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，与高治疗费用、工作能力受损和自杀风险升高有关。它的特征是阳性和阴性症状，但大多数患者也表现出神经认知缺陷，包括工作记忆功能障碍（WM）。先前的研究表明，在SZ的WM处理过程中，神经振荡发生了变化，特别是在theta （4- 7hz）和gamma （> - 30hz）波段。这些研究通常集中在一个特定的WM子域缺陷上，因此很难比较不同实验范式和WM子域的研究结果。到目前为止，还没有全面的尝试直接比较同一组患者中不同WM亚域缺陷的神经基础。这是很重要的，因为它将产生一个更统一的，经验驱动的理论图像，在SZ WM缺陷的神经基础。它还可以帮助选择用于诊断评估这种疾病的神经心理学测试。本项目的主要目的是在相同的研究组中检查SZ中不同WM子域的WM缺陷的神经基础。为此，我们在SZ患者和健康对照组中进行了三个脑电图（EEG）实验。在实验中，我们将研究神经振荡，重点是theta和gamma波段振荡及其交叉频率耦合，以及通过多元模式分析（multivariate pattern analysis， MVPA）获得的WM内容的解码。与单变量方法相比，MVPA的应用有望提高灵敏度，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内容非特异性的一般活动。在实验中，我们将研究以下WM子领域：(1)与记忆负载相关的信息维护；(2) WM内容的选择和排序；(3)通过心理重新定位操纵WM内容。在所有的实验中，将使用相同的刺激材料（人脸和房子的图片），数据将在wm延迟期间进行分析，这将允许数据的交叉实验比较。此外，我们将探讨脑电图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子域神经基础的共性和差异的理解，并将有助于对SZ中WM缺陷及其临床意义的更连贯的理论描述。

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.