PROJECT SUMMARY/ABSTRACT: NeuroMedical Core The newly reorganized, NeuroMedical (NM) Core will have the overall goal of supporting comprehensive neuromedical, laboratory, and neuroimaging assessments for the characterization of people with HIV (PWH) and HIV uninfected (HIV-) controls. The Core will be composed of three integrated components: the Clinical Assessment (CA) and Laboratory (Lab) Units along with a Neuroimaging (NI) “Portal”, which will provide access to extensive UCSD imaging resources. In close collaboration with the other scientific Cores, the NM Core will aim to: 1) Evaluate the impact on mental health outcomes (e.g., depression, neurobehavioral phenotypes) of HIV infection and comorbid conditions (e.g. insulin resistance, metabolic syndrome), coinfections (e.g. CMV, latent toxoplasmosis), antiretroviral therapy (ART) neuroprotection or neurotoxicity, and inflammation (e.g., cytokines, T-cell activation); 2) Evaluate the reciprocal effects over time, of mental health factors (e.g. apathy, stress, resilience, self-efficacy) and cognition, and downstream effects of these neurobehavioral factors on neuromedical and HIV disease outcomes (e.g. virologic suppression, healthcare engagement); 3) Support studies of the central nervous system (CNS) impact of interventions designed to alter HIV reservoirs and achieve functional cure, and treatment of latent or clinically asymptomatic coinfections; and 4) Evaluate how the microbiome influences inflammation, microbial production of neurotransmitters (e.g., serotonin) and in turn, neurobehavioral phenotypes including depression and cognition, as well as circadian rhythms, sleep, and social functioning. We aim to facilitate and enhance multidisciplinary research in neuroHIV by providing resources including a range of services, training and scientific consultation to HNRC-associated projects (e.g., R01s, R21s), international neuroHIV studies, and a variety of extramural investigations. Historically, the Core and its investigators have been leaders in the field, spurring the development of new methods and adapting to the continually evolving scientific landscape. Consistent with this, the Core will provide resources to support the Center's expanded focus on depression and complex neurobehavioral phenotypes. Standard evaluations will continue to include a structured neuromedical history, clinical and laboratory examinations, and establishment of diagnoses of central and peripheral neurological complications. Additional unique services of the Core include stool collection for gut microbiome characterization and lumbar puncture for cerebrospinal fluid (CSF) collection. The Lab Unit will perform blood and CSF biomarker assays and provide expertise in their analysis and interpretation. The NI Portal will provide resources (e.g., training, consultation, technical support) in support of studies investigating the underlying neural mechanisms of mental health disorders in the context of HIV using a broad a...