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学的重要组成部分，也是形式思维障碍的一个促成因素。精神分裂症患者的语言通常表现为言语贫乏、脱轨、联想松散、目标丧失、固执、不切实际和注意力分散。在这个应用程序中，我们将集中在精神分裂症的语言功能障碍的语义方面，更具体地说，精神分裂症的语义记忆的过程和结构。关于精神分裂症患者语义记忆的异常过程，该领域有两个主要的假设。一种观点认为，精神分裂症患者在语义网络中过度激活，激活传播得更快和/或更广泛，从而达到正常个体中不会被激活的语义联想。另一种观点认为，精神分裂症患者的异常是晚期的、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语言的特殊特征。事实上，几乎所有支持这种或那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，还没有发表的研究，探讨在启动范式在精神分裂症，映射功能异常到大脑区域的直接方式大脑激活。这个应用程序的一个主要目标是对比字启动使用短和长的刺激发作的时间（SOA），以评估在正常和精神分裂症患者的SOA的功能在大脑激活的差异。本申请的另一个目标是测试分类和联想启动范式是否与独特的激活模式相关，从而可以告知我们对正常和精神分裂症患者记忆结构的理解。就精神分裂症而言，问题在于，患有这种疾病的人是否具有与非患者相似的语义记忆结构，或者，鉴于精神分裂症部分由遗传介导，并且具有主要的发育成分，这种结构是否不同。因此，语义记忆中可能会出现异常的联系，而这些联系反过来又可能至少部分地导致精神分裂症中观察到的异常语言的某些方面。因此，本申请的另一个目标是探索与正常和精神分裂症个体中通过类别成员关系或关联强度相关的词对处理相关的脑激活模式.同样，目前还没有关于精神分裂症患者语义记忆结构的功能磁共振成像研究，只有一项关于正常人的功能磁共振成像研究。精神分裂症患者经常使用混乱的语言，这使得成功的社会交往变得困难。然而，对精神分裂症语言障碍的根本原因的理解还远未完成，大多数证据来自行为或事件相关的潜在研究。因此，在本申请中，我们建议使用功能磁共振成像来描述精神分裂症的语义记忆结构中可能存在的异常，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.