Technology for an advanced cochlear nucleus auditory prosthesis

描述（由申请人提供）：我们建议开发一种技术，可以更好地将声音的频谱和时间特征传达给使用人工耳蜗的人。耳蜗核水平的听觉假体（“听觉脑干植入物，ABI”）可以为缺乏功能性听觉神经的人恢复有用的听力，但他们的言语感知比大多数耳蜗植入物使用者差得多，特别是患有2型神经纤维瘤病（NF2）的人，这是双侧第8神经丧失的最常见病因。NF2患者也表现出较高的调制检测阈值，这是唯一的心理声学变量，可以区分使用ABIs的NF2患者与其他病因的耳聋患者。现有数据表明，所有abi用户，包括NF2患者，都将受益于改进的调制检测。大多数ABIs利用脑干表面的大电极阵列，这种阵列允许一些但有限的进入耳蜗核的张力组织。在动物实验中，穿透性微电极能够更好地传递声音的光谱信息，并且NF2患者的听觉脑干植入包括表面和穿透电极阵列的患者受益于混合阵列。然而，我们对现有穿透阵列的经验揭示了我们将在拟议的研究中解决的几个问题。我们将在24个多点硅衬底柄微电极上设计一个由96个微刺激电极位点组成的阵列，这将确保在人类耳蜗腹侧核内放置至少16个微刺激位点，即使在切除第8个神经肿瘤后阵列的位置存在已知的不确定性。包含该阵列的探针将通过深度反应离子蚀刻（DRIE）光刻技术制造，其产生的探针柄足够耐用，可以穿透覆盖在人类耳蜗核上的神经胶质界限。我们将通过反复插入猫脊髓来验证该阵列的机械耐久性。DRIE探针阵列将被长期植入猫的耳蜗核，以评估在植入机械坚固的DRIE探针期间可能造成的组织损伤。比较的标准将是密歇根式的探针，它比drive探针薄得多。此外，在cat模型中，我们将确定与目前临床ABI系统中使用的250 Hz电荷平衡脉冲刺激相比，是否以及如何增强耳蜗腹侧核1型多极细胞的调制检测。我们将评估更高的刺激脉冲率（500和1000 pps）和模拟电刺激的优点。为了支持上述活动，我们将开发一种适合于慢性植入猫下丘的64位4柄记录阵列。公共卫生相关性：在耳蜗核水平植入听觉假体（一种“听觉脑干植入物，ABI”）可以恢复缺乏功能性听神经的人的有用听力，但他们的语言感知和对环境声音的识别比大多数耳蜗植入物使用者差得多，特别是患有2型神经纤维瘤病（NF2）的人，这是双侧听神经丧失的最常见病因。典型的是，在手术切除双侧前庭神经鞘瘤的过程中，神经被破坏，这是典型的这种情况。目前使用的abi不能有效地向使用者传达声音的时间调制，NF2患者在这方面表现尤其差。在动物模型中，我们将比较几种将声音编码为电刺激的方案，并将其传递到刺激电极。我们的目标是开发一种向ABI用户传达声音时间特征的改进方法。大多数ABIs利用脑干表面的大电极阵列，允许一些但有限的进入耳蜗核的张力组织。在动物实验中，穿透微电极能够更好地传递声音和NF2患者的频谱信息，其听觉脑干植入物包括一系列表面电极和一系列穿透电极，混合阵列受益。此外，穿透电极已被证明在患者无法从表面电极接收到听觉感知的情况下是有用的。然而，我们对现有穿透阵列的经验揭示了我们将在拟议的研究中解决的一些问题。鉴于NF2的患病率相对于双侧听神经丧失的其他原因，最不幸的是，NF2患者并没有从他们的听觉脑干植入物中获得与其他病因耳聋患者一样多的益处。然而，NF2的患病率大约是4万分之一，双侧听力学肿瘤的概率很高，因此，尽管这种情况非常罕见，但仅在发达国家，就有成千上万的人可以从这些设备中受益，除了手术切除肿瘤之外，风险和不适也很小。因为这些装置是在切除肿瘤的同一手术过程中植入耳蜗核的。因此，有必要改进植入物本身，并改进将声音编码为电刺激的方法，以优化植入耳蜗核的听觉假体。

DESCRIPTION (provided by applicant): We propose to develop technology that will better convey both the spectral and the temporal features of sound to persons with cochlear nucleus auditory prostheses. An auditory prosthesis at the level of the cochlear nucleus ("Auditory brainstem implant, ABI") can restore useful hearing to persons who lack functional auditory nerves, but their speech perception is much poorer than that of most users of cochlear implants, and is especially poor for persons afflicted with Type 2 Neurofibromatosis (NF2), the most prevalent etiology for bilateral loss of the 8th nerves. The NF2 patients also exhibit high modulation detection threshold which is the only psychoacoustic variable that has been found to distinguish the NF2 users of the ABIs from those whose deafness is of other etiologies. The available data suggests that all users of ABIs, including those with NF2, would benefit from improved modulation detection. Most ABIs utilize an array of macroelectrodes on the surface of the brainstem, and this array allows some, but limited access to the tonotopic organization of the cochlear nucleus. In animal studies, penetrating microelectrodes are better able to convey the spectral information of sound, and NF2 patients whose auditory brainstem implants includes arrays of surface and penetrating electrodes derive benefit from the hybrid array. However, our experience with the existing penetrating array has revealed several issues that we will address in the proposed studies. We will design an array of 96 microstimulating electrode sites on 24 multisite silicon substrate shanks microelectrodes, that will insure placement of at least 16 microstimulating sites within the human ventral cochlear nucleus, even with the known uncertainly as to where to position the array after removal of the 8th nerve tumor. The probes comprising this array will be fabricated by deep reactive ion etching (DRIE) photolithography, which yields probe shanks that are sufficiently durable to penetrate the glia limitans overlying the human cochlear nucleus. We will verify the mechanical durability of