Brain functional correlates of lexical, semantic and executive dysfunction in formal thought disorder in schizophrenia
Formal thought disorder (FTD), speech that is difficult to follow to the point of complete incomprehensibility, has been much studied as one of the main symptoms of schizophrenia, but its underlying mechanisms remain poorly understood. Linguistic studies, based on the analysis of the discourse from thought-disordered patients with schizophrenia, have shown that speech from such patients is characterized by multiple uses of unclear reference and overuse of a particular reference mechanism, lexical cohesion. A different approach proposes that FTD is characterized by altered semantic memory processes (the knowledge about word meanings, the world and abstract concepts, and which is believed to be organized as a network). A third hypothesis is that FTD is a consequence of executive dysfunction: impaired planning and monitoring leads to the speech of patients with FTD being poorly formulated and prone to errors during execution. Lastly, another possibility is that FTD arises from a combination of executive and semantic dysfunction. However, to date, these hypotheses have not been systematically and exhaustively tested. Functional brain imaging has the potential to further and more decisively test these approaches to understanding FTD; however, relatively few such studies have been carried out. A meta-analysis found evidence of activation changes in the left superior temporal gyrus and the posterior medial temporal gyrus during task performance associated with the presence of FTD. A recent review reported that FTD during free speech production was associated with abnormality in several language areas, as well as regions outside the language network. During the performance of semantic processing tasks, FTD was also associated with activity changes in language areas and other regions. Brain activity associated with FTD during the performance of executive tasks is difficult to assess as very few studies in these two reviews employed tasks with an explicit executive component. The current proposal aims to examine, in a systematic manner, the above-described hypotheses of FTD, using novel fMRI paradigms. fMRI will be used to study brain activity associated with the production of free speech in schizophrenia patients with and without FTD (and healthy controls). Using event-related fMRI we will additionally look for differences in brain activity at moments when phoric reference or lexical cohesion occurs. We will also use a semantic processing task, sensitive to the activation of the semantic memory network. To examine executive function independently from language, we will look at brain activity during performance of a novel fMRI-adapted executive task, the Computerized Multiple Elements Test (CMET), which is sensitive to goal management and maintenance, and hence highly relevant to executive processes believed to be involved in FTD. Finally, we will examine the possibility that FTD in schizophrenia is the result of a combination of impaired executive and altered semantic function (at either the lexical or semantic network level). For this, we will examine brain activity during a semantic verbal fluency task.
48.400 €
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