Project 4: Neuroimaging Investigations of gamma-and theta-band controls & subject

认知和其他信息处理障碍是精神分裂症的一个突出的致残特征 和功能结果的强预测因子。因此，了解病理生理机制 这些缺陷的基础已经成为开发用于该疾病的新疗法的关键焦点。 该中心的一个中心假设是，GABA神经传递的障碍是一种神经生物学的 这些赤字的基板凭借其在产生和维持同步振荡的作用， 皮层网络似乎对各种认知过程至关重要。在这个项目中，我们将调查 首次发作，抗精神病药初治精神分裂症患者的振荡紊乱（FEAN-S）。我们将 还研究了首次发作、抗精神病药物初治、非精神分裂症精神病（FEAN-NS）受试者， 对我们发现的诊断特异性进行系统研究。我们将采用多模式成像 方法，包括EEG和fMRI。EEG测量将用于评估伽马干扰（30-80 Hz）和theta（4-8 Hz）振荡，使用任务范例和检查大脑区域是有效的测试 在这两个频段的振荡中的扰动。将采用密切类似的EEG任务 在项目4-Olson的猴子中，但在更精细的生理条件下测量神经回路功能 分辨率，从而允许更详细地评估振荡动力学，包括它们对 GABA神经传递的药理学操作。使用相同的任务范例，功能磁共振成像测量 将提供局部皮层回路活动的指数，从而提供关于 发现的解剖分布。项目-6马西斯将提供GABA的体内PET测量 神经传递的一个子集相同的主题，从而允许有关的依赖性推断 GABA神经传递的脑电图和功能磁共振成像结果。学习FEAN-S科目将允许评估 振荡紊乱是疾病早期出现的核心病理生理学发现的程度， 在没有可能的治疗效果的情况下，并将为潜在的结果推广提供基础 精神分裂症患者中的一员该项目与该中心的其他项目一起， 丰富的研究结果融合，有可能提供新疗法中重要的生物标志物 精神分裂症的发展。

Cognitive and other information processing impairments are a prominent, disabling feature of schizophrenia and a strong predictor of functional outcome. Thus, understanding the pathophysiologic mechanisms underlying these deficits has become a critical focus in the development of novel therapeutics for the illness. A central hypothesis of the Center is that disturbances in GABA neurotransmission are a neurobiological substrate for these deficits by virtue of their role in generating and sustaining the synchronous oscillations in cortical networks that appear to be critical for various cognitive processes. In this project, we will investigate oscillatory disturbances in first-episode, antipsychotic-nai've individuals with schizophrenia (FEAN-S). We will also study first-episode, antipsychotic-naTve, non-schizophrenia psychotic (FEAN-NS) subjects to permit a systematic investigation of the diagnostic specificity of our findings. We will employ a multimodal imaging approach, including EEG and fMRI. EEG measures will be used to assess disturbances in gamma (30-80 Hz) and theta (4-8 Hz) oscillations, using task paradigms and examining brain regions that are effective tests of disturbances in oscillations at these two frequency bands. Closely analogous EEG tasks will be employed in monkeys in Project 4-Olson, but with measures of neural circuit functioning at a much finer physiologic resolution, thus allowing more detailed assessment of oscillatory dynamics, including their sensitivity to pharmacologic manipulations of GABA neurotransmission. Using the same task paradigms, fMRI measures will provide an index of local cortical circuit activity and thus provide critical information regarding the anatomic distribution of findings. Project-6 Mathis will provide in vivo PET measures of GABA neurotransmission in a subset of the same subjects, thus permitting inferences concerning the dependence of EEG and fMRI findings on GABA neurotransmission. Studying FEAN-S subjects will permit an evaluation of the extent to which oscillatory disturbances are a core pathophysiologic finding present early in the illness, in the absence of possible treatment effects, and will provide the basis for potential generalization of findings to the schizophrenia population at large. This project, together with other projects in the Center, could lead to a rich convergence of findings with the potential to provide biomarkers important in novel therapeutics development in schizophrenia.