AUDITORY NEURAL FUNCTION IN IMPLANTED PATIENTS WITH USHER SYNDROME

项目摘要/摘要 USH综合征(USH)是一种常染色体隐性遗传性疾病，其特征是听力损失，视力障碍， 在某些情况下，还有前庭功能障碍。它是人类遗传性聋盲的主要原因。乌什 导致耳蜗神经(CN)广泛变性，尤其是支配耳蜗神经根部的CN纤维 耳蜗骨。虽然没有治疗方法来阻止这种退化过程或恢复视力损失，但 植入人工耳蜗术可以恢复听觉输入。由于视力逐渐下降， 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患者来说，通过人工耳蜗(CI)进行听觉输入是至关重要的。然而，USH患者 与普通CI患者相比，有更高的神经、精神或行为障碍发生率， 这限制了他们提供可靠的行为反应或对其听觉的充分口头描述的能力 知觉，尤其是对儿科病人。此外，针对具有CN的CI用户的最优编程参数 由于CN对电刺激的反应性降低，损伤不同于典型CI用户的损伤。 因此，植入USH患者的临床规划过程可能极具挑战性。至 目前，USH患者电刺激的听神经编码还没有得到系统的研究 已评估。因此，该领域缺乏管理植入患者的循证实践指南。 与USH合作。对于那些不能提供可靠反馈的患者，临床医生依靠一种“试错”的方法 调整CI编程设置，这最终可能不会产生适当的编程地图 个别病人。因此，迫切需要开发客观的临床工具来优化CI设置 对这些病人来说。作为开发管理USH患者的循证实践的第一步， 这项研究评估了局部神经健康状况，以及CN对时间和光谱线索的神经编码 植入的USH患者。目的1将通过评估USH患者的本地CN健康状况来确定 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将确定在中枢神经对时间和光谱线索的神经编码方面的群体差异 USH患者和特发性耳聋患者。目标3将使用有监督的机器学习 开发评估单个电极上的电极-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，因为它们将确定CN如何退化 影响神经编码和电刺激的处理，并识别识别丢失的测试 螺旋神经节神经元外周轴突的丢失。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、循证的临床实践指南奠定基础 管理USH患者，以及2)产生一个客观的工具来评估特定部位的电极-神经元 所有CI用户的界面，这是为个别患者创建最佳规划地图的基础。

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.