Semantic knowledge and its underlying structures in schizophrenia-an fMRI study

描述（由申请人提供）：精神分裂症的语言功能障碍被认为是精神分裂症精神病理的重要组成部分，也是导致形式思维障碍的一个因素。精神分裂症患者的语言特征包括语言贫乏、脱轨、松散联想、失去目标、坚持不懈、切线和分心。在这个应用程序中，我们将重点关注精神分裂症语言功能障碍的语义方面，更具体地说，精神分裂症语义记忆的过程和结构。关于精神分裂症的语义记忆异常过程，目前学界主要有两种假说。一种观点认为，精神分裂症患者患有语义网络的过度激活，从而激活传播得更快和/或更广泛，从而达到正常人不会激活的语义关联。另一种观点认为，精神分裂症的异常是晚期的、受控的过程，而不是早期的自动激活过程。这两种理论都可以解释精神分裂症患者语言的特殊特征。事实上，几乎所有支持其中一种观点的证据都来自使用行为或事件相关电位（ERP）测量的启动研究。然而，目前还没有发表的研究在精神分裂症的启动范式中探索大脑激活，以直接的方式将功能异常映射到大脑区域。本应用程序的一个主要目标是对比使用短时间和长时间刺激启动异步（SOA）的单词启动，以评估正常和精神分裂症个体中作为SOA功能的大脑激活的差异。本应用程序的另一个目的是测试分类和联想启动范式是否与独特的激活模式相关，从而可以为我们理解正常和精神分裂症个体的记忆结构提供信息。在精神分裂症的案例中，问题是患有这种疾病的人的语义记忆结构是否与未患这种疾病的人相似，或者这种结构是否不同，因为精神分裂症部分是遗传介导的，主要是发育成分。因此，语义记忆中可能会出现异常链接，而这些链接反过来，至少在一定程度上，导致了精神分裂症中观察到的语言异常的某些方面。因此，本应用程序的进一步目标将是探索与正常和精神分裂症个体中与类别隶属关系或联想强度相关的词对处理相关的大脑激活模式。同样，没有发表过关于精神分裂症语义记忆结构的fMRI研究，只有一项针对正常人的fMRI研究。精神分裂症患者经常使用紊乱的语言，这使得成功的社会交往变得困难。然而，对精神分裂症中语言障碍的潜在原因的理解远未完成，大多数证据来自行为或事件相关的潜在研究。因此，在本应用中，我们建议使用功能磁共振成像来描述精神分裂症患者语义记忆结构的可能异常，并确定哪些大脑结构参与介导这些异常。

DESCRIPTION (provided by applicant): Language dysfunction in schizophrenia is believed to be an important component of schizophrenic psychopathology and a contributing factor to formal thought disorder. The features commonly observed in schizophrenic language include poverty of speech, derailment, loose associations, loss of goal, perseveration, tangentiality, and distractibility. In this application, we will focus on semantic aspects of language dysfunction in schizophrenia, more specifically the processes and structure of semantic memory in schizophrenia. There are two major hypotheses in the field regarding abnormal processes in semantic memory in schizophrenia. One holds that schizophrenia patients suffer from overactivation within semantic networks whereby activation spreads faster and/or more broadly, thus reaching semantic associates that would not be activated in the normal individuals. The other view holds that it is the late, controlled processes rather than early processes of automatic activation, which are abnormal in schizophrenia. Both theories can account for peculiar characteristics of schizophrenic language. In fact, almost all of the evidence in support of one or the other view comes from priming studies using either behavioral, or event related potential (ERP) measures. However, there are no published studies that explore brain activation in a priming paradigm in schizophrenia that map functional abnormalities onto the brain areas in a direct way. A major goal of this application is to contrast word priming using short and long stimulus onset asynchronies (SOAs) in order to evaluate differences in brain activation as a function of SOA in both normal and schizophrenic individuals. An additional goal of this application is to test whether categorical and associative priming paradigms are associated with unique patterns of activation and thus can inform our understanding of memory structure in both normal and schizophrenic individuals. In the case of schizophrenia, the question is whether persons suffering from this disorder have a structure of semantic memory similar to non-afflicted individuals, or whether that structure is different, given the fact that schizophrenia is partially genetically mediated and with a major developmental component. It is thus possible that abnormal links might develop within semantic memory and these may, in turn, contribute, at least in part, to some aspects of abnormal language observed in schizophrenia. Accordingly, a further goal of this application will be to explore brain activation patterns associated with processing of word- pairs that are related by either category membership or associative strength in both normal and schizophrenic individuals. Again, there are no published fMRI studies of semantic memory structure in schizophrenia, and only one fMRI study in normal individuals. Schizophrenia sufferers often use disordered language which makes successful social interactions difficult. However, understanding of underlying causes of language disorder in schizophrenia is far from complete, with most evidence coming from behavioral or event related potential studies. Thus, in this application we propose to use fMRI to describe possible abnormalities in semantic memory structure in schizophrenia and identify which brain structures are involved in mediating these abnormalities.