Safe Direct Current Neural Stimulation System

描述(申请人提供)：该项目的中心目标是开发一种创新的“安全直流(DC)刺激器”，以创造能够兴奋、抑制和调节神经组织敏感性的神经假体。虽然在治疗一些神经疾病方面有效，但现有的神经假体是有限的，因为它们可以兴奋神经元，但不能有效地抑制它们。这一限制源于需要使用短暂的交流电(AC)两相脉冲来维持金属-盐水界面的电荷平衡。直流电流既能兴奋又能抑制神经活动，但它是不安全的，因为它在金属电极-组织界面上引起电化学反应。虽然人工耳蜗和视网膜假体成功地利用交流脉冲通过调节传入纤维的放电率来编码感觉信息，而不是自发活动，但其他神经假体无法单靠兴奋来提供有效的治疗。例如，用于辅助排尿的假体必须兴奋骶神经以激活逼尿肌，同时抑制腰神经以放松尿道括约肌。为了保持适当的平衡，内耳前庭传入纤维不仅需要兴奋来编码头部朝向受刺激一侧的运动，也需要抑制来编码头部远离刺激侧的运动。此外，几种高度流行的疾病，如耳鸣、慢性疼痛和癫痫等以高不受控制的神经放电率为特征的疾病，可以通过能够神经抑制的植入性假体有效地治疗。使直流电安全的一种方法是通过将充满盐水的H桥的机械阀门与施加在盐水中的电极上的交流方波同相切换，将直流电离子引导到靶组织中。这种方法在电极-盐水界面使用交流，同时保持通过组织的直流离子电流。第一个目标是建立一个功能安全的DC刺激器(SDCS)原型，它可以由神经假体控制来调节组织中的渐变阴极和阳极刺激电流。目的2是验证神经假体可以使用SDCs在体内控制神经活动的假设。在一个非常有特色的前庭神经假体刺激的龙猫模型中，我们将比较采用SCDS技术的神经假体和使用双相脉冲刺激的“传统”前庭假体的性能。目的3是验证SDCs刺激对体内慢性操作是安全的这一假设。我们将对三组植入的龙猫进行持续的慢性刺激，以检测SDCs的耐久性和安全性。接受恒频脉冲刺激、恒定阳极直流刺激和恒定阴极直流刺激的组将被比较。我们将在每周的会议中分析前庭神经对电调制的反应，最终通过进行组织学检查。

DESCRIPTION (provided by applicant): The central goal of this project is to develop an innovative "safe direct current (DC) stimulator" to enable creation of neural prostheses that can excite, inhibit and modulate sensitivity of neural tissue. While effective in treating some neurological disorders, existing neural prostheses are limited because they can excite neurons but not efficiently inhibit them. This limitation stems from the need to use brief alternating current (AC) biphasic pulses maintain charge-balance across the metal-saline interface. DC current can both excite and inhibit neural activity; however, it is unsafe because it causes electrochemical reactions at the metal electrode-tissue interface. While cochlear and retinal prostheses successfully use AC pulses to encode sensory information by modulating firing rates of afferent fibers above their spontaneous activity, other neural prostheses fail to deliver effective treatment with excitation alone. For example, prostheses intended to assist micturition must excite sacral nerves to activate the detrusor muscle and simultaneously inhibit lumbar nerves to relax the urethral sphincter. For proper balance, inner ear vestibular afferent fibers require not only excitation to encode head motion toward the stimulated side of the head, but also inhibition to encode head motion away from it. Furthermore, several highly prevalent disorders characterized by high uncontrolled neural firing rates such as tinnitus, chronic pain, and epilepsy could be effectively treated by an implantable prosthesis capable of neural inhibition. One way to make DC safe involves directing DC flow of ions into the target tissue by switching mechanical valves of a saline-filled H-bridge in phase with AC square waves applied to electrodes immersed in the saline. This approach uses AC at the electrode-saline interfaces while maintaining DC ionic current through the tissue. Aim 1 is to build a functional safe DC stimulator (SDCS) prototype that can be controlled by a neural prosthesis to modulate graded cathodic and anodic stimulation currents in tissue. Aim 2 is to test the hypothesis that a neural prosthesis can use SDCS to control neural activity in vivo. In a very well-characterized chinchilla model of prosthetic stimulation of the vestibular nerve, we will compare performance of a neural prosthesis incorporating SCDS technology to that of a "traditional" vestibular prosthesis using biphasic pulse stimuli. Aim 3 is to test the hypothesis that SDCS stimulation is safe for chronic operation in the body. We will conduct constant chronic stimulation with three groups of implanted chinchillas to examine the durability and safety of SDCS. Groups receiving constant frequency pulsatile stimulation, constant anodic DC stimulation, and constant cathodic DC stimulation from the SDCS will be compared. We will assay responses to electrical modulation of the vestibular nerve in weekly sessions and ultimately by performing histological examinations.