AUDITORY NEURAL FUNCTION IN IMPLANTED PATIENTS WITH USHER SYNDROME

项目总结/摘要 Usher综合征（USH）是一种常染色体隐性遗传疾病，其特征是听力损失，视力障碍， 在某些情况下，前庭功能障碍。它是人类遗传性眼盲的主要原因。USH 引起耳蜗神经（CN）的广泛变性，特别是在支配基底的CN纤维中 耳蜗然而，没有治疗方法可以阻止这种退化过程或恢复视力丧失， 通过耳蜗植入可以恢复听觉输入。由于视力的逐渐恶化， 使用视觉提示进行交流最终将变得不可能。因此，优化的重要性 对于USH患者，通过人工耳蜗（CI）进行听觉输入至关重要。然而，USH患者 与一般CI患者人群相比，神经系统、精神或行为障碍的发生率要高得多， 这限制了他们提供可靠的行为反应或足够的听觉语言描述的能力。 特别是对于儿科患者来说。此外，还给出了CN用户CI的最佳编程参数 由于CN对电刺激的反应性下降，损伤不同于典型CI用户中使用的损伤。 因此，植入USH的患者的临床程控过程可能极具挑战性。到 迄今为止，USH患者的电刺激听觉神经编码尚未系统地 评估。因此，该领域缺乏管理植入患者的循证实践指南 关于USH对于无法提供可靠反馈的患者，临床医生依赖于“试错”方法， 调整CI编程设置，这最终可能不会产生适当的编程映射， 个别患者。因此，迫切需要开发用于优化CI设置的客观临床工具 对于这些患者。作为发展循证实践管理USH患者的第一步， 这项研究评估了中枢神经系统的健康状况，以及中枢神经系统对时间和频谱线索的编码 在植入USH的患者中。目标1将通过评估以下因素来确定USH患者的局部CN健康： 电诱发复合动作电位对相间间隙和脉冲极性变化的敏感性。 目标2将确定CN的时间和频谱线索的神经编码的组差异， USH患者和特发性听力损失患者。Aim 3将使用监督机器学习 开发用于评估单个电极处的电极-神经元界面的客观工具的技术 地点这项研究的结果具有很高的科学意义，因为他们将建立CN变性如何 影响电刺激的神经编码和处理，并确定区分神经元丢失的测试。 螺旋神经节神经元周围轴突的损失。本研究结果也具有较高的临床意义 因为它们将1）为制定有效的、基于证据的临床实践指南奠定基础， 管理USH患者，以及2）产生用于评估位点特异性电极神经元的客观工具 所有CI用户的界面，这是为个体患者创建最佳程控图的基础。

PROJECT SUMMARY/ABSTRACT Usher syndrome (USH) is an autosomal recessive disorder characterized by hearing loss, visual impairment, and in some cases, vestibular dysfunction. It is the leading cause of hereditary deaf-blindness in humans. USH causes extensive degeneration in the cochlear nerve (CN), especially in CN fibers innervating the base of the cochlea. Whereas there is no treatment for arresting this degenerative process or for restoring visual loss, the restoration of auditory input is possible with cochlear implantation. Due to the progressive deterioration in vision, using visual cues for communication will eventually become impossible. Therefore, the importance of optimizing auditory inputs through cochlear implants (CIs) for patients with USH is paramount. However, patients with USH have much higher rates of neurological, mental, or behavioral disorders than the general CI patient population, which limits their ability to provide reliable behavioral responses or sufficient verbal descriptions of their auditory perception, especially for pediatric patients. In addition, optimal programming parameters for CI users with CN damage differ from those used in typical CI users due to declined CN responsiveness to electrical stimulation. As a result, the clinical programming process in implanted patients with USH can be extremely challenging. To date, auditory neural encoding of electrical stimulation in patients with USH has not been systematically evaluated. Consequently, the field lacks evidence-based practice guidelines for managing implanted patients with USH. For patients who cannot provide reliable feedback, clinicians rely on a “trial-and-error” approach for adjusting CI programming settings, which ultimately may not result in appropriate programming maps for individual patients. Therefore, there is an urgent need to develop objective clinical tools for optimizing CI settings for these patients. As the first step toward developing evidence-based practice for managing patients with USH, this study evaluates local neural health, as well as the neural encoding of temporal and spectral cues at the CN in implanted patients with USH. Aim 1 will determine local CN health in patients with USH by assessing the sensitivity of the electrically evoked compound action potential to changes in interphase gap and pulse polarity. Aim 2 will determine group differences in neural encoding of temporal and spectral cues at the CN between patients with USH and patients with idiopathic hearing loss. Aim 3 will use supervised machine learning techniques to develop an objective tool for assessing the electrode-neuron interface at individual electrode locations. Results of this study have high scientific significance because they will establish how CN degeneration affects neural encoding and processing of electrical stimulation, and identify tests that distinguish the loss of spiral ganglion neurons from the loss of peripheral axons. Results of this study also have high clinical significance because they will 1) lay the groundwork for developing effective, evidence-based clinical practice guidelines for managing patients with USH, and 2) yield an objective tool for assessing the site-specific electrode-neuron interface in all CI users, which is foundational for creating optimal programming maps for individual patients.