Spatiotemporal dynamics of executive function in schizo

描述(由申请人提供)：这是一份修改后的申请，旨在使用补充神经成像技术研究精神分裂症执行功能缺陷的神经基础。执行功能缺陷反映在受刺激约束的行为中，而不是受环境的引导、坚持不懈和刻板印象。他们可靠地预测了不良的功能结局(Green等人，2000年)。我们最近报道了在精神分裂症的单一范式中，在缺乏扫视抑制的情况下，完整的任务切换(Manoach等人，2002b)。这种行为分离表明，精神分裂症患者的执行功能缺陷是选择性的，并表明这些功能是由不同的神经回路介导的。这项拟议工作的主要目的是使用同样适用于神经成像的扫视范式来识别这种备用和受损的神经回路。然而，纯粹的解剖学方法可能太有限了。越来越多的证据，包括我们的初步数据，表明跨区域神经元过程的时间可能是理解这些缺陷的关键。为了探索这种可能性，我们将结合事件相关功能磁共振成像(FMRI)和脑磁图(MEG)的结果。脑磁图本身的空间分辨率很差，但通过使用解剖和功能磁共振提供的详细空间信息作为约束，可以辨别出每个区域贡献的确切时间。 我们将招募20名首发(FE)患者(如果可能的话，服用抗精神病药物)、20名慢性药物治疗患者和20名健康受试者参与配对的FMRUMEG眼跳研究。眼球跳动利用神经解剖学和生理学很好描述的控制系统。它们将在扫描过程中进行测量，以便区分正确和错误的试验。我们将分离涉及抑制和任务转换的过程。通过整合功能磁共振成像和脑磁图的结果，我们将创建与任务相关的大脑活动变化的时空图。精神分裂症组和健康组将在任务相关的fMRI和脑磁图信号变化的时间、位置和幅度方面进行比较。这将使我们能够准确地描绘出精神分裂症患者中与抑制和任务转换相关的激活时空模式的差异。识别完整和缺陷执行功能背后的神经过程将有助于神经病理学的研究，并有助于制定更有针对性的干预和康复策略。

DESCRIPTION (provided by applicant): This is a revised application to study the neural bases of executive function deficits in schizophrenia using complementary neuroimaging techniques. Executive function deficits are reflected in behavior that is stimulus-bound rather than guided by context, perseverative, and stereotyped. They reliably predict poor functional outcome (Green et al 2000). We recently reported intact task-switching in the context of deficient saccadic inhibition during a single paradigm in schizophrenia (Manoach et al 2002b). This behavioral dissociation demonstrates that executive function deficits in schizophrenia are selective and suggests that these functions are mediated by distinct neural circuitry. The primary aim of the proposed work is to identify this spared and impaired neural circuitry using the same saccadic paradigm adapted for neuroimaging. However, a purely anatomical approach may be too limited. Accumulating evidence, including our preliminary data, suggests that the timing of neuronal processes across regions may be key to understanding these deficits. To explore this possibility, we will integrate the findings of event-related functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG). MEG alone has poor spatial resolution, but by using the detailed spatial information provided by anatomical and functional MRI as constraints, the exact timing of the contribution of each region can be discerned. We will recruit 20 first episode (FE) patients (neuroleptic naive when possible), 20 chronic medicated patients and 20 healthy subjects to participate in the paired fMRUMEG saccadic studies. Saccadic eye movements utilize a control system with a well-delineated neuroanatomy and physiology. They will be measured during scanning so that correct and error trials can be separated and compared. We will isolate processes involved in inhibition and task-switching. By integrating the findings of fMRI and MEG, we will create spatiotemporal maps of task-related brain activity changes. The schizophrenic and healthy groups will be compared with regard to the timing, location, and magnitude of task-related fMRI and MEG signal changes. This will allow us to precisely delineate differences in the spatiotemporal patterns of activation associated with inhibition and task-switching in schizophrenia. Identifying the neural processes underlying intact and deficient executive function will aid investigations of neuropathology and contribute to the development of more focused interventions and rehabilitative strategies.