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。这项拟议工作的首要目标是了解精神分裂症患者行为自我控制的两个核心组成部分--反应抑制和反应监测。扫视反击范式通过标示一个人停止启动动作的能力，为量化控制动作的机制提供了一个理想的框架。范德比尔特大学正在对眼跳逆转的计算模型和神经生理学进行研究。人类和非人类灵长类动物的工作相结合，为精神分裂症执行控制功能障碍的特殊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式，以及空间和时间上精确的大脑活动测量，以了解精神分裂症受损和保留的过程及其潜在机制。该项目的具体目标是在精神分裂症患者中使用反向任务来明确反应抑制和表现监测缺陷的行为和神经标记物，并阐明这两个过程在健康对照组和患者中是如何相关的。将检查精神分裂症患者在操作监控和反应抑制方面的缺陷，并将在健康对照组和精神分裂症患者中检查基于先前反应的逐次试验反应时间调整与反应抑制的量化措施之间的关系。为了阐明行为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组的行为监控和反应抑制的电生理相关性进行研究。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，精神分裂症认知缺陷的补救是一项紧迫而重要的公共卫生挑战。因此，对认知缺陷的组成部分有更具体的了解，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.