PROJECT 1: PROJECT SUMMARY/ABSTRACT In cochlear implant (CI) users, mechanisms underlying difficulties in understanding speech in complex listening environments remain poorly understood, which hinders our capabilities of implementing precision medicine in this patient population. In this study, we will take a bottom-up approach to identify neurophysiological mechanisms underlying speech perception deficits in CI users. Our central hypothesis is that preservation of the structural and functional integrity of the peripheral auditory system will result in improved clinical outcomes, especially in challenging listening conditions. Surgical trauma of cochlear implantation and the foreign body reaction to CI electrode array cause inflammatory response, which reduces the structural and functional integrity of the peripheral auditory system. There are two newly developed strategies for minimizing surgical trauma and immunological response to CI electrode: steroid-eluting electrode array and robotics-assisted electrode insertion. To date, the functional benefits of using these two novel strategies in preserving the functional and structural integrity of the peripheral auditory system in human CI users have not been established. To address this critical need, Aim 1 and Aim 2 will determine the effect of steroid-eluting electrode arrays and robotic-assisted electrode insertion on structural and functional integrity of the peripheral auditory system in human CI users, respectively. Another factor which affects the structural and functional integrity of the peripheral auditory system is genetic variation. To date, the effect of genetic variation on the ability of the peripheral auditory system to respond to acoustic and electrical stimulation in human listeners remains poorly understood. To address this critical need, Aim 3 will determine the effect of genetic variation on the ability of the CN to respond to acoustic and electrical stimulation. Results of this study have high scientific significance because they will establish 1) the benefits of using steroid-eluting electrode array and robotics-assisted electrode insertion preserving structural and functional integrity of the peripheral auditory system, and 2) the effects of genetic variation on the ability of the peripheral auditory system to respond to acoustic and electrical stimulation in human CI users. Results of this study also have high clinical significance because they will 1) serve as the scientific foundation for shifting the current clinical practice for CI patients by including steroid-eluting electrode array or robotics-assisted electrode insertion as part of standard clinical care, and 2) lay the groundwork for developing effective, evidence-based clinical practice guidelines for managing CI patients based on genetic data.