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Characteristics of the neural correlates of diminished metaphor comprehension in schizophrenia.

Principal Investigator: dr Przemysław Adamczyk

1. Aim: This project's objective is to identify the neural mechanism behind the deficit of metaphor comprehension in schizophrenia. In order to achieve this goalwe planned complex network analysis using state-of-the-art neuroimaging methods including functional, structural and connectivity methods. Furthermore, as continuation of our previous researchconcerning on the neural correlates of diminished humor comprehension, additional aim of this project is to investigate on specificity and/or differentiation of the various brain regions activated during figurative meaning of speech processing. Thismay better describe their role in communication deficits observed in schizophrenia.The analysis of the current literature data indicates that problem of understanding and use of the figurative aspects of language in schizophrenia, such ashumor and metaphor,is not sufficiently studied. To our knowledge this is the first attempt to applythe network approach to study this problem. Thus, based on our previous research, in this project we want to verify the hypothesis of impaired efficiency of the processes involved in the integration of metaphorical meaning within the semantical context of the language.Concluding from the available data, we suppose that this impairment is connected with a dysfunction in fronto-temporo-parietal regions of the brain, responsible for impaired context-based semantic organization.We also suppose that the disorders in the above mentioned process result in different pattern of neural network activation, precisely, insufficient activation of the areas responsible for semantic-shift required to understanding of the metaphorical meaning. Moreover we suppose that brain activity impairments in the inferior frontal gyrus (IFG, BA 45/47)and inferior parietal lobule (IPL,BA 39/40) will be stronger inpatients with severe negative syndrome and thinking disorders.

2. Methods: In order to test hypotheses and answering the question about causes of this deficit, we plan the present study to include:-functional Magnetic Resonance Imaging assessments including BOLD signal analysis in order to analyze functional abnormalities in activation of structures related to this deficit.-the structural connectivity analysis with use of Diffusion Tensor Imaging method in order to analyze the volume of axonal connections between regions engaged in metaphor processing–the effective connectivity analysis which reflects the strength and direction of propagation of activation within neuronal network using information flow analysis of the EEG recordings (Directed Transfer Function). Summing up, the present study will serve to provide possibly full description of the neural network engaged in metaphor processing by describing its structural and functional characteristics.Thecomparison of results in healthy people and in schizophrenic outpatients will allow to determine the potential cause of metaphor comprehensiondeficit in schizophrenia. The subjects in the clinicalgroup (n=30) will be recruited from the ambulatory outpatients with diagnosis of paranoid schizophrenia in current symptomatic remission (PANSS assessment). For purposes of comparison a matching (sex, age, education level) control group of healthy individuals will be recruited (n=30). The exclusion criteria are: neurological disorders, severe somatic disorders, psychoactive substance dependence, severe cognitive deficits (assessment with MOCA), reading difficulties. The planned study involves two experiments with use of EEG and fMRI methods. Experimental stimuli were constructed in that way, that each story(a setup) will have three endings: metaphoric, neutral and nonsensical. Such stimuli will enable analyses of different stages of metaphorical meaning processing and the detection of differences in strength andpropagation of activation in each condition. The adopted methodology of assessment and whole-brain methods of analysis will allow to perform a complex analysis of the neuronal network involved in cognitive processing of metaphors.The next step in analysis of the obtained structural and functional data will investigate their associations with the severity of psychopathological symptoms, especially the negative syndrome and thinking disorders.

3. Expected impact:The study will serve to broaden the knowledge concerning the mechanism of deficits in understanding the figurative meaning of speech in schizophrenia. In particular, the knowledge of their neuronal basis (the analysis of the information flow in neuronal networks) by application of the network approach, which is relatively new and most complex and comprehensive state of the art methods. As it will contribute to better understanding of the causes of communicationdeficits, it will become a starting point for determining the potential areas of therapeutic intervention aimed at improvement of social functioning and social integration of people suffering from schizophrenia