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

描述(申请人提供)：精神分裂症的语言障碍被认为是精神分裂症精神病理学的一个重要组成部分，也是导致正式思维障碍的一个因素。精神分裂症患者语言中常见的特征包括语言贫乏、脱轨、联系松散、目标丧失、坚持不懈、离题和分心。在这项应用中，我们将重点研究精神分裂症患者语言功能障碍的语义方面，更具体地说，精神分裂症患者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加工，该领域有两个主要假说。一种观点认为，精神分裂症患者在语义网络中受到过度激活的困扰，激活传播得更快和/或更广泛，从而到达正常个体不会被激活的语义联系。另一种观点认为，在精神分裂症患者中，不正常的是晚期的受控过程，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探索精神分裂症患者启动范式下的大脑激活，直接将功能异常映射到大脑区域。该应用程序的一个主要目标是对比使用短刺激起始异步和长刺激起始异步(SOA)的单词启动，以便评估正常个体和精神分裂症患者作为SOA功能的大脑激活的差异。这个应用程序的另一个目标是测试分类启动范式和关联启动范式是否与独特的激活模式相关联，从而可以帮助我们理解正常人和精神分裂症患者的记忆结构。在精神分裂症的案例中，问题是，患有这种障碍的人是否具有类似于非精神分裂症患者的语义记忆结构，或者考虑到精神分裂症部分由基因调节，并带有主要的发育成分，这种结构是否不同。因此，在语义记忆中可能会形成异常联系，而这反过来又可能至少部分地导致精神分裂症患者语言异常的某些方面。因此，这项应用的另一个目标将是探索与处理词对相关的大脑激活模式，这些词对在正常人和精神分裂症患者中都与类别成员资格或联想强度相关。同样，目前还没有发表过关于精神分裂症患者语义记忆结构的功能磁共振研究，只有一项针对正常人的功能磁共振研究。精神分裂症患者经常使用混乱的语言，这使得成功的社交活动变得困难。然而，对精神分裂症语言障碍的根本原因的了解还远未完成，大多数证据来自行为或事件相关电位研究。因此，在这一应用中，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可能的异常，并确定哪些大脑结构参与了这些异常的调节。

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.