MICROELECTRODE ARRAYS FOR DEEP BRAIN STIMULATION AND REC

本提案是为了响应RFA NS-99-006：“帕金森病治疗脑深部电刺激联盟”而提交的。该提案解决了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品的微电极”。 我们建议开发15个离散的激活铱记录和/或刺激微电极的阵列，适合于非常长期的植入到苍白球或丘脑底核。 我们将开发两种阵列配置。 在类型1中，所有的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区域，以便每个电极能够记录单位动作电位，并能够刺激苍白球和丘脑底核中的附近神经元。 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，并且将具有对于该功能最佳的几何表面积。与9个记录电极穿插的是6个微电极，其几何表面积为10，000 mum 2，将保留用于刺激。我们将研究苍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，这可能与帕金森病的治疗特别密切相关。 我们将评估的阵列中的猫，其中一个短暂的帕金森氏综合征已引起MPTP，我们将试图确定的参数之间的关系，应用在苍白球或丘脑底核的电刺激，附近的神经元的微刺激的反应，并在猫的神经症状的变化。我们将把多位点硅基底记录微电极阵列连接到一些铱轴上，这些微电极阵列将长期植入猫苍白球和丘脑底核中长达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.