Neurophysiology of social processing and underlying perceptual deficits in schizophrenia

摘要 精神分裂症（SZ）是一种具有许多症状的衰弱和复杂的疾病，目前的治疗方法通常 不能解决疾病的全部。一个经常被忽视的症状是社会处理缺陷， 这些困难可对这些患者造成严重的功能损害。SZ患者也是 已知有微妙的知觉缺陷，这些可能与社会处理有关 赤字更多的研究探讨了这些社会和感知处理困难如何在大脑中表现出来 特别是利用模仿真实的生活的自然刺激的研究。在这里，我们使用的情节 喜剧电视节目，办公室，作为我们的刺激，因为它包含了丰富多样的社会互动，包括 有些可能违反社会规范（即，尴尬的事件）。这些插曲也是丰富的言论 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，以检查患者的社会脑网络差异 与SZ以及更基本的知觉语言处理缺陷如何影响这些措施。我们 分析将使我们能够量化与社会理解相关的特定刺激参数，如 笨拙，和语言处理，如低层次的信封跟踪和更高层次的语言 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，我们将使用功能性磁共振成像（fMRI）技术来表征神经元的功能。 SZ的社会和知觉处理缺陷的动态。我们将首先评估 语言特征在情节期间利用一般线性模型方法（GLM）。接下来，我们将量化 大脑如何跟踪社交参数的群体差异，比如尴尬。我们还将描述 社会处理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fMRI相比。我们还将研究社会特征如何反映在神经信号中， 在特定频率范围内的社会处理区域的功能连接。我们预测， 这两个目标，SZ患者的大脑将跟踪较少的知觉和社会特征的刺激， 任何知觉缺陷都可能导致社交缺陷。我们的目标是招募相同的参与者 因此，我们可以利用这两种方法的优势，并研究这些措施如何 提供有关语言和社会处理缺陷的补充信息。我们希望这一 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患者的结局。

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.