The Neuronal Correlates of Theory of Mind in Schizophrenia

Hartford Hospital, Hartford CT

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Social function deficits are among the most disabling features of schizophrenia (SZ) and are a significant factor in the resulting social isolation and unemployment experienced by many patients. Since recent studies show that general neurocognitive impairments commonly seen in SZ do not fully explain patients' social deficiencies, it has been postulated that specific deficits in the 'Theory of Mind' (ToM) reasoning process underlie the neuropathology of social dysfunction in SZ. ToM reasoning, or 'mentalizing', refers to the crucial social process of attributing states of mind (including emotions, desires and goals) to other people to allow prediction and interpretation of others' behavior and consequent adjustment of one's own behavior. There is strong evidence that abnormal mentalizing functions underlie the social dysfunction in SZ. Although researchers have started to explore the neuronal networks that process implicit mentalizing in healthy individuals, the neuropathology that underlies this social cognitive deficit in SZ is not yet understood. Using functional MRI (fMRI), we will measure brain activation patterns in a defined brain network that subserves implicit mentalizing in 30 chronic SZ patients and 30 carefully matched healthy controls (HC) during a social interaction task, the Domino task. While undergoing the fMRI scans, participants will play an average of 12 Domino games against a human- and a computer-opponent. The former uniquely involves attributing a state of mind to another person (i.e. predicting their strategy), and processing emotions associated with reward and punishment, while being involved in a social two-player competitive game. In order to win, players occasionally have to choose to bluff their opponent, and thus risk being caught and punished (as in poker). When players play fairly they are rewarded if challenged by the opponent. We will analyze the critical intervals during the game when players are engaged in trying to predict their human-opponent's responses (vs. computer-opponent) to avoid punishments and gain rewards (i.e. implicit mentalizing process). We will estimate the differences between SZ brain activation patterns and those of HC related to this process. An fMRI probability prediction paradigm will evaluate the specificity of activation patterns during the domino paradigm to mentalization as opposed to probability prediction. Additionally, we will explore the relationship between patients' activation patterns during implicit mentalization and their social competence, symptoms heterogeneity and cognitive abilities in four domains: attention, working memory, intelligence, and executive functions. This study is designed to explore the neuropathology underlying social dysfunction in SZ and its association with patients' neurocognitive abilities, social competence and symptomatology. This in turn will be an essential step in identifying a subgroup of SZ patients that has the potential to benefit the most from cognitive and pharmacological rehabilitation remedies specifically targeting ToM social cognition and thus advancing future research (including genetic) of development of new treatment tools for SZ. This study is designed to explore the hypothesis that deficits in mentalizing processes (i.e. attributing states of mind, including emotions, desires and goals, to other people) underlie the neuropathology of social dysfunction in SZ. It will also assess the relationship between brain activations abnormalities associated with mentalizing and patients' neurocognitive abilities, social competence and symptomatology. The results of these analyses will help us in identifying a subgroup of SZ patients that has the potential to benefit the most from cognitive and pharmacological rehabilitation remedies specifically targeting ToM social cognition and thus pave the way for future research (including genetic) of development of new treatment tools for SZ. [unreadable] [unreadable] [unreadable]