Spatiotemporal dynamics of contextual processing in schizophrenia

描述(申请人提供)：优化行为依赖于持续的监测和灵活的反应调整。精神分裂症的特点是反应僵化、刻板和坚持不懈，而不是受环境的指导。我们建议研究认知功能的神经基础，这些功能对于适应和灵活反应是必不可少的，以及它们在精神分裂症中是如何出错的。首先，我们将检查‘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。虽然从有关过去业绩的反馈中吸取教训是至关重要的，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，精神分裂症患者过去和现在的影响之间的平衡被打破，导致坚持--反应的不适应持续。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坚持的潜在机制。我们建议在这些实验中使用不同的抗眼跳(AS)范式，因为它有很好的神经解剖学和神经生理学。我们将结合事件相关功能磁共振成像(FMRI)的空间精度和脑磁图(MEG)的高时间分辨率来识别AS表现不同阶段涉及的区域及其贡献的时间。由于性能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)来评估白质束的完整性。总之，这些方法将使我们能够准确地描绘出精神分裂症患者完整和受损的认知功能的神经基础。为了适应环境，既要吸取过去的教训，又要回应当前的任务要求。精神分裂症患者的大脑网络对评估表现、纠正行为和灵活应对当前的任务要求至关重要，这可能会导致僵化和不适应的行为模式。这项研究将确定认知过程异常和受损的神经基础，指导神经病理学的研究，并提供旨在改善精神分裂症认知的干预靶点。

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.