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。无序思维具有很高的遗传外显率，在精神分裂症患者的亲属中检测到的比例很高，即使这些亲属没有表现出明显的精神病。因此，对思维问题的检查可能对理解精神分裂症特别有见地。这项建议的广泛目标是将行为测量和大脑活动测量结合起来，以进一步了解语义-概念记忆神经网络和言语工作记忆系统的潜在异常，这些系统允许人类在面对独特的当前情况时做出适应性和灵活的行为。更具体地说，其目的是了解自动语义激活与受控的言语工作记忆抑制，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语境抑制过程和相关的大脑活动进行对比(同形词如box；to box，the box)。其次，我们将考察期望对语言处理的影响。第三，词汇通达过程中的高频脑活动(伽马波)将被检测，以评估语义记忆神经网络结构的完整性。记忆存储在分布式网络中，伽马活动很可能使分散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，以评估最近过去对患者当前表现的益处或减损。这些研究将有助于确定，在信息处理流程中，思维障碍的最大罪魁祸首是在自动语义记忆系统的早期，还是在受控的工作记忆系统，以及行为与底层大脑系统的关系。总而言之，这些数据将有助于从实际的大脑结构和功能方面澄清精神分裂症患者思维障碍和认知异常的性质。

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.