Advanced technology for neural interfaces based on microstimulation

描述(申请人提供)：这项提议有两个相互支持的目标：推进多部位微刺激阵列和微刺激技术的设计，将其用于康复医学和基础神经科学，并推动耳蜗核听觉假体的发展，以提供至少与人工耳蜗术用户相同的语音识别。缺乏功能听神经的人不能从人工耳蜗术中受益，但通过在耳蜗核内或其上植入假体可以恢复一些听力。然而，目前临床使用的设备无法恢复可与人工耳蜗术相媲美的听力。它们机械坚固，用它们的地面尖端可以以最小的创伤插入大脑。在猫模型中，我们将评估在500pps脉冲频率下对猫耳蜗核进行140小时微刺激的安全性，以确定当脉冲频率高(250~500pps)、电极几何表面积处于微刺激范围的上限(2,000~4,000μm2)时，刺激脉冲频率和刺激电荷密度在刺激性神经元损伤中的作用。我们将确定电极几何表面积和每相刺激电荷的组合，该组合不会对靠近电极的神经元和其他类型的细胞造成伤害。穿透性微电极对中枢神经系统的功能性电刺激在临床医学和基础神经科学中有潜在的应用，高频率刺激可以传递更多的时间信息，并可能通过最大限度地减少神经元活动对个体刺激脉冲的锁定而引起更接近自然活动的神经元活动，并可能在临床医学中找到其他用途，包括治疗运动障碍。在刚刚完成的一项研究中，我们发现，在使用500pps的脉搏频率时，耳蜗核中微刺激幅度调制的编码得到了改善。我们将改进我们的多点硅衬底微刺激探针，以延长它们在体内的寿命，目标是使它们有资格用于临床。我们的设备在每个小腿上有5个独立的电极位置，允许在最小组织位移和损伤的情况下将大量电极放置到目标核中。硅小腿机械坚固，其接地尖端可以以最小的创伤插入大脑。我们将开发这种配置的探头，在39oC的缓冲盐水中浸泡一年后，将至少满足以下性能标准，并且加速测试表明，这些标准将至少满足8年：(1)同一探针柄上的电极在受控电流脉冲期间的通道间串扰(沟道相互作用)；(2)探针柄上所有通道的电流脉冲低于5%；(2)每个通道到盐水浴的泄漏阻抗大于1 mgΩ。维持这些性能标准的多部位刺激阵列将保留基本完整的功能。我们将优化将声音的调幅(AM)编码为应用于耳蜗核腹侧的电刺激的程序。根据我们实验室完成的猫下丘神经元对幅度调制的编码工作，这将需要高刺激脉冲率(500pps)。这项工作也将作为我们将开发的长寿命微刺激阵列的试验台。

DESCRIPTION (provided by applicant): This proposal has two mutually supporting goals; to advance the design of multisite microstimulating arrays and microstimulation technology for their use in rehabilitation medicine and basic neuroscience, and to advance the development of cochlear nucleus auditory prostheses towards providing speech recognition that is at least equivalent to that of users of cochlear implants. Persons who lack a functional auditory nerve cannot benefit form cochlea implants, but some hearing can be restored by a prosthesis implanted in or on the cochlea nucleus. However, the devices now in clinical use do not restore hearing that is comparable to that of cochlea implants. They are mechanically sturdy and with their ground tips can be inserted into the brain with minimal trauma. In a cat model, we will evaluate the safety of 140 hours of microstimulation in the cat cochlear nucleus at a pulse rate of 500 pps, in order to determine the roles of stimulus pulse rate and stimulus charge density in stimulation-induced neuronal injury when the pulse rate is high (250 to 500 pps), and the electrodes' geometric surface areas is in the upper part of the range for microstimulation (2,000 to 4,000 μm2). We will determine a combination of electrode geometric surface area and stimulus charge per phase that is not injurious to the neurons and other cell types close to the electrodes. Functional electrical stimulation in the central nervous system with penetrating microelectrodes has potential applications in clinical medicine and basic neural science, and high-rate stimulation can convey more temporal information and may elicit neuronal activity that more closely resemble naturally-occurring activity by minimizing locking of neuronal activity to the individual stimulus pulses, and may find other uses in clinical medicine, including treatment of movement disorders. In a study just completed, we found that encoding of amplitude modulation by microstimulation in the cochlear nucleus is improved by using a pulse rate of 500 pps. We will enhance our multisite silicon substrate microstimulation probes in order to increase their lifetime in vivo, with the goal of qualifying them for clinical use. Our devices have 5 independent electrode sites on each shank, allowing placement of a large number of electrodes into the target nucleus with the minimum tissue displacement and damage .The silicon shanks are mechanically sturdy and their ground tips can be inserted into the brain with minimal trauma. We will develop probes of this configuration that will meet at least the following performance standards after 1 year of soak in buffered saline at 39oC , and for which accelerated testing indicates that the standards will be met for at least 8 years (1) ; inter-channel crosstalk (channe interaction) between the electrodes on the same probe shank during controlled-current pulsing below 5% for all channels on the probe shank and (2) the leakage impedance of each channel to the saline bath greater than 1 MgΩ. A multisite stimulating array that maintains these performance standards will retain essentially full functionality. We will optimize procedures for encoding the amplitude modulation (AM) of sound into an electrical stimulus that is applied in the ventral cochlear nucleus. Based on work completed in our laboratory on encoding of amplitude modulation by neurons in the inferior colliculus of the cat, this will require a high stimulus pulse rate (500 pps). This work also will serve as a test bed for the long-lived microstimulation arrays we will develop.