Understanding Functional Connectivity Abnormalities In Individual Patients with Psychosis

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Abstract This is an application for a K01 award for Dr. Danhong Wang, a physician-scientist at Massachusetts General Hospital and Harvard Medical School. Dr. Wang is establishing herself as a young investigator in patient- oriented neuroimaging research on psychiatric disorders. This K01 award will provide Dr. Wang with the support necessary to accomplish the following goals: (1) to become an expert in patient-oriented research in psychiatric neuroimaging; (2) to conduct experimental investigations of neurobiological correlates in patients with psychosis; (3) to implement revolutionary individual-level functional mapping techniques in clinical studies; and (4) to develop an independent clinical research career. To achieve these goals, Dr. Wang has assembled a mentoring team comprised of three mentors: Dr. Dost Öngür, Chief of the McLean Hospital Psychotic Disorders Division, who leads a neuroimaging laboratory studying the biology of psychotic illness; Dr. Randy Buckner, Professor of Psychology and Neuroscience at Harvard University and Director of Psychiatric Neuroimaging at Massachusetts General Hospital, one of the pioneers in functional MRI research; and Dr. Suzanne Haber, Professor of Pharmacology and Physiology at the University of Rochester, a leading scientist in the field of neuroanatomy. In addition, Dr. Hesheng Liu, Associate Professor of Radiology at Harvard Medical School and a computational neuroscientist with expertise in functional imaging, will collaborate on this project. Dr. Wang will engage in multiple career development activities to expand her ability to develop mechanistic insights about psychiatric disorders. These include new training in patient-oriented experimental research, a better understanding of the psychopathology of psychosis, and a stronger grasp of neuroanatomy. She will also receive advanced training in cognitive and clinical neuroscience. Determining the disconnected neural circuits underlying psychosis has proved elusive. Dr. Wang's research project aims to reveal circuitry abnormalities in psychotic patients using a subject-specific, cross-diagnostic approach. In Aim 1, Dr. Wang will establish methods for accurately characterizing the cortical and subcortical functional connectivity networks in individual patients. In Aim 2, leveraging a cross-diagnostic cohort of psychotic patients that will be scanned using the protocol optimized for individual-level functional analyses, as well as an existing patient data set, Dr. Wang will identify and validate cortical and subcortical functional connectivity abnormalities related to the severity of psychotic symptoms. In Aim 3, Dr. Wang will investigate the temporal variations of connectivity in individual patients and reveal abnormalities in dynamic functional connectivity related to symptoms. A series of preliminary studies conducted by Dr. Wang have laid the solid foundation for each specific aim. This research will form the basis of a study for identifying the “connectivity hubs” in individual patients for potential modulation, to be proposed in an R01 grant application before the end of the K award.