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着特征，也是这种致残性疾病功能结果的最强预测因素。关键缺陷之一是上下文处理，它描述了表示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，精神分裂症患者的情境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，伽马范围（30-80 Hz）同步 PFC 振荡的干扰与精神分裂症的上下文处理受损有关。脑电图和功能磁共振成像结果的这些相似之处提出了一种可能性，即功能磁共振成像研究中皮质同步性的紊乱可能是前额叶皮层激活紊乱的基础。 PFC 伽马同步性的紊乱也与精神分裂症的快速尖峰中间神经元选择性紊乱的尸检结果一致，这对于维持伽马范围同步至关重要。在本提案中，我们的目标是综合上述发现，假设 PFC 伽马同步性受到干扰会导致精神分裂症的情境处理受损。我们将开发一个神经生物学上真实的精神分裂症上下文处理任务表现受损的计算模型，同时解释表现受损和同步紊乱。为了为我们的建模研究提供信息和补充，脑电图和功能磁共振成像的情境处理研究将尝试综合以前的研究结果，证明同一组精神分裂症受试者的脑电图 PFC 伽玛同步性降低，功能磁共振成像 PFC 激活降低。建立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经验发现，将是实现利用生物学现实模型促进精神分裂症认知新治疗候选者和综合脑电图-功能磁共振成像方法评估其疗效的长期目标的重要一步。精神分裂症的认知障碍是该疾病最令人衰弱的方面之一。认知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。这项研究旨在深入了解与此类障碍相关的大脑机制，以促进治疗精神分裂症认知的新疗法的开发。

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.