Computational and Neural Mechanisms of Context Processing in Schizophrenia

精神分裂症情境处理的计算和神经机制

基本信息

批准号：
8018106
负责人：
RAYMOND Y CHO
金额：
$ 17.15万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-05-01 至 2013-01-31
项目状态：
已结题

项目摘要

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.

描述（由申请人提供）：认知障碍是精神分裂症的重要特征，也是这种残疾疾病中功能结果的最强预测指标。关键缺陷之一是在上下文处理中，它描述了表示与任务相关信息以指导目标指导行为的能力。功能磁共振成像的研究表明，情境处理受损与精神分裂症的前额叶皮质（PFC）活化有关。同样，脑电图研究发现，伽马范围（30-80 Hz）中同步PFC振荡的干扰与精神分裂症的上下文处理受损有关。 EEG和FMRI发现中的这些相似之处增加了扰动皮质同步的可能性可能是fMRI研究中PFC激活扰动的基础。 PFC伽马同步中的干扰也与快速尖刺中间神经元中选择性干扰的验尸后发现一致，这对于维持伽马范围同步至关重要。在此提案中，我们旨在提供上述发现的综合，假设受干扰的PFC伽马同步会导致精神分裂症的上下文处理受损。我们将开发一个具有神经生物学现实的计算模型，以减少精神分裂症的上下文处理任务性能，这既是绩效受损和同步障碍。为了告知和补充我们的建模研究，脑电图和功能磁共振成像的上下文处理研究将尝试综合以前的发现，表明脑电图中PFC伽马同步降低，而fMRI中的PFC激活降低了，同一组精神分裂症受试者。建立关于上下文处理障碍及其神经基础的经验发现的神经生物学约束的理论说明和综合，将是朝着长期目标迈出的重要一步，即采用生物学上现实的模型来促进新颖的治疗候选者，以促进schizophrenia的认知和整合EEG-FMRI方法来评估其效率。精神分裂症的认知障碍是该疾病最令人衰弱的方面之一。认知的关键干扰之一是能够组织对环境中刺激和事件的适当反应的能力。这项研究试图深入了解与这种障碍相关的大脑机制，以促进用于治疗精神分裂症认知的新型疗法。