MICROELECTRODE ARRAYS FOR DEEP BRAIN STIMULATION AND REC

本提案是为响应RFA NS-99-006《脑深部刺激治疗帕金森氏病联盟》而提交的。该提案回应了RFA的邀请，即“开发可以同时刺激和记录并执行微透析或注入化学物质的微电极”。我们建议开发15个离散的激活Ir微电极阵列，适合于长期植入苍白球或丘脑底核。我们将开发两种阵列配置。在类型1中，所有微电极将可用于刺激和记录单一神经元动作电位。我们将确定暴露尖端的最佳面积，以便每个电极都能够记录单位动作电位，并能够刺激苍白球和丘脑底核附近的神经元。在类型2阵列中，9个微电极将被指定用于记录单一神经元动作电位，并且将具有最适合该功能的几何表面积。与9个记录电极穿插的是6个几何表面积为10,000-2的微电极，将保留用于刺激。我们将研究苍白球和丘脑底核神经元活动与电刺激参数之间的关系。这些将包括一项关于长期刺激引起的神经元兴奋性抑制的研究，这可能与帕金森氏症的治疗特别相关。我们将评估MPTP诱导的暂时性帕金森样综合征猫的阵列，并试图确定苍白球或丘脑底核施加的电刺激参数、附近神经元对微刺激的反应与猫神经症状的变化之间的关系。我们将把多点硅衬底记录微电极阵列连接到一些Ir轴上，这些微电极将被长期植入猫科动物的苍白球和丘脑底核，最长可达180天。

This proposal is submitted in response to RFA NS-99-006; "Consortium on deep brain stimulation for the treatment of Parkinson's Disease." The proposal addresses the RFA's invitation to "develop microelectrodes that can simultaneously stimulate and record and perform microdialysis or infuse chemicals". We propose to develop arrays of 15 discrete activated iridium recording and/or stimulating microelectrodes suitable for very long-term implantation into the globus pallidus or the subthalamic nuclei. We will develop two array configurations. In Type 1, all of the microelectrodes will be usable for stimulating and recording of unitary neuronal action potentials. We will determine the optimal area of the exposed tips so that each electrodes will be capable of recording unit action potentials and also capable of stimulating nearby neurons in the globus pallidus and the subthalamic nucleus. In the Type 2 arrays, 9 of the microelectrodes will be designated for recording of unitary neuronal action potential, and will have geometric surface areas that are optimal for this function. Interspersed with the 9 recording electrodes will be 6 microelectrodes with geometric surface areas of 10,000 mum2, which will be reserved for stimulation. We will examine the relation between neuronal activity in the globus pallidus and subthalamic nuclei, and the parameters of electrical stimulation. These will include an investigation of long-lasting stimulation-induced depression of neuronal excitability, which may be especially germane to the treatment of Parkinson's disease. We will evaluate the arrays in cats in which a transient Parkinson's-like syndrome has been induced by MPTP, and we will attempt to identify a relation between the parameter of the electrical stimulation applied in the globus pallidus or subthalamic nuclei, the response of nearby neurons to the microstimulation, and changes in the cat's neurologic symptoms. We will attach multisite silicon substrate recording microelectrode arrays to some of the iridium shafts and these will be chronically implanted into the feline globus pallidus and subthalamic nuclei for up to 180 days.