Spatiotemporal dynamics of contextual processing in schizophrenia

描述（由申请人提供）：优化行为取决于持续监测和灵活调整反应。精神分裂症的特征是反应僵化、刻板、固执，而不是受上下文的指导。我们建议研究认知功能的神经基础，这些认知功能对适应性、灵活反应至关重要，以及它们在精神分裂症中是如何出错的。首先，我们将研究“错误处理”的备用和受损方面的神经基础。一个完整的错误处理系统对于检测和提供关于错误发生的反馈是必要的，以便可以进行行为调整。虽然从关于过去表现的反馈中学习至关重要，但行为也必须对当前的突发事件做出反应。我们提出的证据表明，过去和现在的影响之间的平衡是打乱了精神分裂症导致持续-适应不良的反应持久性。我们的第二个目标是通过研究抑制优势行为的要求如何导致对反应系统的异常持续影响来研究持续行为的机制。我们建议在这些实验中使用反跳（AS）范式的变体，因为它有很好的神经解剖学和神经生理学。我们将联合收割机结合事件相关功能磁共振成像（fMRI）的空间精度和脑磁图（MEG）的高时间分辨率，以确定所涉及的区域及其在AS表现的各个阶段的贡献时间。由于AS的表现是分布式网络中协调活动的产物，我们还将使用扩散张量成像（DTI）评估白色物质束的完整性。总之，这些方法将使我们能够精确地描绘精神分裂症患者完整和受损认知功能的神经基础。为了适应环境，既要从过去学习，又要对当前的任务要求作出反应。在精神分裂症患者中，对评估表现、矫正行为和灵活应对当前任务需求至关重要的大脑网络受损，这可能导致行为模式僵化和适应不良。这项研究将确定幸存和受损的认知过程的神经基础，指导神经病理学的调查，并提供旨在改善精神分裂症认知的干预目标。

DESCRIPTION (provided by applicant): Optimizing behavior depends on the ongoing monitoring and flexible adjustment of responses. Schizophrenia is characterized by responses that are rigid, stereotyped, and perseverative rather than guided by context. We propose to study the neural bases of cognitive functions that are essential to adaptive, flexible responding and how they go awry in schizophrenia. First, we will examine the neural bases of spared and impaired aspects of 'error processing'. An intact error processing system is necessary for detecting and providing feedback regarding the occurrence of errors so that behavioral adjustments can be made. While it is critical to learn from feedback regarding past performance, behavior also has to be responsive to current contingencies. We present evidence that the balance between past and present influences is upset in schizophrenia leading to perseveration - the maladaptive persistence of responses. Our second aim is to study the mechanisms underlying perseveration by examining how the requirement to inhibit a prepotent behavior leads to abnormally persistent effects on the response system. We propose to use variations of the antisaccade (AS) paradigm in these experiments because of its well-charted neuroanatomy and neurophysiology. We will combine the spatial precision of event-related functional magnetic resonance imaging (fMRI) with the high temporal resolution of magnetoencephalography (MEG) to identify the regions involved and the timing of their contribution at various stages of AS performance. Since AS performance is the product of coordinated activity across a distributed network, we will also assess the integrity of white matter tracts using Diffusion Tensor Imaging (DTI). Together, these methods will allow us to precisely delineate the neural bases of intact and compromised cognitive function in schizophrenia. In order to adapt to the environment, it is necessary to both learn from the past and to respond to present task demands. Brain networks that are critical to evaluating performance, remediating behavior, and responding flexibly to current task demands are impaired in schizophrenia, and this likely contributes to rigid and maladaptive patterns of behavior. This research will identify the neural basis of both spared and impaired cognitive processes, guide investigations of neuropathology, and provide targets for intervention aimed at improving cognition in schizophrenia.