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Multifactorial Modeling of Impairment of Evoked Gamma Range Oscillations in Schizophrenia

机译:精神分裂症诱发伽马范围振荡损害的多因素建模

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Despite a significant increase in efforts to identify biomarkers and endophenotypic measures of psychiatric illnesses, only a very limited amount of computational models of these markers and measures has been implemented so far. Moreover, existing computational models dealing with biomarkers typically only examine one possible mechanism in isolation, disregarding the possibility that other combinations of model parameters might produce the same network behavior (what has been termed “multifactoriality”). In this study we describe a step toward a computational instantiation of an endophenotypic finding for schizophrenia, namely the impairment of evoked auditory gamma and beta oscillations in schizophrenia. We explore the multifactorial nature of this impairment using an established model of primary auditory cortex, by performing an extensive search of the parameter space. We find that single network parameters contain only little information about whether the network will show impaired gamma entrainment and that different regions in the parameter space yield similar network level oscillation abnormalities. These regions in the parameter space, however, show strong differences in the underlying network dynamics. To sum up, we present a first step toward an in silico instantiation of an important biomarker of schizophrenia, which has great potential for the identification and study of disease mechanisms and for understanding of existing treatments and development of novel ones.
机译:尽管在识别精神疾病的生物标志物和表型指标方面的工作已大大增加,但到目前为止,仅实施了非常有限的这些标志物和指标的计算模型。此外,处理生物标志物的现有计算模型通常仅独立地检查一种可能的机制,而忽略模型参数的其他组合可能产生相同网络行为的可能性(已被称为“多因素”)。在这项研究中,我们描述了向精神分裂症的内表型发现进行计算实例化的步骤,即精神分裂症的诱发听觉γ和β振动的损害。我们通过建立广泛的参数空间搜索,使用已建立的主要听觉皮层模型探索这种损伤的多因素性质。我们发现单个网络参数仅包含关于网络是否会显示伽马夹带受损的很少信息,并且参数空间中的不同区域会产生类似的网络级振荡异常。但是,参数空间中的这些区域在底层网络动态方面显示出很大的差异。综上所述,我们向精神分裂症的重要生物标志物的计算机模拟技术迈出了第一步,这对于识别和研究疾病机制以及理解现有治疗方法和开发新的疾病方法具有巨大的潜力。

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