Control of Efferent and Afferent Peripheral Nerve Activity with Intrafascicular Microstimulation

通过束内微刺激控制传出和传入周围神经活动

• 批准号: 1134545
• 负责人: Richard Normann
• 金额: $ 19.85万
• 依托单位: University of Utah
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1134545&HistoricalAwards=false
• 关键词: Control; Efferent; Afferent; Peripheral; Nerve

1134545NormannThe proposed work is focused on electrophysiological studies of the axons in the fascicles of the pudendal nerve of anesthetized felines. It is motivated by recently developed high-electrode-count microelectrode arrays, such as Utah Slanted Electrode Arrays (hereafter, ?Utah arrays?). Utah arrays can be inserted intrafascicularly into the peripheral nervous system to selectively stimulate small groups of axons within the fascicles. The limitations of this evolving technology on the selective control of distal musculature have not been fully explored, which provides the motivation for the proposed work. Low frequency stimuli, delivered via individual microelectrodes in a Utah array implanted intrafascicularly into the feline sciatic nerve can selectively activate up to nine muscles of the animal?s hind limb. High frequency alternating current stimulation via microelectrodes in a Utah array can selectively block orthodromic neural activity in the sciatic nerve, and thereby, selectively block activation of a targeted muscle. These studies did not optimize the stimulation parameters to produce prolonged selective excitation or blocking of distal musculature, nor did they localize the stimulation sites to particular fascicles, or to axon subsets within individual fascicles. Finally, the blocking of orthodromic action potentials was associated with a transient increase in muscular contraction preceding the block, and stimulation protocols that may reduce this transient onset contraction were not investigated. The proposed work will investigate these limitations of intrafascicular microelectrode stimulation in the feline pudendal nerve using a recently developed Utah array that was designed specifically to provide improved access to the axons of this nerve. Compared to a conventional Utah array, this new design has electrodes spaced at 200 microns and provides a four-fold increase in the spatial density of the electrodes implanted into the feline pudendal nerve. The proposed work is focused on the feline pudendal nerve because it has afferent and efferent fibers running within a single fascicle which will allow the investigation of the feasibility of simultaneous excitation of afferent and blocking of efferent axonal subsets within a single fascicle. Further, the consequences of activation and blocking the axons in this single fascicle have specific motor consequences that are readily monitored: activation of the afferent fibers evokes a reflexive contraction of the bladder wall (the detrusor muscle), and activation of the efferent fibers will evoke electromyograms in the external urethral sphincter. These latter axons will be targeted for blocking of orthodromic action potentials, thereby, producing controlled relaxation of the sphincter. The proposed work will also take advantage of the precise geometric location of the electrode tips in the Utah array and allow mapping of the functional organization of this nerve, which includes neuronal pathways involved in reflexive bladder contractions, reflex erection, and contraction of the external urethral and anal sphincters.

1134545 Norman提出的工作集中于麻醉猫阴部神经束中轴突的电生理学研究。 它的动机是最近开发的高电极计数微电极阵列，如犹他州倾斜电极阵列（下文中，？犹他州阵列？）。犹他州阵列可以被插入到周围神经系统内，以选择性地刺激神经束内的小轴突群。这种不断发展的技术对远端肌肉组织的选择性控制的局限性尚未得到充分探讨，这为所提出的工作提供了动力。低频刺激，通过个人微电极在犹他州阵列植入到猫坐骨神经内，可以选择性地激活多达9个肌肉的动物？的后肢。通过犹他州阵列中的微电极的高频交流电刺激可以选择性地阻断坐骨神经中的顺向神经活动，从而选择性地阻断靶肌肉的激活。这些研究没有优化刺激参数以产生长时间的选择性兴奋或阻断远端肌肉组织，也没有将刺激部位定位到特定的神经束或单个神经束内的轴突子集。最后，顺向动作电位的阻断与阻断前肌肉收缩的短暂增加相关，并且没有研究可能减少这种短暂开始收缩的刺激方案。拟议的工作将调查这些限制的神经束内微电极刺激在猫阴部神经使用最近开发的犹他州阵列，专门设计用于提供更好的访问这个神经的轴突。与传统的犹他州阵列相比，这种新设计的电极间距为200微米，植入猫阴部神经的电极的空间密度增加了四倍。拟议的工作是集中在猫阴部神经，因为它有传入和传出纤维运行在一个单一的束，这将允许调查的可行性，同时兴奋的传入和传出轴突子集在一个单一的束。此外，激活和阻断这一单纤维束中的轴突的结果具有易于监测的特定运动结果：传入纤维的激活引起膀胱壁（逼尿肌）的反射性收缩，传出纤维的激活将引起尿道外括约肌中的肌电图。这些后一种轴突将被靶向用于阻断顺向动作电位，从而产生括约肌的受控松弛。拟议的工作还将利用电极尖端在犹他州阵列中的精确几何位置，并允许映射该神经的功能组织，其包括参与反射性膀胱收缩、反射性勃起以及尿道外括约肌和肛门括约肌收缩的神经元通路。