Spatiotemporal dynamics of abnormal saccadic inhibition in schizophrenia

描述（由申请人提供）：行为灵活性是人类行为的重要组成部分。它允许人类监控反应并调整它们以满足当前情况的要求。精神分裂症的特点是反应僵化、刻板和持久，而不是受环境的引导。这种持续性可能是精神分裂症异常抑制的结果，这在广泛的任务中被观察到。本提案的目的是使用多模态神经成像技术来确定精神分裂症中异常抑制和行为持续的机制。我们将使用扫视任务来研究抑制优势行为的需求如何导致对精神分裂症反应系统的异常强烈和持久的影响。与此目标相关，我们将测试关于反扫视任务中抑制来源的假设。眼跳任务将被使用，因为它们有一个明确的神经回路，精神分裂症患者在反眼跳任务中表现出可靠的抑制缺陷。精神分裂症患者和对照组受试者将在功能磁共振成像（fMRI）和脑磁图（MEG）期间执行前扫视、反扫视和NO-GO任务。与反扫视任务类似，NO-GO任务需要反应抑制；然而，它不需要眼动生成。通过比较这三种情况下的大脑活动，我们将确定抗扫视任务的哪个部分导致了持久性。将事件相关fMRI的空间精度与MEG的高时间分辨率相结合，将使我们能够识别涉及的区域以及它们对正常和异常抑制和持久性的贡献时间。除了功能性神经成像数据，行为测量将在每次会议期间被记录下来。多模态神经成像将使我们能够精确地描绘精神分裂症中完整和受损的认知功能的神经基础。精神分裂症患者的认知缺陷严重致残，而且对目前的治疗方法相对有抵抗力。了解它们的神经机制将通过提供干预目标，为这些缺陷的治疗提供信息。

DESCRIPTION (provided by applicant): Behavioral flexibility is an important component of human behavior. It allows humans to monitor responses and adjust them to meet the demands of the current situation. Schizophrenia is characterized by responses that are rigid, stereotyped, and perseverative, rather than guided by context. This perseveration may be a consequence of abnormal inhibition in schizophrenia, which has been observed over a wide range of tasks. The objective of this proposal is to use multimodal neuroimaging techniques to identify mechanisms underlying abnormal inhibition and behavioral perserveration in schizophrenia. We will use saccade tasks to examine how the requirement to inhibit a prepotent behavior leads to abnormally strong and persistent effects on the response system in schizophrenia. Related to this goal, we will test hypotheses regarding the source of inhibition during the antisaccade task. Saccade tasks will be used because they have a well defined neural circuitry, and schizophrenia patients show reliable deficits in inhibition during the antisaccade task. Schizophrenia patients and control subjects will perform prosaccade, antisaccade, and NO-GO tasks during both functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) sessions. Similar to the antisaccade task, the NO-GO task requires response inhibition; however, it does not require saccade generation. By comparing brain activity during these three conditions, we will determine which component of the antisaccade task leads to perseveration. Combining the spatial precision of event-related fMRI with the high temporal resolution of MEG will allow us to identify the regions involved and the timing of their contribution to normal and abnormal inhibition and perseveration. In addition to the functional neuroimaging data, behavioral measures will be recorded during each session. Multimodal neuroimaging will allow us to precisely delineate the neural bases of intact and compromised cognitive function in schizophrenia. Cognitive deficits in schizophrenia are extremely disabling and relatively resistant to current treatments. Understanding their neural mechanisms will inform the development of treatment for these deficits by providing targets for intervention.