Neurophysiology of social processing and underlying perceptual deficits in schizophrenia

摘要 精神分裂症 (SZ) 是一种使人衰弱且复杂的疾病，具有多种症状，目前的治疗方法通常是 不解决疾病的全部问题。经常被忽视的一种症状是社交处理缺陷，并且 这些困难可能会导致这些患者出现严重的功能障碍。 SZ 患者还 已知有微妙的知觉缺陷，这些缺陷可能与社会处理有关 赤字。更多研究探讨这些社交和知觉处理困难如何在大脑中体现 需要，特别是利用模仿现实生活的自然刺激进行研究。在这里，我们使用 喜剧电视节目《办公室》作为我们的刺激因素，因为它包含丰富多样的社交互动，包括 有些可能违反社会规范（即尴尬事件）。这些情节也是言语丰富 这些内容将使我们能够在许多不同的处理层次上检查语言。我们将使用 两种互补的神经影像学成像模式来检查患者的社交大脑网络差异 与 SZ 以及更基本的感知语言处理缺陷如何影响这些测量。我们的 分析将使我们能够量化与社会理解相关的特定刺激参数，例如 尴尬和语言处理，例如低级包络跟踪和高级语言处理 意义。然后，我们将使用线性方法量化神经信号如何反映这些刺激参数。 对于目标 1，我们将使用功能磁共振成像 (fMRI) 技术来表征神经元 深圳社会和知觉处理缺陷的动态。我们将首先评估神经跟踪 利用通用线性模型方法 (GLM) 分析剧集中的语言特征。接下来我们将量化 大脑如何跟踪社交参数（例如尴尬）存在群体差异。我们还将表征 社会处理大脑网络中重要节点之间的神经动力学。对于目标 2 将使用 脑电图 (EEG) 以更高的时间精度表征语音特征的神经跟踪 与功能磁共振成像相比。我们还将研究社会特征如何反映在神经信号中并表征 特定频率范围内社会处理区域的功能连接。我们预测，跨 为了实现这两个目标，精神分裂症患者的大脑将较少追踪刺激的感知和社会特征， 任何知觉缺陷都可能导致社会缺陷。我们的目标是招募相同的参与者 对于目标 1 和 2，我们可以利用这两种方法的优势，并研究这些措施如何发挥作用 提供有关语言和社会处理缺陷的补充信息。我们希望这 研究可用于为 SZ 生物标志物的未来研究提供信息，并最终改善医疗保健 SZ 患者的结果。

ABSTRACT Schizophrenia (SZ) is a debilitating and complex disorder with many symptoms, and current treatments often don't address the totality of the illness. One symptom that is often overlooked is social processing deficits, and these difficulties can cause significant functional impairment for these patients. Patients with SZ are also known to have subtle perceptual deficits, and it is possible that these may be related to social processing deficits. More research examining how these social and perceptual processing difficulties manifest in the brain is needed, especially research utilizing naturalistic stimuli that mimic real life. Here, we use episodes of the comedy TV show, The Office, as our stimulus because it contains a rich variety of social interactions, including some that may be violating social norms (i.e., awkward events). These episodes are also rich in speech content that will allow us to examine language at many different hierarchical levels of processing. We will use two complementary neuroimaging imaging modalities to examine social brain network differences in patients with SZ and how more basic perceptual language processing deficits may be influencing these measures. Our analysis will allow us to quantify specific stimulus parameters related to social understanding, like awkwardness, and language processing, such as low-level envelope tracking and higher-level linguistic meaning. We will then quantify how the neural signal reflects these stimulus parameters using linear methods. For Aim 1, we will use functional magnetic resonance imaging (fMRI) techniques to characterize neural dynamics of social and perceptual processing deficits in SZ. We will first assess the neural tracking of language features during the episodes utilizing a general linear model approach (GLM). Next, we will quantify group differences in how the brain tracks with social parameters, like awkwardness. We will also characterize neural dynamics between important nodes in the social processing brain network. For Aim 2 will use electroencephalography (EEG) to characterize neural tracking of speech features with more temporal precision compared to fMRI. We will also examine how social features are reflected in the neural signal and characterize functional connectivity of social processing regions within specific frequency ranges. We predict that across both aims, the brains of patients with SZ will track less with the perceptual and social features of the stimulus, and that any perceptual deficits may be contributing to social deficits. We aim to recruit the same participants for aim 1 and 2, so we can capitalize on the strengths of both methods and examine how these measures may be providing complementary information about language and social processing deficits. We hope that this research can be used to inform future research for biomarkers of SZ and ultimately improve healthcare outcomes for patients with SZ.