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行为上，即受刺激约束，而不是由上下文引导，固执和刻板。它们可靠地预测了不良的功能结局（绿色等，2000）。我们最近报道了在精神分裂症的单一范例中，在缺乏扫视抑制的背景下完整的任务转换（Manoach et al 2002 b）。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扫视范例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）的结果。单独的MEG具有较差的空间分辨率，但是通过使用由解剖和功能MRI提供的详细空间信息作为约束，可以辨别每个区域的贡献的确切时间。 我们将招募20例首次发作（FE）患者（可能时未接受过抗精神病药物治疗）、20例长期用药患者和20例健康受试者参与配对fMRUMEG扫视研究。扫视眼球运动利用具有良好描绘的神经解剖学和生理学的控制系统。它们将在扫描过程中进行测量，以便将正确和错误的试验分开并进行比较。我们将分离出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发现，我们将创建与任务相关的大脑活动变化的时空图。精神分裂症和健康组将比较任务相关的功能磁共振成像和脑磁图信号变化的时间，位置和幅度。这将使我们能够精确地描绘与精神分裂症中的抑制和任务转换相关的激活的时空模式的差异。识别完整和缺陷的执行功能的神经过程将有助于神经病理学的调查，并有助于更有针对性的干预和康复策略的发展。

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.