为运动计划和运动计划的基础的各个加工阶段 将使用侧化就绪性潜在ERP组件和 行为反应时(RT)变异性(即RT的标准差)。目标1中的神经测量将是 根据已知的反映DA介导的异常运动的行为运动测量(即运动障碍)进行验证 电路(目标2)。为了跟踪临床进展和风险，目标1和目标1中的测量之间的关联 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：一个 已经制定了广泛的培训计划，使申请者能够有效地完成项目。 通过课程作业、座谈/会议出席、讲习班和与主办方的每周会议， 申请者将发展在精神病的运动病理学方面的理论专长，以及 企业资源计划技术和纵向研究设计。该培训计划旨在促进 申请者作为一名具有良好理论基础和方法的研究科学家的职业抱负 进行自己的独立研究计划所需的专业知识。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- 现场的边缘资源、设备和课程作业。此外，赞助商和共同赞助商都位于 他们都是满足申请人培训目标所需的理论和方法方面的专家。

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.