The 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.
The key outcomes of the N.S.F. support were 1) The development of the new High-Density, Utah Slanted Electrode Array (HD-USEA). This silicon-based peripheral nerve interface consists of 100 microelectrodes of lengths that vary from 0.3 to 1 mm across the array, and that are spaced 200 microns from each other (shown in the attached figure). 2) The demonstration that such a high spatial density of penetrating microelectrodes (25 electrodes/mm2) can be implanted intrafascicularly in rodent sciatic nerve over an eight week period. Such implantation into small peripheral nerves only transiently impaired motor function (monitored with averaged wheel running, noxious sensory paw withdrawal reflexes, footprints, and nerve morphology). 3) In spite of their high spatial density, HD-USEAs allow the recording of efferent and afferent motor and sensory single-unit neural activity from implanted nerves. 4) The demonstration that passing high frequency electrical current via selected electrodes in a HD-USEA implanted in the feline pudendal nerve can block targeted efferent neural activity in the nerve and that low frequency electrical stimulation passed via other selected electrodes in the implanted array can excite targeted efferent fibers. 5) That this selective electrical stimulation delivered via HD-USEAs implanted intrafascicularly in the feline pudendal nerve can restore urinary continence in anesthetized animals that have been made incontinent by bilateral transection of both pudendal nerves (shown in the attached figure). 6) That selective electrical stimulation via HD-USEAs implanted in the feline pudendal nerve can either produce sustained bladder contractions or inhibit distension evoked bladder contractions depending upon the frequency of electrical stimulation, and on the use of selected electrodes in the implanted arrays. The results of this work suggest that targeted electrical stimulation delivered via penetrating microelectrode arrays implanted in the pudendal nerve could form the basis of clinical devices for the restoration of urinary function in individuals who have lost this function.
