CORE B: ABSTRACT Core B (Clinical and Imaging Core) will support Projects 1-3 for new clinical and translational research in schizophrenia (SZ) and relevant animal models. Core B is built on our established cohesive and committed team of investigators, with experts in clinical enrollment and characterization, olfactory imaging, and cortical imaging [as a productive outcome of long-term collaboration between the Johns Hopkins Schizophrenia Center (JHSZC) and the Center for Imaging Science (CIS) at Johns Hopkins University]. Smell deficits are one of the most reproducible changes in SZ. One key feature of the deficits is their tight association with specific clinical features, such as negative symptoms (e.g., avolition, anhedonia) and some cognitive deficits (e.g., social cognitive deficits), but not with positive symptoms (e.g., hallucination, delusion). Since 2009, the NIMH Research Domain Criteria (RDoC) framework has facilitated studies that focus on neurobiological processes underlying behavioral domains/constructs, instead of considering each psychiatric diagnosis as one homogeneous entity. One innovation of this P50 is translational research with both human and mouse studies under specific behavioral domains/constructs of interest (mainly, positive valence systems and social processes) in a mechanistic association with the olfactory-prefrontal circuits to account for specific clinical domains in SZ. Thus, we will leverage the RDoC research framework to organize our research design. Based on this framework, this Core B will assist Projects in addressing the central hypothesis that, mediated by the olfactory-prefrontal circuits, molecular and cellular changes in the olfactory epithelium (OE) significantly contribute to specific clinical manifestations that correlate with smell deficits in SZ patients. Accordingly, Core B will recruit new study participants and conduct clinical assessments, combining with the existing cohort (Aim 1). We will leverage a recently established alliance of patient recruitment with the Maryland Psychiatric Research Center (MPRC) and 10 hospitals in the MedStar Health network. We will pay a special attention to the confounding factors associated with COVID-19 in study participant recruitment and data analysis in collaboration with Core C (Core for data analysis). Core B will also collect and process brain imaging data (Aim 2) to provide ex vivo mouse olfactory bulb (OB) imaging (for Project 1), process 3T resting-state functional magnetic resonance imaging data from human healthy subjects (for Project 2), and obtain 3T structural imaging of the OB and prefrontal cortex from newly recruited subjects in this grant proposal (for Project 3). In summary, this Core B will acquire multimodal data from both humans and mice under a specific scientific focus on the olfactory-prefrontal circuits.