Ivy F. Tso, M.S., M.Phil. - US grants

Project Summary/Abstract 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.

Project Summary/Abstract Social dysfunction is an intractable problem in a wide spectrum of psychiatric illnesses, undermining patients? capacities for employment, independent living, and maintaining meaningful relationships. Identifying common markers of social impairment across disorders and understanding their mechanisms are prerequisites to developing targeted neurobiological treatments that can be applied productively across diagnoses and illness stages to improve functional outcome. This project focuses on eye gaze perception, the ability to accurately and efficiently discriminate others? gaze direction, as a potential biomarker of social functioning that cuts across psychiatric diagnoses. This premise builds on both the monkey and human literatures showing gaze perception as a basic building block supporting higher-level social communication and social development, and reports of abnormal gaze perception in multiple psychiatric conditions accompanied by prominent social dysfunction (e.g., psychosis-spectrum disorders, autism-spectrum disorders, social phobia). A large sample (n= 225) of adolescent and young adult (age 14-30) psychiatric patients (regardless of diagnosis) with various degrees of impaired social functioning, and 75 demographically matched healthy controls will be recruited for this study. Participant?s psychiatric phenotypes, cognition, social cognition, and community functioning will be dimensionally characterized. Eye gaze perception will be assessed using a psychophysical task, and two metrics (precision, self-referential bias) that respectively tap into gaze perception disturbances at the visual perceptual and interpretation levels, independent of general deficits, will be derived using Bayesian modeling. A subset of the participants (150 psychiatric patients, 75 healthy controls) will additionally undergo multimodal fMRI to determine the functional and structural brain network features of altered gaze perception. The specific aims of this project are three fold: Aim 1) Determine the generality of gaze perception disturbances in psychiatric patients with prominent social dysfunction; 2) Map behavioral indices of gaze perception disturbances to dimensions of psychiatric phenotypes and core functional domains; and 3) Identify the neural correlates of altered gaze perception in psychiatric patients with social dysfunction. Successfully completing these specific aims will identify the specific basic deficits, clinical profile, and underlying neural circuits associated with social dysfunction that can be used to guide targeted, personalized treatments, thus advancing NIMH?s Strategic Objective 1 (describe neural circuits associated with mental illnesses and map the connectomes for mental illnesses) and Objective 3 (develop new treatments based on discoveries in neuroscience and behavioral science).