Brain Activity and Language Comprehension in Psychosis

描述（申请人提供）：思维障碍是精神分裂症的主要症状，通过异常语言推断。思维障碍具有很高的遗传外显率，并且在精神分裂症患者的亲属中检测到的比率很高，即使这些亲属没有表现出明显的精神病。因此，思考问题的检查可能对理解精神分裂症特别有见地。该建议的主要目的是结合行为测量和大脑活动测量，以进一步了解语义/概念记忆神经网络和语言工作记忆系统的潜在异常，这些系统允许在面对独特的当前情况下适应性和灵活的人类行为。更具体地说，目的是了解自动语义激活与受控言语工作记忆抑制，并将这些功能障碍与潜在的大脑系统联系起来，从而了解精神病的神经生理学。首先，在使用词汇歧义的语言处理任务中，自动记忆过程和相关的大脑活动将与受控的上下文抑制过程和相关的大脑活动进行对比（同音异义词，如box； to box, the box）。其次，研究期望对语言加工的影响。第三，研究词汇获取过程中的高频脑活动（伽马波），以评估语义记忆神经网络结构的完整性。记忆存储在分布的网络中，伽马活动可能使分布的大脑区域协同工作。最后，将检查最近记忆痕迹和最近反应结果痕迹对患者当前行为的影响，以评估最近的过去如何对患者当前的表现有利或不利。这些研究将有助于确定在信息处理过程中，思维障碍的罪魁祸首在哪里，是在自动语义记忆系统的早期，还是在受控工作记忆系统的后期，以及行为与潜在大脑系统的关系。这些数据将有助于从实际的大脑结构和功能方面阐明精神分裂症患者思维障碍和认知异常的本质。

DESCRIPTION (provided by applicant): Thought disorder is a cardinal symptom of schizophrenia, and is inferred through abnormal language. Disordered thought has a high genetic penetrance, and is detected in relatives of schizophrenia patients at a high rate, even when these relatives do not exhibit overt psychosis. Thus, examination of thinking problems may be especially insightful for understanding schizophrenia. The broad aim of this proposal is to combine behavioral measures and brain activity measures to further understand the underlying abnormalities of semantic\conceptual memory neural networks and of verbal working memory systems that allow adaptive and flexible human behavior in the face of unique current situations. More specifically, the aims are to understand automatic semantic activation versus controlled verbal working memory inhibition and to relate these dysfunctions to underlying brain systems, so as to understand the neurophysiology of psychosis. First, automatic memory processes and related brain activity will be contrasted with controlled contextual inhibitory processes and related brain activity during language processing tasks using lexical ambiguities (homographs like box; to box, the box). Second, the effects of expectations on language processing will be examined. Third, high frequency brain activity (gamma waves) during lexical access will be examined to assess the integrity of semantic memory neural network structure. Memories are stored in distributed networks, and gamma activity likely allows distributed brain areas to work in concert. Lastly, the effects of recent memory traces and recent response outcome traces on the current behavior of patients will be examined, to assess how the recent past benefits or detracts from current performance in patients. The studies will help determine where in the information processing stream most blame can be laid for thought disorder, early in the automatic semantic memory system, or later in the controlled working memory system, and how behavior relates to underlying brain systems. Together the data will help clarify the nature of thought disorder and cognitive abnormalities in schizophrenia with respect to actual brain structure and function.