The purpose of this K01 Mentored Research Scientist Development Award is to promote the candidate's development as an independent researcher in clinical neuroscience, with a focus on understanding the neurobiological relation between positive mood, motivation, and functional outcome in schizophrenia and eventually, in other serious mental illnesses. Dr. Subramaniam's long-term career goal is to develop a deep knowledge base on brain-behavior relationships underlying positive mood-cognition interactions in individuals with serious mental illnesses such as schizophrenia. The ultimate objective is to use this knowledge to inform the development of successful treatments and preventive interventions. Towards this end, this K01 award proposes to investigate the neural underpinnings of an intact process in schizophrenia-- the ability to experience positive moods-and to examine whether (and how) it mediates motivated behavior. The rationale for this study emerges from evidence indicating that motivational impairment is one of the principal determinants of impaired long-term functioning in schizophrenia, and that it is present as early as the prodromal phase of the illness. And yet, while recent findings indicate that motivation and subsequent goal- directed behaviors are enhanced by positive mood states in healthy individuals, nothing is known about these processes in people with schizophrenia. Thus, three specific aims will be studied in participants with schizophrenia and healthy comparison individuals in order to investigate: 1) Structural connectivity within motivation networks;2) The influence of a positive mood on functional connectivity linking brain regions important for motivated behavior;and 3) The influence of a positive mood on functional activation in brain regions that support motivation. This proposal includes formal mentored training through coursework and tailored didactics in clinical research methodologies, advanced multimodal structural and functional neuroimaging analyses, and responsible conduct of research. The University of California, San Francisco is an ideal environment for the proposed training as it provides access to experts and mentors in multimodal imaging, translational and clinical research methodologies, and schizophrenia research who work in laboratory settings as well as in field-based community settings. Successful completion of the proposed research and career development activities will inform the development of an R01 proposal and ensure Dr. Subramaniam's development as an independent investigator in the field of positive mood-cognition interactions in schizophrenia.
Motivational impairment is a central predictor of impaired functioning in people with schizophrenia, and is present in the earliest phases of the illness;yet motivational impairment in schizophrenia is poorly understood and there are currently no successful available treatments. A deeper understanding of the brain-behavior relationships underlying motivated behavior in individuals with schizophrenia and other serious mental illness is critical if we are to develop successful treatments and preventive interventions. In this projec, we will investigate the neural underpinnings of how mood states influence motivated behavior in schizophrenia, with an aim to deepening our knowledge of how such mechanisms can inform the design of novel treatment approaches.