Spatiotemporal dynamics of abnormal saccadic inhibition in schizophrenia

描述(申请人提供)：行为灵活性是人类行为的重要组成部分。它允许人类监控响应并调整它们，以满足当前情况的需求。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。这种坚持可能是精神分裂症患者异常抑制的结果，人们在一系列任务中观察到了这种情况。这项建议的目的是使用多模式神经成像技术来识别精神分裂症患者异常抑制和行为坚持的潜在机制。我们将使用眼跳任务来研究抑制优势行为的要求如何导致精神分裂症患者反应系统的异常强烈和持久的影响。与这一目标相关，我们将测试关于反眼跳任务中抑制来源的假设。眼跳任务将被使用，因为它们有一个定义良好的神经电路，精神分裂症患者在反眼跳任务期间显示出可靠的抑制缺陷。精神分裂症患者和对照受试者将在功能磁共振成像(FMRI)和脑磁图(MEG)期间进行扫视、反扫视和不进行任务。与反眼跳任务类似，no-go任务需要反应抑制；然而，它不需要产生眼跳。通过比较这三种情况下的大脑活动，我们将确定反眼跳任务的哪个组成部分会导致持之以恒。结合事件相关fMRI的空间精度和脑磁图的高时间分辨率，将使我们能够识别所涉及的区域及其对正常和异常抑制和坚持的贡献的时间。除了功能神经成像数据外，还将在每次治疗期间记录行为测量。多模式神经成像将使我们能够准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。精神分裂症的认知缺陷是极其残疾的，对目前的治疗相对耐受。了解它们的神经机制将通过提供干预目标来指导这些缺陷的治疗发展。

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.