Configuring microelectrodes for safe and effective chronic electrical stimulation

项目描述（由申请人提供）：项目目标是量化刺激电荷密度（QD）和每相电荷(Q)在大脑皮层长时间微刺激诱导神经元兴奋性降低和神经元丢失中的作用和相互作用。我们将研究在猫大脑皮层十字后回刺激微电极附近的微刺激的这些影响，以及在相邻的十字前回的远程影响。对于更大的“大电极”，已经确定了Q、QD与神经元损伤发生（或不存在）之间的关系，并使安全有效的神经接口电刺激方案得以发展，我们建议对脑实质内微刺激进行同样的研究。在某些特定情况下，已经确定了安全（和有害）的肺实质内微刺激方案，但对于微刺激，尚未对Q、QD与生理和组织学反应的相互作用进行系统研究。该研究将采用硅衬底微电极和微丝电极长期植入成年猫的感觉运动皮层。我们将确定Q和QD的组合能够在200小时的刺激（每天8小时，持续25天）中激发大脑皮层锥体束神经元，而不会产生神经元兴奋性的抑制或丧失。待评估的Q范围（2至16 nC/相）将跨越可能用于临床界面的全部或大部分范围。刺激将每天持续7小时，共210小时，脉搏频率为50pps。这旨在成为临床神经接口中使用的参数的现实代表。由于Q/QD = A，电极的几何表面积，该研究的数据将定义A的值，该值是必要和足够的，可以在大脑皮层中使用每个阶段指定的电荷进行安全有效的慢性微刺激。

DESCRIPTION (provided by applicant): The project goal is to quantify the roles and interactions of stimulus charge density (QD) and charge per phase (Q) in the induction of depression of neuronal excitability and loss of neurons during prolonged microstimulation in the cerebral cortex. We will examine these effects of the microstimulation in the immediate vicinity of the stimulating microelectrodes in the feline post-cruciate gyrus of the cerebral cortex, and also the remote effects in the adjacent pre-cruciate gyrus. The relations between Q, QD and the occurrence (or absence) of neuronal injury have been determined for larger "macroelectrodes" and has enabled development of protocols for safe and effective electrical stimulation with neural interfaces, and we propose to do the same for intraparenchymal microstimulation. Safe (and damaging) protocols for intraparenchymal microstimulation have been determined for some specific situations, but for microstimulation a systematic study has not been performed for the interactions of Q,QD and the physiologic and histologic responses. The proposed study will employ silicon substrate microelectrodes and microwire electrodes implanted chronically in the sensorimotor cortex of adult cats. We will identify combinations of Q and QD that are able to excite pyramidal tract neurons of the cerebral cortex without producing depression of neuronal excitability or loss during 200 hours of stimulation (8 hrs/day for 25 days). The range of Q to be evaluated (2 to 16 nC/phase) will span all or most of the range that is likely to be used in a clinical interface. The stimulus will be delivered for 7 hour per day, for a total of 210 hours at a pulse rate of 50 pps. This is intended to be a realistic representative of the parameters that would be used in a clinical neural interface. Since Q/QD = A, the electrodes' geometric surface area, the data from the study will define the value of A that is necessary and sufficient to allow safe and effective chronic microstimulation in the cerebral cortex using a specified charge per phase.