Multiple sessions of therapeutic electrical stimulation using implantable thin-film wireless nerve stimulators improve functional recovery after sciatic nerve isograft repair.

INTRODUCTION/AIMS: Although therapeutic electrical stimulation (TES) of injured peripheral nerve promotes axon regeneration and functional recovery, clinical applications of this therapy are limited to the intraoperative timeframe. Implantable, thin-film wireless nerve stimulators offer a potential solution to this problem by enabling delivery of electrical stimuli to an injured nerve over a period of several days post-surgery. The aim of this study was to determine the optimal time course of stimulation for maximizing functional recovery in a rat sciatic nerve isograft repair model. METHODS: Adult male Lewis rats underwent thin-film wireless nerve stimulator implantation following sciatic nerve transection and 40 mm nerve isograft repair. Immediately after surgery, animals began a daily regimen of TES for up to 12 consecutive days. Functional recovery was assessed by compound muscle action potential (CMAP), evoked muscle force, wet muscle mass, and axon counting. RESULTS: Serial CMAP measurements increased in amplitude over the course of the study, yet no significant difference between cohorts for serial or terminal CMAPs was observed. Axon counts and wet muscle mass measurements were greatest in the 6-day stimulation group, which correlated with a significant increase in evoked muscle force for the 6-day stimulation group at the terminal time point. DISCUSSION: Six daily sessions of TES were found to be most effective for augmenting functional recovery compared to other time courses of stimulation. Future studies should incorporate additional subjects and track axonal sprouting or measure neurotrophin levels during the therapeutic window to further elucidate the mechanisms behind, and ideal amount of, TES.

A custom interface for the joint operation of Med Associates and Tucker-Davis Technologies hardware in a rodent behavioral model.

BACKGROUND: Rodent behavioral models with an electrophysiological component may require the joint operation of hardware from Med Associates, Inc. (St. Albans, VT) and Tucker-Davis Technologies (TDT; Alachua, FL). Although these manufacturers do produce supplemental hardware for interfacing with each other, investing in such hardware may be untenable for research groups with limited funds who wish to use equipment already in their possession. NEW METHOD: We designed a printed circuit board (PCB) in KiCad and had it fabricated by Advanced Circuits (Aurora, CO), with components sourced from Digi-Key (Thief River Falls, MN). The PCB provided 8 channels of bidirectional communication for the transmission of signals between Med Associates' SG-716B SmartCtrl connection panel and TDT's RZ5D base station. This setup enabled the coordinated operation of programs running separately on each set of hardware. RESULTS: The custom-built PCB facilitated the joint operation of Med Associates and TDT hardware in a go/no-go detection task involving rats with electrical implants in their sciatic nerves. COMPARISON WITH EXISTING METHODS: Conventional methods for interfacing Med Associates and Tucker-Davis Technologies rely on the purchase of pre-built hardware whose costs can add up to thousands of dollars. The present method offers a viable alternative that is easily implemented and considerably less expensive (below $200). CONCLUSION: The present approach provides an inexpensive yet effective alternative to far more costly interfacing solutions offered by Med Associates and Tucker-Davis Technologies.

Sensory Percepts Elicited by Chronic Macro-Sieve Electrode Stimulation of the Rat Sciatic Nerve.

Objective: Intuitive control of conventional prostheses is hampered by their inability to provide the real-time tactile and proprioceptive feedback of natural sensory pathways. The macro-sieve electrode (MSE) is a candidate interface to amputees' truncated peripheral nerves for introducing sensory feedback from external sensors to facilitate prosthetic control. Its unique geometry enables selective control of the complete nerve cross-section by current steering. Unlike previously studied interfaces that target intact nerve, the MSE's implantation requires transection and subsequent regeneration of the target nerve. Therefore, a key determinant of the MSE's suitability for this task is whether it can elicit sensory percepts at low current levels in the face of altered morphology and caliber distribution inherent to axon regeneration. The present in vivo study describes a combined rat sciatic nerve and behavioral model developed to answer this question. Approach: Rats learned a go/no-go detection task using auditory stimuli and then underwent surgery to implant the MSE in the sciatic nerve. After healing, they were trained with monopolar electrical stimuli with one multi-channel and eight single-channel stimulus configurations. Psychometric curves derived by the method of constant stimuli (MCS) were used to calculate 50% detection thresholds and associated psychometric slopes. Thresholds and slopes were calculated at two time points 3 weeks apart. Main Results: For the multi-channel stimulus configuration, the average current required for stimulus detection was 19.37 µA (3.87 nC) per channel. Single-channel thresholds for leads located near the nerve's center were, on average, half those of leads located near the periphery (54.92 µA vs. 110.71 µA, or 10.98 nC vs. 22.14 nC). Longitudinally, 3 of 5 leads' thresholds decreased or remained stable over the 3-week span. The remaining two leads' thresholds increased by 70-74%, possibly due to scarring or device failure. Significance: This work represents an important first step in establishing the MSE's viability as a sensory feedback interface. It further lays the groundwork for future experiments that will extend this model to the study of other devices, stimulus parameters, and task paradigms.

Interfacing peripheral nerve with macro-sieve electrodes following spinal cord injury.

Macro-sieve electrodes were implanted in the sciatic nerve of five adult male Lewis rats following spinal cord injury to assess the ability of the macro-sieve electrode to interface regenerated peripheral nerve fibers post-spinal cord injury. Each spinal cord injury was performed via right lateral hemisection of the cord at the T9-10 site. Five months post-implantation, the ability of the macro-sieve electrode to interface the regenerated nerve was assessed by stimulating through the macro-sieve electrode and recording both electromyography signals and evoked muscle force from distal musculature. Electromyography measurements were recorded from the tibialis anterior and gastrocnemius muscles, while evoked muscle force measurements were recorded from the tibialis anterior, extensor digitorum longus, and gastrocnemius muscles. The macro-sieve electrode and regenerated sciatic nerve were then explanted for histological evaluation. Successful sciatic nerve regeneration across the macro-sieve electrode interface following spinal cord injury was seen in all five animals. Recorded electromyography signals and muscle force recordings obtained through macro-sieve electrode stimulation confirm the ability of the macro-sieve electrode to successfully recruit distal musculature in this injury model. Taken together, these results demonstrate the macro-sieve electrode as a viable interface for peripheral nerve stimulation in the context of spinal cord injury.