Brain Correlates of Executive Function during Semantic Retrieval in Schizophrenia

描述（由申请人提供）：工作记忆的执行功能（如注意力和反应抑制）和语义功能已知在精神分裂症中受损。前者与一般认知缺陷有关，而后者更具体地与精神分裂症的思维障碍和语言使用有关。目前，文献中正在进行的一场辩论将语义系统的组织与执行功能对立起来，作为精神分裂症患者语言紊乱的基础。然而，最近的行为、生理和影像学证据表明，语言缺陷，特别是思维障碍，很可能是执行过程和语义系统之间相互作用的结果。因此，该提案的长期目标是详细说明相互作用的程度，以便它们可以用于识别对精神分裂症早期诊断有用的生物和行为系统，因为语言异常通常是该疾病的第一个指标之一。语义系统在感觉、音素、单词、短语、句子和文本层面上与执行过程相互作用。这些相互作用增加了复杂性，从而增加了认知需求，因为上下文从单词移动到文本水平。本研究的具体目的是评估上下文复杂性操作过程中执行和语义处理之间的相互作用，并潜在地证明语义任务过程中行为表现与语义处理的其他措施和相关的潜在大脑系统之间的关系。我们将特别研究执行过程对语义检索的影响，并研究在精神分裂症中，额-后连通性的失败，以及由此导致的额-额连通性的代偿性增加，是语言紊乱的一部分。这将使用最近开发的语义性能和语义组织的行为测量，结合功能性磁共振成像和建模来指定与我们的结果相关的生物系统。健康志愿者、精神分裂症患者及其亲属将参加。我们的行为和建模结果将增加对精神分裂症语义缺陷机制的理解，这是公共卫生领域的重要关注点，并有可能成为该疾病的早期标志。

DESCRIPTION (provided by applicant): Both executive functions in working memory (e.g. attention and response inhibition) and semantic functions are known to be compromised in schizophrenia. The former has been associated with general cognitive deficits, while the latter, more specifically with thought disorder and language use in schizophrenia. Currently, an ongoing debate in the literature pits the organization of the semantic system against executive functions as underlying the language disorganization seen in persons with schizophrenia. However, recent behavioral, physiological and imaging evidence suggests that language deficits, specifically thought disorder, are likely to be a result of interactions between executive processes and the semantic system. Accordingly, the long-term objectives of the proposal are to specify the interactions to the extent that they may be used for Identification of a biological and behavioral system useful for the early diagnosis of schizophrenia, as language abnormalities are often one of the first indicators of the disease. The semantic system interacts with executive processes at sensory, phonemic, word, phrase, sentence, and text levels. These interactions increase in complexity and thereby increase cognitive demands as the context moves from words to text levels. The specific aims of this proposal are to evaluate the interaction of executive and semantic processing during manipulations of contextual complexity, and potentially demonstrate both the relationship between behavioral performance during semantic tasks to other measures of semantic processing and the underlying brain system involved. We will specifically examine the effect of executive processes on semantic retrieval and examine the idea that in schizophrenia the failure of fronto-posterior connectivity, with a resulting compensatory increase in fronto- frontal connectivity, are part of language disorganization. This will be done using recently developed behavioral measures of semantic performance and semantic organization, in tandem with functional Magnetic Resonance Imaging and modeling to specify the biological system associated with our results. Healthy volunteers, persons with schizophrenia and their relatives will participate. Our behavioral and modeling results will increase the understanding of the mechanisms underlying semantic deficits in schizophrenia, which is of significant concern in the domain of public health, and has the potential to be an early marker of the disease.