Computational and Neural Mechanisms of Context Processing in Schizophrenia

描述（由申请人提供）：认知障碍是精神分裂症的一个突出特征，也是这种致残性疾病功能结局的最强预测因子。关键缺陷之一是上下文处理，它描述了表征任务相关信息以指导目标导向行为的能力。功能磁共振成像研究表明，受损的上下文处理与减少前额叶皮层（PFC）激活精神分裂症。类似地，EEG研究发现，伽马范围（30-80 Hz）内的同步PFC振荡的干扰与精神分裂症患者的背景处理受损有关。EEG和fMRI结果的这些相似之处提出了一种可能性，即在fMRI研究中，皮质同步性的紊乱可能是PFC激活紊乱的基础。PFC γ同步的干扰也与精神分裂症的尸检结果一致，即快速尖峰中间神经元的选择性干扰，这对维持γ范围同步至关重要。在这个建议中，我们的目标是提供一个综合上述研究结果，假设干扰PFC γ同步引起精神分裂症的背景处理受损。我们将开发一个神经生物学现实的计算模型受损的上下文处理任务的性能在精神分裂症，占受损的性能和干扰同步。为了告知和补充我们的建模研究，EEG和fMRI研究的背景下处理将尝试综合以往的研究结果，证明减少PFC γ同步性EEG和减少PFC激活功能磁共振成像与同一组精神分裂症受试者。建立一个神经生物学约束的理论帐户和合成的经验研究结果的背景下处理障碍和他们的神经基础将是一个重要的一步，长期目标采用生物现实的模型，以促进新的治疗候选人的认知精神分裂症和集成的脑电图功能磁共振成像方法，以评估其疗效。精神分裂症中的认知障碍是该疾病最令人衰弱的方面之一。认知中的关键障碍之一是对环境中的刺激和事件组织适当反应的能力。本研究旨在深入了解与此类障碍相关的脑机制，以促进开发治疗精神分裂症认知的新疗法。

DESCRIPTION (provided by applicant): Cognitive impairments are a prominent feature of schizophrenia and the strongest predictor of functional outcome in this disabling disorder. One of the critical deficits is in context processing, which describes the ability to represent task-relevant information to guide goal-directed behavior. fMRI studies have shown that impaired context processing is associated with decreased prefrontal cortical (PFC) activations in schizophrenia. Similarly, EEG studies have found that disturbances in synchronous PFC oscillations in the gamma range (30-80 Hz) are associated with impaired context processing in schizophrenia. These parallels in the EEG and fMRI findings raise the possibility that disturbed cortical synchrony may underlie the PFC activation disturbances in fMRI studies. Disturbances in PFC gamma synchrony are also consistent with the post-mortem findings in schizophrenia of selective disturbances in fast-spiking interneurons, which are critical for sustaining gamma range synchrony. In this proposal, we aim to provide a synthesis of the above findings, hypothesizing that disturbed PFC gamma synchrony gives rise to impaired context processing in schizophrenia. We will develop a neurobiologically realistic computational model of impaired context processing task performance in schizophrenia, accounting for both impaired performance and disturbed synchrony. To inform and complement our modeling studies, EEG and fMRI studies of context processing will attempt a synthesis of previous findings demonstrating decreased PFC gamma synchrony in EEG and decreased PFC activation in fMRI with the same group of schizophrenia subjects. Establishing a neurobiologically constrained theoretical account and synthesis of empirical findings regarding context processing impairments and their neural basis will be an important step towards the long-term objective of employing biologically realistic models to facilitate novel therapeutic candidates for cognition in schizophrenia and integrated EEG-fMRI methods to evaluate their efficacy. Cognitive disturbances in schizophrenia are one of the most debilitating aspects of the disorder. One of the critical disturbances in cognition is the ability to organize appropriate responses to stimuli and events in the environment. This study seeks to attain a deep understanding of the brain mechanisms associated with such disturbances to facilitate the development of novel therapies for treating cognition in schizophrenia.