Research and mentoring on cognitive neuroscience and high-field MRI of the thalamus in schizophrenia

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ABSTRACT A K24 Mid-Career Investigator Award in Patient-Oriented Research (POR) is requested to: 1) augment my capabilities in POR to include new expertise in network science, and the cognitive neuroscience and neuroimaging of the human thalamus; 2) apply these new expertise to perform novel studies of thalamic connectivity, function, and structure in psychotic disorders; and 3) enhance my mentorship skills and provide protected time to mentor trainees. My research program investigating the neural basis of psychotic disorders serves as a platform for training POR trainees. This includes mentoring junior faculty, postdoctoral fellows, graduate students, and MD/PhD medical students in psychotic disorders, neuroimaging, and neuropsychology. For the past several years my lab has focused on investigating thalamocortical circuit abnormalities in psychotic disorders. We were among the first to show that functional connectivity of the thalamus in schizophrenia is characterized by a combination of lower connectivity with the prefrontal cortex (PFC) and hyper-connectivity with sensorimotor cortical areas. Our findings coincided with groundbreaking discoveries in the cognitive neuroscience of the thalamus. However, many recent advances in the fundamental neuroscience of the thalamus have yet to translate to improved understanding of the mechanisms of psychosis phenotypes. This translational gap is impeding progress in identifying potential treatment targets for cognitive impairment. Progress is further hindered by limitations of conventional neuroimaging methods which are unable to directly visualize individual thalamic nuclei in humans. This proposal provides the foundation for addressing these challenges. Specifically, I will develop new research skills in network science (Aim 1) and the cognitive neuroscience of the thalamus (Aim 2A), extend existing expertise in neuroimaging to include state-of-the-art methods for imaging the human thalamus in vivo (Aim 2B), and apply these new expertise to characterize thalamic nuclei structure and function abnormalities in early stage schizophrenia (Aim 3). This proposal will: 1) enhance ongoing work in my lab characterizing brain connectivity in psychopathology and normal cognitive development; and 2) provide me with critical expertise required for future studies focused on informing thalamocortical mechanisms of psychosis phenotypes.