Spatiotemporal imaging of language in schizophrenia

长期以来，思维和语言障碍一直被认为是精神分裂症的核心特征。这项建议的广泛目标是利用多模式成像技术识别精神分裂症患者语言处理的神经动力学异常。我们假设，随着语境的建立，单个词之间的语义关系在时间-前额叶网络(左上、中、双侧、左下前额叶皮质)内的神经/突触活动异常增加，从而导致时间-前额叶活动的异常调节，因为语境是一个词一个词地、句子内部和句子之间的。这一精神分裂症患者语言障碍的认知神经生物学理论将在一系列实验中得到验证，这些实验研究(A)词对之间的语义关系，(B)句子内语境的建立和(C)句子(语篇)的语境整合。为了调查“何时”和“何处”，将采取多模式方法，整合两种互补的神经成像技术的优势。首先，电生理实验将通过检测N400和晚期正向成分-已知对语境整合敏感的事件相关电位-来确定精神分裂症患者在语言处理过程中神经认知异常的时间进程。其次，事件相关功能(磁共振成像)研究将通过检测在颞叶-前额叶语义网络内血流动力学反应的范围、大小和时间动力学来表征精神分裂症语言异常的功能神经解剖学特征。第三，使用这些互补技术获得的数据将被直接比较，从而可以对潜在的神经/突触活动做出推断，并进行定量组合，从而可以描绘精神分裂症患者在语言处理过程中跨颞叶和前额叶皮质的激活时空模式。

A disorder of thought and language has long been considered a core feature of schizophrenia. The broad objective of this proposal is to identify abnormalities in the neural dynamics of language processing in schizophrenia using multimodal imaging techniques. It is hypothesized that abnormally increased neural/synaptic activity within a temporal-prefrontal network (left superior and middle temporal, bilateral inferior temporal and left inferior prefrontal cortices) to semantic relationships between individual words leads to abnormal modulation of temporal-prefrontal activity as context is built up, word by word, within and across sentences. This cognitive neurobiological theory of language dysfunction in schizophrenia will be tested in a series of experiments studying (a) semantic relationships between word pairs, (b) the build up of context within sentences and (c) contextual integration across sentences (discourse). In order to investigate "when" and "where", a multimodal approach will be taken, integrating the advantages of two complementary neuroimaging techniques. First, electrophysiological experiments will determine the time course of neurocognitive abnormalities during language processing in schizophrenia by examining the N400 and late positive components - event related potentials that are known to be sensitive to contextual integration. Second, event-related functional (magnetic resonance imaging studies will characterize the functional neuroanatomy of language abnormalities in schizophrenia by examining the extent, magnitude and temporal dynamics of the hemodynamic response within the temporal-prefrontal semantic network. Third, data obtained using these complementary techniques will be directly compared, allowing inferences to be made about underlying neural/synaptic activity, and quantitatively combined, allowing the delineation of spatiotemporal patterns of activation across temporal and prefrontal cortices during language processing in schizophrenia.