Neural Noise and Cognitive Control in Schizophrenia

描述（由申请人提供）：精神分裂症患者有记录证明前额叶皮层（PFC）介导的认知控制异常。有一群健康的人既没有精神分裂症的症状，也没有精神分裂症的体征，但却表现出认知控制能力受损。在这个健康的群体中，任务表现和大脑活动都像在精神分裂症患者中观察到的那样。然而，精神分裂症是一种独特的疾病，它必须由神经偏差引起，这些神经偏差与仅与PFC介导的认知控制不良的表现相关的神经偏差不同。这个项目将证明，非特异性神经噪声（作为认知控制要求的函数）加重和表征精神分裂症认知控制不良的行为和神经表现。长期目标：这项工作将表明，认知控制异常导致类似的行为表现有不同的神经病因。它将把看似不同的行为和大脑活动偏差联系起来，形成一个统一的精神分裂症理论，从而为这种疾病的转化研究提供一个模板。具体目标：这个项目将解决4个关键问题，以了解神经噪音，认知控制，感觉系统的调节和精神分裂症的行为表现之间的关联：（i）过度（非特异性）神经噪声作为一个主要的神经生理偏差;（ii）PFC激活和PFC介导的调制的感觉处理作为一个功能的认知控制要求;（iii）调节感觉输入以支持视觉注意和感知目标检测，作为刺激密度的函数;和（iv）（i）-（iii）中的偏差对精神分裂症的特异性。研究方法：在视觉任务期间，将使用EOG记录眼球运动，并使用设计用于同时测量的组合MEG（143通道）/ EEG（64传感器）设备收集神经活动数据。组合EEG/MEG产生最佳的空间精度和时间确定性，用于解决源定位问题，因为它们对大脑活动具有共同和独特的敏感性，因为它们协同作用以改善源定位。组合成像技术（如EEG/MEG）来解决源定位问题的优点已经被知道了一段时间，但是它仍然是一种不常见的实践，尽管我们已经证明了我们使用扫视任务来执行组合EEG/MEG源定位的能力（McDowell等人，2005年）。这项研究将对理解精神分裂症固有的认知控制问题的神经基础以及这些问题与对照人群的差异具有重要意义。我们还旨在对PFC问题在精神分裂症中的作用有一个更连贯的理解，这将指导转化研究，并为开发康复和治疗技术提供信息。

DESCRIPTION (provided by applicant): People with schizophrenia have documented evidence of abnormal prefrontal cortex (PFC) mediated cognitive control. A group of healthy people exist who manifest neither signs nor symptoms of schizophrenia but who nevertheless show impaired cognitive control. In this healthy group, both task performance and brain activities are like those observed in people schizophrenia. Yet, schizophrenia is a unique disorder that must be caused by neural deviations differentiable from those solely associated with manifestations of poor PFC-mediated cognitive control. This project will demonstrate that nonspecific neural noise (as a function of cognitive control requirements) accentuates and characterizes the behavioral and neural manifestations of poor cognitive control in schizophrenia. Long-term Goals: This work will show that cognitive control abnormalities resulting in similar behavioral manifestations have different neural etiologies. It will link seemingly disparate behavioral and brain activity deviations for a unified theory of schizophrenia, thus providing a template for translational studies of the illness. Specific Aims: This project will address 4 critical issues for understanding associations between neural noise, cognitive control, regulation of sensory systems, and behavioral performance in schizophrenia: (i) excess (nonspecific) neural noise as a primary neurophysiological deviation; (ii) PFC activation and PFC-mediated modulation of sensory processing as a function of cognitive control requirements; (iii) regulation of sensory input to support visual attention and perceptual target detection as a function of stimulus density; and (iv) specificity of deviations in (i)-(iii) to schizophrenia. Methods: During visual tasks, eye movements will be recorded using EOG and neural activity data will be collected with combined MEG (143 channel) / EEG (64 sensor) equipment designed for simultaneous measurements. Combining EEG/MEG yields the best spatial accuracy and temporal certainty for solving source localization problems given their shared and unique sensitivities to brain activities because they act synergistically to improve source localizations. The advantages of combining imaging technologies like EEG/MEG to solve source localization problems has been known for some time but it is still an uncommon practice, although we have demonstrated our ability to perform combined EEG/MEG source localizations using saccade tasks (McDowell et al., 2005). This research will have important implications for understanding the neural bases of cognitive control problems inherent to schizophrenia and how those differ from comparison populations. We also aim to develop a more coherent understanding of the role of PFC problems in schizophrenia, which would guide translational research and inform strategies for developing rehabilitation and treatment techniques.