Technology for an advanced cochlear nucleus auditory prosthesis

描述(由申请人提供)：我们建议开发更好地将声音的频谱和时间特征传达给耳蜗核听觉假体患者的技术。对于缺乏功能性听神经的人来说，耳蜗核水平的听觉假体(“听性脑干植入物，ABI”)可以恢复有用的听力，但他们的言语感知比大多数人工耳蜗者差得多，尤其是患有II型神经纤维瘤病(NF2)的人，NF2是导致双侧第8神经丧失的最常见病因。NF2患者还表现出高的调制检测阈值，这是已发现的唯一能将ABI的NF2用户与其他原因所致耳聋区分开来的心理声学变量。现有数据表明，ABI的所有用户，包括那些具有NF2的用户，都将受益于改进的调制检测。大多数ABI利用脑干表面的一个大电极阵列，这个阵列允许一些但有限的访问耳蜗核的立位组织。在动物研究中，穿透微电极能够更好地传递声音的光谱信息，而其听觉脑干植入物包括表面和穿透电极阵列的NF2患者从混合阵列中受益。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个多点硅衬底小腿微电极上设计一个由96个微刺激电极组成的阵列，即使在切除第8个神经肿瘤后阵列的位置不确定的情况下，也将确保在人类耳蜗核腹侧核内至少放置16个微刺激电极。组成这个阵列的探针将通过深度反应离子刻蚀(DRIE)光刻技术制造，这种技术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限制层。我们将通过反复插入猫脊髓来验证该阵列的机械耐用性。DRIE探头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探头期间可能造成的组织损伤。比较的标准将是密歇根式的探头，它们比DRIE探头薄得多。同样在CAT模型中，我们将确定相对于目前临床ABI系统中使用的250赫兹电荷平衡脉动刺激，是否以及如何增强耳蜗腹核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)以及模拟电刺激的优点。为了支持上述活动，我们将开发一种适合于猫下丘慢性植入的现场4小腿记录阵列。与公共卫生相关：植入耳蜗核水平的听觉假体(“听性脑干植入物，ABI”)可以为缺乏功能听神经的人恢复有用的听力，但他们对环境声音的言语感知和识别能力比大多数人工耳蜗者差得多，对于患有II型神经纤维瘤病(NF2)的人尤其糟糕，NF2是双侧听神经丧失的最常见病因。通常，在手术切除这种情况下典型的双侧前庭神经鞘瘤时，神经会被破坏。现在使用的ABI不能有效地向用户传达声音的时间调制，并且NF2的人在这方面表现得特别差。在动物模型中，我们将比较几种将声音编码成电刺激的方案，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ABI利用脑干表面的一组大电极，允许一些但有限的途径进入耳蜗核的立位组织。在动物研究中，穿透微电极能够更好地传达声音和NF2患者的光谱信息，这些患者的听觉脑干植入物包括一组表面电极和一组穿透电极，这些电极受益于混合阵列。此外，穿透电极在患者无法从表面电极接收到听觉感知的情况下被证明是有用的。然而，我们对现有版本的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相对于其他原因导致双侧听神经丧失的患病率，最不幸的是，NF2患者没有像其他原因耳聋的患者那样从听性脑干植入物中获得如此多的好处。然而，NF2的患病率约为每40,000名活产儿中就有1人患有双侧听神经瘤，因此，尽管幸运的是这种情况相当罕见，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，而且除了与手术切除肿瘤相关的风险和不适之外，风险和不适感都很小，因为这些设备是在手术切除肿瘤的同一手术过程中植入耳蜗核的。因此，需要改进植入物本身和将声音编码成电刺激的方法，这些方法对于植入耳蜗核的听觉假体来说是优化的。

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.