Safe Direct Current Neural Stimulation System

描述（由申请人提供）：该项目的中心目标是开发一种创新的“安全直流（DC）刺激器”，以创建能够激发，抑制和调节神经组织敏感性的神经假体。虽然现有的神经假体在治疗某些神经系统疾病方面是有效的，但由于它们只能激发神经元而不能有效地抑制它们，因此存在局限性。这种限制源于需要使用简短的交流（AC）双相脉冲来维持金属-盐界面上的电荷平衡。直流电既能激发神经活动，又能抑制神经活动；然而，它是不安全的，因为它会在金属电极-组织界面引起电化学反应。虽然耳蜗和视网膜假体成功地利用交流脉冲来编码感觉信息，通过调节传入纤维的放电频率超过其自发活动，但其他神经假体无法仅通过兴奋来提供有效的治疗。例如，辅助排尿的假体必须激发骶神经激活逼尿肌，同时抑制腰神经放松尿道括约肌。为了达到适当的平衡，内耳前庭传入纤维不仅需要兴奋来编码头部向受刺激一侧的运动，还需要抑制来编码远离头部的运动。此外，一些以高度不受控制的神经放电率为特征的高度流行的疾病，如耳鸣、慢性疼痛和癫痫，可以通过具有神经抑制功能的植入式假体有效治疗。使直流电安全的一种方法是，通过与浸泡在盐水中的电极上的交流方波相开关充满盐水的h桥的机械阀，引导直流电离子流进入目标组织。这种方法在电极-盐水界面上使用交流电，同时保持通过组织的直流离子电流。目标1是建立一个功能安全的直流刺激器（SDCS）原型，可以通过神经假体控制来调节组织中的梯度阴极和阳极刺激电流。目的2是验证神经假体可以利用SDCS控制体内神经活动的假设。在一个非常有特征的龙猫前庭神经假体刺激模型中，我们将比较采用SCDS技术的神经假体与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刺激对体内慢性手术是安全的假设。我们将对三组植入的龙猫进行持续的慢性刺激，以检验SDCS的持久性和安全性。将SDCS中接受恒频脉冲刺激、恒阳极直流刺激和恒阴极直流刺激的组进行比较。我们将在每周的会议中检测前庭神经电调节的反应，并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.