PROJECT SUMMARY/ABSTRACT Cochlear nerve deficiency (CND) refers to a small or absent cochlear nerve (CN) as revealed by high- resolution magnetic resonance imaging. Cochlear implantation has been used as a treatment option for children with CND for nearly two decades. Due to the lack of understanding of how electrical stimulation is encoded and processed in their auditory system, there is still no evidenced-based clinical practice for managing this unique patient population. To further complicate matters, more than half of children with CND cannot provide reliable behavioral responses despite their age due to severe comorbidities. As a result, clinicians often use a combined “one-size-fits-all” and “try-and-see” approach to program cochlear implant (CI) speech processors for children with CND. This practice typically results in stimulating all intra-cochlear CI electrodes with similar programming parameters. However, recent work from our lab showed that the likelihood of measuring CN neural responses in children with CND reduced as the stimulating CI electrode site moved from the base to the apex of the cochlea. This unique response-deterioration pattern is not observed in children with normal-sized CNs. In addition, our compiling preliminary data show that information transmitted by CI electrodes with no measurable CN response is only adequate for auditory detection but not sufficient for auditory discrimination, which explains why the majority of children with CND do not make satisfactory progress in speech and language development despite good auditory detection thresholds with their CIs. These new findings suggest that the current clinical practice is unlikely to provide appropriate CI programming settings for this unique patient population. Therefore, there is an urgent need to develop objective clinical tools for optimizing CI settings for individual children with CND. As the first step toward developing such objective clinical tools, this study aims to better understand neural encoding and processing of electrical stimulation in both the CN and the central auditory system in implanted children with CND. Aim 1 will compare effects of changing pulse-phase duration, inter-phase gap and pulse rate on neural representation of electrical stimulation in the CN between children with CND and children with normal-sized CNs. Aim 2 will determine effects of variation in CN neural survival on cortical sensitivity to amplitude modulation and electrode discrimination in children with CND and children with normal-sized CNs. Results of this study have high scientific significance because they will establish how variations in neural survival of CN fibers affect neural encoding of electrical stimulation in the CN, as well as how variations in the peripheral input affect cortical neural encoding and processing of electrical stimulation. Results of this study also have high clinical significance because they will 1) provide scientific evidence for identifying and excluding the nonfunctional intra-cochlear CI electrodes from programming maps, 2) establish the importance of selecting pulse-phase durations, inter-phase gaps and pulse rates based on CN neural survival for individual CI electrodes, and 3) lay the knowledge foundation for developing evidence-based clinical practice guidelines for managing children with CND.

PROJECT NARRATIVE The proposed study is relevant to public health because it aims to better understand neural encoding and processing of electrical stimulation in children with cochlear nerve deficiency (CND) - a poorly understood hearing disorder affecting up to 19% of children with congenital sensorineural hearing loss. Results from this study will have 1) a broad impact on the field by establishing how variations in neural survival of cochlear nerve fibers affect neural encoding of electrical stimulation in both the cochlear nerve and the central auditory system; and 2) a targeted impact on children with CND who are cochlear implant users by laying the groundwork for developing an effective, evidence-based clinical practice for managing these patients. This project is relevant to the mission of NIH because it seeks fundamental knowledge about the nature of electrical hearing in patients with CND and strives to apply this knowledge to reduce disability in these patients.