PROJECT SUMMARY/ABSTRACT Dr. Jacob Goldsmith is focused on identifying effective therapies to improve neural control of motor and cardiovascular function in persons with SCI. He completed a two-year postdoctoral fellowship at the McGuire VA Medical Center in Richmond, Virginia, where he studied electrical stimulation and testosterone (T) treatment to improve motor and cardiovascular function, as well as for improving quality of life in persons with chronic SCI. Since November 2022, he has worked at the James J. Peters VA Medical Center, Bronx, NY as a postdoctoral trainee in the labs of Drs. Noam Y. Harel and Jill Wecht to learn neurophysiological assessments and cardiovascular autonomic assessments in persons with SCI, respectively. Over his research career, Dr. Goldsmith has displayed an extraordinary commitment to improving the health and welfare of Veterans with SCI. He has served as first-author or co-author on an impressive list of publications given his early stage of professional development: 20 published articles (first author on three), one first author review article, two book chapters. In addition, he has presented at numerous regional and national conferences, as well as the national VA Grand Rounds. The current proposal focuses on assessing the relationships between circulating T, nerve function, and cardiovascular autonomic function in male Veterans with SCI. Hypogonadism (low T) is a prevalent issue in men with SCI, which may exacerbate the deleterious consequences of SCI. There is evidence that testosterone replacement therapy (TRT) positively influences body composition and energy expenditure, although there is little to no research examining the associations between endogenous T concentrations and neural and cardiovascular autonomic function after SCI. This is particularly relevant as several lines of human and animal research have indicated that normal T is crucial for optimal neural and cardiovascular health and function in males. Intranasal TRT delivery represents a useful tool to quickly elevate circulating and central nervous system T concentrations. Moreover, intranasal TRT appears to possess a reduced risk profile and may facilitate the maintenance of fertility compared to other TRT delivery methods. However, the effects of intranasal TRT on corticospinal excitability and cardiovascular autonomic function are unknown in any population. The current CDA-1 proposal will examine associations between endogenous total T and its subfractions (free and bioavailable T) and neural control of motor and cardiovascular function in male Veterans with SCI. In addition, an Exploratory Aim will determine the acute effects of a single dose of intranasal TRT versus placebo on corticospinal excitability and cardiovagal reflex function in men with SCI who exhibit low T. We hypothesize that the endogenous total T and/or its subfractions will predict corticospinal and cardiovagal function in men with SCI (Aim 1). Because the Exploratory Aim is...