the array by repeated insertions into cat spinal cords. Arrays of DRIE probes will be implanted chronically into cats' cochlear nucleus to evaluate possible tissue damage during implantation of the mechanically robust DRIE probes. The standard of comparison will be Michigan-style probes that are much thinner than the DRIE probes. Also in a cat model, we will determine if and how modulation detection by Type 1 multipolar cells of the ventral cochlear nucleus can be enhanced, relative to that with a 250 Hz charge-balanced pulsatile stimulus used in the present clinical ABI systems. We will evaluate the merits of a higher stimulus pulse rate (500 and 1000 pps) and also of analog electrical stimulation. To support the activities described above, we will develop a 64-site, 4-shank recording array suitable for chronic implantation into the cats' inferior colliculus. PUBLIC HEALTH RELEVANCE: An auditory prosthesis implanted at the level of the cochlear nucleus (an "Auditory brainstem implant, ABI") can restore useful hearing to persons who lack functional auditory nerves, but their speech perception and recognition of environmental sounds is much poorer than that of most users of cochlear implants, and is particularly poor for persons afflicted with Type 2 Neurofibromatosis (NF2), the most prevalent etiology for bilateral loss of the auditory nerves. Typically, the nerves are destroyed during surgical resection of each of the bilateral vestibular schwannomas that are typical of this condition. The ABIs now in use do not efficiently convey to the users the temporal modulation of sound and persons with NF2 fare particularly poorly in this respect. In an animal model, we will compare several protocols for encoding sound into the electrical stimulation that is delivered to the stimulating electrodes. Our objective is to develop an improved method of conveying the temporal features of sound to ABI users. Most ABIs utilize an array of macroelectrodes on the surface of the brainstem that allows some, but limited access to the tonotopic organization of the cochlear nucleus. In animal studies, penetrating microelectrodes are better able to convey the spectral information of sound and NF2 patients whose auditory brainstem implants includes an array of surface electrodes and an array of penetrating electrodes derive benefit from the hybrid array. Also, the penetrating electrodes have proved useful in those instances when the patient does not receive auditory percepts from the surface electrodes. However, our experience with the existing version of the penetrating array has revealed a number of issues that we will address in the proposed studies. In view of the prevalence of NF2 relative to that of other causes of bilateral loss of the auditory nerves, it is most unfortunate that persons with NF2 have not obtained as much benefit from their auditory brainstem implants as have patients whose deafness is of other etiologies. However, the prevalence of NF2 is approximately 1 in 40,000 live births with a high probability of bilateral acoustic tumors, and so while the condition fortunately is quite rare, in developed countries alone, there are many thousands of persons who can benefit from these devices, and with minimal risk and discomfort in addition to those related to the surgical removal of the tumors, since the devices are implanted into the cochlear nucleus during the same surgical procedure in which the tumor is surgically removed. Thus there is a need for improvements to the implants themselves and for methods of encoding sound into electrical stimulus that are optimized for an auditory prosthesis implanted in the cochlear nucleus.