Disrupted neural synchrony during naturalistic perception in schizophrenia: Toward a new biomarker of social dysfunction

项目总结/摘要 社会功能障碍是精神分裂症的核心特征。许多精神分裂症患者会经历社交 与朋友和家人缺乏社交联系。社会脱节与减少 生活质量和许多负面的健康影响，但大多数目前的治疗方法并没有解决它。 新干预措施的开发目前受到缺乏科学认识的阻碍， 个人大脑处理信息的方式差异导致了社会脱节，缺乏 与社会功能相关的生物标志物。非临床社会神经科学的最新研究指出， 一个令人信服的模型，可能有助于解释精神分裂症的社会脱节，并提供基础 一种新的社交功能障碍的生物标志物。具体来说，使用功能性磁共振成像的研究 功能磁共振成像（fMRI）和受试者间相关性（ISC）分析方法表明， 对动态的、自然的刺激更规范（例如，视频剪辑）倾向于具有更多的社会联系， 也许是因为更多的人以类似的方式体验世界，而那些不那么规范的人， 回应者的社会联系往往较少。越来越多的证据表明， 精神分裂症患者对这种自然主义刺激的反应可能较少，这可能有助于 解释为什么社会脱节在这种疾病中很常见。然而，ISC方法尚未使用 研究精神分裂症患者的社交功能障碍本项目将通过翻译ISC的研究来填补这一研究空白 方法从非临床研究，以调查如何ISCs涉及社会脱节， 精神分裂症精神分裂症个体（N=200）和匹配的健康对照（N=100）将分别 完成一次功能性磁共振成像扫描，在此期间，他们将观看自然主义的视频刺激，并完成两次既定的 评估社会处理的重要领域的范式：社会线索感知和心理化。我们将 基于对自然主义视频刺激的响应来表征ISC，并表征与以下相关的大脑活动： 社会线索知觉和心理化使用标准分析。该研究将测试ISCs是否在 两个参与者组，并评估在何种程度上组ISC差异与个体差异有关， 社会关系我们还将描述精神分裂症组每个成员的ISC正常性， 使用对照组作为参考，以评估大脑反应正常性是否与社会相关。 断连，以及是否可以从中预测个人的社会断连程度。该项目将 还测试是否ISC为基础的措施是更敏感的社会脱节的个体差异比 功能性磁共振成像该项目的结果将提高对大脑活动如何与 精神分裂症的社会功能障碍ISC措施也有望构成社会的生物标志物， 功能障碍，可能有助于识别处于社会脱节高风险的个体， 对最有可能从中受益的个体进行治疗，或在未来的临床试验中评估结果。

PROJECT SUMMARY/ABSTRACT Social dysfunction is a core feature of schizophrenia. Many individuals with schizophrenia experience social disconnection, a lack of social contact with friends and family. Social disconnection is associated with reduced quality of life and many negative health effects, but most current treatments do little to address it. The development of new interventions is currently hindered by a lack of scientific understanding about how differences in the way individuals’ brains process information contribute to social disconnection, and a lack of biomarkers associated with social functioning. Recent research in non-clinical social neuroscience points to a compelling model that may help to explain social disconnection in schizophrenia and would provide the basis for a new biomarker of social dysfunction. Specifically, research using functional magnetic resonance imaging (fMRI) and inter-subject correlation (ISC) analysis methods shows that people whose brains tend to respond more normatively to dynamic, naturalistic stimuli (e.g., video clips) tend to have more social connections, perhaps because more other people experience the world in a similar way, whereas people with less normative responses tend to have fewer social connections. Converging evidence suggests that many individuals with schizophrenia are likely to have less normative responses to such naturalistic stimuli, which could help to explain why social disconnection is common in the disorder. However, the ISC method has not yet been used to study social dysfunction in schizophrenia. This project will fill this research gap by translating ISC research methods from non-clinical research in order to investigate how ISCs relate to social disconnection in schizophrenia. Individuals with schizophrenia (N=200) and matched healthy controls (N=100) will each complete one fMRI scan during which they will view naturalistic video stimuli and complete two established paradigms that assess important domains of social processing: social cue perception and mentalizing. We will characterize ISCs based on responses to the naturalistic video stimuli and characterize brain activity related to social cue perception and mentalizing using standard analyses. The study will test whether ISCs differ between the two participant groups and evaluate to what extent group ISC differences relate to individual differences in social connection. We will also characterize ISC normativity for each member of the schizophrenia group, using the control group as a reference, to assess whether brain response normativity is associated with social disconnection, and whether individuals’ degree of social disconnection can be predicted from it. The project will also test whether an ISC-based measure is more sensitive to individual differences in social disconnection than established fMRI measures. Results from this project will improve understanding of how brain activity relates to social dysfunction in schizophrenia. ISC measures are also expected to constitute a biomarker of social dysfunction that may be useful for identifying individuals at high risk of social disconnection, targeting treatments toward individuals most likely to benefit from them, or assessing outcomes in future clinical trials.