Advanced technology for neural interfaces based on microstimulation

描述（由申请人提供）：本提案有两个相互支持的目标；促进多位点微刺激阵列和微刺激技术在康复医学和基础神经科学中的应用，推动耳蜗核听觉假体的发展，使其语音识别能力至少相当于人工耳蜗用户的语音识别能力。缺乏功能性听神经的人不能从耳蜗植入中获益，但在耳蜗核内或耳蜗核上植入人工耳蜗可以恢复部分听力。然而，目前临床使用的设备并不能像人工耳蜗那样恢复听力。它们在机械上是坚固的，并且它们的尖端可以以最小的创伤插入大脑。在猫模型中，我们将评估以500 pps脉冲速率对猫耳蜗核进行140小时微刺激的安全性，以确定当脉冲速率高（250 ~ 500 pps）且电极几何表面积处于微刺激范围的上半部分（2000 ~ 4000¿m2）时，刺激脉冲速率和刺激电荷密度在刺激诱导的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，这对靠近电极的神经元和其他细胞类型没有伤害。利用穿透性微电极对中枢神经系统进行功能性电刺激，在临床医学和基础神经科学中具有潜在的应用前景，高速率的电刺激可以传递更多的时间信息，并可能通过最小化单个刺激脉冲对神经元活动的锁定，引发更接近自然发生活动的神经元活动，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，我们发现使用500 pps的脉冲速率可以改善耳蜗核微刺激的幅度调制编码。我们将改进我们的多位点硅衬底微刺激探针，以增加它们在体内的使用寿命，目标是使它们符合临床使用的要求。我们的设备在每个柄上有5个独立的电极位点，允许在最小的组织位移和损伤的情况下将大量电极放置到目标核中。硅柄在机械上是坚固的，并且它们的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针，在39oC的缓冲盐水中浸泡1年后至少满足以下性能标准，并且加速测试表明至少可以满足8年的标准(1)；在控制电流脉冲低于5%时，同一探头柄上所有通道的电极之间的通道间串扰（通道相互作用）；(2)每个通道对盐水浴的泄漏阻抗大于1mg。保持这些性能标准的多站点刺激阵列将基本上保留全部功能。我们将优化程序编码的振幅调制（AM）的声音成电刺激，应用于腹侧耳蜗核。根据我们实验室完成的猫下丘神经元振幅调制编码工作，这将需要高刺激脉冲率（500 pps）。这项工作也将作为我们将开发的长寿命微刺激阵列的测试平台。

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 ¿m2). 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 Mgs . 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.