This is an application for an NIMH Patient-Oriented Research Career Development Award (K-23) entitled """"""""The Neural Basis of Delusions in Schizophrenia: Studies of Emotional Perception."""""""" The candidate's interest is in the study of the neural correlates of psychotic symptoms in schizophrenia, with a specific focus on delusions. Previous studies indicate that patients with schizophrenia with active delusions exhibit abnormalities in emotional perception. A network of brain regions, which includes the amygdala, hippocampus, medial prefrontal cortex, and striatum, is active during emotional perception in healthy individuals. The candidate will test two hypotheses: 1) delusions arise from an increased tendency to attribute emotional significance to emotionally neutral or ambiguous information, and 2) this tendency results from abnormal neural activity within the network of brain regions involved in emotional perception. To address the research questions arising from this model, the candidate seeks training in cognitive and affective neuroscience, functional neuroimaging techniques, the statistical analyses of clinical, psychological and neuroimaging data, and the ethical conduct of clinical research. The proposed research plan, didactic courses, and individual instruction from mentors, advisors and consultants will help the candidate develop into an independent clinical researcher in the functional neuroimaging of emotional perception in schizophrenia. The candidate proposes to identify the specific abnormality in emotional perception in delusional schizophrenia patients using signal detection analyses to quantify a delusion-associated bias towards attributing emotional significance to neutral or ambiguous information. Experiments using two types of functional magnetic resonance imaging (blood oxygenation level dependent and arterial spin labeling) will be conducted to identify the changes in brain responses and resting neural activity associated with emotional perception abnormalities in delusional patients. Thus, the proposed experiments will test the candidate's model of delusions using the complementary techniques of cognitive neuroscience and functional magnetic resonance imaging. It is hoped that, by identifying perceptual and neural markers of delusions, these studies will lead to the development of methods for the detection of early, evolving psychosis. Such early detection methods would provide critical tools for the design of treatment interventions aimed at reducing the severity or preventing the onset of schizophrenia and other psychotic disorders.
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