MICROELECTRODE ARRAYS FOR DEEP BRAIN STIMULATION AND REC

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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.