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，但这些缺陷的机制仍不确定。拟议的工作的总体目标是了解两个核心组成部分的自我控制的行动，反应抑制和反应监测，在精神分裂症。眼跳撤销范式提供了一个理想的框架，量化的机制控制的行动，索引一个人的能力，停止发起的运动。范德比尔特大学正在进行眼跳撤销的计算模型和神经生理学研究。在人类和非人类灵长类动物的工作相结合，提供了前所未有的杠杆作用，这些关键问题的特异性，精神分裂症的执行控制功能障碍，因为它允许应用复杂的行为模型，以及空间和时间精确的测量大脑活动，了解的过程和他们的潜在机制，受损和保存在精神分裂症。该项目的具体目标是指定的行为和神经标记的反应抑制和性能监测赤字在精神分裂症中使用的countermanding任务，并阐明这两个过程是如何在健康对照组和患者相关。将检查精神分裂症患者的表现监测和反应抑制缺陷，并在健康对照和精神分裂症患者中检查基于既往反应的逐试验反应时间调整与反应抑制定量测量之间的关系。为了阐明行动控制困难的神经基础，将在精神分裂症患者和健康对照组中研究表现监测和反应抑制的电生理相关性。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局，精神分裂症认知缺陷的补救是一个紧迫而重要的公共卫生挑战。因此，对认知缺陷的组成部分的更具体的理解有可能为改善行为和药理学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.