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.
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