Working memory dysfunction in schizophrenia: an investigation of multivariate activation pattern and neural synchrony

精神分裂症(SZ)是一种严重的精神障碍，与高昂的治疗费用、工作能力受损和自杀风险增加有关。它的特点是阳性和阴性症状，但大多数患者也表现出神经认知障碍，包括工作记忆功能障碍(WM)。以前的研究表明，在深圳的WM处理过程中，神经振荡发生了变化，特别是在theta(4-7赫兹)和伽马(&gt；30赫兹)频段。这些研究通常集中在一个特定的WM亚域缺陷上，因此，很难比较实验范式和WM亚域的结果。到目前为止，还没有全面的尝试来直接比较同一组患者中不同WM亚域缺陷的神经基础。这一点很重要，因为它将为深圳工作记忆缺陷的神经基础产生一幅更统一、更经验主义的理论图景。本项目的主要目标是研究同一研究组中不同WM亚域中SZ WM缺陷的神经基础。为此，我们建议在SZ患者和健康对照组参与者中进行三项脑电(EEG)实验。在实验中，我们将研究神经振荡，重点是theta和Gamma带振荡及其交叉频率耦合，以及通过多变量模式分析(MVPA)获得的WM内容的解码。MVPA的应用有望提高对单变量方法的敏感性，并有助于区分与特定WM内容的维持和处理相关的神经活动与非特定内容的一般活动。在实验中，我们将考察以下WM子域：(1)与记忆负荷有关的信息的维持；(2)WM内容的选择和优先顺序；(3)通过心理重定位来操纵WM内容。在所有的实验中，将使用相同的刺激材料(有脸和房子的图片)，数据将在WM延迟期内进行分析，这将允许对数据进行交叉实验比较。此外，我们还将研究EEG与患者阳性和阴性症状的行为数据之间的关系。该项目将进一步加深我们对患者和对照组之间WM亚域神经基础的共性和差异的理解，并将有助于对SZ的WM缺陷及其临床意义有一个更连贯的理论图景。

Schizophrenia (SZ) is a severe mental disorder that is associated with high treatment costs, impaired working capacity, and elevated suicide risk. It is characterized by positive and negative symptoms, but most patients also show neurocognitive deficits, including working memory dysfunction (WM). Previous studies have shown alterations in neural oscillations, especially in the theta (4-7 Hz) and gamma (> 30 Hz) band, during WM processing in SZ. These studies usually focused on one specific WM subdomain deficit and hence, it is difficult to compare findings across experimental paradigms and WM subdomains. Thus far, no comprehensive attempt has been made to directly compare the neural basis of the different WM subdomain deficits in the same group of patients. This is important because it would generate a more unified, empirically-driven theoretical picture of the neural basis of WM deficits in SZ. It could also help in the selection of neuropsychological tests used for the diagnostic assessment of this disorder.The key objective of this project is to examine the neural basis of WM deficits in SZ across different WM subdomains in the same study groups. To this end, we propose three electroencephalography (EEG) experiments in SZ patients and healthy control participants. In the experiments we will investigate neural oscillations, with a focus on theta and gamma band oscillations and their cross-frequency coupling, and the decoding of WM content, as obtained through multivariate pattern analysis (MVPA). The application of MVPA promises increased sensitivity over univariate methods and can help in distinguishing neural activity related to maintenance and processing of specific WM content from content-unspecific general activity. In the experiments we will examine the following WM subdomains: (1) Maintenance of information in relation to memory load; (2) Selection and prioritizing of WM content; (3) Manipulation of WM content through mental relocation. In all experiments the same stimulus material will be used (pictures with faces and houses) and the data will be analyzed in a WM-delay period, which will allow a cross-experiment comparison of data. Moreover, we will investigate the relationships between EEG and behavioral data with positive and negative symptoms in patients. The project will further our understanding of commonalities and differences in the neural basis of WM subdomains between patients and controls and will contribute to a more coherent theoretical picture of WM deficits and their clinical significance in SZ.