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显著特征，也是这种致残障碍中功能结局的最强预测因子。其中一个关键缺陷是上下文处理，它描述了表现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，精神分裂症患者的背景处理受损与前额皮质（PFC）激活减少有关。同样，脑电图研究发现，在伽马范围内（30-80赫兹）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。脑电图和功能磁共振成像结果的相似之处提出了一种可能性，即在功能磁共振成像研究中，皮层同步紊乱可能是PFC激活紊乱的基础。PFC伽玛同步的紊乱也与精神分裂症患者死后发现的快速尖峰中间神经元选择性紊乱相一致，后者对维持伽玛范围同步至关重要。在这一建议中，我们的目标是综合上述发现，假设PFC γ同步紊乱会导致精神分裂症患者的语境处理受损。我们将开发一个神经生物学上现实的计算模型，用于分析精神分裂症患者的情境处理任务表现受损，同时考虑到表现受损和同步障碍。为了补充我们的建模研究，脑电图和功能磁共振成像的背景处理研究将尝试综合先前的研究结果，证明在同一组精神分裂症受试者中脑电图中PFC伽马同步减少，功能磁共振成像中PFC激活减少。建立一个受神经生物学约束的理论解释，并综合有关情境处理障碍及其神经基础的实证研究结果，将是朝着采用生物学现实模型促进精神分裂症认知的新治疗方案和综合脑电图-功能磁共振成像方法评估其疗效的长期目标迈出的重要一步。精神分裂症的认知障碍是这种疾病最使人衰弱的方面之一。认知中的一个关键障碍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大脑机制，以促进精神分裂症认知治疗新疗法的发展。

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.