Spatiotemporal dynamics of executive function in schizo

描述（由申请人提供）：这是一份修订后的申请，旨在利用补充神经成像技术研究精神分裂症患者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上，而不是受环境、毅力和刻板印象的引导。它们可靠地预测了不良的功能预后（Green et al . 2000）。我们最近报道了在精神分裂症的单一范式中，在缺乏跳眼抑制的背景下完整的任务转换（Manoach等人，2002b）。这种行为分离表明，精神分裂症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。所提出的工作的主要目的是使用适用于神经成像的相同的眼跳范式来识别这种保留和受损的神经回路。然而，单纯的解剖入路可能过于有限。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，我们将整合事件相关功能磁共振成像（fMRI）和脑磁图（MEG）的发现。单独MEG的空间分辨率较差，但通过使用解剖和功能MRI提供的详细空间信息作为约束，可以识别每个区域贡献的确切时间。

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.