Neural Encoding and Auditory Processing of Electrical Stimulation in Pediatric Cochlear Implant Users

项目总结/摘要 耳蜗神经缺陷（CND）是指耳蜗神经（CN）小或缺失，如高血压所显示。 分辨率磁共振成像。髋关节植入已被用作儿童的治疗选择 近20年来，由于缺乏对电刺激如何编码的理解， 在他们的听觉系统中处理，仍然没有基于证据的临床实践来管理这种独特的 患者人群。更复杂的是，超过一半的CND儿童不能提供可靠的 行为反应，尽管他们的年龄，由于严重的合并症。因此，临床医生经常使用组合 儿童人工耳蜗语音处理器的“一刀切”和“试看”编程方法 关于CND这种做法通常导致以类似的编程刺激所有耳蜗内CI电极 参数然而，我们实验室最近的工作表明，测量CN神经反应的可能性 CND患儿随着刺激CI电极位置从耳蜗底部向顶部移动而降低。 这种独特的反应恶化模式在氯化萘大小正常的儿童中未观察到。另外我们 汇编初步数据显示，CI电极传输的信息没有可测量的CN响应， 仅适用于听觉检测，但不足以用于听觉辨别，这解释了为什么 大多数患有CND的儿童在言语和语言发育方面没有取得令人满意的进展， 良好的听觉检测阈值及其CI。这些新的发现表明，目前的临床实践是 不太可能为这一独特的患者人群提供适当的CI程控设置。因此，有一个 迫切需要开发客观的临床工具，以优化CND儿童个体的CI设置。为 第一步，发展这样的客观临床工具，这项研究的目的是更好地了解神经编码 植入儿童CN和中枢听觉系统的电刺激和处理 CND。目的1比较改变脉冲时相宽度、相间间隙和脉冲频率对神经元的影响 CND儿童和正常大小CN儿童之间CN电刺激的代表性。 目的2将确定CN神经存活的变化对皮层对振幅调制的敏感性的影响， CND儿童和正常大小CN儿童的电极辨别力。本研究结果 具有很高的科学意义，因为他们将确定CN纤维神经存活的变化如何影响神经元的功能。 CN中电刺激的编码，以及外周输入的变化如何影响皮层神经元 电刺激的编码和处理。本研究结果也具有较高的临床意义 因为它们将1）为识别和排除无功能耳蜗内CI提供科学证据 2）确定选择脉冲相位持续时间、相位间 间隙和脉冲率基于CN神经存活为个别CI电极，和3）奠定了知识 基金会制定循证临床实践指南，用于管理儿童CND。

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.