Control of action in schizophrenia: Countermanding saccades and ERP

描述（由申请人提供）：大量文献表明，认知控制障碍在精神分裂症中起着核心作用，但这些缺陷背后的机制仍未确定。提出的工作的总体目标是了解自我控制的行动，反应抑制和反应监测的两个核心组成部分，在精神分裂症。扫视反命令范式提供了一个理想的框架，通过索引一个人停止发起运动的能力来量化控制行动的机制。范德比尔特大学（Vanderbilt University）正在对眼跳反控制的计算模型和神经生理学进行研究。在人类和非人类灵长类动物身上的结合工作，为精神分裂症中执行控制功能障碍的特异性这些关键问题提供了前所未有的杠杆作用，因为它允许应用复杂的行为模型，以及对大脑活动的空间和时间精确测量，来理解精神分裂症中受损和保留的过程及其潜在机制。本项目的具体目标是明确精神分裂症中使用反命令任务的反应抑制和表现监测缺陷的行为和神经标记，并阐明这两个过程如何在健康对照和患者中相互关联。将研究精神分裂症患者在表现监测和反应抑制方面的缺陷，并研究健康对照组和精神分裂症患者基于先前反应的逐次反应时间调整与反应抑制定量测量之间的关系。为了阐明动作控制困难的神经基础，我们将对精神分裂症患者和健康对照者的行为监测和反应抑制的电生理相关进行研究。公共卫生相关性：对公共卫生的影响：认知缺陷比临床症状更能预测功能结果，精神分裂症患者认知缺陷的补救是一项紧迫而重要的公共卫生挑战。因此，更具体地了解认知缺陷的组成部分有可能为改进行为和药物治疗和干预提供途径。

DESCRIPTION (provided by applicant): A substantial body of literature indicates that impairments in cognitive control play a central role in schizophrenia but the mechanisms underlying these deficits are still undetermined. The overarching goal of the proposed work is to understand two core components of self-control of action, response inhibition and response monitoring, in schizophrenia. The saccade countermanding paradigm provides an ideal framework for the quantification of the mechanisms of control of action by indexing one's ability to stop an initiated movement. Research on both the computational model and neurophysiology of saccade countermanding is being conducted at Vanderbilt University. Combination of work in humans and non-human primates provides unprecedented leverage on these crucial questions of the specificity of executive control dysfunction in schizophrenia as it allows the application of sophisticated models of behavior, as well as spatially and temporally precise measures of brain activity, to understanding the processes and their underlying mechanisms that are impaired and preserved in schizophrenia. The specific aims of this project are to specify the behavioral and neural markers of response inhibition and performance monitoring deficits using the countermanding task in schizophrenia and to articulate how these two processes are related in healthy controls and patients. Deficits in performance monitoring and response inhibition in patients with schizophrenia will be examined, and the relationship between trial-by-trial reaction time adjustments based on prior responses and quantitative measures of response inhibition will be examined in healthy controls and patients with schizophrenia. To elucidate the neural basis of difficulties in control of action, the electrophysiological correlates of performance monitoring and response inhibition will be investigated in patients with schizophrenia and healthy controls. PUBLIC HEALTH RELEVANCE: Implications for public health: Cognitive deficits predict functional outcome better than clinical symptoms and the remediation of cognitive deficits in schizophrenia is an urgent and important public health challenge. Thus, more specific understanding of the components of cognitive deficits has the potential to allow avenues for improved behavioral and pharmacological treatment and intervention.