Functional impairment of schizophrenia (SZ) poses a tremendous burden on society and shows limited response to pharmacologic treatments. Previous work by the Candidate (Dr. Ivy Tso) and others suggest that early visual processing and eye gaze perception are two cognitive processes with important functional implications, but unanswered questions about the source of these deficits and dynamic interactions between these processes limit the usefulness of this knowledge to design effective treatment. This K23 Career Development Award proposal aims to advance research in this area through two broad goals: 1) To delineate a brain network model of gaze perception deficits in SZ using functional MRI and dynamic causal modeling (DCM); and 2) To provide a promising candidate with training in advanced fMRI network techniques and translational research skills to accelerate the translation of research findings to innovative cognitive interventions. The proposed project will study 40 SZ participants and 40 health controls, and probe gaze perception and visual integration using two psychophysics paradigms during fMRI. Behavioral performance and brain activation will be compared between SZ and HC, and the effect of SZ on directional connectivity between key brain regions recruited in gaze perception will be identified using DCM. The specific research aims are: 1) To characterize the brain activation profile of altered visual integration and gaze perception in SZ and its relationship to functional outcome; and 2) To characterize the brain network profile of gaze processing in SZ and identify abnormal effective connectivities underlying gaze perception deficits. This K23 research will help define a treatment target for a future intervention study. Dr. Tso is a clinical psychologist with demonstrated experience in publishing and obtaining funding in behavioral and electrophysiological research in eye gaze perception in SZ. She is committed to translating her research findings to innovative cognitive interventions. She will work closely with a team of experts who collectively provide mentorship in a multitude of training domains: Primary Mentor Stephan Taylor (fMRI, responsible conduct of research), Co- mentor Vaibhav Diwadkar (network analyses and DCM), and Consultants Scott Peltier (fMRI), Timothy Johnson (Bayesian biostatistics), Michael Green (social cognition and functional assessment), Sophia Vinogradov (cognitive training and intervention research), and Emily Mower Provost (human-centered computing). Training will be complemented and augmented by formal coursework, specialized short courses, workshops, scientific meetings, and other training activities as described in the Career Development Plan. Dr. Tso?s short-term career goal is to acquire a new skillset in fMRI network modeling and become an independent translational neuroimaging researcher. Her long-term career goal is to develop a comprehensive research and intervention program to effectively treat and prevent severe and persistent mental illnesses. The proposed K23 Award is a crucial step in fulfilling these career goals.
Schizophrenia is one of the top 10 most debilitating diseases in the world and affects 3 million people in the U.S. This project will identify neural mechanisms underlying a key social cognitive deficit (eye gaze perception) in schizophrenia, thus directing future cognitive training interventions to effectively improve social functioning in schizophrenia and related disorders.
