AUDITORY NEURAL FUNCTION IN IMPLANTED PATIENTS WITH USHER SYNDROME

患有 USHER 综合征的植入患者的听觉神经功能

• 批准号: 10192995
• 负责人: Shuman He
• 金额: $ 19.64万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10192995
• 关键词: Accounting; Action Potentials; Address; Adopted; Affect; Auditory; Auditory Perception; Auditory system; Axon; Behavior Disorders; Blindness; Child; Childhood; Clinical; Clinical Practice Guideline; Cochlea; Cochlear Implants; Cochlear Nerve; Cochlear implant procedure; Communication; Cues; Data Set; Degenerative Disorder; Deterioration; Disease; Electric Stimulation; Electrodes; Electrophysiology (science); Evidence based practice; Feedback; Foundations; Frequencies; Functional disorder; Gap Junctions; Goals; Health; Hearing; Human; Implant; Individual; Inherited; Interphase; Knowledge; Location; Maps; Measures; Mental disorders; Mission; Modeling; Mutation; Nature; Nerve Degeneration; Nerve Fibers; Neurons; Neurophysiology - biologic function; Output; Patients; Pattern; Peripheral; Physiologic pulse; Play; Practice Management; Process; Public Health; Recovery of Function; Refractory; Research; Retinitis Pigmentosa; Sensorineural Hearing Loss; Site; Speech; Speech Perception; Techniques; Testing; United States; United States National Institutes of Health; Usher Syndrome; Vision; Visual; Visual impairment; axonal degeneration; base; behavioral response; clinical care; clinical practice; clinically significant; comorbidity; daily functioning; deaf; disability; evidence base; evidence based guidelines; ganglion cell; hearing impairment; histological studies; individual patient; model development; nerve damage; nervous system disorder; neuron loss; patient population; pediatric patients; point of care; programs; relating to nervous system; response; restoration; spiral ganglion; supervised learning; temporal measurement; tool

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.

项目摘要/摘要 Usher综合征（USH）是一种常染色体隐性疾病，其特征是听力损失，视觉障碍， 在某些情况下，前庭功能障碍。这是人类世袭聋哑人的主要原因。 USH 引起人工耳蜗（CN）的广泛变性，尤其是在CN纤维支配的CN纤维中 耳蜗。虽然没有逮捕这种退化过程或恢复视觉丧失的治疗方法，但 通过人工耳蜗植入可以恢复听觉输入。由于视觉的渐进定义， 使用视觉提示进行通信最终将变得不可能。因此，优化的重要性 USH患者通过人工耳蜗（CI）的听觉输入至关重要。但是，USH患者 与一般CI患者人群相比，神经，精神或行为障碍的率要高得多， 这限制了他们提供可靠的行为反应或听觉的足够口头描述的能力 感知，特别是针对小儿患者。此外，具有CN的CI用户的最佳编程参数 由于CN对电刺激的反应性下降，与典型CI使用者使用的损害不同。 结果，患有USH的植入患者的临床编程过程可能会受到极大的挑战。到 日期，USH患者的电刺激的听觉神经编码尚未系统地 评估。因此，该领域缺乏用于管理植入患者的循证实践指南 与ush。对于无法提供可靠反馈的患者，临床医生依靠一种“试验和纠正”方法 调整CI编程设置，最终可能不会导致适当的编程图 个别患者。因此，迫切需要开发客观的临床工具来优化CI设置 对于这些患者。作为开发基于循证实践来管理USH患者的第一步， 这项研究评估了局部神经健康以及CN临时和光谱线索的神经编码 在患有USH的植入患者中。 AIM 1将通过评估USH患者的局部CN健康 电子诱发的复合动作电位的敏感性对相间间隙和脉冲极性变化的变化。 AIM 2将确定临时和光谱线索的神经编码的群体差异 USH和特发性听力损失的患者。 AIM 3将使用监督的机器学习 开发客观工具来评估单个电极处的电极神经元界面的技术 位置。这项研究的结果具有很高的科学意义，因为它们将确定CN变性 影响电刺激的神经编码和处理，并确定区分损失的测试 螺旋神经节神经元因外周轴突的丧失而产生。这项研究的结果也具有很高的临床意义 因为他们将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的患者，以及2）产生一个客观的工具来评估特定地点电极神经元 所有CI用户的接口，这是为个别患者创建最佳编程图的基础。