MICROELECTRODE ARRAYS FOR DEEP BRAIN STIMULATION AND REC

该提案是根据RFA NS-99-006提交的；“脑深部刺激治疗帕金森病协会”该提案解决了RFA的邀请，即“开发可以同时刺激、记录和执行微透析或注入化学物质的微电极”。我们建议开发15个离散激活的铱记录和/或刺激微电极阵列，适合长期植入白球或丘脑下核。我们将开发两种阵列配置。在类型1中，所有的微电极都可用于刺激和记录单一神经元的动作电位。我们将确定暴露尖端的最佳区域，以便每个电极能够记录单位动作电位，并能够刺激附近的苍白球和丘脑底核神经元。在2型阵列中，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 mum2的微电极，这些微电极将保留用于刺激。我们将研究白球和丘脑底核的神经元活动与电刺激参数之间的关系。这些将包括对长期刺激诱导的神经元兴奋性抑制的研究，这可能与帕金森病的治疗尤其相关。我们将评估MPTP诱发短暂性帕金森样综合征的猫的阵列，我们将试图确定施加在苍白球或丘脑下核的电刺激参数、附近神经元对微刺激的反应以及猫的神经系统症状变化之间的关系。我们将把多位点硅衬底记录微电极阵列连接到一些铱轴上，并将这些电极长期植入猫的苍白球和丘脑下核长达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.