Configuring microelectrodes for safe and effective chronic electrical stimulation

描述（由申请人提供）：该项目的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期间诱导神经元兴奋性抑制和神经元丢失中的作用和相互作用。 我们将研究这些影响的微刺激在刺激微电极在猫后交叉回的大脑皮层附近，也在相邻的前交叉回的远程影响。 Q，QD和神经元损伤的发生（或不存在）之间的关系已被确定为较大的“宏电极”，并使安全和有效的电刺激与神经接口的协议的发展，我们建议做同样的实质内微刺激。 脑实质内微刺激的安全（和破坏）协议已被确定为一些特定的情况下，但微刺激的Q，QD和生理和组织学反应的相互作用尚未进行系统的研究。 拟议的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。 我们将鉴定Q和QD的组合，其能够在200小时的刺激（8小时/天，持续25天）期间兴奋大脑皮层的锥体束神经元而不产生神经元兴奋性的抑制或损失。 待评价的Q范围（2至16 nC/相位）将涵盖可能用于临床接口的全部或大部分范围。 刺激将以50 pps的脉冲率每天输送7小时，总共210小时。 这预期是临床神经接口中使用的参数的现实代表。 由于Q/QD = A，即电极的几何表面积，因此研究数据将定义A值，该值是必要且足够的，以允许在大脑皮层中使用每相指定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.